ORIGINAL ARTICLES. Muhammad Nadir Khan, Shoaib Akbar, Abeer Ashfaq. Jehan Essa, Rashad Siddiqi, Syed Shaheer Haider Bukhari, Rehana Javaid

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2 PAKISTAN ARMED FORCES MEDICAL JOURNAL Vol-68 (Suppl-1) Mar 2018 Recognized by PMDC & HEC Editorial Advisory Board Chairman Dr Zahid Hamid Members Prof Iftikhar Hussain Prof Arshad Mahmood Dr Najm Us Saqib Khan Dr Khawar Rahman Dr Ammar Raza Dr Ahmad Muqeem Editorial Committee Chief Editor Prof Saleem Ahmed Khan Editor Dr Tariq Mahmood Ahmad Joint Editor Prof Khadija Qamar Assistant Editors Prof Muhammad Alamgir Khan Dr Palvasha Waheed Dr Syed Fawad Mashhadi Dr Kulsoom Farhat Dr Aliya Hisam Bibliographer Mr Ch Muhammad Saeed Statistician Miss Sajida Javed Editorial Board Members International Dr. Desley Neil (Birmingham, UK) Prof Mohammad Bagher Rokni (Tehran, Iran) Prof Waheed-uz-Zaman Tariq (Al Ain, UAE) Prof Ali-I-Musani (USA) Dr Ahmed Badar, (University of Dammam, KSA) Dr Xu Jinlian (China) Dr Syed Naveed Aziez (Australia) Dr Imtiaz Ahmad Cheema (UK) Dr Naeem Nabi (Canada) National (Extra-Organizational) Prof Shahid Pervez (Karachi) Prof Muhammad Tayyab (Lahore) Prof Zafar Nazir (Karachi) Prof Shoaib Shafi (Rawalpindi) Prof Assad Hafeez (Islamabad) Prof Ishtiaq Ahmed (Islamabad) National (Organizational) Prof Salim Jehangir Prof Zafar Iqbal Shaikh Prof Shamrez Khan Prof Safdar Abbas Prof Naeem Naqi Prof Tahir Mukhtar Sayed Prof Muhammad Tahir Khadim Prof Sohail Aziz Prof Irfan Ali Sheikh Prof Waseem Ahmed Prof Syed Nusrat Raza Prof Shehla M Baqai Dr Muhammad Manzoor Dr Abdus Sattar Aleem Dr Safdar Hussain ORIGINAL ARTICLES CONTENTS Efficacy of Ivabradine, Metoprolol Alone Vs Ivabradine Plus Metoprolol (Combination) For Heart Rate Reduction And Heart Rate Variability During Computed Tomography Coronary Angiography: A Randomized Controlled Trial Farhan Tuyyab, Rehana Khadim, Shaheer Farhan, Abdul Hameed Siddiqui, Fahad Munir, Tahir Iqbal, Sohail Aziz, Tariq Hussain Khattak, Imtiaz Ahmed Khan, Faheem Hassan Hyperlipidemia Patterns in Newly Diagnosed Young Diabetic Soldiers: A Descriptive Cross-Sectional Study Abdul Hameed Siddique, Imran Ahmad, Muhammad Hafeez, Rehana Khadim, Sohail Aziz, Tahir Iqbal, Farhan Tuyyab, Tariq Hussain, Imtiaz Ahmed Khan, Sarfaraz Ali Zahid A Retrospective Descriptive Study Analysis of Frequency of Totally Occluded Coronary Arteries in Patients of Stable IHD Undergoing Routine Coronary Angiography Muhammad Nadir Khan, Shoaib Akbar, Abeer Ashfaq Transcatheter Closure of Large Persistent Ductus Arteriosus With The Muscular Ventricular Septal Defect Device Amjad Mahmood, Maad Ullah, Nadeem Sadiq, Khurram Akhtar, Mehboob Sultan, Kamal Saleem, Asif Akbar Shah, Aziz Ahmed Differences in Angiographic Characteristics of Young And The Elderly Patients Undergoing Primary Percutaneous Coronary Intervention in AFIC Hafiz Muhammad Shafique, Mubarra Nasir, Farhan Tuyyab, Muhammd Asad, Rehana Khadim, Hassan Shabeer, Mir Waqas Baloch Procedural Outcomes of Chronic Total Occlusin-Percutaneous Coronary Intervention, An Updated Analysis of AFIC/NIHD CTO-PCI Registry Azhar Ali Chaudhry, Sohail Aziz, Tahir Iqbal, Suleman Ahmed, Farhan Tuyyab, Rehana Khadim, Yasir Javed,Kumail Giskikari, Shuja Abbas, Mir Waqas Baloch Electrocardiographic Changes in Acute Pulmonary Embolism With Right Heart Strain And It's Association With Adverse Clinical Events Tariq Hussain Khattak, Muhammad Azmat Khan, Imran Ahmed, Javeria Kamran, Hafsa Khalil, Aysha Siddiqa, Rehana Javaid Effects of Propofol Infusion Versus Sevoflurane on Hemodynamic Response During Cardiopulmonary Bypass in Patients Undergoing Coronary Artery Bypass GRAFT Surgery Jehan Essa, Rashad Siddiqi, Syed Shaheer Haider Bukhari, Rehana Javaid A Comparsion of Contrast Induced Nephropathy Between Normal And High Risk Population Undergoing Coronary Angiography Mir Waqas Baloch, Rehana Khadim, Samra Rehmat, Mohammad Asad, Sohail Aziz, Tahir Iqbal, Imran Fazal, Tariq Hussain Khattak, Azhar Ali Chaudary, Hasnain Iqbal Prevalence And Associated Risk Factors of Renal Complications in Congenital Cardiac Disease Patients Hafsa Khalil, Iftikhar Ahmed, Kamal Saleem, Umair Younas, Rawail Iftikhar, Adeela Khan Short Term Outcomes of Left Main Coronary Artery Stenting Muhammad Nadir Khan, Tahira Muqaddas, Tahir Iqbal Frequency of Angiographically Significant Coronary Artery Disease in Patients Undergoing Valve Replacement Surgery With or Without Risk Factors For Atherosclerosis Hassan Shabeer, Ali Nawaz, Farhan Tayyab, Tariq Hussain Khattak, Rehana Khadim, Hafiz Muhammad Shafique, Azhar Ali Chaudhry Thrombolytic Therapy in Prosthetic Valve Thrombosis; Efficacy And Outcome Tariq Hussain Khattak, Tahir Naqqash, Muhammad Azmat Khan, Javeria Kamran, Aysha Saddiqa, Rehana Javaid, Hafsa Khalil Incidence And Risk Factors of Delerium After Cardiac Surgery Amna, Saira Mahboob, Safdar Ali Khan, Urooj Alam, Quratalain Amjad Efficacy of Tissue Plasminogen Activator, Heparin And Streptokinase in Patients With Sub Massive Pulmonary Embolism in A Tertiary Care Cardiac Hospital Imran Ahmed, Ayesha Riaz, Javeria Kamran, Abdul Hameed Siddiqui, Hasnain Yousaf, Shujja Abbas, Kamran Abbas, Farhan Tuyyab, Tahir Iqbal, Sohail Aziz Immediate Therapeutic Outcomes of Trans Catheter Pulmonary Balloon Valvuloplasty For Critical Pulmonary Stenosis Syed Asif Akbar Shah, Mehboob Sultan, Khurram Akhtar, Aziz Ahmed, Nadeem Sadiq, Amjad Mahmood, Ali Nawaz, Kamal Saleem Dyspnea in Pregnancy-Incidence And Common Causes Asma Ansari, Fayyaz Hussain, Riffat Sultana, Hafsa Khalil Mediastinal Bleeding And Blood Transfusions in Patients Undergoing Coronary Artery Bypass Surgery Performed With or Without Crdiopulmonary Bypass Muddasar Noor, Farrah Pervaiz, Muhammad Afsheen Iqbal, Muhammad Waseem, Asif Mahmood Janjua, Kanwal Afreen, Aysha Saddiqa, Rehana Javaid Arrhythmias Among Young Male Soldiers Up To 40 Years of Age With Structurally Normal Heart Ajab Khan, Imran Ali, Azmat Hayat, Muhammad Shabbir, Rehana Khadim, Ali Nawaz, Hafiz Muhammad Shafiq, Naqib Ullah Knowledge of Food Service Staff Regarding Food Safety And Food Hygiene in AFIC & NIHD Maryam Zahid, Hafsa Khalil, Samina Nazir, Sabat Baber, Safdar Abbass S1 S5 S10 S14 S18 S23 S28 S34 S38 S42 S49 S54 S59 S64 S69 S75 S81 S86 S93 S97

3 The Pakistan Armed Forces Medical Journal (PAFMJ) is an official journal of Army Medical Corps and is being published since Few of the salients of the journal are as below:- Recognized by PMDC & HEC Indexed in ICI Journals Master List - Index Copernicus Indexed in HINARI list of Journals Inclusion of PAFMJ Indexed in WHO Index Medicus (IMEMR), EBSCO Host, DOAJ, Scientific Journals Impact Factor (SJIF), Pak medi net, Scope med, Index Scholar Indexation of PAFMJ in Cumulative Index Medicus of Eastern Mediterranean Region Journals Allocation of International Standard Serial Number France (print & online) Availability of PAFMJ on Internet: [ Online submission of articles through online submissions system-ejmanager Attraction of wider authorship and readership Awareness of Health Care Workers Regarding Alcohal Hand Rub Usage At Tertiary Care Hospitals Javeria Kamran, Farrah Pervaiz, Safdar Abbas, Suhail Aziz, Muhammad Afsheen Iqbal, Rukhsana Roshan, Hafiza Zahid, Rabia Atif Frequency And Predictors of Stent Thrombosis in Primary PCI Patients At AFIC Hafiz Muhammad Shafique, Sohail Aziz, Sarfaraz ali zahid, Rehana Khadim, Mubarra Nasir Cardiac Surgery Associated Acute Kidney Injury in Relation To Cardiopulmonary Bypass Time And Aortic Cross Clamp Time Amna, Etizaz Haider Kazmi, Rashad Siddiqi, Karam Iqbal, Iftikhar Ahmad Zaidi, Rehana Javaid Patterns of Lad Involvement in Individuals Till 40 Years of Age Presenting As Acute Anterior Wall St-Elevated Myocardial Infarction And Undergoing Primary Percutaneous Coronary Intervention Azhar Ali Chaudhry, Imran Ali, Sarfaraz Ali Zahid, Tariq Hussain Khattak, Rehana Khadim, Hazfiz Muhammad Shafique, Asma Shabbir, Tahir Naqqash, Kumail Giskikari, Atif Altaf Comparison of Different Types of Responses To Tilt-Table Testing in Patients of Both Genders With Unexplained Syncope Ayesha Riaz, Azmat Hayat, Zahoor Khattak, Sadaf Shabbir Kiani, Mubarra Nasir, Samra Rehmat, Hassan Kamal, Muhammad Shabbir, Abdul Hameed Siddiqui, Fatima Qayyum Gait Speed A Clinical Maker of Frailty As A Predictor of Cardiac Surgery-Related Complications And in Hospital Morbidity in Patients Undergoing Cardiac Surgery Shiza Ali Khan, Safdar Abbas, Muhammad Waseem, Hafsa Khalil Comparison of Gabapentin And Lorazepam As Premedication To Attenuate The Pressor Response To Intubation in Cardiac Patients Undergoing Coronary Artery Bypass Graft Surgery; A Randomized Controlled Trial Muhammad Adnan Akram, Safdar Abbas, Rehana Javaid, Rashad Siddiqi, Sheza Iftikhar, Javeria Kamran Balloon Atrial Septostomy: Is Bedside Procedure Safe And Effective Under Transthoracic Echocardiographic Guidance? Nadia Quddus, Mehboob Sultan, Maad Ullah, Khurram Akhtar, Nadeem Sadiq, Amjad Mahmood, Kamal Saleem, Asif Akbar Shah, Aziz Ahmed, Muhammad Zahid Frequency And Outcome of Acute Left Ventricular Failure in Patients Undergoing Primary Percutanous Coronary Intervention For St-Segment Elevation Anterior Wall Myocardial Infarction Tahir Naqqash, Tariq Hussain Khattak, Sohail Aziz, Rehana Khadim, Aiza Qayyum, Tahir Iqbal, Farhan Tayyub, Waheed Akhter, Muhammad Yasin Role of Duke Treadmill Score in Assessing The Severity of Coronary Artery Disease in Patients Presenting With Angina Muhammad Asad, Rehana Khadim, Tahir Iqbal, Hafiz Muhammad Shafique, Mir Waqas Baloch, Samra Rehmat, Hasnain Iqbal, Sibtain Iqbal, Mohsin Hayat Transcatheter Management of Coronary Arteriovenous Fistula - Seven Year Experience Mehboob Sultan, Khurram Akhtar, Maad Ullah, Nadeem Sadiq, Amjad Mehmood, Kamal Saleem, Syed Asif Akbar Shah, Aziz Ahmed Single Center Experience on Use of Recombinant Factor Seven For Bleeding After Congenital Heart Surgery Amna, Etizaz Haider Kazmi, Kamal Saleem, Rehana Javaid, Iftikhar Ahmad In-Hospital Outcomes of Patients With Or Without Reciprocal Electrocardiographic Changes Presenting With Acute Inferior Wall Myocardial Infarction Hafiz Muhammad Shafique, Tahir Iqbal, Hassan Kamal, Tariq Hussain, Ajab Khan, Hassan Shabeer Evaluation of Role of Serum Uric Acid As An Indicator of Prognosis in Patients Presenting With Acute St-Segment Elevated Myocardial Infarction Muhammad Asad, Tahir Iqbal, Waheed Ur Rehman, Hafiz Muhammad Shafique, Mir Waqas baloch, Sadaf Shabbir Kiani, Rehana Khadim, Tahir Naqash, Aatika Kamran Frequency And Pattern of Left Main Stem Disease in Patients Reporting At AFIC & NIHD, Rawalpindi Hassan Shabeer, Sohail Aziz, Tahir Iqbal, Rehana Khadim, Hafiz Muhammad Shafique, Bilal Sidique, Azhar Ali Chaudhry Effect of Gender on Operative And Early Results of Coronary Artery Bypass Grafting Iftikhar Paras, Ghulam Hussain, Mirza Ahmad Raza Baig, Sehrish Khalid, Sara Zaheer, Khaliq Mahmood Patency of Bypass Grafts on Msct Angiography, AFIC Experience Muhammad Nadir Khan, Muhammad Adil, Syed Shahid Abbas, Sohail Aziz, Jahanzab Ali, Abdullah Hamid Gondal, Muhammad Hamza Jahangeer, Arslan Mehmood Evaluation of Etiology, Clinico-Pathological Presentation And Outcome of Pericardial Effusion Muhammad Kashif, Tanvir Ahmad Raja, Adeel Ur Rehman, Azhar Mehmood Kiyani, Faizania Shabbir, Tausif Ahmed Rajput REVIEW ARTICLE Left Main Coronary Artery Stenting Muhammad Nadir Khan, Tahira Muqaddas SHORT COMMUNICATION Effect of Recentrifugation on The Levels of High Sensitivity Troponin I Sumbal Nida, Raja Kamran Afzal, Mohammad Zaheer Us Saeed Angiographic Study of Coronary Grafts Asif Nadeem CASE REPORTS Diphtheria Myocarditis: Case Report Muhammad Nadir Khan, Tahira Muqaddas Emergence of Linezolid Resistance in Coagulase-Negative Staphylococcus Isolated From A Post-Surgical Case of Coronary Artery Bypass At A Tertiary Care Cardiac Setup in Pakistan Raja Kamran Afzal, Sumbal Nida, Mohammad Zaheer Us Saeed, Hafsa Khalil Transradial Carotid Stenting in A Patient With Bovine Arch Anatomy Muhammad Nadir Khan, Tahira Muqaddas Dual Lad Coronary Artery - A Rare Congenital Anomaly Hamza Iqbal, Imtiaz Ahmed Chaudhry, Muhammad Imran Asghar S103 S109 S116 S120 S124 S129 S134 S139 S143 S147 S153 S157 S161 S166 S172 S176 S183 S188 S194 S198 S202 S206 S208 S210 S212

4 Open Access Computed Tomography Coronary Angiography Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S1-S4 ORIGINAL ARTICLES EFFICACY OF IVABRADINE, METOPROLOL ALONE VS IVABRADINE PLUS METOPROLOL (COMBINATION) FOR HEART RATE REDUCTION AND HEART RATE VARIABILITY DURING COMPUTED TOMOGRAPHY CORONARY ANGIOGRAPHY: A RANDOMIZED CONTROLLED TRIAL Farhan Tuyyab, Rehana Khadim, Shaheer Farhan, Abdul Hameed Siddiqui, Fahad Munir, Tahir Iqbal, Sohail Aziz, Tariq Hussain Khattak, Imtiaz Ahmed Khan, Faheem Hassan Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSRTACT Objective: To establish the efficacy of Ivabradine, Metoprolol alone vs Ivabradine plus Metoprolol for the heart rate reduction in patients undergoing computed tomography coronary angiography. Study Design: Randomized controlled trial. Place and Duration of Study: Armed Forces Institute of Cardiology & National Institute of Heart Disease, Rawalpindi, from Oct 2017 to Jan Material and Methods: Patients undergoing first CTCA angiography meeting inclusion criteria with heart rates more than 80 beats/min were included. Patients were randomized into three groups using computer generated random tables. Arm A was administered Ivabradibe plus placebo, Arm B was administered Metoprolol plus plecebo while Arm C was administered Ivabradine plus Metoprolol one hour before the scan. All the groups had scans under strictly similar conditions. Heart rate before and during scan along with heart rate variability were recorded. Results: A total of 165 patients were included in the study, 55 patients in each group. Mean age of patients was 53.5 ± 0.5 years. One hundred and seven (64.8%) were males while patients 58 (35.2%) were females. Risk factor profile was almost similar in all the groups. Heart rate reduction in Arm A was 18.3 ± 3.8, in Arm B was 12.6 ± 5.8 and in Arm C was 24 ± 3.0 (p=0.02). Heart rate variability in Arm A was 3.2, in Arm B was 4.0 and in Arm C was 1.8 (p=0.001). Arm C had significantly lower heart rate and significantly less heart rate variability followed by Arm A then Arm B. Conclusion: Ivabradine is an established safe and effective heart rate-reducing agent in patients undergoing CTCA, particularly in those patients, who cannot tolerate beta-blockers or calcium-channel blockers due to their side effects. Keywords: Computed tomography coronary angiography, Heart rate, Heart rate variability, Ivabradine, Metoprolol. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Stable heart rate is the foremost prerequisite for the achievement of excellent image quality and the diagnostic accuracy with computed tomography coronary angiography (CTCA). Therefore, to reduce the coronary artery motion artifacts and enhance the image quality, an heart rate of beats per minutes is essential, while an increase in heart rate is related with nearly linear deterioration of image quality and diagnostic accuracy 1. β-blockers and calcium Correspondence: Dr Farhan Tuyyab, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan farhant65@hotmail.com channel blockers are the basic drugs which are utilize for the heart rate reduction, but their negative inotropic and dromotropic effects restrict their utilization in patients with hypotension, asthma, and peripheral vascular disease as some patients cannot bear the side effects 2. The pacemaker current channel (If) is a hyperpolarization activated cyclic nucleotide gated channel, and Ivabradine is the first sinoatrial node If current inhibitor which is unusual from the conventional heart rate reducing agents. Ivabradine decreases the heart rate without influencing the cardiac contractility, ventricular repolarization, blood pressure, or S1

5 Computed Tomography Coronary Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S1-S4 atrioventricular conduction 3. Ivabradine is undoubtedly a promising attractive substitute for inappropriate sinus tachycardia, stable angina, heart failure, and other cardiovascular diseases and it has beneficial implications for future clinical utilization 4. Many studies 2,5,6 have shown that Ivabradine plays an significant part in the heart rate reduction in CTCA, specially with regard to the quantification of the efficacy of pre-treatment with Ivabradine before CTCA. There is no contemporary data documenting the comparison of effect of Ivabradine and Metoprolol (in combination and alone) on heart rate reduction and heart rate variability in patients undergoing CT Angiography in AFIC & NIHD, Rawalpindi. Therefore we examined whether there was a significant difference between two drugs via randomized control trial. MATERIAL AND METHODS It was an allocation concealed triple blind (Patient-Investigator-Statistician) randomized control trial. Study was conducted at Cardiac Scan Department AFIC & NIHD, Rawalpindi. All the patients of both genders, with heart rates more than 80 beats/min while at rest and age between 25 to 65 years, undergoing first CTCA scan for the probable diagnosis of coronary artery disease were enrolled in the study. Data was collected using history & procedure details Performa. Patients with the previous history of CABG, PTCA/Stenting, with contraindications to beta blockers, patients with arrhythmia, allergy to iodinated contrast, already using beta blockers, anxiolytics, sedative and hypnotics, known cases of ischemic heart disease (IHD) and those patients who already had a CTCA scans were excluded. Patients who underwent scans in emergency were also excluded. Patients were recruited into three groups using randomization technique. Randomization was done through computer generated random tables using list of the patients undergoing CTCA. Sample size was calculated using Harvard Sample size Calculator. Sample size was 165 patients (55 study participants in each group). Arm A was administered tablet Ivabradine 5mg (tab Ivatab by Nabiqasim Industries ) plus a plecebo, Arm B was administered tablet metoprolol 100mg ½ tablet (tab Mepressor by Novartis ) plus a placebo and Arm C was administered tablet Mepressor 100 mg ½ tablet plus tablet Ivabradine 5mg one hour before the scan. All the patients were recruited after the written informed consent and confidentiality of the data was maintained. The variables for this study included heart rate of the patients before the test and heart rate during the test and heart rate variability during the test. Heart rates were recorded by doctor for one complete minute just before the test while patients were still in the waiting room and during the test on the scanning table just after the Calcium scoring. All scans were performed on Somatom Definition DSCT scanner from Siemens using same scan protocols and nonionic iodinated contrast agent Iopromide (Ultravist by Bayer schering pharma). Patients were blinded to the medications; similarly doctor taking the history and recording the heart rate was also blinded to the identity of patient groups. Data of the sample study was of quantitative nature and sample size was enough to make distribution normal. To exclude other factors contributing to heart rate changes consenting doctor, paramedic administering the medication and doctors recording the heart rate were the same for all patients and similarly technicians carrying out the scans, rate auditory instructions and doctors supervising the scan were also the same. All the Patients waited for at least one hour (range 1-3 hours) in the waiting area of cardiac scan department. All the scans were carried out by appointment and done in the morning time before noon and as outdoor procedures. Heart rate variability (HRV) was defined as the standard deviation of the mean heart rate during CT coronary angiography. S2

6 Computed Tomography Coronary Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S1-S4 Data entry and analysis was done by using SPSS (version 21.0). Chi-square test was used to the qualitative variables while ANOVA (Analysis of variance) was used for quantitative variables between three groups. A p-value<0.05 was taken as significant. RESULTS Total 165 patients were enrolled in the study. Table-I illustrates patient baseline characteristics. Table-I: Patient baseline characteristics. Total Arm A Characteristics Patients (Ivabradine + (n=165) Placebo) (n=55) Age 53.5 ± 0.5 Mean ± SD years Gender Male Female 107 (64.8%) 58 (35.2%) who cannot tolerate beta blockers due to the side effects 7. Ivabradine had no marked effect on either systolic or diastolic blood pressure 8. The patient groups comprized of a well-defined patient population referred for their first diagnostic CTCA angiogram with the diagnosis of probable coronary artery disease. Risk factor profile was similar to reported earlier. Peak effect of both metoprolol and Ivabradine was achieved Arm B (Metoprolol + Placebo) (n=55) Arm C Ivabradine + Metoprolol) (n=55) p-value 49.3 ± 2.8 years 51.7 ± 10.3 years 52.9 ± 6.6 years (19.6%) 24 (41.4%) 35 (59.0%) 34 (58.6%) 35 (59.0%) 20 (18.0%) Table-II: Association of Risk factor profile of three groups. Risk Factor Arm A Arm B Arm C n (%) n (%) n (%) p-value Hypertension 22 (60.0%) 47 (85.5%) 36 (65.5%) Diabetes Mellitus 11 (20.0%) 8 (14.5%) 27 (49.1%) Smoking History 20 (36.4%) 11 (83.6%) 46 (83.6%) <0.001 Hyperlipidemia 13 (23.6%) 5 (9.1%) 19 (34.5%) Family History 12 (22.8%) 11 (20.0%) 9 (16.4%) <0.001 of IHD Table-III: Reduction in heart rate and heart rate variability by medication groups. Variables Arm A Arm B Arm C p-value Heart Rate Variability (mean) Reduction in Heart Rate (Mean ± SD) ± 3.8 Beats/min 12.6 ± 5.5 Beats/min 24.4 ± 3.0 Beats/min <0.001 Table-II shows risk factor profile of the three groups. Hypertension was most prevalent among risk factors 105 (63.6%) followed by smoking history 77 (46.6%) and diabetes mellitus 46 (27.8%). Table-III shows that the use of two drugs (i.e. Ivabradine and metoprolol) in combination significantly lowered the heart rate variability 1.8 and significantly lowered the heart rate as well with reduction of 24.4 ± 3.0 beats/min. DISCUSSION Ivabradibe is a potential choice for patients undergoing CTCA, particularly for the patients after an hour. All the treatment groups showed significant drop in the heart rate but the magnitude of was higher in Ivabradine alone group and was much bigger and statistically significant in case of Arm C. Ivabradine is an established safe and effective heart rate- reducing agent 9. Ivabradine is a particular heart rate lowering agent that acts via selective and specific inhibition of the cardiac pacemaker If current, which controls the spontaneous diastolic depolarization in the sinus node and regulates the heart rate 10,11. Its effects on the heart are particular to the sinus node, with no effect on intra atrial, S3

7 Computed Tomography Coronary Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S1-S4 atrioventricular, or intraventricular conduction times, myocardial contractility, or ventricular repolarization Ma et al 16 reported that ivabradine enhance myocardial performance, left ventricular function and ventricular remodeling and even survival in rodent heart failure, including ventricular fibrillation, myocardial infarction, stable angina, and hypertensioninduced cardiomyopathy 16. Its side effects are uncommon and mainly limited to the dose related visual disturbances 10. Hence, ivabradine is appropriate for large variety of patients, including those individuals for whom other heart rate lowering drugs might be contraindicated 1,13. Beta-blockers are contrain-dicated in many conditions, despite the common use of betablockers before CTCA studies, it is quite common to have patients with heart rate continuously above the target range of 65 beats per minutes even though the use of oral as well as intravenous beta-blockers In this way, CTCA with oral ivabradine premedication is a practicable, safer, and better effective way to reduce the heart rate to generate images of diagnostically acceptable quality in nearly all coronary segments in comparison to beta-blockers. CONCLUSION Ivabradine is an established safe and effective heart rate reducing agent in patients undergoing CTCA, particularly in those patients, who cannot tolerate beta-blockers or calciumblockers due to their side effects. ACKNOWLEDGEMENT We would like to thank the whole CT Angio department for their valueable co-orporation in the whole trial. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. 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8 Open Access Hypercholestremia Patterns in Young Diabetic Soldiers Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S5-S9 HYPERLIPIDEMIA PATTERNS IN NEWLY DIAGNOSED YOUNG DIABETIC SOLDIERS: A DESCRIPTIVE CROSS-SECTIONAL STUDY Abdul Hameed Siddique, Imran Ahmad*, Muhammad Hafeez**, Rehana Khadim, Sohail Aziz, Tahir Iqbal, Farhan Tuyyab, Tariq Hussain, Imtiaz Ahmed Khan, Sarfaraz Ali Zahid Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Military Hospital/ National University of Medical Sciences (NUMS) Rawalpindi Pakistan, **Combined Military Hospital Multan Pakistan ABSTRACT Objective: To report the patterns of hyperlipidemia in newly diagnosed young diabetic soldiers. Study Design: A descriptive cross-sectional study. Place and Duration of Study: Combined Military Hospital Multan, from Jan to Sep Material and Methods: All newly diagnosed hospitalized type-ii diabetic male soldiers, were included in the study after having their informed consent. All the data was collected protectively through consecutive sampling. Data collection tool was developed regarding patient demographics, co-morbids, previous medical history and laboratory findings. Results: A Total of 55 patients were recruited for the study. The mean age of the patients was 41.1 ± 5.5 years and the range was 25 years to 50 years. All patients were males. Eight (14.5%) patients had diabetic nephropathy while diabetic retinopathy was present in 7 patients (12.7%). Family history was positive in 22 (40%) soldiers. Six (10.9%) patients were hypertensive while thirty nine patients (70.1%) were having type-ii diabetes and 16 (29.1%) had type-i diabetes mellitus. About 46 (83.6%) patients had trace proteinuria, out of which 3 patients had +1proteinuria and 4 patients had +2 proteinuria. Mean LDL was 1.1 ± 4.1 mmol/l. Mean cholesterol was 4.5 ± 0.9 mmol/l while mean triglycerides was 2.4 ± 1.7 mmol/l andmean HDL 0.9 ± 2.0 mmol/l. Conclusion: The study has clearly demonstrated statistically that high triglyceride levels are more prevalent than high LDL cholesterol levels in this patient group. Keeping the fact in view that hypertriglyceridaemia is a serious risk factor for the development of coronary artery disease it is therefore of paramount importance that this abnormality should be sought out at the outset of diabetes mellitus and addressed accordingly. Keywords: Hyperlipidemia, Diabetic Nephropathy, Diabetic Retinopathy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Diabetes mellitus is one of the leading causes of chronic morbidity and mortality. Diabetes mellitus prevalence is increasing many folds in South Asian population. Many factors like high body mass index, high susceptibility to environmental insulin, high degree of genetic predisposition and high level of insulin resistance are involved in this metabolic disorder 1. It is characterized by absolute deficiency in insulin secretion and insulin action associated with hyperglycemia, metabolism of protein, carbohydrate and lipids are disturbed 2. Different research studies show that body composition components like lipid profile and body fat are responsible for Correspondence: Dr Abdul Hameed Siddiqui, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan drahsans@gmail.com the increased prevalence of this disease 3. In diabetes mellitus the lipid abnormalities are more prevalent because major key enzymes and lipid metabolism pathways are affected due to deficiency of insulin production and secretion 3. Dyslipidemia is one of the major risk factors for cardiovascular disease in hyperglycemic patients. High triglycerides, low High Density Lipoprotein cholesterol, and increased Low Density Lipoprotein cholesterol are the characteristic feature of diabetic dyslipidemia. Type-II diabetes affects an estimated 21 million people in the United States 4. About 70-80% of diabetic patients will die of cardiovascular disease 5. The prevalence of hypercholesterolemia is not increased in patients with diabetes mellitus but mortality from coronary heart disease increases. American Diabetes Association S5

9 Hypercholestremia Patterns in Young Diabetic Soldiers Pak Armed Forces Med J 2018; 68 (Suppl-1): S5-S9 guidelines recommend maintaining serum levels of TG below 150 mg/dl, LDL cholesterol below 100 mg/dl and HDL cholesterol of more than 40 mg/dl in males and 50 mg/dl in females 6. The life style changes of the modern era have complicated the situation further. One has to keep in mind that the metabolic derangements so produced are to a significant extent preventable and reversible 7. In the whole world about 382 million people are the victim of hyperglycemia. The regions of high prevalence are North America and Caribbean about 11% 8. According to International Diabetes Federation estimates in 2013, 35 countries out of 219 countries have about 12% prevalence of diabetes % of Asian population is currently affected due to diabetes 10,16. In Pakistan 7.1 million people suffer due to diabetes 17. The data from Pakistan showed a prevalence rate of 18-46% while 46-75% Pakistani patients with diabetes had metabolic syndrome 9,10. One very important scenario is the triad of hyperlipidemia, type-ii diabetes and coronary artery disease whereby the severity of coronary artery disease is more pronounced 10. This study was conducted to analyse and document the frequency of hypertriglycridaemia and hyperlipidemia in a cohort of young male soldiers of productive age group with newly diagnosed type-ii diabetes mellitus. MATERIAL AND METHODS This study was conducted at CMH, Multan from January to September All newly diagnosed hospitalized type-ii diabetic male soldiers were included in the study after having their informed consent. These patients were from Armed Forces who clustered in a few months time. Data Analysis All the data was collected protectively through consecutive sampling. Data collection tool was developed regarding patient demographics, co-morbids, previous medical history and laboratory findings. Fasting samples were collected and analyzed for LDL cholesterol, total cholesterol and triglyceride levels. The fasting period was at least 9 hours and the maximum 12 hours. Exclusion criteria were patients on lipid lowering drugs as well as those patients who already were on dietary restriction. Patients who were obese were not included in the study. Also excluded were patients on who were alcoholic, on diuretics and beta blockers. High triglyceride levels were considered as readings above 1.7 mmol/l and high LDL cholesterol levels were considered readings above 2.59 mmol/l. Data was entered and analyzed in SPSS version 23. RESULTS A Total of 55 patients were recruited for the study. The mean age of the patients was 41.1 ± 5.5 years and the range was 25 years to 50 years. All patients were males. Eight (14.5%) patients had diabetic nephropathy while diabetic retinopathy was present in 7 patients (12.7%). Macrovascular complications were seen in 2 (3.6%) patients. Family history was positive in 22 (40%) soldiers. Six (10.9%) patients were hypertensive while thirty nine patients (70.1%) were having type-ii diabetes and 16 (29.1%) had type-i diabetes mellitus. About 46 (83.6%) patients had trace proteinuria, out of which 3 patients had +1proteinuria and 4 patients had +2 proteinuria. Mean LDL was 1.1 ± 4.1 mmol/l. Mean cholesterol was 4.5 ± 0.9 mmol/l while mean triglycerides was 2.4 ± 1.7 mmol/l and mean HDL 0.9 ± 2.0 mmol/l. Mean HBA1c was found to be 8.4 ± 1.1 as shown in table. DISCUSSION The risk of cardiovascular heart diseases in hyperglycemic patients is two to four times more as compare to normal. Lipid abnormalities (increased level of LDL, VLDL and triglycerides; and low levels of HDL) are an important cause of atherogenesis and known as atherogenic dyslipidemia 10. Lipid abnormalities may be the result of unbalanced metabolic state of diabetes and improved control of hyperglycemia does moderate diabetes-associated dyslipidemia 11. Fifty five patients were recruited for this study. Majority (78.5%) of the hyperglycemic patients S6

10 Hypercholestremia Patterns in Young Diabetic Soldiers Pak Armed Forces Med J 2018; 68 (Suppl-1): S5-S9 were aged above 40 years. The age of diabetic patients was observed to be above 40 years confirmed by earlier literature, previous studies reported that age plays a major role in the risk of developing type-ii diabetes especially after 40 years 12. The results showed in the present study that in hyperglycemic patients the lipid level are urbanization in the population from villages. Modernized life style associated with increasing urbanization, characterized by less physical activity and change of diet plan causes obesity leads to development of diabetes type-ii. The most common pattern of dyslipidemia was combined dyslipidemia with high LDL and Table: Clinical characteristics of the patients. Variables n (%) Age higher and the similar results were shown by Agrawal et al 2014 and Huang et al In our study prevalence of dyslipidemia was 29.7% in hyperglycemic patients. Two different studies conducted in India showed the prevalence of dyslipidemia in hyperglycemic patients was 89.0% and 92.4% (Udawat et al., 2001, Jayarama et al., 2012) 13. In this study high prevalence of dyslipidemia could be credited to (Mean ± SD) ± 5.5 years (Range) years Diabetic nephropathy 8 (14.5%) Diabetic retinopathy 7 (12.7%) Macrovascular Complications 2 (3.6%) Hyperglycemic Hyperosmolar Non-ketotic 1 (1.8%) Coma history Family History 22 (40.0%) Hypertension 6 (10.9%) Diabetes Type Type I Type II Proteinuria Trace Hyperlipidemia Hypertriglyceridemia LDL HDL Urea Creatinine HbA1C ALT BSF BSR 16 (29.1%) 39 (70.9%) 46 (83.6%) 3 (5.5%) 4 (7.5%) (Mean ± SD) 4.5 ± 0.9 mmol/l (Mean ± SD) 2.4 ± 1.7mmol/L (Mean ± SD)1.1 ± 4.1mmol/L (Mean ± SD) 0.9 ± 2.0mmol/L (Mean ± SD) 3.0 ± 24.0mmol/L (Mean ± SD) 96.7 ± 67.4µmol/L (Mean ± SD) 8.4 ± 1.1mmol/L (Mean ± SD) 49.8 ± 4.8 units/l (Mean ± SD) ± 63.8mg/dL (Mean ± SD) ± 97.5mg/dL low HDL this pattern of combined dyslipidemia was also studied in another study conducted in Southern India by Jayarama 14. It was found that the prevalence of dyslipidemia in type-ii diabetes mellitus as a whole was 86.75% with 29.7% single parameter of dyslipidemia, hypertriglycerides was found in about 56.46% and low HDL was found in about 72.92% 15. The most prevalent lipid abnormality in our study was high LDL 24.3% S7

11 Hypercholestremia Patterns in Young Diabetic Soldiers Pak Armed Forces Med J 2018; 68 (Suppl-1): S5-S9 followed by low HDL 27.6% whereas in another study conducted in Kuwait isolated dyslipidemia is the second most common pattern with increased LDL-cholesterol, observed in 21% of the patients 4. Kandula et al conducted a study in Hyderabad (India) showing that prevalence of dyslipidemia was 86%, while high total cholesterol was 41%, LDL was 64%, triglycerides was 47% and low HDL was 71% 14. This prevalence of dyslipidemia was relevant to our study. A study conducted in Nishtar Hospital Multan showed that 21% patients with diabetes had raised serum cholesterol and 34.2% had raised serum triglyceride level 3,16, while in another study conducted in 2011, 14% diabetic patients had raised cholesterol level while 31% patients had raised TG level 17,18. In our study high cholesterol level was found in 29.7% patients and high serum TG found in 49.0% hyperglycemic patients. Different values of serum cholesterol may be due to different dietary habits of people in different cities of the country. According to different previous studies diabetes mellitus has been one of the most prevailing diseases. Its complications may cause death directly and indirectly 19,20. According to a study of 100 patients, 31% hyperglycemic patients had vision problem, 81% were hypertensive, 40% had neuropathy and 26% had nephropathy 21. But in our study most prevalent complication associated with hypertension, nephropathy and retinopathy was about 6%, 8% and 7% respectively. The complications can be reduced by management of diabetes. Further research would be done to determine the management of dyslipidemia and other complications. Adequate knowledge about the different factors controlling diabetes and its complications are important. Improper diet, treatment and life style may be the leading cause of dyslipidemia and other complications. CONCLUSION The study has clearly demonstrated that high triglyceride levels are more prevalent than high LDL cholesterol levels in our patient group. Keeping the fact in view that hypertriglyceridaemia is a serious risk factor for the development of coronary artery disease it is therefore of paramount importance that this abnormality should be sought out at the outset of diabetes mellitus and addressed accordingly. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Huang KC, Chen CC, Su YC, Lin JS, Chang CT, Wang TY. The relationship between stasis stagnation constitution and peripheral arterial disease in patients with type-2 diabetes. Evid Based Complement. Alternat Med 2014; 2014: Centers for Disease Control and Prevention, Diabetes & trends. cdc.gov/ diabetes /statistics/ prev/ national/ figpersons. html. 3. Gustafsson I, Brendorp B, Seibaek M, Burchardt H, Hildebrandt P, Kober L. The influence of diabetes and the diabetes - gender interaction on the risk of death in patients who were hospitalized with congestive heart failure. J Am Coll Cardiol 2014; 43(5): Elinasri HA, Ahmed AM. Patterns of lipid changes among type- 2 diabetes patients in Sudan. East Mediterr Health J 2008; 14: Abou-Seif MA, Youssef AA. Evaluation of some biochemical changes in diabetic patients. Clin Chim Acta 2009; 346: Agrawal Y, Goyal V, Chugh K, Shanker V, Singh AA. Types of dyslipidemia in type-2 diabetic patients of Haryana region. Sch J App Med Sci 2014; 2(4): Ahmad A, Khan J, Siddiqui TS. Frequency of dyslipidemia in type-2 diabetes mellitus in patients of Hazara division. J Ayub Med Coll Abbotabad 2008; 20(2): Basit A, Shera AS. Prevalence of metabolic syndrome in Pakistan. Metab Syndr Relat Disord 2008; 6(3): Al-adasni Memon A, Suresh A. Pattern and determinants of dyslipidemia in type-2 diabetes mellitus patients in Kuwait. Acta Diabetol 2014; 41(3): American Diabetes Association Dyslipidemia management in adults with diabetes. Diabetes Care 2004; 27(Suppl-1): S68-S Mooradian AD. Dyslipidemia in type-2 diabetes mellitus. Nat Rev Endocrinol 2009; 5: Feher MD. Diabetes preventing coronary heart disease in high risk group. Heart 2010; 90(4): Jayarama N, Reddy M, Lakshmaiah V. Prevlence and pattern of dyslipidemia in type-2 diabetes mellitus patients in a rural tertiary care centre, South India. GJMEDPH 2012; 1(3): Kandula R., Shegokar VA. Study of lipid profile in patients with type-2 diabetes mellitus J Health Sci 2013; 1(1): Sohail SMA, Faisal Z, Umar J. Metabolic syndrome in type-2 diabetes mellitus. Pak J Med Sci 2006; 22: Tagoe DNA, Amo-Kodieh P. Type-2 diabetes mellitus influences lipid profile of diabetic patients. Ann Biol Res 2013; 4(6): American Diabetes Association Economic consequences of diabetes mellitus in the U.S in Diabetes Care 1998; 21(5): Wan YG, Wan M, Fan Y, Fan L, Gu LB, Li M. Effect of compound of chines drug on gene expression of renal endothelin. Zhongguo Zhong Yao Za Zhi 2013; 28(2): S8

12 Hypercholestremia Patterns in Young Diabetic Soldiers Pak Armed Forces Med J 2018; 68 (Suppl-1): S5-S9 19. Torangti GM, Naik RK. Health and nutritional status of diabetics. Department of food and nutrition, College of Rural Home Sciences, India. Karnataka. J Agric Sci 2010; 123(4): Uttra KM, Devrajani BR, Shah SZA, Devrajani T, Das T, Raza S. Naseem Lipid Profile of patients with Diabetes mellitus (a multidisciplinary study) World Appl Sci J 2011; 12(9): Vinter-Repalust N, Jurkomo L, Katie M, Simunovic R, Petric D. The disease duration, patient compliance and the presence of complications in diabetic patients. Acta Med Croatica 2017; 61(1): S9

13 Open Access Original Article Totally Occluded Coronary Arteries in Patients of Stable IHD Pak Armed Forces Med J 2018; 68 (Suppl-1): S10-13 A RETROSPECTIVE DESCRIPTIVE STUDY ANALYSIS OF FREQUENCY OF TOTALLY OCCLUDED CORONARY ARTERIES IN PATIENTS OF STABLE IHD UNDERGOING ROUTINE CORONARY ANGIOGRAPHY Muhammad Nadir Khan, Shoaib Akbar, Abeer Ashfaq Army Cardiac Center, Lahore Pakistan ABSTRACT Objective: To assess the current burden/frequency of chronic coronary total occlusions in patients with stable ischemic heart disease undergoing angiography at Army cardiac centre Lahore. Study Design: Descriptive cross sectional study. Place and Duration of Study: Army cardiac centre Lahore from Jan 2016 to Dec Material and Methods: This is a retrospective descriptive study analysis of the record of 2441 patients who came to Army Cardiac Centre Lahore (ACC) for coronary angiography during the year of Patient s data with completely (100%) occluded arteries (CTO) was analysed for age, gender, specific coronary artery occluded and co-morbidities like diabetes. The data was obtained from ACC registry and then tabulated. Results: Out of 2441 patients 1753 were found to have stable IHD. Out of these 463 patients were found to have completely occluded arteries. Most common occluded artery was found to be proximal RCA followed by proximal LAD. About 84.7% patients with chronic coronary occlusion were males and 30.4% had diabetes. Conclusion: Analysis of data revealed that 26.4% of patients with stable ischemic heart disease undergoing coronary angiography had completely occluded coronary arteries which indicate a significant burden, especially considering the morbidities, mortality and therapeutic challenges associated with CTO. Keywords: Chronic occluded coronary arteries, Coronary angiography, Chronic total occlusion, Interventional cardiology, Ischemic heart disease, Percutaneous intervention, RCA occlusion. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Ischemic heart disease is the leading cause of mortality worldwide, claiming more than 8 million lives in 2015 according to the world health organization statistics. The recent advances in the emergency care, catheter based percutaneous interventions and improved postop care has led to a decrease in the proportion of fatal myocardial infarctions as compared to the non-fatal incidents. Ischemic heart disease is also associated with significant morbidities in patients causing significant impairment to life. One of the challenging problems faced by interventional cardiologists is the chronic totally occluded coronary arteries (CTO). It has been recognized by some as the final frontier of interventional cardiology because it leads to different Correspondence: Dr Muhammad Nadir Khan, Associate Professor, Army Cardiac Center Lahore Pakistan yesnadirkhan@gmail.com therapeutic challenges as compared to the nontotal occlusions. It also causes increased incidence of significant morbidities including angina 1 and left ventricular pump failure 2. As a result of the new technological advances, the success rate of successful PCI is around 75%-80%. However due to the therapeutic challenges CTO is one of the commonest reasons for failure to do PCI ultimately leading to an increase in the need of coronary artery bypass grafting procedures 3. It is hence a topic of significant scientific research in modern interventional cardiology. The purpose of this study was to assess the burden of CTO to determine the magnitude of this problem. Operational Definitions CTO: 100% luminal stenosis with no antegrade flow, known or assumed to be >12 week duration on the basis of previous angiogram or lesions with significant bridging collaterals. S10

14 Totally Occluded Coronary Arteries in Patients of Stable IHD Pak Armed Forces Med J 2018; 68 (Suppl-1): S10-13 Totally occluded coronary arteries of unknown duration with rentrop 2-3 retrograde filling. MATERIAL AND METHODS This descriptive cross sectional study was conducted at the Army Cardiac Center Lahore to assess the frequency of CTO lesion in patients undergoing routine coronary angiography. We included 2441 patients who underwent coronary angiography routine and had stable ischemic heart disease for a period of 1 year between 1 st January to 31 st December The patients clinical characteristis were tabulated retrospectively form a 1 year data obtained from Army Cardiac Center Lahore registry. The data included in the study includes patients characteristics like age, gender, total, number of vessels involved, distribution of CTO lesions among specific branches of coronary arteries, the sub-segment of those braches involved (proximal or distal), patients with more than one CTO lesions and comorbidites like dibetes mellitus. Patients with previous coronary artery bypass graft (CABG) procedure or patients with non ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarctin (STEMI) were indentifiend and excluded form the sample. The patients with previous CABG and those with acute coronary syndrome (NSTEMI=STEMI) were excluded and 1753 patients were indentified as those with stable ischemic heart disease undergoing coronary angiography. RESULTS Out of 1753 stable IHD patients, 463 (26.4%) had coronary CTO. A total of 606 occluded vessels were identified with some patients having more than one CTO lesions. A total of 1290 Table: Frequency (%) of vessels causing CTO (n=606). Vessels n (%) Right coronary Artery(RCA) Proximal RCA 111 (18.3%) Middle RCA 77 (12.7%) Distal RCA 27 (4.4%) PLV/PDA 17 (2.8%) RCA Total 232 (38.2%) Left Anterior Descending (LAD) Proximal LAD 88 (14.5%) Mid LAD 111 (18.3%) Distal LAD 9 (1.4%) Diagonal 16 (2.6%) LAD Total 224 (36.8%) Left Circumflex(LCX) Proximal LCX 67 (11%) Distal LCX 36 (5.9%) OM-Branches 47 (7.7%) LCX Total 150 (24.7%) patients had non total occlusions of coronary arteries. The most commonly involved vessel was the right coronary artery with 38.3% of the total lesions. Left anterior descending was the second most common location of CTO (36.8%) with middle LAD being the most common site in LAD. A total of 24.6% lesions were located in LCX. This study is unique in that it also measures the relative prevalence of CTO lesions in different coronary arteries as shown in fig-1. A more detailed analysis is given in the table. S11

15 Totally Occluded Coronary Arteries in Patients of Stable IHD Pak Armed Forces Med J 2018; 68 (Suppl-1): S10-13 CTO was identified more commonly in males with 392 out of 462 (84.7%). The range of age was years. About 30.4% patients were reported to be diabetics as shown in fig 2 & 3. DISCUSSION The recent advances in diagnostic and therapeutic procedure in the field of interventional cardiology have lowered the morbidity and mortality associated with cardiac disease and have led to an overall improved functional status of patients with coronary artery disease. Newer PCI techniques and stents have led to a decrease in in-hospital major cardiac adverse events including in-hospital death, Q wave MI and transient ischemic attacks 4. CTO lesions are unchartered territory in the field of interventional cardiology because of the therapeutic challenges associated with it. CTO PCI is a complex procedure and has a high operator dependency. It has a long learning curve. The procedural time for CTO PCI is longer than a non CTO PCI leading to prolonged occupation of the catheter lab, increased fluoro time and a higher contrast dosage requirements compared to the non CTO PCI. And this leads to significant occupation of financial and human resources. The equipment for CTO PCI is costly due to the use of multiple guide wires and different types of micro catheters from those used in non CTO stenting e.g. stingray balloon, caravel micro catheter, corsair micro catheter. Due to these issues many patients with CTO lesion go untreated and are ultimately referred for coronary artery bypass surgery. Although costly, but this new equipment e.g sting-ray balloon, caravel super-cross microcatheter etc, for CTO PCI has made the procedure more feasible and successful thereby reducing the need for coronary artery bypass graft surgery. Coronary CTO lesions in patients with ischemic systolic failure are associated with a higher mortality and a worse prognosis than those with non CTO lesions 5. There is also an increased incidence of ventricular arrhythmias in patients who have ischemic cardiomyopathy with CTO lesions than those with non total occlusions 6 Figure-1: CTO Frequency in stable IHD. which increases the risk of sudden cardiac death. However successful CTO recanalization has to be beneficial for the patient as it is associated Figure-2: Gender distribution in CTO. with a reduced all cause mortality and improved long term survival compared to those with failed CTO PCI or those with untreated CTO lesions 7,8,1. Figure-3: Diabetes Mellitus in CTO patients. It improves the overall cardiac function by restoring the appropriate myocardial supply S12

16 Totally Occluded Coronary Arteries in Patients of Stable IHD Pak Armed Forces Med J 2018; 68 (Suppl-1): S10-13 thereby increasing the LV ejection fraction and decreasing the end systolic volume in IHD patients, specially when there is ischemia of the area supplied by the CTO vessel 2. The amount of collaterals of the CTO vessel also impact the overall survival specially in a non CTO related STEMI patient 9. CTO PCI is beneficial as it lowers the risk for coronary artery bypass graft surgery 3,1. Studies show that patients with total occlusion who are diabetic are at an increased risk of being adversely affected by it as compared to the nondiabetics due to a worse vascular status, hence PCI in diabetics yields better results and a reductions in adverse cardiac effects 8. Successful recanalization of CTO vessels leads to improved quality of life with reduction in symptoms of myocardial ischemia and pump failure due to restoration of myocardial perfusion. According to a meta analysis carried out 6, different studies showed a reduction in anginal symptoms after successful recanalization 1. Recent studies show that the current rate of CTO PCI performed ranges between 3-10% among the total PCI done for stable IHD 10. Studies also show that the rate of successful PCI done for CTO lesions is around 75-80% 3,8,11. The current observation of 26.4% prevalence of CTO lesions indicates the magnitude of this problem and a huge potential for improvement. CONCLUSION CTO lesions having a high frequency of 26.4% in stable IHD patients undergoing coronary angiography indicate the significant burden of this pathology. The difficulties approaching it therapeutically due to multiple factors like operator dependency & longer occupation of catheter lab often leads to failure to do PCI in CTO lesions. But the high burden of CTO lesions, the increased morbidities and mortality associated with it and with the recent studies showing positive response to successful recanalization warrants further research on this topic along with development of newer therapeutic modalities and allocation of time and resources to treat it. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Cardona M, Martín V, Prat-Gonzalez S, Ortiz JT, Perea RJ, Caralt TMD, et al. Benefits of chronic total coronary occlusion percutaneous intervention in patients with heart failure and reduced ejection fraction: insights from a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2016; 18: Elias J, Hoebers LP, Dongen IMV, Claessen BE, Henriques JP. Impact of Collateral Circulation on Survival in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention With a Concomitant Chronic Total Occlusion. JACC: Cardiovascular Interventions 2017; 10: Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: A systematic review and meta-analysis. Am Heart J 2010; 160: Nombela-Franco L, Iannaccone M, Anguera I, Amat-Santos IJ, Sanchez-Garcia M, Bautista D, et al. Impact of Chronic Total Coronary Occlusion on Recurrence of Ventricular Arrhythmias in Ischemic Secondary Prevention Implantable Cardioverter- Defibrillator Recipients (VACTO Secondary Study). JACC: Cardiovascular Interventions 2017; 10: Sai TT, Stanislawski MA, Shunk KA, Armstrong EJ, Grunwald GK, Schob AH, et al. Contemporary Incidence, Management, and Long- Term Outcomes of Percutaneous Coronary Interventions for Chronic Coronary Artery Total Occlusions. JACC: Cardiovasc Interv 2017; 10: Prasad A, Rihal CS, Lennon RJ, Wiste HJ, Singh M, Holmes DR. Trends in outcomes after percutaneous coronary intervention for chronic total occlusions: A 25-year experience from the Mayo Clinic. J Am Coll Cardiol 2007; 49(15): Toma A, Gick M, Minners J, Ferenc M, Valina C, Löffelhardt N, et al. Survival after percutaneous coronary intervention for chronic total occlusion. Clinical Research in Cardiology 2016; 105(11): Sanguineti F, Garot P, O'Connor S, Watanabe Y, Spaziano M, Lefèvre T, et al. Chronic total coronary occlusion treated by percutaneous coronary intervention: long-term outcome in patients with and without diabetes. EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 2017; 12(15): e Patel VG, Brayton KM, Tamayo A, Mogabgab O, Michael TT, Lo N, et al. Angiographic success and procedural complications in patients undergoing percutaneous coronary chronic total occlusion interventions: A weighted meta-analysis of 18,061 patients from 65 studies. JACC: Cardiovasc Interv 2013; 6(2): Brilakis ES, Banerjee S, Karmpaliotis D, Lombardi WL, Tsai TT, Shunk KA, et al. Procedural outcomes of chronic total occlusion percutaneous coronary intervention: A report from the NCDR (National Cardiovascular Data Registry). JACC: Cardiovasc Interv 2015; 8(2): Tajstra M, Pyka Ł, Gorol J, Pres D, Gierlotka M, Gadula-Gacek E, et al. Impact of chronic total occlusion of the coronary artery on longterm prognosis in patients with ischemic systolic heart failure: insights from the COMMIT-HF registry. JACC: Cardiovasc Interv 2016; 9(17): S13

17 Open Access Muscular Ventricular Septal Defect Device Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S14-S17 TRANSCATHETER CLOSURE OF LARGE PERSISTENT DUCTUS ARTERIOSUS WITH THE MUSCULAR VENTRICULAR SEPTAL DEFECT DEVICE Amjad Mahmood, Maad Ullah, Nadeem Sadiq, Khurram Akhtar, Mehboob Sultan, Kamal Saleem, Asif Akbar Shah, Aziz Ahmed Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To assess the efficacy of Ventricular Septal Defect device for occlusion of large Patent Ductus Arteriosis with high pulmonary artery pressure. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Armed Forces Institute of Cardiology Rawalpindi from May 2014 to Dec Material and Methods: It was a descriptive cross-sectional study included seventy patients. Patients more than 2 months of age were included. Patients with large PDAs and systemic or near systemic pulmonary artery pressure underwent transcatheter closure using the VSD (SHSMA). Patients had weight less than 3kg were excluded. All patients were followed by echocardiogram 2 weeks and 6 months following the procedure. Results: The mean echocardiographic and angiographic PDA diameter was 8.5 mm (1.8) (range 5-14 mm) and the mean VSD diameter was 11.4 (1.8) mm (range 9-16 mm). Successful device delivery and complete closure occurred in 55 patients (96.5% occlusion rate), Mean systolic pulmonary artery pressures was 65 mm Hg before procedure and 39 mm Hg immediately after the procedure. Fluoroscopy time was 9 min (range 5-25 min). Two devices embolized. Conclusions: VSD device is very effective for closure of large PDAs along with high pulmonary artery pressure. Keywords: Ventricular Septal Defect, Patent Ductus Arteriosis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Transcatheter closure of persistent patent ductus arteriosus (PDA) using various types of devices is a well established procedure. Somehow all patients with PDA are not suitable for this type of treatment, as these devices are not always appropriate for large pulmonary hypertensive ducts (PH-PDA). In the presence of high pulmonary artery pressure such devices are prone to embolisation into the aorta 1,2. The muscular ventricular septal defect device has recently been used successfully for transcatheter closure of muscular ventricular septal defects 11,12. This device is suitable for use with PH-PDA as its double disk tends to hold the device, minimising embolisation into the aorta. In this study we report the successful use of the muscular VSD device for treating PH-PDA. The Memo Part VSD Occluder (LEPU Correspondence: Dr Amjad Mahmood, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan amjpaedcard@yahoo.com Medical Technology, Beijing, China) has been described in detail in multiple studies 11,12. This VSD device is a self centering and repositionable device constructed of inch (0.1 mm) Nitinol wires, tightly woven into two flat round discs with a 7mm connecting waist. The left disc is 4 mm larger than the waist and the right disc is 3 mm larger than the waist. Prostheses are currently available in various sizes. MATERIAL AND METHODS It was a descriptive cross-sectional study conducted at Armed Forces Instititue of Cardiology from May 2014 to Dec 2017 included seventy patients. Patients more than 2 months of age and patients with large PDAs and systemic or near systemic pulmonary artery pressure underwent transcatheter closure using the VSD (SHSMA) were included. Patients had weight less than 3kg were excluded. All patients were followed by echocardiogram 2 weeks and 6 months following the procedure. Informed parental consent for the procedures was obtained S14

18 Muscular Ventricular Septal Defect Device Pak Armed Forces Med J 2018; 68 (Suppl-1): S14-S17 from each patient. Data analysis was done on SPSS version-22. Descriptive statistics was applied to measure mean ± SD and frequency & percentages. The technique of transcatheter closure of PDA using the VSD has been described in various studies. After percutaneous puncture of the femoral artery and vein, a complete haemodynamic evaluation was performed with pressure and saturation measurements taken in all cardiac chambers. A descending aortogram in anteroposterior and lateral projections was performed with a 5 or 6 French pigtail catheter to define the size and anatomy of the PDA (fig-1a). A 5 French JR catheter was advanced percutaneously from the venous side through the into the descending aorta. Using gentle tension on the delivery cable, the sheath was pulled back to deploy the rest of the device. With the device still attached to the delivery cable, cross sectional colour Doppler echocardiography, pulmonary arteriography (fig-2) and descending aortography (hand injection of contrast medium) were done to confirm proper device position and exclude left pulmonary or aortic obstruction 3-5. Once optimal position was confirmed, VSD device was released by counter clockwise rotation of the delivery cable. A repeat aortogram (fig-3) and a complete haemodynamic evaluation were performed to check for residual shunts and change of pressures. Prophylactic antibiotics were not routinely given during the procedure. All Figure-1a: Aortogram in left lateral position showing large tubular PDA. PDA into the descending aorta. Using an exchange 260 cm, inch guide wire, the JR catheter was exchanged for various sizes of delivery sheaths advanced directly through the femoral vein and positioned in the proximal descending aorta. An appropriately sized occluder was screwed to the delivery cable, pulled into the loader, and introduced into the guiding sheath. Under fluoroscopic guidance, the occluder was advanced into the descending aorta, where the left disk was deployed and pulled gently against the orifice of the duct (fig-1b). Correct position was confirmed by injection of contrast medium through the aortic catheter Figure-1b: Aortic end is released and pulled gently against PDA. patients were sent home 24 hours after the procedure on no drug treatment. Endocarditis prophylaxis was discontinued at the 12 month follow up visit if the duct was completely closed. A chest x-ray and colour Doppler echocardiographic studies were performed on all patients at 24 hours, one month, and serially at 3-6 month intervals. RESULTS Seventy patients with clinical and echocardiographic findings of a large PDA and pulmonary hypertension underwent transcatheter closure with the VSD device. Their median age was 8 years (range 2 months to 20 years) and their median body weight was 30 kg S15

19 Muscular Ventricular Septal Defect Device Pak Armed Forces Med J 2018; 68 (Suppl-1): S14-S17 (4 Kg to 65 kg). Ten patients had symptoms of heart failure and failure to thrive. On Doppler echocardiography there was evidence of bidirectional shunting through the PDA with left atrial and left ventricular enlargement. According to Krichenko's PDA classification 13, Fourty five patients had type A, 20 had type C, and five had type E. The length of the duct varied between 7-9 mm.the mean duct diameter (pulmonary end) was 9.8 (1.7) mm (range 7-13 mm). The mean VSD diameter was 12mm. (The pulmonary to systemic flow ratio (Qp/Qs) varied between 2-3. All patients had systemic or near systemic systolic pulmonary artery pressure (mean 102 (11) mm Hg; mean recanalisation, migration, wire fracture, thromboembolism, or endocarditis. No obstruction of the left pulmonary artery or the aorta was noted. Transthoracic echocardiogram one year after implantation of the VSD device, showed complete closure and good position of the device with no evidence of aortic or pulmonary artery obstruction. DISCUSSION PDA closure using the SHSMA VSD device has significantly improved the results of tans catheter closure of moderate to large sized ducts. Its major advantages over previous devices are the smaller delivery sheaths (7-9 French), easy to reposition the device before release, and a Figure-2: Echocardiogram of device placement while still attached to delivery cable. systolic aortic pressure 109 (10) mm Hg). Device delivery was successful and associated with complete closure in all patients (100% closure rate). There was a significant fall (p<0.05) in mean systolic pulmonary artery pressure after the placement of the VSD device (to 50(5) mm Hg). Fluoroscopy time was 8.6 (4.1) minutes (range 4-16 minutes). One patient developed device embolization which was retrieved successfully and closed with 2 mm higher size 6,7. There was fall in the mean systolic pulmonary artery pressure at the six months follow echocardiogram. No complications were observed in the early post procedural period or during the one year follow up. All patients had complete closure with no evidence of device Figure-3: Aortogram to check final position of device before release. significantly lower rate of complications and residual shunts However, the duct occluder devices are not designed to maintain a stable position under high pressure. Therefore in the presence of high pulmonary artery pressure there is a real possibility of systemic embolization. Even with VSD device we had one case of device embolization but it was retrieved and a bigger device was deployed successfully 13,14. This study shows the biggest number of patients treated with this modality with excellent results showing that trans catheter closure of large PH-PDAs is practicable, effective, and safe. Complete occlusion was obtained in all patients, with a significant fall in the pulmonary artery pressure and no complications during the S16

20 Muscular Ventricular Septal Defect Device Pak Armed Forces Med J 2018; 68 (Suppl-1): S14-S17 procedure or at the one year follow up. The device is muscular VSD device and its retention disk system ensures secure positioning in the pulmonary orifice of the duct and prevents device embolization into the systemic circulation in the presence of high pulmonary artery pressure. In addition, because of its construction from tightly woven Nitinol wire, this VSD device exerts an exaggerated stenting effect on the duct wall, giving it greater stability than the PDA device. Finally, this occluding device is available in various sizes, which makes it suitable for transcatheter closure of very large ducts. Our major estimation of device size was based on echocardiographic estimation of PDA in short axis medially angulated view. The selected device size was 2-3 mm larger than the echo estimated size. This method reduced the chances of device embolization and better positioning across the aorta and pulmonary artery. Pulmonary artery pressures were measured in all patients before and after the device closure. The cases with severe pulmonary hypertension having bidirectional shunting and right ventricular dilatation on echocardiography were not subjected to device closure. These cases were supposed to have elevated pulmonary vascular resistance not amenable to device closure. CONCLUSION The SHSMA VSD device was found safe for the closure of large ducts having adequate ampulla. With the use of this device we can minimize the chances of embolization with efficient closure and no residual shunt across PDA. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Rashkind WJ, Mullins CE, Helenbrand WE, Tait MA. Nonsurgical closure of patent ductus arteriosus: Clinical application of the Rashkind PDA occluder system. Circulation 1987; 75(3): Hosking MCK, Benson LN, Musewe N. Transcatheter occlusion of the persistently patent ductus arteriosus: Forty-month followup and prevalence of residual shunting. Circulation 1991; 84: Verin VE, Saveliev VS, Kolody SM, Prokubovski VI. Results of transcatheter closure of the patent ductus arteriosus with the Botalloocluder. J Am Coll Cardiol 1993; 22: Hijazi ZM, Geggel RL. Results of anterograde transcatheter closure of patent ductus arteriosus using single or multiple Gianturco coils. J Am Coll Cardiol 1994; 74: Hijazi ZM, Geggel RL. Transcatheter closure of large patent ductus arteriosus ( 4mm) with multiple Gianturco coils: Immediate and mid-term results. Heart 1996; 76: Uzun O, Hancock S, Parsons JM. Transcatheter occlusion of the atrial duct with Cook detachable coil: Early experience. Heart 1996; 76: Rao PS, Kim SH, Choi JY. Follow-up of transvenous occlusion of patent ductus arteriosus with the buttoned device.j Am Coll Cardiol 1999; 33: Masura J, Kevin P, Thanopoulos B. Catheter closure of moderate- to large-sized patent ductus arteriosus using the new Amplatzer Duct Occluder: immediate and short-term results. J Am Coll Cardiol 1998; 31: Thanopoulos BVD, Hakim FA, Hiari A. Further experience with transcatheter closure of the patent ductus arteriosus using the Amplatzer duct occluder. J Am Coll Cardiol 2000; 35: Faella HJ, Hijazi ZM. Closure of the patent ductus arteriosus with the Amplatzer PDA device: Immediate results of the international clinical trial. Cathet Cardiovasc Intervent 2000; 51: Thanopoulos BVD, Tsaousis GS, Konstadopoulou GN. Transcatheter closure of muscular ventricular septal defects with the Amplatzer ventricular septal defect occluder: Initial clinical application in children. J Am Coll Cardiol 1999; 33: Hijazi ZM, Hakim F, Al-Fadley F, Abdelhamid J, Cao QL. Transcatheter closure of single muscular ventricular septal defects using the Amplatzer muscular VSD occluder: Initial results and technical considerations. Cathet Cardiovasc Intervent 2000; 49: Krichenko A, Benson LN, Burrows P, Möes CA, McLaughlin P, Freedom RM. Angiographic classification of the isolated, persistently patent ductus arteriosus and implications for percutaneous catheter occlusion. Am J Cardiol 1989; 67: Ebeid MR, Gaymes CH, Smith JC, Braden DS, Joransen JA. Gianturco-Grifka vascular occlusion device for closure of patent ductus arteriosus. Am J Cardiol 2001; 87: S17

21 Open Access Primary Percutaneous Coronary Intervention Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S18-S22 DIFFERENCES IN ANGIOGRAPHIC CHARACTERISTICS OF YOUNG AND THE ELDERLY PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN AFIC Hafiz Muhammad Shafique, Mubarra Nasir, Farhan Tuyyab, Muhammd Asad, Rehana Khadim, Hassan Shabeer, Mir Waqas Baloch Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To assess the differences of angiographic features of young and old with STEMI. Study Design: Descriptive cross sectional study. Place and Duration of Study: This study was conducted at Department of Cardiology, AFIC & NIHD Rawalpindi from Jan to Aug Material and Methods: A total of 602 patients with STEMI who underwent Primary PCI from Jan 2017 to Aug 2017, were included in this study. Two groups were formulated on the basis of age group. Group-A were younger age group with 40 years of age or less. Group-B included patients older than 40 years. They were compared with respect to risk factors and angiographic characteristics. Results: A total of 602 patients with STEMI under gone primary PCI. Fifty three patients were in group-a while 549 patients were in group-b. Males were predominant in this cohort with 83% and 87% in group-a and B respectively. Family history of premature CAD was predominate in group-a, i.e. About 12 (22.6%) as compared to group-b i.e. 54 (9.9%). The most common infarct related artery was LAD in group-a. Single vessel disease was common in group-a 34 (64.15%) while triple vessel disease was common in group-b 195 (35.6%). There was no mortality in younger group while mortality rate in group was 16 (2.9%). Conclusion: Single vessel coronary artery disease and anterior wall STEMI was common in younger group. Family history of premature CAD, smoking and dyslipidemia were the associated risk factors in young patients with STEMI. Keywords: St segment elevation myocardial infarction, Primary percutaneous coronary intervention. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Myocardial infarction (MI) is one of the major causes of morbidity and mortality in Pakistan 1. It is a disease that is usually found to be prevalent in the elderly, but now a days the incidence is seen to be increasing in the younger population i.e. in patients of age less than 40 years 2. The recent internationally conducted studies have demonstrated the incidence rates of MI in young ranging between 2% and 10%, based on the local statistics and relevant risk factors 3 5. Pakistan has a distinct racial cohort with increasing incidence of ischemic heart disease and morbidity associated with it. There is limited established data till date on the frequency and clinical presentation of ischemic cardiac Correspondence: Dr Hafiz Muhammad Shafique, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan. Shafique176@gmail.com events in young population. Analysis of the clinical characteristics and overall frequency of ST segment elevation MI, can help elaborating the major determinants of risk in this particular age group and how it is distinct from those who present at an older age. The inferences derived from such analysis can lead to formulation of screening and prevention strategies in our population. Therefore, the objective of the current study was to evaluate the frequency and overall clinical as well as angiographic characteristics of young patients presenting with myocardial infarction. It has been observed, that in western countries, a large number of young patients developing ST elevation MI are cocaine and amphetamine addicts and eventually they were found to have normal coronary angiograms 6-9. In our country, such causes are found to be rare. Despite the before cited difference, there is S18

22 Primary Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S18-S22 increased frequency of younger patients presenting with ST segment elevation MI in our region 10. In the presence of distinct predictors of risk in both the societies, a difference in the angiographic and clinical profile is expected. MATERIAL AND METHODS This descriptive cross sectional study was conducted at the Department of Cardiology, AFIC/NIHD, Rawalpindi. We included consecutive 602 patients with ST segment elevation Myocardial infarction undergoing PPCI, presented in emergency department from Jan to Aug All patients (20-90 years) of both gender presented were included in the study. The inclusion criteria was first episode of acute ST segment elevation MI diagnosed on the basis of history of chest pain lasting >30 minutes associated with an ST-elevation of 1 mm in 2 contiguous leads or new left bundle branch block plus time from symptom-onset to presentation 24 hours. Their coronary angiograms followed by Primary PCI were performed in Catheterization Laboratory of AFIC/NIHD between Jan 2017 and Aug 2017 with standard protocol. The patients with a past history of stenting were not included in the study. The recruited patients were segregated in S19 two groups on the grounds of their respective ages. Group-A comprised of patients who were of age 40 or younger, whereas group-b comprised of patients who were more than 40 years of age. Their coronary angiograms were obtained and analyzed. The extent and severity of coronary artery disease was categorized as minor irregularities of the vessel, insignificant disease i.e. stenosis <50% and significant disease i.e. stenosis >50%. Significant disease also included totally occluded vessels. In addition, the disease severity was also described on the basis of the number of diseased vessels, number and type of Table-I: Clinical Characteristics of study population. GROUP-A GROUP-B Characteristics Stemi in younger 40 Stemi in older >40 p-value years (n=53 ) (8.8%) years (n=549) (92.2%) Age ± ± 8.65 Gender Male 44 (83.0%) 477 (87.0%) Female 9 (17.0%) 72 (13.0%) CO MORBIDS Hypertension 8 (15.09%) 148 (26.95%) 0.05 Diabetes mellitus 4 (6.6%) 93 (17%) 0.07 Smoking 28 (52.8%) 193 (35.15%) 0.01 Family history of CAD 12 (22.6%) 54 (9.9%) BMI 29.7 ± ± HTN+DM 1 (3.5%) 53 (9.6%) 0.05 Dyslipidemia Low HDL levels High Cholesterol 31 (58.49%) 236 (42.98%) 20 (37.77%) 289 (52.64%) 0.03 lesions as defined by the AHA. If more than 50% reduction of vessel diameter was observed in comparison to a normal vessel, the vessel was declared to be diseased. The comparison of the two groups was done on the basis of their gender, presence of co-morbids such as diabetes and hypertension, obesity, dyslipidemia, family history of ischemic heart disease, smoking, and angiographic characteristic of coronary artery disease. Myocardial infarction was defined according to the third universal definition of myocardial infarction 11. The relevant data were collected on a structured proforma. Procedural data was

23 Primary Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S18-S22 assessed from the database at the time of the PPCI, and hospital outcomes was be assessed from chart reviews in the previous records. Risk factors were obtained from reviews of medical records and telephone contact. Data Analysis Statistical analysis was performed using statistical software SPSS version 23. Mean and standard deviation was calculated for continuous variable while Categorical variables were expressed as frequencies and percentages. Statistical analysis were performed with chi square tests for dichotomous data and independent t-tests for continuous data. For all statistical analyses a p-value <0.05 was considered significant. Data analysis was performed using SPSS-23. Associations were calculated applying chi-square test. S20 RESULTS Clinical characteristics of the patients are given in table-i. A total of 602 patients were included in our study (table-i). Mean ± SD age of the patients was ± -4.4 years in younger group and ± in older group. Fifty three patients were in younger age group while 549 patients were more than 40 years of age. About 44 (83%) vs. 477 (87%) were male and 9 (17%) vs 72 Table-II: Comparison of angiographic characteristics of the two groups. GROUP-A GROUP-B Characteristics Stemi in younger 40 Stemi in older >40 years (n=53) (8.8%) years (n=549) (92.2%) LMS 0(0%) 8 (1.4%) Infarct LAD 36 (67.92%) 307 (55.7%) Related RCA 13 (24.5%) 197 (35.8%) artery LCX 4 (7.5%) 36 (6.5%) Recanalized 2 (3.7%) Number of vessels involved Target lesionlen gth (mm) Number of lesions No vessel involved 2 (3.7%) 0 (0%) SVCAD 34 (64.15%) 160 (29%) DVCAD 14 (26.41%) 194 (35.3) TVCAD 5 (9.43%) 195 (35.6%) LAD 30 ± ± 9.5 RCA 28 ± ± 8.5 None 2 (3.7%) 0 One 30 (56.6%) 60 (11%) Two 10 (18.86%) 211 (38.43%) Three 6 (11.3%) 157 (28.59%) Four or more 5 (9.4%) 121 (22.04%) p-value < < Thrombus aspiration 2 (3.5%) 29 (5.14%) 0.59 Access Radial 53 (100%) 545 (99.4) 0.75 site Femoral 0 (0%) 4 (0.6%) Types of stent DES 51 (96.22%) 449 (81.7%) BMS 0 88(16.02%) (13%) were female in the younger and older age group respectively. In group-a, 8 (15.09%) patients were hypertensive and 4 (6.6%) were diabetic, while only 1 (3.5%) was both diabetic and hypertensive. In group-b, 174 (31%) patients were hypertensive and 93 (17%) were diabetic while 53 (9.6%) were both hypertensive and diabetic. Rate of Smoking and dyslipidemia 28 (52.8%) vs 193 (35.15%, and 29 (54.71% vs 340

24 Primary Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S18-S22 (61.93%) were high in both group-a and group-b respectively and both are statistically significant (p-value 0.01 and 0.03 for smoking and dyslipidemia). Family history of premature CAD was prominent in group-a 12 (22.6%) as compared to group-b 54 (9.9%). Table-II shows the angiographic characteristics: the most common infarct related artery was LAD although the preponderance was high in Younger age group as compared to older age group 36 (67.92%) vs 307 (55.7%) respectively. Single vessel disease was common in group A 34 (64.15%) while triple vessel disease was common in group-b 195 (35.6%). Significant lesion was defined as when it causes >50% stenosis of vessel. One lesion disease was predominant in group-a (56.6%) while two or more lesion disease was common in group-b patients (table-ii). Target lesion length was long in group-b as compared to group-a (33 ± -8.5 vs 30 ± -6.5 mm). Use of thrombuster due to high thrombus burden was statistically in significant in both groups. Radial or ulnar access was used in all patients of group- A and 99.4% patients of group-b. Similarly DES was used in all patients with younger age while in group-b 449 (81.7%) and 88 (16.02%) patients were implanted DES and BMS respectively. Twelve patients needed temporary pace maker due to complete heart block in group-b. There was no mortality during stay in hospital and follow up up to 30 days in younger group while mortality rate in group was 16 (2.9%). DISCUSSION Myocardial infarction occurred with acute onset and if it happened in younger age it leads to trauma to the family and increased morbidity. STEMI is one of the leading causes of cardiac mortalities 15, it is important to look into the clinical characteristics and risk factors involved in STEMI among young adults. In western world, myocardial infarction in young with normal coronary angiogram is highly prevalent 12. However, in our study, the younger patients with STEMI were having many characteristics similar to older patients in quite many respects. In our study 8.8% of the patients were 40 years or younger. This is a slightly high percentage of patients compared to previously published data. Hosseini et al 12 studied patients with acute STEMI aged 40 years. Of the total admissions for myocardial infarction, only 5.4% of the patients were 40 years. This may be explained by the reason that the mean age for first MI among south Asians is lower when compared to individuals in other countries 13. We studied both the groups with respect to the gender distribution, presence of hypertension, diabetes mellitus, smoking, BMI, Family history of premature CAD, lipid profile and angiographic characteristics. The higher proportion of males in the younger MI group (83%) in our study is not surprising as the coronary artery disease is usually occur 7 to 10 years earlier in men than women 18. Sevnteen percent of the patients in younger MI group and 13% in older MI group were females. This is in consistency with previous studies which showed the prevalence of 3 25% female sex in young patients 17,18. There were very few studies in the past which have compared the gender distribution among young 19. In this study, smoking and premature CAD in family (52.8% and 22.6% respectively) was the most important medical history factor in younger group. This is closely in line with recent studies of young STEMI patients from the Indian subcontinent 20. The frequency of diabetes and hypertension were found to be lower in the younger STEMI group compared to the older group (15.09% vs 26.95% and 6.6% vs 17% respectively) and it is not statistically significant (p-value 0.05 for hypertension and 0.07 for diabetes mellitus). This is a known fact that incidence of both diabetes mellitus and hypertension increases with age and is in relevance with the previous studies 20. Premature CAD is strongly associated with dyslipidemia especially when in combined with smoking 21. In our study, few patients in younger group had a history of dyslipidemia. However, at the time of presentation, 58.49% of patients in younger group and 42.98% in older group had low HDL levels (p-value 0.03). Screening of S21

25 Primary Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S18-S22 dyslipidemia and then early intervention can prevent acute cardiac events among individual aged <40 years with other risk factors. Young age group in our study had higher frequency of single vessel disease (64.15%) when compared with their older counterparts (29%). The present finding of single vessel disease in young patients versus multivessel disease in the older patients is in accordance with the previous studies 22. Similarly the number of lesions per patient in older age group were more as compared to younger age. Young patients with acute STEMI had a predominance of acute anterior STEMI due to occluded left anterior descending artery (67.92%). These findings are similar to previous study 23. Use of thrombuster for thrombus aspiration in younger and older groups were 3.5% and 5.1% respectively and was statistically in significant. We used radial site for PPCI in majority of patients (table-ii). Similarly DES was implanted in all younger group patients and in 81.9% of older group. There was no documented mortality in younger patients where as in older age group it was 2.9%. CONCLUSION Anterior wall STEMI was common in younger group. Family history of premature coronary artery disease, smoking and dyslipidemia were the main risk factors in young patients with STEMI. Early intervention to treat dyslipidemia in high risk younger population along with smoking cessation can decreased the disease burden in this age. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author REFERENCES 1. Iqbal R, Jahan N, Hanif A. Epidemiology and management cost of myocardial infarction in North Punjab, Pakistan. Iran Red Crescent Med J 2015; 17(7): e Nadeem M, Ahmed SS, Mansoor S, Farooq S. Risk factors for coronary heart disease in patients below 45 years of age. 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26 Open Access Total Occlusin-Percutaneous Coronary Intervention Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S23-S27 PROCEDURAL OUTCOMES OF CHRONIC TOTAL OCCLUSIN-PERCUTANEOUS CORONARY INTERVENTION, AN UPDATED ANALYSIS OF AFIC/NIHD CTO-PCI REGISTRY Azhar Ali Chaudhry, Sohail Aziz, Tahir Iqbal, Suleman Ahmed, Farhan Tuyyab, Rehana Khadim, Yasir Javed, Kumail Giskikari, Shuja Abbas, Mir Waqas Baloch Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To evaluate the procedural outcomes of patients having chronic total occlusion undergoing percutaneous coronary intervention at our clinical setup. Study Design: Descriptive cross sectional study. Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology & National Institute of Heart Diseases, Rawalpindi from Jul 2014 to Jun Material and Methods: A total of 536 patients who underwent for percutaneous coronary intervention- chronic total occlusion were included in our study. Patients with chronic total occlusion lesion 3 months were included in our study. All the patients underwent percutaneous coronary intervention of chronic total occlusion Vessel were selected by non probability sampling technique. Patient s clinical, demographic data and data regarding procedural outcome was recorded. Finally data was analyzed using descriptive statistics. Results: Out of 536 patients 468 (87%) were male while 68 (12%) were female. Mean age was 55.5 ± 11.6 Years from 36 to 81 Years. Two hundred and one (37.5%) patients were diabetic, 181(33.7%) were hypertensive and 224 (41.7%) were smokers. Mean LVEF% was 48.7 ± 7.1 (Mean ± SD). Most common vessel involved was RCA 248 (46.2%) followed by LAD 188 (35.0%). Only drug eluting stents (DES) were implanted in successful cases with average no of stents used per patient were 1.43 ± 0.7. Common reasons for failure of procedure was inability of balloon/microcatheter to cross the lesion, inability to cross through retrograde collaterals but the most common reason was the failure of wire to cross the CTO lesion. The overall procedural success was achieved in 73.1% patients. No deaths were reported during the procedures. Conclusion: The recanalization of CTO lesion was successfully done in 73% cases using PCI. Most common reason for unsuccessful revascularization was failure of guide wire to cross the lesion. With increasing experience and better equipment recanalization of CTO coronary lesions is a safe and effective treatment option for patients with persistent Angina even on optimal medical treatment. Keywords: Chronic total occlusion (CTO), Percutaneous coronary intervention (PCI), Drug eluting stents (DES) This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Chronic total occlusions (CTO) of coronary arteries are present in 15-30% of patients undergoing coronary angiography 1,2. Various studies have suggested that presence of CTO is associated with high mortality 3,4. CTOs are complex lesion with low procedural success rates and even after, successful PCI, chances of restenosis are 1.5 to 4 times greater than nonoccluded coronary artery lesion 5,6. Various prediction risk scores have been devised to Correspondence: Dr Azhar Ali Chaudhry, Armed Force Institute of Cardiology/NHID Rawalpindi Pakistan predict success of the procedure 7. Presence of CTO vessel is also one ofthe major reason for referral to CABG surgery 1. Successful revascularization of CTO can provide significant improvement in symptoms, left ventricular function, reduction in arrhythmias, and better tolerance of an acute coronary syndrome 6. By contrast, failure of CTO revascularization has been found to be associated with an increased risk of mortality and angina pectoris when compared with successful revascularization in meta-analysis 6,8. Despite significant volume of CTO on coronary angiography, due to technical difficulties and failure of procedural success, only S23

27 Total Occlusin-Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S23-S % CTO PCI as compare to total PCI volumes are reported in National cardiovascular data registry USA 9. Very limited centers in Pakistan perform complex coronary intervention especially PCI of CTO vessels and to the best of our knowledge no local studies with such large no of patients are available to show procedural outcomes of CTO PCI in Pakistan. In this study we planned to analyze Armed Forces Institute of Cardiology / National Institute of heart diseases PCI data for CTO cases. This institute is a high volume center and among leading and very few institute in Pakistan with much experience in successful recanalization of CTO-PCI. The analysis will also include the average equipment/ hardware used for CTO- PCI thus encouraging other centers to treat CTO and to reduce overwhelming burden on limited cardiac surgical centers. MATERIAL AND METHODS This was an observational study, carried out at AFIC/NIHD Rawalpindi from July 2014 to June All patients who underwent CTO PCIs which include 536 patients at AFIC/NIHD cardiac catheterization laboratory were included in the study. A chronic total occlusion (CTO) was defined as the complete obstruction of a coronary artery, exhibiting TIMI 0 or TIMI 1 flow, with an occlusion duration of >3 months. Procedural success was defined as TIMI 3 grade flow S24 achieved without any MACE. Most common indication for CTO PCI was persistent angina despite optimal medical treatment. All patients underwent the CTO PCI as per protocol after getting the written informed consent. Data Analysis Categorical variables are presented as frequencies and continuous variables are presented as means with standard deviation. Comparisons were done with Pearson chi-square test for parametric data and with Mann-Whitney Wilcoxon test for nonparametric data (SPSS Version 21). A p-value of <0.05 was considered Table-I: Demographics and Risk Factors. Variables n (%) Age (Mean ± SD) 55.5 ± 11.6 Years (Range) Years Gender Males Females 468 (87.3%) 68 (12.6%) Diabetes Mellitus 201 (37.5%) Hypertension 181 (33.7%) Smoking History 224 (41.7%) LVEF% (Mean ± SD) 48.7 ± 7.1 (Range) Table-II: Yearly Analysis of Complete Total Occlusion-Percutaneous Coronary Intervention. Year 2014 Year 2015 Year 2016 Year 2017 Total CTO Cases Successful Cases 69 (76.66%) 134 (74.44%) 134 (76.13%) 59 (65.5%) 396 (73.1%) Unsuccessful Cases 21 (23.34%) 46 (25.56%) 42 (23.87%) 31(34.5%) 140 (26.1%) statistically significant. The data is also breakdown on basis of years and a comparison is done for procedural success. RESULTS The registry data showed that total numbers of PCI done in AFIC/NIHD are out of which 536 (4.7%) was CTO cases. Demographic characteristics of our patient s registry showing highest amount of intervention done for male patients as most patients entitled at our center are male as shown in table-i. Smoking was commonest risk factor for presence of CTO followed by diabetes mellitus. The mean left ventricular ejection fraction was 48.7 ± 7.1%. Most common vessel involved was RCA 248 (46.2%) followed by LAD 188 (35.0%), LCX (18.8%), while

28 Total Occlusin-Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S23-S27 only 0.98% patients had double CTO vessels. Procedural success rate for 4 years was 73.1%. Almost all patients underwent Antegrade wire escalation with retrograde approach accounting only for 4.85%. Most common access site for CTO PCI used was Radial (51%), followed by femoral approach (47%) and DUAL Injections were used in 35% of the cases. All the patients with successful recanalization were implanted with drug eluting stents. No deaths were reported during the procedures. Table-II shows that procedural success rate for 4 years is 73.1% with highest success rate achieved in 2014 and highest number of cases done in Almost all patients underwent Antegrade wire escalation with for treating symptoms, usually angina and dyspnea 11,12. In the SYNTAX trial, percutaneous coronary intervention (PCI) of CTO lesions was successful in 49% percent of patients, while the surgical success rate was only marginally better at 68%13. Currently, PCI success rates of greater than 80% are being reported in specialist Japanese, American and European Centers. DECISION CTO and EURO-CTO TRIALS are new addition to controversies surrounding the challenging revascularization of CTO PCI 14,15. It has generated lot of debate among the experts around the world, some favoring to keep patients on optimal medical treatment as it has been shown to be non-inferior to revascularization in Table-III: Complete total occlusion approach, complete total occlusion access site, culprit artery and equipment used. Antegrade Approach 510 (95.1%) Retrograde Approach 26 (4.85%) Radial 275 (51.3%) Femoral 254 (47.3%) Ulnar 7 (1.3%) Dual Injection (Radial + Femoral) 188 (35.0%) AD 188 (35.0%) LCX 101 (18.8%) RCA 248 (46.2%) Double CTO 5 (0.93%) Wires (Mean ± SD) 2.13 ± 0.92 Balloons (Mean ± SD) 2.74 ± 1.10 Stents (Mean ± SD) 1.43 ± 0.71 Contrast (Mean ± SD) 192 ± 47.3 ml retrograde approach accounting only for 2.98%. The access site of PCI was also shown in table-iii. Although recommended approach to access CTO is dual injection (double stick) but at our setup routine CTO access site is radial or femoral to reduce the patient cost. Table-III shows that RCA followed by LAD are common sites for CTO in our registry. The average equipment use for recanalizing CTO was shown in table-iii. DISCUSSION Revascularization of CTO coronary vessels remains a challenge irrespective of the modality chosen CTO PCI is done in most patients S25 DECISION CTO TRIAL. While some experts like Emmanuel S. Brilakis, believe that this trial will not change the contemporary practice as this trial has its own flaws in recruitment and hard end points. Our center is veteran hospital and amongst the highest PCI volume centre in the country with huge experience in complex PCI cases. In our CTO registry data majority of the patients were males as AFIC is the biggest a referral Centre in the Armed Forces with major volume of male entitled patients. Smoking was the commonest risk factor for presence of CTO followed by Diabetes Mellitus 5,14,15. This result is in consistence with the study done by Brilaki et al

29 Total Occlusin-Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S23-S27 which showed smoking and diabetes to be a significant risk factor for CTO. In our study average procedural success rate was 73.18% which is comparable to the success rate reported in international studies like Stone et al, Suero et al, and TOAST-GISE14, 16,17. Highest success rate was achieved in 2014 (76.66%) and highest number of cases done in 2015 (190). In a previous study registry data from Feb 2012 to Dec 2013 AFIC/NIHD) reported success rate was 98%, but the no of patients were very low (n=50) as compared to our data. Reasons for relatively low success rate in 2017 (65.6%) are multi-factorial including increasing complexity of cases, new less experienced operators attempting CTOs. Experienced operators at our Centre have a steady success rate of more than 80%. The volume of CTO PCI has remained steady over the last few years. So this trend in our result is not against the fore mentioned studies which showed significant success in CTO PCI over the years. In our study most common vessel involved was RCA 248 (46.2%) followed by LAD 188 (35.0%), LCX (18.8%), while only 0.98% patients had double CTO vessels. The findings are consistent with Canadian Multicenter CTO Registry showed that 47% of solitary CTOs occur in the right coronary artery, 20% in the LAD, and 16% in the left circumflex. Similar distributions of CTOs have been reported by other investigators Majority of the CTO cases were attempted through Antegrade approach with wire escalation strategy. While only 4.85% cases were attempted through retrograde approach after failure of antegrade technique. The most common access for CTO PCI was radial (51%) followed by femoral (47%). Dual injections were used in only 35% of the cases. Reason for less use of dual injections and common Antegrade approach is operator experience, and high cost of equipment in retrograde approach. Most common wire used was Run-through followed by pilot 50 and Fielder XT. Average no of wires usedper patient were 2.13 ± Average no of balloons and stents used per patient were 2.74 ± 1.10 and 1.47 ± 0.71 stents. All the patients with successful revascularization were implanted drug eluting stents which is in keeping with the evidence that DES implantation in CTO PCI is associated with better outcomes Common reasons for failure of procedure was inability of balloon/micro catheter to cross the lesion due to severe calcification or tortuosity of the vessel, inability to cross through retrograde collaterals but the most common reason was the failure of wire to cross the CTO lesion. There were no intra-procedural or in hospital deaths reported. CONCLUSION CTO prevalence in angiography was found very high as compared to CTO PCI. Fear of failure, lack of CTO experience and higher cost of CTO PCI inventory in a developing country can be attributed to this lower rate of CTO PCI in Pakistan. Descriptive statistics of CTO in Pakistan is in accordance to international studies. With higher retrograde PCI and more use of Dual injection can improve CTO PCI success. LIMITATION OF STUDY Our study results cannot be generalized as it does not show randomized data. Cost is the primary factor in all PCI in Pakistan, the success rate and volume cannot be compared to international studies. The lack of large data for retrograde PCI which is a very important procedure to open complex CTO also limits the findings of our study. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1 Christofferson RD, Lehmann KG, Martin GV, Every N, Caldwell JH, Kapadia SR. Effect of chronic total coronary occlusion on treatment strategy. Am J Cardiol 2005; 95(9): Claessen BE, Hoebers LP, van der Schaaf RJ, Kikkert WJ, Engstrom AE, Vis MM, et al. Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on long-term mortality in diabetic patients with ST elevation myocardial infarction. Heart 2010; 96(24): Kahn JK. Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting. Am Heart J 1993; 126(3 Pt 1): Tajstra M, Gasior M, Gierlotka M, Pres D, Hawranek M, Trzeciak P, et al. Comparison of five-year outcomes of patients with and without chronic total occlusion of noninfarct coronary S26

30 Total Occlusin-Percutaneous Coronary Intervention Pak Armed Forces Med J 2018; 68 (Suppl-1): S23-S27 artery after primary coronary intervention for ST-segment elevation acute myocardial infarction. Am Heart J 2011; 109(2): Chai WL, Agyekum F, Zhang B,, Liao HT, Ma DL, Zhong ZA, et al. Clinical Prediction Score for Successful Retrograde Procedure in Chronic Total Occlusion Percutaneous Coronary Intervention. Cardiology 2016; 134(3): Van der Schaaf RJ, Vis MM, Sjauw KD, Koch KT, Baan J, Jr., Tijssen JG, et al. Impact of multivessel coronary disease on longterm mortality in patients with ST-elevation myocardial infarction is due to the presence of a chronic total occlusion. Am Heart J 2006; 98(9): Van den Branden BJ, Rahel BM, Laarman GJ, Slagboom T, Kelder JC, Ten Berg JM, et al. Five-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II study). EuroIntervention 2012; 7(10): Godino C, Latib A, Economou FI, Al-Lamee R, Ielasi A, Bassanelli G, et al. Coronary chronic total occlusions: mid-term comparison of clinical outcome following the use of the guided- STAR technique and conventional anterograde approaches. Catheter Cardiovasc Interv 2012; 79(1): Garcia S, Abdullah S, Banerjee S, Brilakis ES. Chronic total occlusions: patient selection and overview of advanced techniques. Current cardiology reports 2013; 15(2): Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: A systematic review and metaanalysis. Am Heart J 2010; 160(1): Brilakis ES, Banerjee S, Karmpaliotis D, Lombardi WL, Tsai TT, Shunk KA, et al. Procedural outcomes of chronic total occlusion percutaneous coronary intervention: a report from the NCDR (National Cardiovascular Data Registry). JACC Cardiovascular interventions 2015; 8(2): Fefer P, Knudtson ML, Cheema AN, Galbraith PD, Osherov AB, Yalonetsky S, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol 2012; 59(11): Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: Five-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013; 381(9867): Park S. Drug eluting stent implantation versus optimal medical treatment in patients with chronic total occlusion (DECISION CTO). American College of Cardiology's 66th Annual Scientific Session & Expo; Washington, DC; Werner G. A randomized multicentre trial to evaluate the utilization of revascularization or optimal medical therapy for the treatment of chronic total coronary occlusions (EuroCTO). Euro PCR; Paris, France; Saeed, B, Kandzari, D, Agostoni, P. "Use of drug-eluting stents for chronic total occlusions: a systematic review and metaanalysis". Catheter Cardiovasc Interv 2010; 77: Kimura M, Katoh O, Tsuchikane E, Nasu K, Kinoshita Y, Ehara M, et al. "The efficacy of a bilateral approach for treating lesions with chronic total occlusions the CART (controlled antegrade and retrograde subintimal tracking) registry". JACC Cardiovasc Interv 2009; 2(11): Valenti R, Vergara R, Migliorini A, Parodi G, Carrabba N, Cerisano G, et al. Predictors of reocclusion after successful drugeluting stent-supported PCI of CTOJ Am Coll Cardiol 2013; 61 (5): Rathore S, Hakeem A, Pauriah M, Roberts E, Beaumont A, Morris JL. Morris Comparison of the transradial and the transfemoral approach in chronic total occlusion percutaneous coronary intervention Catheter Cardiovasc Interv 2009; 73(7): Karmpaliotis D, Lembo N, Kalynych A, Carlson H, Lombardi WL, Anderson CN, et al. Anderson Development of a highvolume, multiple-operator program for percutaneous chronic total coronary occlusion revascularization: procedural, clinical, and cost-utilization outcomes. Catheter Cardiovasc Interv 2013; 82(1): Claessen BE, Dangas GD, Godino C, Henriques JP, Leon MB, Park SJ, et al. Impact of target vessel on long-term survival after percutaneous coronary intervention for chronic total occlusions Catheter Cardiovasc Interv 2013; 82(1): Fefer P, Knudtson ML, Cheema AN, Galbraith PD, Osherov AB, Yalonetsky S, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol 2012; 59(11): Banerjee S, Master RG, Peltz M, Willis B, Mohammed A, Little BB, et al. Influence of chronic total occlusions on coronary artery bypass graft surgical outcomes. J Card Surg 2012; 27: Jeroudi OM, Alomar ME, Michael TT, El Sabbagh A, Patel VG, Mogabgab O, et al. Prevalence and management of coronary chronic total occlusions in a tertiary Veterans Affairs hospital. Catheter Cardiovasc Interv 2014; 84: S27

31 Open Access Electrocardiographic Changes in Acute Pulmonary Embolism Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S28-S33 ELECTROCARDIOGRAPHIC CHANGES IN ACUTE PULMONARY EMBOLISM WITH RIGHT HEART STRAIN AND IT'S ASSOCIATION WITH ADVERSE CLINICAL EVENTS Tariq Hussain Khattak, Muhammad Azmat Khan*, Imran Ahmed**, Javeria Kamran, Hafsa Khalil, Aysha Siddiqa, Rehana Javaid Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Combined Military Hospital/ National University of Medical Sciences (NUMS) Rawalpindi Pakistan, **Military Hospital/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the frequency of electrocardiographic changes in right heart strain RHS due to acute pulmonary embolism PE and its effect on mortality. Study Design: Prospective cross-sectional study. Place and Duration of Study: AFIC/NIHD Rawalpindi, from Dec 2015 to Jan Material and Methods: 70 patients with acute pulmonary embolism were enrolled in this study. The primary outcome was right heart strain (RHS) on echocardiogram. The secondary outcome was mortality. Results: Mean age was ± and male were 51 (72.9%). Thirty eight (54.28%) had right heart strain RHS on echocardiography. Mortality was 14 (20%). Provocating factors were identified in 34 (48.6%). Major contributing factors were high altitude in 11 (15.7%) and postoperative and malignancy cases in 7 (10%) each. ECG changes with significant association with RHS included: Tachycadia in 13 (34%) (p-value 0.013), S wave in lead I in 12 (31.57%) (p-value 0.039), T wave inversion TWI in lead VI and lead V2 in 10 (26.31%) and TWI in lead VI to V3 in 8 (21.05%) (p-value 0.03). ECG changes with significant association with mortality included- Tachycardia 100 bpmin 7 (50%) (p-value 0.012), SIQ3T3 in 5 (35.71%) (p-value 0.022), S wave in lead I in 8 (57.14%) (p-value 0.001), TWI in leads V1 through V2 in 5 (35.71%) (p-value 0.054) and TWI in leads V1 through V3 in 5 (35.71%) (p-value 0.013). Conclusions: ECG can identify patients with RHS in acute PE and this in turn helps in identifying patients vulnerable to adverse clinical events. Keywords: Pulmonary embolism, Right heart strain, Thrombolysis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Acute pulmonary embolism (PE) is a serious complication of venous thromboembolism (VTE) with an annual incidence of 100 ± 200 per 100,000 persons 1. Depending upon the thrombotic burden it can have In-hospital mortality as high as 59% 2. Four year adverse event rate of 50% 3 and a 5 year mortality rate of up to 32% 4 speaks of the high long term morbidity and mortality despite treatment 5. PE can be classified as massive, sub-massive, or non-massive based on the hemodynamic. Status and right ventricular (RV) function of Correspondence: Dr Tariq Hussain Khattak, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan tariq_khattak63@yahoo.com the patient. Massive PE is characterized by systemic hypotension or cardiogenic shock, submassive PE is characterized by RV dysfunction without hypotension, and nonmassive PE has neither systemic hypotension nor RV dysfunction 6. In-hospital mortality varies with severity as high as 25-50% with massive PE, 3-15% with submassive and 5% or less with non-massive PE 7 Sub-massive PE can have mortality approaching massive PE with attendant difficult risk assessment 8. While there is a consensus that in patients with massive PE should receive either systemic thrombolysis, catheter directed interventions, or surgery 6. The management of patients with submassive PE remains controversial, the risk-benefit S28

32 Electrocardiographic Changes in Acute Pulmonary Embolism Pak Armed Forces Med J 2018; 68 (Suppl-1): S28-S33 ratio of thrombolytic or invasive therapies versus bleeding is unclear 8. Patients with PE are risk stratified so as to estimate the probability of circulatory shock and 30-day all-cause mortality 6. Patients with low risk PE might be considered for immediate treatment at home 9,10. Fibrinolytic therapy is recommended for patients with PE and RV failure as they may have hemodynamic collapse 6. Risk stratification includes clinical scoring systems, biomarkers (troponins I and T, brain natriuretic peptides), RV strain on echocardiography and RV dilatation on computed tomography (CT) scanning 14,15. Right heart strain (RHS) is suggested by certain ECG findings and this helps in prioriting care in high risk patients Several ECG components (particularly heart rate, inverted T waves in leads V2 and V3, and ST elevation in avr) have ORs higher than echocardiographic/ CT scanning/biomarker findings of RV strain 6,20. Echocardiography is not available during the whole day in many hospitals 21 which makes ECG a useful risk stratifying tool. The purpose of this study is to ascertain the frequency of electrocardiographic changes with RHS and its association withmortality, so as to recommend ECG as a risk marker of RHS and identifying patients in need of thrombolytic therapy in centers where echocardiographic facility is unavailable. MATERIAL AND METHODS This is a prospective cross-sectional study carried out at AFIC/NIHD Rawalpindi from December 2015 to January Institutional ethical review board approval was obtained. Verbal consent was obtained from patients. Data collection tool was developed to measure demographics, response to treatment and outcome. Doppler ultrasound of lower limbs was carried out for DVT. Diagnosis of Pulmonary Embolism was based on CTPA showing filling defect. 12-lead electrocardiogram was obtained on arrival at ER and was used as the primary predictor. The ECG was assessed for heart rate (HR), rhythm, S wave in lead I,SIQIIITIII pattern, Q wave /T wave inversion in lead III, incomplete or complete right bundle branch block (RBBB), ST-segment elevations/depressions, and T-wave inversions (TWI). Primary outcome was right heart strain on echocardiography. Echocardiography was carried out within 24 hours. RHS was based on RV dilatation, hypokinesis, Mc Connel Sign, Peak pulmonary artery pressure and Trans annular peak systolic excursion TAPSE. TAPSE was determined by the longitudinal motion of annulus at peak systole with the M-mode cursor at the lateral tricuspid annulus. Secondary outcome was death as the only adverse clinical event, assessed during the period of hospitalization. Statistical analysis was carried out on IBM SPSS version 23. Categorical data was presented as percentages and frequency whereas descriptive statistics were expressed as mean and standard deviation for quantitative analyses. Chi square test was applied to analyze the data. A p-value of 0.05 was considered statistically significant. RESULTS Between December 2015 and January 2018, 70 patients with pulmonary embolism were enrolled. Table-I shows basic characteriatics of the enrolled patients. Mean age was ± Male were 51 (72.9%). An Emergency deptt ECG was available for review in all 70 (100%) patients. CTPA confirmed acute PE in 70 (100%). Doppler study was carried out in all patients and revealed DVT in 29 (42%). Echocardiography was carried out in all patients and revealed Right heart strain RHS in 38 (54.28%). Mortality was 14 (20%). Provocating factors were identified in 34 (48.6%). Major contributing factors were high altitude in 11 (15.7%) and postoperative and malignancy cases in 7 (10%) each. ECG changes with significant association with RHS included; Tachycadia in 13 (34%) (p-value 0.013), Swave in lead I in 12 (31.57%) S29

33 Electrocardiographic Changes in Acute Pulmonary Embolism Pak Armed Forces Med J 2018; 68 (Suppl-1): S28-S33 (p-value 0.039), T wave inversion TWI in lead VI and lead V2 in 10 (26.31%) and TWI in lead VI to V3 in 8 (21.05%) (p-value 0.03). ECG changes with significant association with mortality included-tachycardia 100 bpmin 7 (50%) (p-value 0.012), SIQ3T3 in 5 (35.71%) (p-value 0.022), S wave in lead I in 8 (57.14%) (p-value 0.001), TWI in leads V1 through V2 in 5 (35.71%) (p-value 0.054) and TWI in leads V1 through V3 in 5 (35.71%) (p-value 0.013). DISCUSSION In a patient with symptoms suggestive of pulmonary embolism ECG is usually the first investigation to be carried out. Its role is primarily to exclude other conditions like acute myocardial infarction. However with certain findings it provides clue to the possibility of S30 pulmonary embolism. Recently its role has been enhanced as a tool for detection of right heart strain. This is particularly important from the fact that echocardiography is not available in all the centers. The right ventricular (RV) strain and severe pulmonary hypertension after PE is corroborated by certain ECG findings 21. Daniel et al in 2001 Table-I: Baseline characteristics of enrolled patients no (70). Characteristic n (%) or ± SD Mean age (years) ± Male 51(72.9%) Symptom Dyspnoe 62 (88.57%) Haemoptysis 10 (14.28%) Chest discomfort 20 (28.57%) Syncope 2 (2.8%) Comorbidity Hypertension 7 (10%) Diabetes mellitus 1 (1.4%) Chronic kidney disease 17 (24.63%) Smoker 1 (1.4%) Hypothroidism 1 (1.4%) Cerebrovascular accident 2 (2.9%) Past history pulmonary embolism 3 (4.3%) Past history ischaemic heart disease 3 (4.3%) Table-II: Provocating factors. Characteristic No (%) Provoked 34 (48.6%) High altitude 11 (15.7%) Fracture 7 (10%) Postoperative 7 (10%) Bedridden 5 (7.1%) Long travel 1 (1.4%) Steroid intake 1 (1.4%) developed a scoring system that predicted increased pulmonary arterial pressure 16. It was based on scores as in parenthesis: sinus tachycardia (2); incomplete right bundle branch block (2); complete right bundle branch block (3); T-wave inversion, graded by magnitude (V1 [0 to 2], V2 [1 to 3], V3 [1 to 3], V1 through V4 all inverted 2 mm [4]); S1Q3T3 complex components (S wave in lead I [0], Q wave in lead III [1], inverted T wave in lead III [1], and the entire

34 Electrocardiographic Changes in Acute Pulmonary Embolism Pak Armed Forces Med J 2018; 68 (Suppl-1): S28-S33 S1Q3T3 complex [2]). The maximum score was 21 points. At a cutoff point of 10 points, it was 97.7% specific and 23.5% sensitive for the detection of PE with severe pulmonary hypertension, and 52% of patients had fatal PE 16. A systematic review and meta-analysis of 3,007 patients by Shopp et al found six ECG findings (heart rate, S1Q3T3, crbbb, inverted T waves in V1 V4, ST elevation in avr, and atrial fibrillation) which predict hemodynamic collapse points) makes RHS unlikely, which further limits further tests 23. TWI in leads V1 through V3) has the strongest association with RHS 21. In our study ECG changes with significant association with RHS included as shown in table-ii; Tachycadia in 13 (34%) (p-value 0.013), S- wave in lead I in 12 (31.57%) (p-value 0.039), T wave inversion TWI in lead VI and lead V2 in 10 (26.31%) and TWI in lead VI to V3 in 8 (21.05%) (p-value 0.03). Mortality was significantly Table-II: ECG changes in Pulmonary embolism with and without RHS. Characteristic RHS present 38 RHS absent 32 (54.28%) (45.72%) p-value Sinus tachycardia 13 (34%) 3 (9.3%) S wave lead 1 12 (31.57%) 3 (9.3%) Q wave lead III 7 (18.42%) 4 (12.5%) NS T wave lead III 11 (28.94%) 7 (21.87%) NS S1QIIITIII pattern 7 (18.42%) 3 (9.3%) NS TWIV1-V2 10 (26.31%) 2 (6.25%) TWI V1-V3 8 (21.05%) 1(3.12%) Partial RBBB 4 (10.52%) 1 (3.12%) NS Complete RBBB 4 (10.52%) 1 (3.12%) NS Non sinus rhythm 3 (8.5%) 0 (0%) NS ECG, Electrocardiogram; RHS, Right heart strain; TWI,T wave inversion;rbbb, Right bundle branch block. Table-III: ECG changes in acute PE and association with mortality. ECG Characteristics Death14 (%) Alive 56 (%) p-value Tachycardia 100 bpm 7 (50%) 9 (16.07%) SIQ3T3 5 (35.71%) 5 (8.92%) S wave in lead I 8 (57.14%) 7 (12.5%) TWI in leads V1 through V2 5 (35.71%) 7 (12.5%) TWI in leads V1 through V3 5 (35.71%) 4 (7.14%) Complete RBBB 2 (14.2%) 3 (5.35%) Incomplete RBBB 2 (14.2%) 3 (5.35%) ECG: Electrocardiogram, PE: Pulmonary embolism and death within 30 days after acute PE 22. In another study by Hariharan et al in 2015, 3 ECG characteristics were independently associated with RHS. This was the basis of a ten point score as in parenthesis: TWI in leads V1 through V3 (5 points), S wave in lead I (2 points), and sinus tachycardia (3 points). 85% of acute PE patients could be effectively stratified using this score. A TwiST ECG score 2 points excludes RHS with 85% sensitivity, and a score of 5 points has 93% specificity for RHS in acute PE. A Twist score ( 2 S31 associated with ECG changes that included- Tachycardia 100 bpmin in 7 (50%) (p-value 0.012), SIQ3T3 in 5 (35.71%) (p-value 0.022), S wave in lead I in 8 (57.14%) (p-value0.001), TWI in leads V1 through V2 in 5 (35.71%) (p-value 0.054) and TWI in leads V1 through V3 in 5 (35.71%) (p-value 0.013) as shown in table-iii. Our findings are corroborated by a systematic review and meta-analysis by Qaddoura et al, in which ECG signs that were good predictors of a negative outcome for in-hospital mortality

35 Electrocardiographic Changes in Acute Pulmonary Embolism Pak Armed Forces Med J 2018; 68 (Suppl-1): S28-S33 included S1Q3T3 (OR: 3.38, 95% CI: , p<0.001), complete right bundle branch block (OR: 3.90, 95% CI: , p<0.001), T-wave inversion (OR: 1.62, 95% CI: , p=0.002), right axis deviation (OR: 3.24, 95% CI: , p<0.001), and atrial fibrillation (OR: 1.96, 95% CI: , p<0.001) 18. Our study has provided simple ECG findings that suggest RHS and help in risk stratifying significant number of patient with pulmonary embolism who are at risk of adverse clinical event. This is important for centers without echocardiography facility. CONCLUSION ECG is a simple easily available investigation which not only rules out other conditions like acute myocardial infarction but also helps in risk stratifying patients with PE, which makes it a useful investigative tool in centers without echocardiography facility. This can help in decision making in intermediate risk patients for consideration of thrombolytic therapy as well as for decision making for home treatment. ACKNOWLEDGEMENT We thank Dr Farrah Pervaiz and her team of Research and development department at AFIC/NIHD Rawalpindi for help in Data collection and data analysis. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. The authors certify that they have no affiliation with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in the manuscript. REFERENCES 1. Ho WK, Hankey GJ, Eikelboom JW. The incidence of venous thromboembolism: A prospective, community-based study in Perth, Western Australia. Med J Aust 2008; 189(3): Vieillard-Baron A, Page B, Augarde R, Prin S, Qanadli S, Beauchet A, et al. Acute cor pulmonale in massive pulmonary embolism: Incidence, echocardiographic pattern, clinical implications and recovery rate. Intensive Care Med 2001; 27(9): Klok FA, Zondag W, van Kralingen KW, van Dijk AP, Tamsma JT, Heyning FH, et al. Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events. Am J Respir Crit Care Med 2010; 181(5): Ng AC, Chung T, Yong AS, Wong HS, Chow V, Celermajer DS, et al. Long-term cardiovascular and noncardiovascular mortality of 1023 patients with confirmed acute pulmonary embolism. Circ Cardiovasc Qual Outcomes 2011; 4(1): Den Exter PL, van der Hulle T, Lankeit M, Huisman MV, Klok FA. Long-term clinical course of acute pulmonary embolism. Blood Rev 2013; 27(4): Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, et al. ESC Guidelines on the diagnosis and management of acute pulmonary embolism: The task force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC) Endorsed by the European Respiratory Society (ERS). 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36 Electrocardiographic Changes in Acute Pulmonary Embolism Pak Armed Forces Med J 2018; 68 (Suppl-1): S28-S33 pulmonary embolism: A systematic review and meta-analysis. Clin Cardiol 2017; 40(10): Digby GC, Kukla P, Zhan ZQ, Pastore CA, Piotrowicz R, Schapachnik E, et al. The value of electrocardiographic abnormalities in the prognosis of pulmonary embolism: A consensus paper. Ann Noninvasive Electrocardiol 2015; 20(3): Kukla P, McIntyre WF, Fijorek K, Mirek-Bryniarska E, Bryniarski L, Krupa E, et al. Electrocardiographic abnormalities in patients with acute pulmonary embolism complicated by cardiogenic shock. Am J Emerg Med 2014; 32(6): Jones AE, Kline JA. Availability of technology to evaluate for pulmonary embolism in academic emergency departments in the United States. J Thromb Haemost 2003; 1: Shopp JD, Stewart LK, Emmett TW, Kline JA. Findings From 12-lead Electro - cardiography That Predict Circulatory Shock From Pulmonary Embolism: Systematic Review and Meta-analysis. Acad Emerg Med 2015; 22(10): Hariharan P, Dudzinski DM, Okechukwu I, Takayesu JK, Chang Y, Kabrhel C. Association between electrocardiographic findings, right heart strain, and short-term adverse clinical events in patients with acute pulmonary embolism. Clin Cardiol 2015; 38(4): S33

37 Open Access Effects of Propofol Infusion Versus Sevoflurane Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S34-S37 EFFECTS OF PROPOFOL INFUSION VERSUS SEVOFLURANE ON HEMODYNAMIC RESPONSE DURING CARDIOPULMONARY BYPASS IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFT SURGERY Jehan Essa, Rashad Siddiqi, Syed Shaheer Haider Bukhari, Rehana Javaid Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: The aim of this study was to compare hemodynamic effects of propofol with that of sevoflurane during cardiopulmonary bypass time in patients undergoing coronary artery bypass surgery to avoid high lactate level which is an indicator of poor prognosis. Study Design: Randomized control trial. Place and Duration of Study: Armed Forces Institute of Cardiology/National Institute of Heart Diseases, from Jan 2017 to Aug Material and Methods: Hemodynamic of 120 patients during CPB were studied after either propofol or Sevoflurane was applied with initiation of a Standard cardiopulmonary bypass technique, applying cross clamp, administering cardioplegia and allow time to develop stable perfusion pressure. Base line lactate level from initial arterial blood gases was recorded, total bypass time, cross clamp time, Noradrenalin dose, flow rate, mean arterial pressure during CPB and post rewarming lactate level were recorded for all patients. Results: There was no significant difference in lactate level and noradrenalin dose that given in two groups when rewarming was established. Propofol group showed a significant lower MAP 63.1 ± 2.6 mmhg in comparison to sevoflurane group 69.5 ± 5.3 mmhg and significant higher flow rate p-value < Conclusion: Patients in both groups remained hemodynamically stable with lower MAP in propofol group requiring higher flow rate. Keywords: Cardiopulmonary bypass, Propofol, Sevoflurane, Noradrenaline, MAP, lactate level. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Propofol (2,6 Di-isopropylphenol) is one of the most widely and frequently used intravenous anesthetic 1,2. It has high lipid solubility. The kinetics of Propofol allows rapid induction of anesthesia, adequate maintenance, and rapid return of consciousness 2. Sevoflurane is fluorinated methyl isopropyl ether, a newer halogenated volatile anesthetic, has some chemical advantages, lower blood gas solubility resulting in a faster onset and rapid emergence, pleasant to inhale, offers good hemodynamic stability, Moreover, there appears to be an opinion among cardiac anesthesiologists that sevoflurane is superior to Isoflurane 3,4. It has Correspondence: Dr Jehan Essa, Department of Cardiac Anaesthesia, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan jehanalzain29@gmail.com vasodilator effect on systemic vascular resistance during CBP 5 due to its direct relaxant action on vascular smooth muscle, reduction in sympathetic output and ineffective ness of other stimuli on the vascular smooth 6. There are still many controversies on the impact of sevoflurane versus propofol on cardiovascular stability. Some authorshave not found any differences betweensevoflurane and propofol 7. It is an established fact that tissue hypoperfusion is associated with lactic acidosis secondary to anaerobic metabolism, hence measurement of blood lactate levels can be used as a marker to assess the adequacy of tissue perfusion 8, which is at risk during CPB and in the immediate postoperative period. lactate level is affected by many potential factors such as pump flow rate that affect Oxygen delivery, the duration of CPB, degree of hypothermia, rewarming, the hematocrit value and intra- S34

38 Effects of Propofol Infusion Versus Sevoflurane Pak Armed Forces Med J 2018; 68 (Suppl-1): S34-S37 operative hemodynamic effects of maintenance anesthetics might contribute to high lactatelevel 9,10. High lactate level after cardiac surgery is common, it is regarded as predictors of major complications, patients may require prolonged inotropic and ventilatory support 11,12 and it associated with morbidity and mortality 13, some studies regard CPB lactate level one of the factors that could significantly affect ICU free survival days 14 but the implications of raised levels remainmultifactorial and controversial. According to what previously mentioned and to Barolia et al study published in May 2017 coronary heart disease (CAD) is one of the top leading cause of death in Pakistan 15 and the conventional CABG surgery with CPB is still the gold standard treatment method for treatment of CAD and CPB has been considered a useful model for studying the isolated effect of drugs on the systemic vasculature as cardiac effects are excluded during aortic cross clamp 18, this study was conducted with objective to correlate hemodynamics effects of Propofol and sevoflurane that may affect perfusion pressure and hence blood lactate level and allow intervention in a suitable time to reduce patient complication. MATERIAL AND METHODS One hundred and twenty consecutive patients were included (88 male and 32 female), under-went elective CABG surgery at Armed Forces Institue of Cardiology/National Institute of Cardiology (AFIC/NIHD), from January to August 2017, after approval from ethical committee of the institute. All patients had a standard anesthesia technique as per our cardiac anesthesia unit protocol, were induced with tit rated dose of fentanyl (5-15μg/kg), midazolam ( mg/kg), propofol (1-1.5mg/ kg), atracurium (0.5 mg/kg) and maintainedwith inhalation of Isoflurane (1-2%) and incremental doses of fentanyl and Atracurium till initiation of CPB. Patients selected randomly using card drawing system and divided into two groups A and B, in group-a Propofol infusion with HUAXI medical infusion pump was applied for maintenance of anesthesia during standard CPB technique, in a dose range of 75 to 125μg/ kg/min 17. In group-b inspired concentration of sevoflurane was kept between 1 to 2% using Dragger vaporizer connected to CPB oxygenator gas supply system with constant gas flow of 3 liters/min. During CPB, the following conditions were continuously monitored and maintained; a mild hypothermia of 32 C using hemotherm stockertand monitored by nasal probe, perfusion pressure of mmhg using invasive blood pressure monitoring,through pre-determined non pulsatile flow rate according to body surface area and cardiac index at 2.4 L/min/m 2 with titrating and recording Noradrenaline dose and/or increasing perfusion flow to maintain stable hemodynamics if needed. Hemoglobin was monitored by frequent arterial blood gases (ABGs) and maintained between 8 and 9 gm%, base line lactate level was recorded from initial ABG using blood gas analyzer ABL800 and after heart isolation by applying cross clamp, intermittent antegrade or retrograde cold blood cardioplegia was used, final blood lactate level was recorded from last ABG after established rewarming. Total bypass time, cross clamp time, were recorded for all patients. Data Analysis Descriptive statistics were performed for frequency and percentage. Pearson Chi Square test was applied for comparison of categorical variables and independent t-test was applied for continuous variables. RESULTS The patients in this study were in the age group of years, 88 were males and 32 were females. There were no significant differences between groups in the mean age or weight as shown in table-i & II. The results are given as Mean ± SD. A p-value<0.05 values is significant with equal variances assumed. S35

39 Effects of Propofol Infusion Versus Sevoflurane Pak Armed Forces Med J 2018; 68 (Suppl-1): S34-S37 DISCUSSION Hemodynamic stability is important requirement of modern anesthesia generally and maintenance of appropriate hemodynamic goals is essential to improve outcomes after cardiac surgery and determine prognosis. As it is well-known that circulatory insufficiency due to CPB and hemodynamic in stability caused by anesthesia synergistically may lead to high lactate which is considered as a prognostic factor intra operatively. Anesthesia is considered as one of the factors that may determine lactate level and hemodynamic stability, our study confirms the lack of significant change in mean lactate levels (p-value was 0.9) in patients whose anesthesia both results were not confirming these studies. Temperature was maintained at moderate hypothermia (32 C) in both groups as it helps an easier management of temperature after completion of CPB 20. Hemodilution and using catecholamines have a well-known effect on lactate level, in our study total Noradrenaline dose that given to maintain the MAP was insignificant between the two groups (p-value 0.3) and hemoglobin maintained between 8-9 g/dl to maintain oxygen delivery because many Previous studies has indicated that increase lactate level is considered as an indicator of inadequate perfusion and tissue oxygen delivery together with CPB effect and its related Table-I: Demography of Patients of both groups. Parameters Group-I Mean ± SD Group-II Mean ± SD Mean Age (years) ± ± Mean Weight (kgs) 68.09± ± No. of Male Patients No. of Female Patients Table-II: Hemodynamic parameters of both groups. Parameters Group-I Mean ± SD Group-II Mean ± SD p-value Pre-cross clamp lactate level (mmol /L) 1.78 ± ± Post- rewarming lactate (mmol /L) ± ± Total Noradrenaline dose μg/kg MAP during CPB mmhg 63.1 ± ± Flow rate L/min = (CI BSA) ± ± <0.001 Total bypass time (min) ± ± Cross clamp time (min) ± ± was maintained by Propofol, and those whose anesthesia maintained by sevoflurane during CPB period and have shown insignificant differences in parameters that may determine lactate production between the study groups; in regards of CPB duration (p-value was 0.3). Ranucci et al and Shinde et al 18,19 indicated that the relation between CPB time and spike lactate level was not linear and the cut off value for CPB time was 96 minutes. Our mean CPB time in Propofol group was ± minutes and ± 4.25 minutes in sevoflurane group and S36 factors Knowing the body surface area (BSA) of the patient, the required pump flow is as follows; pump flow rate=bsa cardiac index (CI) cardiac index of a 70 kg adult with normal metabolism at 37 C is L/m 2 /min. For each 1 C decrease in temperature, the required cardiac output reduces by 7%, and the pump flow can be reduced by an equivalent factor 24,25. A main potential intervention that may alter organ perfusion and tissue oxygen delivery during CPB is manipulation of perfusion pressure and flow rates 26,27. Flow rates in our

40 Effects of Propofol Infusion Versus Sevoflurane Pak Armed Forces Med J 2018; 68 (Suppl-1): S34-S37 study were significantly higher in propofol group, (p-value <0.001) which may off set the vasodilatory effects of Propofol and the fact that fall in systemic vascular resistance may decrease organ perfusion. CONCLUSION To conclude, patients who were undergoing CABG under CPB, choice of Propofol infusion or Sevoflurane has no significant effect in lactate level during CPB period but MAP decreased more in Propofol group which may influence the decision of which anesthetic to use in special cases. Large randomized trials are indicated to support this study. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Bensel BM, Guzik-Lendrum S, Masucci EM, Woll KA, Eckenhoff RG, Gilbert SP.Common general anesthetic Propofol impairs Kinesin processivity. Proc Natl Acad Sci USA 2017; 114(21): E Shireen Ahmad, De Oliveira Jr GS, Paul C. 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41 Open Access Contrast Induced Nephropathy in Coronary Angiography Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S38-S41 A COMPARSION OF CONTRAST INDUCED NEPHROPATHY BETWEEN NORMAL AND HIGH RISK POPULATION UNDERGOING CORONARY ANGIOGRAPHY Mir Waqas Baloch, Rehana Khadim, Samra Rehmat, Mohammad Asad, Sohail Aziz, Tahir Iqbal, Imran Fazal, Tariq Hussain Khattak, Azhar Ali Chaudary, Hasnain Iqbal Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the frequency of contrast induced nephropathy in patients undergoing coronary angiography and compare frequency of contrast induced nephropathy in low and high risk patients. Study Design: A comparative cross-sectional study. Place and Duration of study: Cardiac cath department, Armed forces institute of cardiology and National institute of heart diseases, Rawalpindi from Jul 2017 to Dec Material and Methods: Patients undergoing elective percutaneous coronary angiography with co-morbids (diabetes mellitus and hypertention) were included. Diabetics who are on oral hypoglycemic agents i.e. metformin was stopped 48 hours prior to the procedure. Patients were enrolled into two groups; one with normal baseline creatinine level and the second group with abnormal baseline i.e. creatinine >1.5, diabetes and hypertention which was pre-hydrated. All patients were administered intravenous fluid (normal saline) before the procedure. Results: Total 115 patients were included according to the inclusion criteria of the study. Mean age was ± 7.09 years while there were 60 (52.2%) male and 55 (47.8%) female patients in the study. Frequency of contrast induced nephropathy in patients undergoing coronary angiography was 11 (9.3%), whereas frequency of contrast induced nephropathy in low and high risk patients was 8 (72.7%) and 3 (27.3%) respectively which was statistically not significant (p-value 0.980). Conclusion: The study showed that occurrence of contrast induced nephropathy in patients undergoing coronary angiography was although not statistically significant but more studies should be done in order to contribute in the existing research through validation of risk factors (predictors) for contrast induced nephropathy in diabetic and hypertensive patients. Keywords: Contrast Induced Nephropathy, Coronary angiography, High risk patients, low risk patients. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION The use of radio contrast media has increased greatly from the past decades for diagnostic radiography and interventional procedures and it is estimated that approximately 60 million people in the world are administered radio contrast medium each year 1. Contrast induced nephropathy (CIN) has gained increased attention in the clinical setting, particularly during cardiac intervention but also in many other radiological procedures in which iodinated contrast media are used 2. There is at present good clinical evidence from well-controlled randomized studies that CIN is a common cause Correspondence: Dr Mir Waqas Baloch, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan. mirwaqas8@gmail.com) of acute renal dysfunction 3. After radiographic contrast procedures 12 to 14 percent of patients suffer from acute renal insufficiency during hospitalization 4. CIN is the third primary cause of hospital-acquired acute renal failure 5,6. Contrast induced nephropathy is the acute deterioration of renal function after parenteral administration of radiocontrast media in the absence of other causes. Contrast Induced Nephropathy is generally defined as an increase in serum creatinine concentration of >0.5 mg/dl or 25% above baseline within 48 hours after contrast administration 5,7. Although the exact mechanisms of CIN have yet to be fully elucidated, several causes have been described. Increased adenosine, endothelia, and free radical induced vasoconstriction and reduced S38

42 Contrast Induced Nephropathy in Coronary Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S38-S41 nitric oxide and prostaglandin-induced vasodilatation have been observed 5. Contrast agents also have direct toxic effect on renal tubular cells causing vacuolization and altered mitochondrial function 2,6. According to minnesota registry of interventional cardiac procedures, RCIN was found in 22 percent of patients with serum creatinine >2 mg/ dl and in 30 percent of patients with serum creatinine >3 mg/dl 2. CIN in patients undergoing percutaneous coronary intervention has been reported to have 30 percent mortality rate with risk factors such as dehydration, diabetes mellitus, nephrotoxic drugs and quantity of contrast dye used 3. The incidence of CIN in the general population has been calculated to be less than 3 percent 4. In high-risk patients, i.e., patients with preexisting renal dysfunction, diabetes mellitus, congestive heart failure, and older age; the incidence has been calculated to vary extensively from 12 to 50 percent 4. The occurrence of CIN in diabetic patients ranges from 5.2 to 35.7 percent in recent studies 7. The chances of progressive deterioration can rise to 42 percent in patients with abnormal baseline renal function 2 Eleven (7.10%) out of 155 patients undergoing coronary angiography experienced contrast induced nephropathy 7. CIN has been associated with increased morbidity, extended length of hospital stay 5 and increased costs 8. This study aims to investigate the occurrence of CIN in patients undergoing coronary angiography as there is inevitable clinical need for it. As suggested by literature CIN is more common in patients with diabetes mellitus and hypertension which is why the present study would verify the extent of CIN in diabetic and hypertensive patients undergoing coronary angiography. Moreover, there is a lack of research regarding this complication, hence local data would be available. Thus, the study would contribute in the existing research through validation of risk factors (predictors) for CIN in diabetic and hypertensive patients undergoing coronary angiography and help undertake preventive measures. MATERIALS AND METHOD Permission was sought from hospital ethical committee. A descriptive cross sectional study conducted in Armed forces institute of cardiology and National institute of heart disease, Rawalpindi with duration of study was 6 month from Jul 2017 to Dec Non probability consecutive samplying techniques was used as a samplying technique. Contrast induced nephropathy was taken as greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5mg/dl after using iodine contrast agent in 48 hours without another clear cause for kidney injury. High risk patients included any one of following parameters; diabetes mellitus documented H/o diabetes mellitus >2 years, hypertension documented H/o hypertension >2 years and baseline-creatinine level > Low risk patients included any one of the following parameters; Diabetes mellitus not documented of diabetes mellitus, hypertension not documented of hypertensionand baseline-creatinine level <1.5. Patients undergoing Elective PCI, gender (both male & female) with ages between years and Low risk and high risk patients were considered as inclusion criteria of the study whreas patients with chronic kidney disease-v, baseline creatinine >2, prior history of coronary artery by-pass graft surgery, cardiogenic shock, left ventricular ejection fraction less than 30 percent and History of exposure to contrast with in previous 6 months, were considered as exclusion criteria of the study. Particulars of all the patients who meet the inclusion and exclusion criteria was recorded in the Performa. Patients undergoing elective percutaneous coronary angiography with co-morbids (diabetes mellitus and hypertention) were included. Diabetics who are on oral hypoglycemic agents i.e. metformin was stopped 48 hours prior to the procedure. Patients were enrolled into two groups; one with normal baseline creatinine level and the other with abnormal baseline i.e. creatinine >1.5, diabetes and hypertention which was prehydrated. All patients were administered S39

43 Contrast Induced Nephropathy in Coronary Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S38-S41 intravenous fluid (normal saline) before the procedure. Intravenous hydration consisted of 1ml normal saline per kilogram of body weight per hour which was started 12 hours before contrast agent injection and continued for 12 hours after the injection. renal function tests after the procedure was done. Followed by 24 hours and 48 hours interval to observe any late changes in renal functions. Both high and low risk groups were hydrated and limited amount of dye was used i.e cc. Statistical analysis was performed using SPSS version 23. Mean and standard deviation was calculated for quantitative variable like age. Frequency and percentage was calculated for qualitative variable like gender, contrast induced nephropathy, low and high-risk patients. Low and high risk was compared for contrast induced nephropathy by applying chi-square test. A p-value <0.05 was taken as significant. RESULTS Total 115 patients were included according to the inclusion criteria of the study. Mean age of the patients was ± 7.09 years while there were 60 (52.2%) male and 55 (47.8%) female patients as shown in table-i. Frequency of contrast induced nephropathy in patients undergoing coronary angiography was 11 (9.3%), followed by high and low risk patients in undergoing coronary angiography was 84 (73.0%) and 31 (27.0%) respectively. Frequency of contrast induced nephropathy in low and high risk patients was 8 (72.7%) and 3 (27.3%) respectively S40 which was statistically not significant (p-value 0.980), as shown in table-ii. DISCUSSION Table-I: Descriptive statistics of Age (years) of patients. Age (Mean ± SD) 45.11± 7.09 years n (%) Gender Male 60 (52.2%) Female 55 (47.8%) Table-II: Comparsion of high and low risk patients with Contrast-Induced Nephropathy. Contrast Induced Nephropathy Total p-value* YES No High risk 08 (72.7%) 76 (73.1%) 84 (73.0%) Low risk 03 (27.3%) 28 (26.9%) 31 (27.0%) Total 11 (9.3%) 104 (90.4%) *A p-value<0.05 was taken as significance. Contrast-induced nephropathy (CIN), also known as contrast-induced acute kidney injury, is an iatrogenic renal injury that follows intravascular administration of radio-opaque contrast media (CM) in susceptible individuals 9. CIN was first described during the 1950s in case reports of fatal acute renal failure that had occurred following intravenous pyelography in patients with renal disease arising from multiple myeloma. Despite technological advances, CIN remains responsible for a third of all hospitalacquired acute kidney injury (AKI) and affects between 1% and 2% of the general population and up to 50% of high-risk subgroups following coronary angiography (CA) or percutaneous coronary intervention (PCI) 6,8. The serum creatinine levels begin to rise within hours, peak at 2-3 days and return to the baseline values within 2 weeks. The most commonly used definition of CIN in the literature is either a relative increase in serum creatinine of 25% or an absolute increase of 0.5 mg/dl from a baseline value within 48 to 72 hours after contrast exposure 10. The proliferation of imaging methods and interventional procedures involving administration of intravascular CM in both noncardiac modalities (e.g. vascular CT angiography and interventional vascular angiography) 11 and in established (e.g. CA and PCI) and emerging

44 Contrast Induced Nephropathy in Coronary Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S38-S41 cardiac modalities (e.g. CT coronary angiography (CTCA) and transcatheter aortic valve implantation (TAVI)) has significantly increased the number of patients exposed to CM and thus the number at risk of CIN. The widespread adoption of primary PCI for the treatment of acute myocardial infarction (AMI), despite significantly improving cardiovascular outcomes, has increased the incidence of CIN due to the inherent difficulties in rapidly assessing CIN risk, instigating prophylactic measures, attendant haemodynamic compromise and higher contrast volumes, all known risk factors for the development of CIN 12,13. Despite several therapeutic approaches, the rising age and incidence of comorbidity within the broad cohort of cardiac patients receiving CM has ensured that the prevention of CIN remains a significant clinical challenge 14,15. In a study by Sajjad et al 7, mean age in years was 58.4 ± Similarly, in our study, mean age (years) in the study was ± In our study, the frequency and percentage of males were 60(52.2%) and females were 55 (47.8%). Likewise, in a study conducted in , there were 83(53.55%) male and 72 (46.45%) female patients respectively. Study conducted by Sajjad et al 7, CIN developing in diabetics, undergoing coronary angiography was recorded in 11 (7.10%). In the same way, frequency of contrast induced nephropathy in patients undergoing coronary angiography was 11 (9.3%). In our study, frequency of contrast induced nephropathy in high risk patients were 03 (27.3%). Similarly, in a study presented in showed that frequency and percentage of CIN patients with high risk was 19 (67.85%). CONCLUSION The study showed that occurrence of contrast induced nephropathy in patients undergoing coronary angiography was although not statistically significant but more studies should be done in order to contribute in the existing research through validation of risk factors (predictors) for contrast induced nephropathy in diabetic and hypertensive patients undergoing coronary angiography which will help to undertake preventive measures. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Assareh A, Yazdankhah S, Majidi S, Nasehi N, Mousavi SS. Contrast induced nephropathy among patients with normal renal function undergoing coronary angiography. J Renal Inj Prev 2016; 5(1): Hung Y, Lin S, Hung S, Huang W, Wang PY. Preventing radio contrast-induced nephropathy in chronic kidney disease patients undergoing coronary angiography. World J Cardiol 2012; 4(5): Kumar V, Dev N, Vasudha KC. Risk of contrast induced nephropathy in patients undergoing primary coronary angioplasty. Int J of Biomed & Adv Res 2012; 3(6): Nough H, Eghbal F, Soltani MH, Nejafi F, Falahzadeh H, Fazel H, et al. Incidence and main determinants of contrast induced nephropathy following coronary angiography or subsequent balloon angioplasty. Cardiorenal Med 2013; 3(2): Rear R, Bell RM, Hausenloy DJ. Contrast induced nephropathy following angiography and cardiac interventions. Heart 2016;102(8): Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-term high-dose vitamin e to prevent contrast medium-induced acute kidney injury in patients with chronic kidney disease undergoing elective coronary angiography: a randomized placebo-controlled trial. J Am Heart Assoc. 2016; 5(3): e Sajjad U, Ali I, Akram Z. Frequency of contrast induced nephropathy following exposure to contrast in coronary angiography in diabetics with previously normal renal function. Ann King Edward Med Uni 2016; 22(1): Atkuri KR, Mantovani JJ, Herzenberg LA: N-Acetylcysteinea safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 2007; 7(4): Thaha M, Widodo, Pranawa W, Yogiantoro M, Tomino Y. Intravenous N-acetylcysteine during hemodialysis reduces asymmetric dimethylarginine level in end-stage renal disease patients. Clin Nephrol 2008; 69(1): Klass O, Walker M, Siebach A, Stuber T, Feuerlein S, Juchems M, et al. Prospectively gated axial CT coronary angiography: comparison of image quality and effective radiation dose between 64- and 256- slice CT. Eur Radiol 2010; 20(5): Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int 2006; 100: s Maioli M, Toso A, Gallopin M, Leoncini M, Tedeschi D, Micheletti C et al. Preprocedural score for risk of contrast-induced nephropathy in elective coronary angiography and intervention. J Cardiovasc Med 2010; 11(6): Solomon R. Contrast-induced acute kidney injury: is there a risk after intravenous contrast? Clin J Am Soc Nephrol 2008; 3(5): Romano G, Briguori C, Quintavalle C, Zanca C, Rivera NV, Colombo A, et al. G. Contrast agents and renal cell apoptosis. Eur Heart J 2008; 29(20): Nyman U, Bjork J, Aspelin P, Marenzi G. Contrast medium dose-to- GFR ratio: a measure of systemic exposure to predict contrastinduced nephropathy after percutaneous coronary intervention. Acta Radiol 2008; 49(6): S41

45 Open Access Renal Complications in Congenital Cardiac Disease Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 PREVALENCE AND ASSOCIATED RISK FACTORS OF RENAL COMPLICATIONS IN CONGENITAL CARDIAC DISEASE PATIENTS Hafsa Khalil, Iftikhar Ahmed, Kamal Saleem, Umair Younas, Rawail Iftikhar, Adeela Khan Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To investigate the risk factors associated with renal complications and comparison of peritoneal dialysis survival and non-survival patients after open heart surgery. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Pediatric cardiac anesthesia Department of Armed Forced Institute of Cardiology & National Institute of Heart Diseases from Jul 2017 to Jan Material and Methods: Retrospective data was collected from hospital based registry. Demographics, clinical characteristics, complications and outcome of patients were recorded. Data analysis of 199 patients was done on SPSS version 22. Results: Total of 199 patients were enrolled in the study, mean age was 4.9 ± 5 years (p=0.01), 117 (59.1%) were male and 82 (40.9%) were female patients. Out of total, 24 (12%) patients had kidney disease (KD) and underwent peritoneal dialysis (PD). Sixteen children (66.7%) died after PD while 08 children (33.3%) survived after PD. 09 (37.5%) had pulmonary edema (p<0.001), 05 (20.8%) had pulmonary hypertension (p=0.005), 09 (37.5%) had high inotropic duration (p=0.004) and 13(54.2%) patients had low cardiac output (p=0.001). Conclusion: It was concluded that patients with renal impairment who underwent peritoneal dialysis had poor outcomes as they had longer hospital stay and high mortality rate. Risk factors associated with renal complications included pulmonary edema, high inotropic support, low cardiac output and pulmonary hypertension. Longitudinal follow-up studies with robust methodology are needed to fill significant knowledge gaps. There are currently no clear guidelines for clinicians in terms of renal assessment in the long term follow up after cardiac surgery in childhood. Keywords: Acute kidney injury, Kidney Disease, Peritoneal Dialysis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION With advances in care, children undergoing complex cardiac repairs are surviving more frequently, resulting in a markedly increasing number of adults with congenital heart disease 1,2. It is important to think about the impact that these intensive interventions have on organ systems, including the kidney. The kidney is at high risk of long-term negative impact, given the pathophysiological changes that occur in the context of congenital heart disease, surgical intervention and cardiopulmonary bypass, postoperative critical care and recurrent exposure to potential renal insults 3. Patients with congenital heart disease use substantial healthcare resources, Correspondence: Dr Hafsa Khalil, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan. hafsakhalid100@gmail.com) and not just during the time of cardiac repair, but also as surviving adults with congenital heart disease 4. Kidney disease (KD) also causes significant personal and economical health care burden and is associated with worse long term outcome, quality of life and well being in the general population 5. Hence KD in patients with congenital heart disease has potential for synergistic negative impact. Although there are a significant gaps in the knowledge related to the renal outcomes of children with congenital heart disease and children who have had cardiac surgery, current evidence demonstrates KD as an increasingly prevalent and important problem in these patients 6. RF was defined as a creatinine level of more than 1.2 mg/dl or oliguria (<0.5 ml/kg/hour) for more than 4 hours despite aggressive diuretic therapy and optimization of S42

46 Renal Complications in Congenital Cardiac Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 the inotropic support, or a combination of both 7. Infants and children who undergo surgical repair of complex congenital heart diseases are more prone to develop renal dysfunction. The development of renal failure (RF) is a frequently reported complication after cardiopulmonary bypass surgery in infants and children. Studies have reported a high mortality rate ranging from 30-79% 7-8. Fluid restrictions, diuretics, and inotropic agents have been the initial therapeutic strategies for mild renal dysfunction and low cardiac output syndrome. The more severe cases require a slow and continuous removal of the fluid by hemofiltration or peritoneal dialysis (PD) 9. Compared with hemofiltration, PD in pediatric patients is associated with advantages in the establishment of vascular access, avoidance of systemic anticoagulation, and decreased associated risks of ischemic and embolic complications 10. The feasibility and efficacy of PD, optimal timing of application, complications, prognosis, and predictive risk factors of the mortality in children undergoing PD after open heart surgery are currently under discussion 11. We reviewed our experience with PD in treating children with RF after surgical repair of congenital heart disease. The aims of this study were: To determine the differences in clinical and laboratory variables between survivors and non-survivors receiving PD. To investigate the risk factors associated with prolonged peritoneal dialysis (PD) and the mortality of pediatric patients with renal failure after open heart surgery. Given the potential to mitigate KD development and progression in many different populations, with universally accepted interventions, clinicians, researchers, and policy makers should be interested in this problem from both an economical and patient-centered outcome point of view. MATERIAL AND METHODS This was a descriptive cross-sectional study, conducted at paeds cardiac anaesthesia department. from, the medical records of 199 children that underwent open heart surgery at Pediatric surgery and anesthesia department of Armed Forced Institute of Cardiology & National Institute of Heart Diseases were reviewed retrospectively. Among them, 24 (12%) received PD. Study duration was from July 2017 to Jan The age, height, weight, diagnosis of the congenital heart disease, surgical procedure performed, cardiopulmonary bypass time, and aorta clamping duration were recorded. Serum sodium & potassium levels, serum creatinine levels, and daily urinary output were recorded before PD. The indications for PD included: (1) hypervolemia with severe edema; (2) anuria or oliguria for more than 4 hours despite aggressive diuretic and inotropic support; (3) hyperkalemia (>5.5 mmol/l); (4) metabolic acidosis (serum ph <7.3, HCO3 < 18 mmol/l) persistent after failing to be corrected by at least two boluses of an intravenous sodium bicarbonate infusion and adjustment of the fluid status with an inotropic support; (5) low cardiac output with renal insufficiency. The PD catheter was connected to a closed system for peritoneal drainage. The dialysate solutions used were standard commercial preparations (Dianel PD-2; Baxter International Inc., Deerfield, IL, USA); heparin (500 U/L of dialysate) and potassium chloride were added. The dextrose concentration varied from %, and the choice of dextrose concentration depended on the presence of serum hyperglycemia. PD was started with a dwell volume from 10 ml to 20 ml/kg with a dwell time of 1-2 hours. The recovery of the urine output was defined as a urine output >1 ml/kg/hour, and the recovery of serum creatinine was defined as a decline in serum creatinine to preoperative levels. Indications for stopping PD included a return to a sufficient urine output, maintaining a negative fluid balance, and normalization of the serum electrolytes and acid-base status 12,13. Serum creatinine at the day of surgery was extracted. For the patients who did not have laboratory S43

47 Renal Complications in Congenital Cardiac Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 measurements on the day of surgery, measurements obtained within 3 days before procedure were taken as the baseline value. Renal function was estimated as glomerular filtration rate (GFR) by using the simplified modification of diet in renal disease equation (estimated glomerular filtration rate [egfr] [ml/min/1.73 m 2 ] _ _ [serum creatinine] _1.154 _ age_0.203 _ [0.742 if female]) 5. Estimated and comparison between groups was performed using independent t-test. In non-normally distributed data, values are expressed as median and interquartile range and comparison of values was performed using the Mann Whitney U test. The comparison of categorical values was assessed using the chi-squared test and for continuous variables, association was found by using independent sample t-test. The differences Table: Comparison of peritoneal dialysis groups (survival & non-survival). Patients had Peritoneal Dialysis (PD) n Variables Survived Non-survived Gender Male Female Disease VSD (ventrciular septal defect) PDA (paternt ductus arterious) PS (pulmonary stenosis) TGA (transposition of the great arteries) TOF (tetralogy of fallot) ASD (Atrial septal defect) DORV (double outlet right ventricle) IAA (Interputed aortic arch) Tricuspid atresia PAVSD Repair CAVSD Type of surgery Open Close Inotropic support Mild Moderate high Inotrope duration: >72 hrs <72 hrs GFR values _200 ml/min/1.73 m 2 were set equal to 200 ml/min/1.73 m 2, according to Coresh et al 14. Data Analysis Normality was assessed using the Shapiro- Wilk test. In normally distributed parameters, values are expressed as mean ± standard error were evaluated using microsoft excel 2016 and SPSS version 22. RESULTS p-value Low cardiac output Pulmonary hypertension Cardiac failure 0 15 <0.001 Re-ventilated Pulmonary edema Total of 199 patients were enrolled in our study, out of which 24 (12%) patients had kidney disease (KD) and undergone peritoneal dialysis (PD). We divided the patients who underwent S44

48 Renal Complications in Congenital Cardiac Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 PD into two groups depending on the outcome: group-i, sixteen children (66.7%) died after PD; group-ii, 08 children (33.3%) survived after PD but there was not any significant difference found between the two groups except cardiac failure (p<0.001) and re-ventilated (p=0.033) as both groups were having the PD patients. Their outcome is mentioned in table. In our study population mean age was 4.9 ± 5 years (p=0.01), 117 (59.1%) were male and 82 (40.9%) were female. When we compared the patients had renal complications 24(12%) with other 175 (88%) no renal complication group, significant difference was found as shown in figure. About 16(66.7%) patients expired and intra glomerular hemodynamics, and derangements in neurohormonal activation. Several drugs used frequently in the setting of congenital heart disease have known nephrotoxicity 15. In our study out of 199 patients, only 24 (12%) patients had renal dysfunction. A recent retrospective study of 206 hospitalized neonates with congenital heart disease demonstrated a significant decrease in renal function (estimated creatinine clearance) 42% of patients had AKI (with 70 % of these being classified as renal failure by modified prifle criteria) 16. In children, there is some retrospective data demonstrating AKI as a risk factor for CKD; Mammen et al, evaluated 126 critically ill Figure: Comparison of patients who had renal complications and who do not had. (p<0.001), 09 (37.5%) had pulmonary edema (p<0.001), 05 (20.8%) patients had pulmonary hypertension (p=0.005), 09 (37.5%) had high inotropic duration (p=0.004), 13 (54.2%) patients had low cardiac output (p=0.001). PD patients had longer ICU stay (8.6 ± 6 days, p=0.007). DISCUSSION Pathophysiology in congenital heart disease can lead to long-term changes in kidney structure and function children with congenital heart disease have a number of risk factors for potential development of CKD later in life, including pathophysiological changes related to a structurally abnormal heart and circulation. These may include polycythemia, cyanosis and chronic hypoxia, changes in renal blood flow children with AKI and demonstrated that at 1-3 years of follow-up, 10 % of children developed CKD (defined as estimated glomerular filtration rate (egfr) <60 ml/ min/1.73 m 2 or persistent albuminuria) 16,17. Forty-seven percent of children with a history of AKI were considered at risk of CKD (defined as egfr of ml/min/ 1.73 m 2, hyperfiltration (egfr >150 ml/min/ 1.73 m 2 ), or hypertension) 17. There are large, multicenter research studies currently underway, with primary aims of determining the risk of developing future KD. Long term follow up studies are also needed to predict the associated risk factors involved in developing kidney disease (KD) in congenital heart disease patients. A number of older, small studies have suggested S45

49 Renal Complications in Congenital Cardiac Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 that renal dysfunction exists in adults with congenital heart disease. Aperia et al. demonstrated decreased GFR (by inulin clearance) in 5 out of 10 adults with tetralogy of fallot, a mean of 20 years post blalock-taussig shunt; mean GFR in these adults was 80 mls/min/1.73m 218. In a renowned study, Flanagan et al. demonstrated a cohort of young adults (n 83) had proteinuria in one-third of cyanotic congenital heart disease patients. Risk of proteinuria was significantly higher than in an acyanotic control group with surgically corrected cyanotic congenital heart disease (Tetralogy of Fallot or transposition of the great vessels) 18,19 while in our study no significant difference was found between cyanotic and acyanotic groups, Reasons for differences between these groups were not explored in detail, particularly in relation to their early childhood course, prior surgical procedures, or concomitant medication use; however as expected, many patients with cyanotic congenital heart disease had more complex heart disease. Chronic glomerular injury as a prominent feature of cyanotic congenital heart disease has similarly been suggested by additional data demonstrating both an elevated albumin/creatinine ratio and an elevated protein/creatinine ratio in 38% (n=26) of longstanding cyanotic congenital heart disease 20. In a small study of 43 children with cyanotic and acyanotic congenital heart disease, Agras et al, found a significant increase in the fractional excretion of sodium and N-acetyl-B-Dglucosaminidase (used as a marker of proximal tubular damage) in children with cyanotic congenital heart disease 21. These markers of proximal tubular dysfunction and injury were also elevated in non-cyanotic congenital heart disease relative to controls, although to a lesser extent than in cyanotic congenital heart disease. A more recent study of 58 children with congenital heart disease (with healthy matched controls) confirmed similar findings 22 of note, in both of these studies, the majority of children in this study were in lower risk congenital heart surgery classes (by Risk Adjustment for Congenital Heart Surgery-1), the duration of follow-up was not specified, and it was not clear if urine evaluations occurred before or after cardiac repair. Recent data from a large, well designed study confirms the presence of CKD in patients with congenital heart disease 23. When compared to the general population, the prevalence of significant renal impairment in another study was 18-fold higher in non-cyanotic and 35-fold higher in cyanotic congenital heart disease patients 23. A study importantly demonstrated that it is not just those patients with cyanotic congenital heart disease that are at increased risk of CKD but also non-cyanotic, and changes occur fairly early in adulthood with a mean age at assessment of 36 ± 14 years 24. KD contributes significantly to increase the risk of cardiovascular events and mortality in the general population which was 66.7% (p<0.001), there is not yet a clear understanding of the impact of KD in patients with congenital heart disease. A study demonstrates the young adults with congenital heart disease who have decreased GFR have lower survival than those with normal GFR. This is not simply because they have lower heart function; there is a clear additional effect of renal impairment over that of functional class and systemic ventricular function 22. A population-based study in congenital heart disease patients surviving to >65 years demonstrated that one of the most powerful predictors of mortality was KD; the mortality risk associated with KD was larger than that associated with cancer, heart failure, myocardial infarction, or diabetes 25. Children with pulmonary hypertension were at high risk of developing KD as it is demonstrated in other studies that endothelial dysfunction is present in KD, which is associated with pulmonary hypertension, left ventricle hypertrophy, and increased cardiovascular disease events such as myocardial infarction We found it to be significant factor (p=0.005). The extent of vascular change is associated with the number of risk factors, their intensity, and exposure duration Thus, KD associated S46

50 Renal Complications in Congenital Cardiac Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 cardiovascular disease pathogenesis in children appears to begin early in life with exposure to the atherogenic milieu of CKD, speaking to the potential importance of early KD detection and identifying risk factors of child KD development 32. Given the large negative impact of KD on health outcomes in the general population and the child s potentially long life time to accumulate risk, KD development in children with congenital heart disease could place them at high risk for future cardiovascular disease. In addition, the presence of congenital heart disease concomitantly places patients at risk of exposure to factors that cause AKI, including cardiopulmonary bypass and nephrotoxins 15. The risk of KD is higher with cyanotic congenital heart disease but it is also present with non cyanotic congenital heart disease. Many questions still need to be answered, yet this population represents one in whom long-term primary and secondary prevention strategies to reduce KD occurrence and KD progression could be instituted to significantly change outcomes. There should be an opportunity to mitigate KD progression and negative renal outcomes by instituting universally accepted interventions including stringent blood pressure control and its treatment. Ongoing generation, synthesis, and translation of evidence in this area are critically important, as the population of adult survivors of congenital heart disease expands. Patients with congenital heart disease should be recognized as a population at risk of developing KD. Although limited, the current epidemiological evidence suggests that renal dysfunction occur in patients with congenital heart disease with higher frequency than the general population and are detectable early in follow-up (i.e. during childhood). Despite a relatively young age, the best evidence suggests that approximately 30 to 50% of adult patients with congenital heart disease have significantly impaired renal function 1,16,20,32. CONCLUSION It was concluded that patients with renal impairment who underwent peritoneal dialysis had poor outcomes as they had longer hospital stay and high mortality rate. Risk factors associated with renal complications included pulmonary edema, high inotropic support, low cardiac output and pulmonary hypertension. Long-term studies with robust methodology are needed to fill significant gaps. There are currently no clear guidelines for clinicians in terms of renal assessment in the long term follow up after cardiac surgery in childhood. ACKNOWLEDGEMENT We are thankful to our research team members of Paeds Cardiac Surgery / Anaesthesia department including KPO Saquib Shahzad and KPO Hussain for their cooperation in data collection and data entry to make this study feasible. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation 2007; 115(2): Billett J, Cowie MR, Gatzoulis MA, Vonder Muhll IF, Majeed A. Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: crosssectional, population-based study with case-control analysis. Heart 2008; 94(9): Hongsawong N, Khamdee P, Silvilairat S, Chartapisak W. Prevalence and associated factors of renal dysfunction and proteinuria in cyanotic congenital heart disease. Pediatr Nephrol 2018; 33(3): Mackie AS, Pilote L, Ionescu-Ittu R, Rahme E, Marelli AJ. Health care resource utilization in adults with congenital heart disease. Am J Cardiol 2007; 99(6): Gorodetskaya I, Zenios S, McCulloch CE, Bostrom A, Hsu CY, Bindman AB, et al. Health-related quality of life and estimates of utility in chronic kidney disease. Kidney Int 2005; 68(6): Morgan C, Al-kalbi M, Garcia Guerra G. Chronic kidney disease in congenital heart disease patients: A narrative review of Evidence. Can J Kidney Health Dis 2015; 2: Chien JC, Hwang BT, Weng ZC, Chun-Chang Meng L, Lee PC. Peritoneal Dialysis in Infants and Children After Open Heart Surgery. Pediatr Neonatol 2009; 50(6): Lin MC, Fu YC, Fu LS, Jan SL, Chi CS. Peritoneal dialysis in children with acute renal failure after open heart surgery. Acta Paediatr Taiwan 2003; 44: Sorof JM, Stromberg D, Brewer ED, Feltes TF, Fraser CD Jr. Early initiation of peritoneal dialysis after surgical repair of congenital heart disease. Pediatr Nephrol 1999; 13(8): Picca S, Principato F, Mazzera E, Corona R, Ferrigno L, Marcelletti C, et al. Risks of acute renal failure after cardiopulmonary bypass surgery in children: a retrospective S47

51 Renal Complications in Congenital Cardiac Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S42-S48 10-year case-control study. Nephrol Dial Transplant 1995; 10(5): Fleming F, Bohn D, Edwards H, Cox P, Geary D, McCrindle BW, et al. Renal replacement therapy after repair of congenital heart disease in children: a comparison of hemofiltration and peritoneal dialysis. J Thorac Cardiovasc Surg 1995; 109: Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20(3): Smilde TD, van Veldhuisen DJ, Navis G, Voors AA, Hillege HL. Drawbacks and prognostic value of formulas estimating renal function in patients with chronic heart failure and systolic dysfunction. Circulation 2006; 114(15): Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298(17): Lindle KA, Dinh K, Moffett BS, Kyle WB, Montgomery NM, Denfield SD, et al. Angiotensin-converting enzyme inhibitor nephrotoxicity in neonates with cardiac disease. Pediatr Cardiol. 2014; 35(3): MC Lin, YC Fu, LS Fu, SL Jan. Acute renal failure complicating pediatric cardiac surgery: A comparison of survivors and nonsurvivors following acute peritoneal dialysis. Pediatr Cardiol 1992; 13: Mammen C, Al Abbas A, Skippen P, Nadel H, Levine D, Collet JP, et al. Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study. Am J Kidney Dis 2012; 59(4): Aperia A, Bjarke B, Broberger O, Thoren C. Renal function in Fallot s tetralogy. Acta Paediatr Scand 1974; 63(3): Dittrich S, Haas NA, Buhrer C, Muller C, Dahnert I, Lange PE. Renal impairment in patients with long-standing cyanotic congenital heart disease. Acta Paediatr 1998; 87(9): Flanagan MF, Hourihan M, Keane JF. Incidence of renal dysfunction in adults with cyanotic congenital heart disease. Am J Cardiol 1991; 68(4): Agras PI, Derbent M, Ozcay F, Baskin E, Turkoglu S, Aldemir D, et al. Effect of congenital heart disease on renal function in childhood. Nephron Physiol 2005; 99(1): Zheng J, Yao Y, Han L, Xiao Y. Renal function and injury in infants and young children with congenital heart disease. Pediatr Nephrol 2013; 281: Dimopoulos K, Diller GP, Koltsida E, Pijuan-Domenech A, Papadopoulou SA, Babu-Narayan SV, et al. Prevalence, predictors, and prognostic value of renal dysfunction in adults with congenital heart disease. Circulation 2008; 117(18): Sommers C, Nagel BH, Neudorf U, Schmaltz AA. Congestive heart failure in childhood. An epidemiologic study. Herz. 2005; 30(7): Afilalo J, Therrien J, Pilote L, Ionescu-Ittu R, Martucci G, Marelli AJ. Geriatric congenital heart disease: burden of disease and predictors of mortality. J Am Coll Cardiol 2011; 58(14): London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18(9): Qunibi WY. Consequences of hyperphosphatemia in patients with end-stage renal disease (ESRD). Kidney Int Suppl 2004; 6690: S Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease. J Am Coll Cardiol 2002; 39(4): Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, et al. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation 2005; 112(7): Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed - Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 1989; 32(4): Atiyeh BA, Dabbagh SS, Gruskin AB. Evaluation of renal function during childhood. Pediatr Rev 1996; 17(5): Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3(1): S48

52 Open Access Left Main Coronary Artery Stenting Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S49-S53 SHORT TERM OUTCOMES OF LEFT MAIN CORONARY ARTERY STENTING Muhammad Nadir Khan, Tahira Muqaddas, Tahir Iqbal Army Cardiac Center, Lahore Pakistan ABSTRACT Objective: To determine the short term outcomes of left main coronary artery stenting and whether stenting of unprotected left main coronary artery (ULMCA) stenosis in carefully selected patients with normal left ventricular (LV) systolic function is safe and thus may provide an alternative treatment to coronary artery bypass graft (CABG). Study Design: Descriptive study. Place and Duration of Study: Army Cardiac Center Lahore from Jan 2016 to Jun Patients and Methods: A total of 50 patients with ULMCA stenosis who were treated with stent angioplasty by using drug eluting stents were evaluated. Patients were followed closely with monthly telephone interviews and follow-up angiography was done at 3 months. The occurrence of major in hospital complications like death, fatal and non fatal myocardial infarction (MI), acute or subacute stent thrombosis and urgent CABG in these patients were recorded. Along with this occurrence of angiographic restenosis and target vessel revascularization rates were recorded after 3 months of angiographic followup. Results: The procedural success rate was 100%. Major events like acute or subacute stent thrombosis, death, fatal or nonfatal MI, urgent CABG didn t occur in any patient. Three months follow-up angiography was performed in 20 of 50 patients. Other patients (without angiographic follow-up) remained asymptomatic. All of 20/50 patients had patent stents of left main coronary artery and hence target vessel revascularization rate was zero in these patients. Conclusion: Stenting of ULMCA stenosis may be a safe and effective alternative to CABG in carefully selected patients. Keywords: Coronary artery bypass graft, Left main coronary artery, Per cutaneous coronary intervention. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION The prevalence of left main coronary artery disease in patients with coronary artery atherosclerosis varies from 5% to 7% 1. Mortality of such patients with ULMCA disease at 3 years who were treated medically was 60%. Coronary artery bypass graft (CABG) remains the standard treatment of choice in patients with unprotected left main coronary artery (ULMCA) disease. However, stenting of unprotected LMCA stenosis has been attempted in selected patients with prohibitive surgical risk, usually as a result of noncardiac related comorbidities. A few cases of stenting of such unprotected LMCA stenotic lesions have also been reported in bailout situations. Initially, rates of restenosis following Correspondence: Dr Muhammad Nadir Khan, Associate Professor, Army Cardiac Center, Lahore Pakistan yesnadirkhan@gmail.com PCI with balloon angioplasty were 30-40% and 20-25% with bare-metal stent 2. Sirolimus-Eluting Stents have demonstrated persistent neointimal hyperplasia inhibition for up to 2 years, while many other studies have shown restenosis rates to less than 10%. The advent of aggressive antiplatelets protocols and drug-eluting stents has led to renewed interest in the applicability of PCI as modality for LMCA stenosis. It has been shown in various studies that with the advent of newer drug eluting stents, better intravascular imaging modalities like intravascular ultrasound, fractional flow reserve (FFR), optical coherence tomography (OCT) and careful selection of patients, use of per cutaneous coronary intervention (PCI) in this setting is increasing with results showing non inferiority of PCI as compared to CABG 3. The objective of the current study was to determine short term outcomes of LMCA stenting by using drug eluting stents in S49

53 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S49-S53 terms of major in hospital complicatins like death, fatal or non fatal myocardial infaction, acute or sub acute stent thrombosis, urgent CABG angiographic evidence of restosis and target vessel revascularization in carefully selected patients with normal left ventricular (LV) systolic function as an alternative treatment to CABG. PATIENTS AND METHODS A descriptive study was conducted at myocardial ischemia during stress test in form of ETT or pharmacological thallium scan and 2) coronary angiographic evidence of 50% diameter stenosis of the LMCA. The criteria for exclusion were 1) contraindication for dual antiplatelets and 2) reduced LV function (ejection fraction 40%). Predilation before stent implantation was performed with conventional angioplasty balloons. The stents were then deployed by Table: Patients, angiographic and procedural characteristics. Age (years) >70 Male 34 Female 16 Lesion confined to shaft 4 Lesion involving distal bifurcation 46 Size of stent <3.0 mm mm > mm >4.0 mm Type of stent Xience xpedition Xience v Xlimus Firebird Excel Ultimaster Biomatrix Partner Army Cardiac Center Lahore from Jan 2016 to Jun 2017, 50 patients with significant unprotected LMCA stenosis who either declined CABG or were at high risk case for CABG due to non cardiac comorbidities were treated with stent implantation as shown in table. Forty six out of 50 Stent implantation was performed electively and in bailout situations in the other four patients. The inclusion criteria were 1) clinical symptoms or objective evidence of inflating the stent delivery balloon at nominal pressure. The stented segment was post dilated with high pressure balloon inflation to achieve angiographic optimization. The balloon inflation time were brief (<30 s) and multiple ( 3) to avoid prolonged ischemia and its-related complications. Angiographic success of stenting was defined as residual stenosis <30% by visual analysis in the presence of Thrombolysis in Myocardial Infarction (TIMI) 3 flow grade as shown in S50

54 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S49-S53 fig-1. The size of stent was mm in 80% of the lesions. The lesions at the ostium or shaft without involvement of the distal bifurcation comprised 12% of the lesions as in fig-2. During the procedure, all patients received a 10,000-U bolus of heparin with a repeat bolus of 5,000 U every 30 min to maintain an activated clotting time >250 s. Patients were preloaded with 300 mg clopidogrel and 300 mg aspirin and were advised life-long aspirin together with 75 mg clopidogrel/day for at least 3 months. Glycoprotein IIb/IIIa inhibitors was given after the operator s discretion. All patients were kept in the coronary care unit for 24 h post stenting. Post stenting, all patients were given dual antiplatelets with the intent of keeping dual anitplatelets for 1 year and continuing aspirin for rest of the life. Major in-hospital complications including acute or subacute stent thrombosis, fatal or non fatal myocardial infarction, emergency CABG or death didn t occur in any patient. Clinical follow-up was obtained by monthly telephonic interviews. All patients were requested to visit outpatient clinics at 1and 3 months and to have followup angiograms at 3 months if symtomatic. Angiographic restenosis was defined as luminal diameter stenosis 30% at follow-up. Angiographic follow-up data were obtained for 20 of the 50 eligible patients who underwent LMCA stenting. Other patients who refused angiographic follow-up were asymptomatic. Follow-up angiography for the remaining patients is scheduled to be performed 3 months after the intervention. Angiographic restenosis did not occur in any of 20 patients who were angiographically followed up. RESULTS This study showed that LMCA stenting is safe and alternative treatment in carefully selected patients with normal left ventricular function. The procedure was successful in all patients, and there were no episodes of acute or subacute stent thrombosis. Angiographic restenosis didnot occur in any of the 20 patients who were followed up angiographically and hence there was zero target vessel revascularization rates. There were no incidences of sudden death, fatal or non fatal myocardial infarction and urgent CABG during the follow-up period. DISCUSSION Balloon angioplasty of unprotected LMCA stenosis has been generally associated with poor long-term prognosis.coronary artery bypass surgery is considered the gold standard Figure-1: success of stenting as residual stenosis. Figure-2: Showing size of stent. treatment of unprotected left main coronary artery (ULMCA) disease. Compared with balloon angioplasty, low restenosis rates after stenting of LMCA disease may be attributed to larger poststent arterial lumen dimensions and to the resistant effect of stent against pathologic arterial remodeling and acute recoil. S51

55 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S49-S53 An additional benefit of PCI over CABG is seen in the duration of hospital stay. Patients undergoing PCI require a shorter hospital stay than the patients undergoing CABG, an issue of growing importance in a resourcescarce era (PCI days vs. CABG days) 4. The SYNTAX (synergy between percutaneous intervention with taxus and cardiac surgery) provides the largest data regarding early and late outcomes of PCI of LMS ( left main stem) stenosis. The primary end point of death, stroke, myocardial infarction and repeat revascularization favored CABG over PCI. Whereas, the secondary end point of death, stroke and MI was not different between those who undergo PCI or CABG. Primary end point favoring CABG was driven primarily by increased rate of repeat revascularization in PCI group (13.7% with CABG vs 25.9% with PCI), though the rate of stroke was also significantly lower in PCI group (3.7% with CABG vs 2.4% with PCI) 5. Calculating SYNTAX score is a class I indication for left main stem disease or multi vessel coronary artery disease as per recent AHA/ ACC PCI guidelines. Patients with low (0-22) and intermediate syntax score (23-32) can be treated with PCI or CABG with equal results. Those with high syntax score (>32) do better with CABG. SYNTAX score II 6 (SSII) provides 4-year mortality after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in order to facilitate decision-making between these two modalities. SSII has robust prognostic accuracy, both in CABG and in PCI patient groups and was more accurate as compared to syntax score 1 in stratifying patients for late mortality. The recent EXCEL trial 7 (evaluation of Xience Prime or Xience V-eluting stent vs. CABG for effectiveness of LM revascularization) evaluated the safety and efficacy of PCI with Xience Prime or Xience V everolimus eluting stents (EES) vs. CABG in patients with ULMCA disease with a low or intermediate SYNTAX score (<33). This trial concluded that PCI with everolimus-eluting stents was noninferior to CABG in terms of the rate of composite end point of death, stroke, or myocardial infarction at 3 years. Intracoronary Stenting and Angiographic Results: Drug-eluting Stents for Unprotected LM Lesions (ISAR-LM2) 8 evaluated the efficacy and safety of everolimus EES vs zotarolimus eluting stent (ZES) and provided comparable clinical and angiographic outcomes at 1-year follow-up. In the ERACI IV 9 study, patients treated with second generation DES were compared to the firstgeneration DES in patients with multiple vessel disease and unprotected left main stenosis. Those treated with second generation DES had lower incidence of MACCE. Bio resorbable vascular scaffolds (BVS) in ostial left main stem lesions has the advantage of avoiding permanent metal struts protruding into the aorta 10. As per Pil et al 11, the observed 3-year rates of target-vessel failure were not significantly different for the different types of second generation DES [16.7% for the CoCr-EES (cobaltchromium everolimus-eluting stent), 13.2% for the BP-BES (biodegradable polymer-biolimus eluting stent), 18.7% for the PtCr-EES (platinum chromium everolimus-eluting stent), and 14.7% for the Re-ZES (resolute zotarolimus-eluting stent); p=0.15]. As per european society of cardiology guidelines 2014, PCI of LMS disease with low syntax score is a class Ib indication and in case of intermediate score PCI is class IIa indication. The current study indicates that stenting of LMCA stenosis improves procedural success and clinical outcomes in part because of the low subacute stent thrombosis rate using optimal stent implantation techniques. Most of the procedures in this study were elective and balloon inflations were intentionally kept short. These facts may S52

56 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S49-S53 explain the high procedural success rate in our cases. Major in-hospital complications did not occur in any of our patients. This finding suggests that antiplatelet therapy alone might be an effective post-stent antithrombotic regimen even in the LMCA stenting. CONCLUSION Stenting of unprotected LMCA stenosis may be a safe and effective alternative to CABG in carefully selected patients. CONFLICT OF INTEREST This study has no conflict of interest to be declared by any author. REFFERNCES 1. Nitesh N, Francis JH, Kunal PV, Martin RB, James DC, Ian TM, et al. Percutaneous coronary intervention using drug-eluting stents versus coronary artery bypass grafting for unprotected left main coronary artery stenosis. Circulation: Cardiovasc Interv 2016; 9(12): e Mohammed A, Alan H, Brendan M, Rory O, Thomas G, Richard S, et al. Long-term clinical outcomes after unprotected left main coronary artery stenting in an all-comers patient population. Catheter Cardiovasc Interv 2013; 82: E411 E Stuart JH, Milan M, Joost D, Jung-Min A, Eric B, Evald HC et al. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: A pooled analysis of individual patient data. The lancet-elsevier, 23 rd feb Serruys PW, Morice MC, Kappetein AP. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009; 360: Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013; 381: Marie-Claude, Patrick WS, Pieter KA, Ted EF, Elisabeth S, Antonio C et al. Five-Year Outcomes in Patients with Left Main Disease Treated with Either Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting in the SYNTAX Trial. Circulation 2014; 137(4): Gregg WS, Joseph FS, Patrick WS, Charles AS, Philippe G, John Puskas et al. Everolimus-eluting stents or bypass Surgery for left main coronary artery disease. N Engl J Med 2016; 375: Mehilli J, Richardt G, Valgimigli M, Schulz S, Singh A, Abdel- Wahab M et al. Zotarolimus- versus everolimus-eluting stents for unprotected left main coronary artery disease J Am Coll Cardiol 2013; 62(22): Rodriguez AE. Second versus first generation DES in multiple vessel disease and unprotected left main stenosis: insights from ERACI IV Study. Minerva Cardioangiol 2015; 63(4): Everaert B, Capranzano P, Tamburino C, Seth A, van Geuns RJ. Bioresorbable vascular scaffolds in left main coronary artery disease. Euro Interv 2015; 11 Suppl V: V Pil HL, Osung K, Jung-Min A, Cheol HL, Do-Yoon K, Jung-Bok L. Safety and Effectiveness of Second-Generation Drug-Eluting Stents in Patients With Left Main Coronary Artery Disease. J Am Coll Cardiol 2018; 71(8): S53

57 Open Access Angiographically Significant Coronary Artery Disease Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S54-S58 FREQUENCY OF ANGIOGRAPHICALLY SIGNIFICANT CORONARY ARTERY DISEASE IN PATIENTS UNDERGOING VALVE REPLACEMENT SURGERY WITH OR WITHOUT RISK FACTORS FOR ATHEROSCLEROSIS Hassan Shabeer, Ali Nawaz, Farhan Tayyab, Tariq Hussain Khattak, Rehana Khadim, Hafiz Muhammad Shafique, Azhar Ali Chaudhry Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the frequency of angiographically significant coronary artery disease in patients undergoing valve replacement surgery with or without risk factors for atherosclerosis. Study Design: A single center, descriptive cross-sectional study. Place and Duration of Study: Adult Cardiology department of AFIC & NIHD from 1 st Jan 2017 to 30 th Jun Material and Methods: All consecutive patients who underwent coronary angiography before valve replacement /repair surgery were included in the study. Excluded Patients were those who had previous valve surgery, known CAD, post CABG and Post PCI patients, associated risk factors like diabetes, hypertension, dyslipidemia, family history of coronary artery disease, smoking and BMI of the patients were recorded. All the information was entered in an annexed pro-forma. All the collected data was entered and analyzed using the SPSS-23. Results: A total of 136 patients underwent coronary angiography before valve replacement/repair surgery during study period and were recruited. Mean Age of the patients was ± 5.2 years with minimum age 31 years and maximum 67 years. There were 80 (58.8%) male patients while 56 (41.2%) female patients. Smoking was found to be the most prevalent risk factor 98 (72.1%) followed by family history 67 (49.3%), hypertension 65 (48.0%), Obesity (BMI 30) 63 (46.3%), diabetes mellitus 42 (30.9%) and dyslipidemia 35 (25.7%). Out of total patients, 63 (46.3%) patients had significant CAD. 33 (24.3%) had AVR, 89 (65.4%) patients had MVR while 14 (10.3%) patient had DVR. Conclusion: Our study shows that significant proportion of patients above 40 years of age have asymptomatic underlying CAD (46%), this frequency of angiographically significant CAD in our patient population signifies pre valve replacement screening by coronary angiogram so that coronary bypass grafting can be offered to those patients concomitantly with valve replacement. Keywords: Angiography, Atherosclerosis, Coronary artery disease. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Coronary artery disease is the leading cause of death in Asian population 4.9%, compared to 7.0% of the total population and this prevalence is expected to increase globally 1. Valvular heart disease is a growing problem particularly in developing countries like Pakistan but interestingly with a different spectrum of valvular disease than west, as we all know that most of valvular lesions are degenerative in western population while in developing countries the commonest etiology for Correspondence: Dr Hassan Shabeer, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan hassanshabeer@gmail.com valvular lesions is rheumatic valvular disease 2. Among those patients with valvular heart disease many have concomitant coronary artery disease (CAD) as well, but considering our spectrum of valvular disease there are only limited data regarding optimal strategies for diagnosis and treatment of CAD in such patients 3. The prevalence of CAD in patients undergoing valve replacement / repair is 30% in developed countries 4. It is important to devise a screening strategy for coronary artery disease in patients with rheumatic valvular disease undergoing valve replacement surgery in our population subgroup considering more and more number of patients from that subgroup are presenting nowadays to tertiary care centers with CAD. S54

58 Angiographically Significant Coronary Artery Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S54-S58 However, the data regarding that subgroup of patients with concomitant CAD is limited. Marchant et al studied 100 patients with rheumatic valvular disease undergoing valve replacements and reported the prevalence of significant coronary artery disease (>50% stenosis) 14% in that subgroup of population 5, however, it is important to consider that coronary angiograms were only performed in patients with clinical evidence of ischemia (Angina, ECG changes suggestive of ischemia) or who were >50 years of age as incidence of CAD rises significantly after 50 years of age in general population studies. In another study by Bozbas et al, of 346 patients with rheumatic valvular disease who underwent surgery, 218 (63%) who were found eligible for coronary angiogram as per guidelines, 18.8% of them had significant coronary artery disease 6. However, it was reported that out of them only seven patients were <50 years of age with the youngest being a 40 year old male with history of angina pectoris. They concluded that in patients less than 40 years of age if there was no history of angina or any coronary risk factors then coronary angiography can be omitted in such patients. Comparing patients with mitral stenosis CAD was found to be more common in patients with AS 9. Among those patients with AS and history of angina the prevalence of coronary artery disease was reported from 40 to 80% in different studies 7,8. Coronary artery disease often coexist with hemodynamically compromised aortic stenosis 8. In another study of > 40 years of age patients with rheumatic heart disease, planned for valve replacement/repair and underwent coronary angiography. 46 (12.2%) patients out of total 376 were found to have significant CAD. Among those patients 13.5% had mitral valve disease, while 15.3% patients had aortic valve disease and 9% of them had combined mitral as well aortic valve disease 10. In another study. Significant CAD was found in 7% of cases, and its prevalence was 3% in mitral, 10% in aortic, and 6% in combined mitral and aortic valve disease 11. Patients with CAD are older than patients without significant CAD. In addition to that risk factors like smoking, hypertension, diabetes mellitus and dyslipidemia were more prevalent among patients with significant CAD 12. A significant reduction in mortality is seen in such patients with aortic stenosis who had CAD and underwent concomitant valve replacement and CABG. Therefore, it is desirable to identify CAD in patients presenting for valve surgery 13,14. American College of Cardiology (ACC)/ American Heart Association (AHA) recommendations for patients with planned valve replacement surgery is to undergo coronary angiography before surgery if they have history of angina or any objective evidence of coronary ischemia, impaired LV systolic function, risk factors for coronary artery disease including men >40 years age or postmenopausal women 15. The purpose of this study is to determine the frequency of significant CAD in patients undergoing valve replacement surgery in our population considering our spectrum of valvular disease is different than western population so as to determine the need for concomitant CABG surgery or not. MATERIAL AND METHODS A descriptive cross-sectional study was carried out at department of Cardiology at Armed Forces Institute of Cardiology & National Institute of Heart Disease, Rawalpindi from 1 st January 2017 to 30 th June 2017 through consecutive non probability sampling. All patients of either gender who underwent coronary angiography before valve replacement surgery were included in the study. Excluded Patients were those who had prior valve surgery, known CAD patients, post CABG patients and Post PCI patients. All patients were assessed for eligibility and enrolled in study according to inclusion criteria after informed consent. Permission from the institutional ethical review board was taken before the commencement of study. Risk factors like diabetes, hypertension, dyslipidemia, family history of coronary artery disease, smoking and BMI of the patients were S55

59 Angiographically Significant Coronary Artery Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S54-S58 recorded. All the patients planned for Valvular heart surgery meeting the inclusion criteria underwent coronary angiography before surgery and their significant findings were noted. All the information was entered in a annexed pro-forma. All the collected data was entered and analyzed using the SPSS version 23. RESULTS Continuous variable such as age was reported as mean ± standard deviation while categorical variables such as gender, diabetes, hypertension, family history of premature coronary artery disease, obesity, dyslipidemia, history of premature coronary artery disease, obesity, smoking and diabetes. Total 136 patients were recruited in the study. Mean Age of the patients was ± 5.2 years with minimum age 31 years and maximum 67 years. There were 80 (58.8%) male patients while 56 (41.2%) female patients. Out of total patients, 63 (46.3%) patients had significant CAD. 33 (24.3%) had AVR, 89 (65.4%) patients had MVR while 14 (10.3%) patient had DVR as shown in table-i, Smoking was found to be the most prevalent risk factor 98 (72.1%) followed by family history 67 (49.3%), hypertension 65 Table-I: Showing baseline and risk factors profile. Variables n (%) Age Gender Male Female smoking and type of valve surgery were reported using frequency and percentages Frequency of angiographically significant CAD was also recorded as percentage. Confounding factors and interactions were addressed using stratified analysis for variables such as age, gender, family S56 (mean ± SD) ± 5.2 years (Range) years 80 (58.8%) 56 (41.2%) Family History of CAD 67 (49.3%) Hypertension 65 (48.0%) Obesity(BMI 30) 63 (46.3%) Smoking History 98 (72.1%) Diabetes Mellitus 42 (30.9%) Dyslipidemia 35 (25.7%) Type of Valve Surgery AVR MVR DVR 33 (24.3%) 89 (65.4%) 14 (10.3%) Significant CAD 63 (46.3%) Table-II: Distribution of type of valve surgery with respect to age groups. Type of Valve Surgery Age Group Age Group <40 years 40 years AVR - 33 (24.3%) MVR 52(38.2%) 37 (27.2%) DVR - 14 (10.3%) p-value <0.001 (48.0%), Obesity (BMI 30) 63 (46.3%), diabetes mellitus 42 (30.9%) and dyslipidemia 35 (25.7%). Chi-square test was applied to find out the association between Type of Valve Surgery and age groups. Association was found to be statistically significant with p-value<0.001 as shown in table-ii.

60 Angiographically Significant Coronary Artery Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S54-S58 DISCUSSION Assessment of significant CAD is of utmost importance in patients undergoing for valve replacement surgeries beforehand who fulfill AHA criteria for prescreening by coronary angiogram in order to know if there is any need for concomitant coronary artery bypass grafting 4. In our study we found that the frequency of CAD was 58.8% among study population Males were more at risk of CAD, compared to females. People with smoking history, diabetes mellitus, hypertension, Dyslipidemia and symptoms of angina also had increased risk of CAD in study population and this was similar to various studies across the globe 7,12,14. In Sonmezetal study 10, out of 760 patients (357 males, 403 females; mean age 54.4 ± 18.1 years) planned for valve replacement surgeries and underwent coronary angiography between 1995 and 2000 were enrolled retrospectively. Significant CAD was reported in 46.3% of patient, the commonest valve lesion was aortic stenosis. Among them CAD was not seen commonly in patients <40 years of age. The highest correlation found was between CAD and smoking, family history of CAD, followed by hypertension, obesity, DM and hyperlipidemia. Li et al 9 studied consecutive 651 patients aged >40 who were scheduled for valve surgery underwent diagnostic coronary angiography. Seventy-one male patients and 17 females were detected as with CAD. The atheromatous lesion mostly involved the left descending branch (38.12%), and 38 patients (53.52%) showed lesions in 2 or more branches. The prevalence rates of diabetes mellitus and hypertension in the CAD group were 32.39% and 29.58% respectively, both significantly higher than those in the non-cad 9. In Jose et al 6 study out of 376 patients who underwent diagnostic angiograms before valve replacement surgery the prevalence of coronary artery disease in subgroup of patients with rheumatic heart disease was reported around 12.2% 11. In another study by altar etal, of 1075 patients (658 females, 61.2%; mean age: 53.2 ± 9.9 years) the prevalence of CAD was found 11.1% 11. Ayazetal showed in his retrospective study that, out of 144 patients, 99 (68.8%) found to have <50% coronary stenosis and remaining 45 (31.3%) had >50% stenosis. Among them 32.9% of patients were found to have significant CAD who underwent MVR, whereas 31.9% underwent AVR while 25% of patients with dual valve replacement were found to have coronary artery disease 9. A prospective study of 387 patients with coronary evaluation for risk factors with valvular heart disease, revealed that 36.6% of the study population had angina 10. Whereas, in our study only 6.5% of the subjects with CAD had reported angina in the study population. CONCLUSION Our study shows that significant proportion of patients above 40 years of age have asymptomatic underlying CAD (46%). This being of therapeutic as well as of prognostic importance, the frequency of angiographically significant CAD in our patient population signifies pre valve replacement screening by coronary angiogram so that coronary bypass grafting can be offered to those patients concomitantly with valve replacement. CONFLICT OF INTEREST This study has no conflict of interest to be declared by any author. REFERENCES 1. World Health Organization. World Health Statistics Geneva, Switzerland: World Health Organization, Kaplan E, Talbot R, Nordet P. Strategy for controlling rheumatic fever rheumatic heart disease, with emphasis on primary prevention: memorandum from a Joint WHO/ISFC meeting. Bull World Health Organ 1995; 73(5): Manjunath CN, Agarwal A, Bhat P, Ravindranath KS, Ananthakrishna R, Ravindran R, et al. Coronary artery disease in patients undergoing cardiac surgery for non-coronary lesions in a tertiary care centre. Indian Heart J 2014; 66(1): Sonmez K, Gencbay M, Akcay A, Yilmaz A, Pala S, Onat O, et al. Prevalence and predictors of significant coronary artery disease in Turkish patients who undergo heart valve surgery. J Heart Valve Dis 2002; 11(3): Marchant E, Pichard A, Casanegra P. Report: Association of coronary artery disease and valvular heart disease in chile. Clin Cardiol 1983; 6(7): Bozbaş H, Yildirir A, Küçük MA, Ozgül A, Atar I, Sezgin A, et al. Prevalence of coronary artery disease in patients undergoing valvular operation due to rheumatic involvement. Anadolu Kardiyol Derg 2004; 4(3): S57

61 Angiographically Significant Coronary Artery Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S54-S58 7. Basta L, Raines D, Najjar S, Kioschos J. Clinical, haemodynamic, and coronary angiographic correlates of angina pectoris in patients with severe aortic valve disease. Br Heart J 1975; 37(2): Moraski RE, Russell RO, Mantle JA, Rackley CE. Aortic stenosis, angina pectoris, coronary artery disease. Cathet Cardiovasc Diagn 1976; 2(2): Emren ZY, Emren SV, Kılıçaslan B, Solmaz H, Susam İ, Sayın A, et al. Evaluation of the prevalence of coronary artery disease in patients with valvular heart disease. J Cardiothorac Surg 2014; 9(1): Jose VJ, Gupta SN, Joseph G, Chandy ST, George OK, Pati PK, et al. Prevalence of coronary artery disease in patients with rheumatic heart disease in the current era. Indian Heart J 2003; 56(2): Gupta K, Loya Y, Bhagwat A, Sharma S. Prevalence of significant coronary heart disease in valvular heart disease in Indian patients. Indian Heart J 1989; 42(5): Atalar E, Yorgun H, Canpolat U, Sunman H, Kepez A, Kocabas U, et al. Prevalence of coronary artery disease before valvular surgery in patients with rheumatic valvular disease. Coronary Artery Dis 2012; 23(8): Tempe DK, Virmani S, Gupta R, Datt V, Joshi C, Dhingra A, et al. Incidence and implications of coronary artery disease in patients undergoing valvular heart surgery: The Indian scenario. Ann Card Anaesth 2013; 16(2): Mullany CJ, Elveback LR, Frye RL, Pluth JR, Edwards WD, Orszulak TA, et al. Coronary artery disease and its management: Influence on survival in patients undergoing aortic valve replacement. J Am Coll Cardiol 1987; 10(1): Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, et al. AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63(22): e57-e185. S58

62 Open Access Thrombolytic Therapy in Prosthetic Valve Thrombosis Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S59-S63 THROMBOLYTIC THERAPY IN PROSTHETIC VALVE THROMBOSIS; EFFICACY AND OUTCOME Tariq Hussain Khattak, Tahir Naqqash, Muhammad Azmat Khan*, Javeria Kamran, Aysha Saddiqa, Rehana Javaid, Hafsa Khalil Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Combined Military Hospital/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the efficacy of thrombolytic therapy and its complications in PVT. Study Design: Prospective cross-sectional study. Place and Duration of Study: Study was conducted at AFIC/NIHD Rawalpindi from first Jan 2016 to Dec Material and Methods: A total of 51 patients admitted with Prosthetic valve thrombosis PVT were enrolled in this study, through non-consecutive sampling technique. The primary outcome was complete response to thrombolytic therapy. The secondary outcome was a composite of death, Central nervous system CNS embolism, non CNS systemic embolism or major bleeding. Results: Mean age was (± 11.72). Twenty (43.13%) were male while 29 (56.86%) were female. Mitral PV was involved in 40 (78.4%) and aortic in 11 (21.6%). About 21 (41.2%) were in NYHA-I class and 29 (58.8%) in NYHA- III/IV class. All had bileaflet valve with involvement of one leaflet in 36 (70.6%) and both leaflet in 15 (29.4%). International normalized ratio INR was sub therapeutic in 37 (72.5%). Complete response was observed in 24 (47.05%) while secondary outcome was seen in 15 (29.41%) with death in 13 (25.49%) and CNS embolism in 2 (3.92%). There was no case of non-cns embolism or major bleeding. Complete responses varied with the severity of patient and was 14 (66.66%) in NYHA I/II and 10 (28.57%) in NYHA-III/IV, with p-value Conclusion: This study reveals the burden of prosthetic valve thrombosis in a developing country. It also reveals a high mortality and a suboptimal response to thrombolytic therapy. This study also underscores the advanced stage in which patients present. Keywords: Fibrinolysis, Prosthesis, Thrombosis, Valves. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Correspondence: Dr Tariq Hussain Khattak, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan tariq_khattak63@yahoo.com Prosthetic valve PV implantation is at risk of prosthetic valve thrombosis PVT, a serious complication with a high morbidity and mortality. Its incidence varies from 0.3 to 1.3 per 100 patient years in developed countries 1 to 6.1% in developing countries 2. Mechanical prosthetic heart valve MHV obstruction may be caused by thrombus formation, pannus ingrowth, or a combination of both 3. Urgent diagnosis, evaluation, and therapy are indicated because rapid deterioration can occur if there is thrombus causing malfunction of leaflet opening. Initial evaluation includes Transthoracic echocardiography TTE followed by Transesophageal echocardiography TEE in cases with suboptimal findings. TEE has a greater diagnostic accuracy over TTE 4. Fluoroscopy provides accurate assessment of opening angle and mobility of MHVs. Bioprosthetic heart valves BHVs being radiolucent are not assessed with fluoroscopy 4. Multidetector computed tomography is of value when TTE and TEE are inconclusive. It not only provides an accurate evaluation of the prosthetic valve structure and functional status, but is also helpful in identifying masses amenable to thrombolysis 5. Current guide lines recommend fibrinolytic therapy if the thrombus is less than 14 days old, the patient has NYHA class I-II symptoms and thrombus is small I size (<0.8 cm2) 6,7. The purpose of this study was to evaluate efficacy of thrombolytic therapy with S59

63 Thrombolytic Therapy in Prosthetic Valve Thrombosis Pak Armed Forces Med J 2018; 68 (Suppl-1): S59-S63 streptokinase in PVT. In addition it will determine the frequency of complications in these patients. MATERIAL AND METHODS This is a prospective cross-sectional study carried out at AFIC/NIHD Rawalpindi from January 2016 to December Institutional ethical review board approval was obtained. Verbal consent was obtained from patients. Data collection tool was developed to measure demographics, response to treatment and outcome. PVT was suspected clinically in patients with dyspnea or chest pain or both with duration less then 14 days. Definitive diagnosis was based on fluoroscopy revealing immobile or hypomobile leaflets with or without increased pressure gradient on Doppler echocardiography 9. Transesophageal echocardiography was carried out where it was feasible. Patients with contraindication to fibrinolytic therapy i.e. any previous intracranial hemorrhage, ischemic stroke within the last 3 months, presence of a left atrial thrombus on transthoracic echocardiography, and pregnancy were excluded. Patients were advised IV heparin followed by IV streptokinase 0.25 MU over 30 minutes followed by 0.1 MU/hr infusion. Serial TTE was carried out and SK infusion was stopped on symptomatic improvement and improvement in leaflet movement and significant improvement in trans-valvular gradient. Infusions of streptokinase were continued for up to 72 hours depending upon the response and development of complication. Outcomes The primary outcome was the occurrence of a complete response to thrombolytic therapy. Secondary outcome was a composite of death, major bleeding, Central nervous system CNS embolism, or non CNS systemic embolism. Patients were monitored for adverse events until they were discharged from the hospital. Operational Definition Complete response was defined as complete normalization of valve function in the absence of death, major bleeding, or embolic stroke. Complete normalization of valve function was defined as normal leaflet motion on fluoroscopy and normalization of trans-valvular pressure gradients on Doppler echocardiography. Partial response was defined as >50% improvement in trans-valvular gradients from baseline but with incomplete normalization of leaflet motion on fluoroscopy. Fibrinolytic therapy failure was defined as reduction in transvalvular gradient by less than 50%, persistent leaflet motion abnormality on fluoroscopy or if death occurred. Early valve thrombosis was defined as valve thrombosis occurring within 12 months of surgery. Statistical analysis was carried out on IBM SPSS version 23. Categorical data was presented as percentages and frequency whereas descriptive statistics were expressed as mean and standard deviation for quantitative analyses. Chi square test was applied to analyze the data. A p-value of 0.05 was considered statistically significant. RESULTS From January 2016 to December 2017, 51 patients with PVT were enrolled. All had diagnosis confirmed on fluoroscopy and underwent Echocardiography. Baseline characteristics are shown in table-i: Mean age was (± 11.72). 22 (43.13%) were male while 29 (56.86%) were female. Mitral PV was involved in 40 (78.4%) and aortic in 11 (21.6%). 21 (41.2%) were in NYHA-I/II class and 29 (58.8%) in NYHA-III/IV class. All had bileaflet valve with involvement of one leaflet in 36 (70.6%) and both leaflet in 15 (29.4%). International normalized ratio INR was subtherapeutic in 37 (72.5%). Metallic valve was involved in 98%. Late valve thrombosis was observed in 84.3%. Efficacy of Streptokinase Complete response was observed in 24 (47.05%) while secondary outcome was seen in S60

64 Thrombolytic Therapy in Prosthetic Valve Thrombosis Pak Armed Forces Med J 2018; 68 (Suppl-1): S59-S63 15(29.41%) with death in 13 (25.49%) and CNS embolism in 2 (3.92%). There was no case of non- CNS embolism or major bleeding. Complete responses varied with the severity of patient and was seen in 14 (66.66%) of NYHA I/II and in 10 patients with PVT over two years. The study evaluated efficacy of standard infusion of streptokinase in prosthetic valve thrombosis. Our main findings include an overall complete response in 24 (47.05%) while secondary outcome Table-I: Baseline Caharaceristics. Characteristic No (%) Age mean (± 11.72) Gender Male Female Valve involved Mitral Aortic Valve type Metallic Bioprosthetic Post surgery Early Late Severity NYHA I/ II NYHA III/IV Number of leaflet involved Single Double INR Therapeutic Subtherapeutic Response Complete Partial Failed Secondary outcome Death CNS/non-CNS embolism 22 (43.13%) 29 (56.86%) 40 (78.4%) 11 (21..6%) 50 (98%) 1 (2%) 8 (15.7%) 43 (84.3%) 21 (41.2%) 29 (58.8%) 36 (70.6%) 15 (29.4%) 14 (27.5%) 37 (72.5%) 24 (47.05%) 13 (25.49%) 14 (27.45%) 15 (29.41%) 13 (25.49%) 2 (3.92%) (28.57%) of NYHA-III/IV, with p-value as shown in table-ii. DISCUSSION Prosthetic valve thrombosis PVT is a serious complication of PV, and has a high mortality. Early diagnosis is paramount in guiding management. Our study represents single center study in a developing country enrolling 51 was seen in 15 (29.41%) with death in 13 (25.49%) and CNS embolism in 2 (3.92%). There was no case of non-cns embolism or major bleeding. Complete responses varied with the severity of patient and was seen in 14 (66.66%) of NYHA-I/II and in 10 (28.57%) of NYHA-III/IV, with p-value Complete response of 47.05% in our study is below generally reported in studies. Consensus S61

65 Thrombolytic Therapy in Prosthetic Valve Thrombosis Pak Armed Forces Med J 2018; 68 (Suppl-1): S59-S63 statements suggest at least 80% success rate with fibrinolytic therapy 8. Complete hemodynamic success was achieved in 76.3% of the 93 obstructed valves in an international multi-center registry (PRO-TEE study), in which thrombolytic agents used were streptokinase (54.7%), urokinase (17%), and t-pa (28.9%). Thrombolytic success was similar among different valves and lytic agents 4. Relatively low complete response observed in our study is due to a high number of cases in advanced NYHA class III/IV and in circulatory shock at presentation. In our study only streptokinase was used. Alternative streptokinase administration technique and alternative fibrinolytic agents: In a randomized controlled trial by Karthikeyan et al compared an accelerated infusion with the conventional infusion of streptokinase in 120 patients. Complete clinical response occurred in 38 (64.4%) of 59 patients with the accelerated infusion compared with 32 (53.3%) of 60 with the conventional infusion (hazard ratio 1.6, 95% confidence interval 0.9 to 2.5, p 0.055). There was no significant difference in the occurrence of the composite secondary outcome (hazard ratio 1.4, 95% confidence interval 0.5 to 3.5, p 0.50) or major bleeding (hazard ratio 2.2, 95% confidence interval 0.6 to 7.7, p 0.24) with the accelerated infusion. The success rate with fibrinolytic therapy was low overall (59%) and very low in patients in New York Heart Association functional class III/IV (24%) 9. In another study by Ozkan et al streptokinase was compared with tissue plasminogen activator t-pa, with 182 consecutive patients divided into 5 groups. These included rapid (group-i), slow (group-ii) streptokinase, high-dose (100 mg) tissue plasminogen activator (t-pa) (group-iii), a halfdose (50 mg) and slow infusion (6 h) of t-pa without bolus (group-iv), and a low dose (25 mg) and slow infusion (6 h) of t-pa without bolus (group-v). According to this study, low dose (25 mg) and slow (6 hours) infusion of tissue-type plasminogen activator (t-pa) without bolus with repetition as needed as a first-line therapy have been reported to be the safest regimen compared with higher doses or faster infusions of t-pa or streptokinase. The overall success rate in the whole series was 83.2%; it did not differ significantly among Groups-I through V (68.8%, 85.4%, 75%, 81.5%, and 85.5%, respectively; p 0.46). The overall complication rate in the whole series was 18.6%. Although the overall complication rate was similar among Groups-I through IV (37.5%, 24.4 %, 33.3%, and 29.6%, Table-II: Outcome of thrombolytic therapy. Outcome NYHA I/II 21 NYHAIII/IV 29 p-value Primary outcome Complete response 14 (66.66%) 10 (28.57%) Secondary outcome Death CNS/non-CNS embolism 4 (19.04%) 3 (14.28%) 1 (4%) 11 (37.93%) 10 (34.48%) 1 (3.4%) NS NS NS respectively; p 0.05 for each comparison), it was significantly lower in Group V (10.5%, p 0.05 for each). The study concluded that low-dose slow infusion of t-pa repeated as needed without a bolus provides effective and safe thrombolysis in patients with prosthetic valve thrombosis 10. In a study by Özkan et al, Ultraslow infusion (25hours) of low-dose (25mg) t-pa, was used in all patients a with PVT, with an overall success rate of 90% (95% CI ) with low complications and mortality 11. In another study in elderly patients prolonged and low dose infusions of thrombolytics showed an initial and cumulative success rates of 40.7% and 85.2%, respectively 12. Wei et al studied a non-thrombolytic regimen based on clopidogrel plus warfarin with initial 5 days of LMWH resulted in recovery of normal valve function in 73% of patients with PVT and stable hemodynamics, after an average of 36.4 ± 23.1 days observation 13. S62

66 Thrombolytic Therapy in Prosthetic Valve Thrombosis Pak Armed Forces Med J 2018; 68 (Suppl-1): S59-S63 Surgery versus thrombolytic therapy: In a meta-analysis and a systematic review by Castilho et al, surgery was compared with thrombolysis. There was a highly significant difference in mortality between the two groups: surgery, 18.1% (CI, %) and thrombolysis, 6.6% (CI, %) (p<0.001) 14. In a literature survey by Huang et al, results revealed 30-day mortality in the group treated with surgery at 15% (98 deaths in 662 patients) vs. 8% (61 deaths in 756 patients) in the thrombolysis pooled. The rates of recurrence and complications, however, were higher in patients treated with thrombolysis 15. CONCLUSION PVT is a serious complication of prosthetic heart valves with high mortality and morbidity both due to disease and treatment. It is recommended that urgent surgery be carried out once failed fibrinolytic therapy is observed after 24 hours. Management requires a wellcoordinated heart team approach not only to rapidly diagnose the condition but also to define the optimal treatment for the patient. LIMITATION OF STUDY Our study is limited due to lesser use of TEE, which is important not only in evaluation of valve function but also in quantification of thrombus size. ACKNOWLEDGEMENT We thank Dr Farrah Pervaiz and her team of Research and development department at AFIC/NIHD Rawalpindi for help in Data collection and data analysis. CONFLICT OF INTEREST This study has no conflict of interest to be declared by any author. REFERENCES 1. Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations. Heart 2007; 93(1): Talwar S, Kapoor CK, Velayoudam D, Kumar AS. Anticoagulation protocol and early prosthetic valve thrombosis. Indian Heart J 2004; 56(3): Barbetseas J, Nagueh SF, Pitsavos C, Toutouzas PK, Quinones MA, Zoghbi WA. Differentiating thrombus from pannus formation in obstructed mechanical prosthetic valves: An evaluation of clinical, transthoracic and transesophageal echocardiographic parameters. J Am Coll Cardiol 1998; 32(5): Tong AT, Roudaut R, özkan M, Sagie A, Shahid MSA, Pontes SC, et al. Transesophageal echocardiography improves risk assessment of thrombolysis of prosthetic valve thrombosis: Results of the international PRO-TEE registry. J Am Coll Cardiol 2004; 43(1): Gündüz S, Özkan M, Kalçık M, Gürsoy OM, Astarcıoğlu MA, Karakoyun S, et al. Sixty-Four section cardiac computed tomography in mechanical prosthetic heart valve dysfunction-thrombus or pannus. Circ Cardiovasc Imaging 2015; 8: e Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, et al. AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(23): Nishimura RA, Otto CA, Bonow RO, Carabello BA, Erwin JP, Fleisher LA et al. AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Circulation 2017; 135(25): e1159-e Lengyel M, Horstkotte D, Voller H, Mistiaen WP. Recommendations for the management of prosthetic valve thrombosis. J Heart Valve Dis 2005; 14(5): Karthikeyan G, Math RS, Mathew N, Shankar B, Kalaivani M, Singh S, et al. Accelerated infusion of streptokinase for the treatment of left-sided prosthetic valve thrombosis: A randomized controlled trial. Circulation 2009; 120(12): Özkan M, Gündüz S, Biteker M, Astarcioglu MA, Çevik C, Kaynak E, et al. Comparison of different TEE guided thrombolytic regimens for prosthetic valve thrombosis. The TROIA Trial. j Am Coll Cardiol 2013: 6(2): Özkan M, Gündüz S, Gürsoy OM, Karakoyun S, Astarcıoğlu MA, Kalçık M, et al. Ultraslow thrombolytic therapy: A novel strategy in the management of PRO sthetic ME chanical valve Thrombosis and the predictors of outcome: The Ultra-slow PROMETEE trial. Am Heart J 2015; 170(2): Gundu S, Ozkan M, Yesin M, Kalc M, Gursoy MO, Karakoyun S, et al. Prolonged infusions of low-dose thrombolytics in elderly patients with prosthetic heart valve thrombosis: Clinical and Applied Thrombosis/Hemostasis; 2017; 23(3): Wei W, Dong T, Zheng Z, Huang S. Effect of a combined antithrombotic therapy of thrombosis on prosthetic heart valves: J Thorac Dis 2015; 7(3): Castilho FM, Sousa MR, Mendonca ALP, Ribeiro ALP, Caceres- Loriga FM. Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and metaanalysis. J Thromb Haemost 2014; 12(8): Huang G, Schaff HV, Sundt TM, Rahimtoola SH. Treatment of obstructive thrombosed prosthetic heart valve. J Am Coll Cardiol 2013; 62(19): S63

67 Open Access Delerium After Cardiac Surgery Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S64-S68 INCIDENCE AND RISK FACTORS OF DELERIUM AFTER CARDIAC SURGERY Amna, Saira Mahboob, Safdar Ali Khan, Urooj Alam, Quratalain Amjad Armed Forces Institute of Cardiology /National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the incidence and associated risk factors for post-operative delirium after cardiac surgery. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Adult cardiac anesthesia department of Armed Forces Institute of Cardiology, Rawalpindi, from Mar to Apr Material and Methods: A total of 176 patients who had undergone cardiac surgery were studied in our descriptive-cross sectional study lasting 02 months at Armed Forces Institute of Cardiology, Rawalpindi. Age more than 18 years, elective cardiac surgery, and post cardiac surgery stay in ICU more than 24 hours. Postoperative CVA or intracranial bleed, Pre-operative cognitive impairment. Results: Out of 176 patients, 20 (11.4%) developed post-operative delirium. Mean mechanical ventilation time in patients who developed delirium was 10.8 hours ± 6.13 and was 6.47 ± 4.75 hours in patients who did not developed delirium (p= 0.000). The 14 (70%) patients who developed delirium were found to be hyperglycemic in our study versus 59 (37.8%) patients who had neither delirium nor hyperglycemia (p=0.006). ICU stay was prolonged in patients with delirium was 3.52 days ± 5.12 as compared to patients who did not developed delirium 2.45 ± 3.21 days (p=0.002). Conclusion: Our study revealed that advanced age, prolonged mechanical ventilation and hyperglycemia are significant risk factors of delirium in post cardiac surgery patients. Keywords: Post operative delirium, Cardiac surgery This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Delirium is defined as a disturbance of consciousness, a change in cognition or the development of a perceptual disturbance; with acute onset and fluctuating course with an evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a medical condition, substance intoxication or medication side effect 1. Post operative delirium is one of the common problems after cardiac surgery 1 Post op delirium is associated with morbidity, mortality and longer hospital stay 3,4. It can be very disturbing and distressing for patients and their families and nursing staff 5. Patients who have undergone cardiac surgery, delirium may increase postoperative complications like respiratory insufficiency, sternum instability and need for Correspondence: Dr Amna, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan amna.amc@gmail.com re-opening of sternum, self extubation, exit of catheters and asynchrony between patient and ventilator 6,7. The incidence of post-operative delirium varies from (10-46%) in general surgical population and reaches (50-67%) in patients after cardiac surgery 8,9. There is wide variation because of methodology differences between studies and study population The purpose of our study was to study the frequency and risk factors of delirium in patients undergoing cardiac surgery for earlier detection and reduction in the complications associated with this seemingly benign disorder. MATERIAL AND METHODS After approval by the ethical committee of our institute; 176 patients who had undergone open heart surgery were studied in our comparative cross sectional study lasting 02 months (March- April 2015). Before surgery, preanesthesia assessment was done by cardiac anesthetist as per institute protocol. The S64

68 Delerium After Cardiac Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S64-S68 assessment forms were scrutinized for the presence of risk factors for delirium as well as history of any alcohol or drug use preoperatively. None of the patients suffered from pre-operative dementia or cognitive impairment. Preoperative evaluation, premedication, anesthesia and surgery were performed according to institutional protocols; no adjustments were made for study participants. After the surgery patients were immediately transported to the ICU. All the patients were assessed for risk stratification and diagnosis of postoperative delirium by the investigators. Patients of age more than 18 years with planned open heart surgery, post cardiac surgery stay in ICU more than 24 hours were included in Operational Definitions According to the diagnostic and statistical manual of mental disorders fourth edition, the key characteristics are a change in mental status with reduced awareness of environment and a disturbance in attention; along with perceptual symptoms (hallucinations) or cognitive symptoms (including disorientation or temporary memory dysfunction). (CAM ICU) confusion assessment method was used to diagnose delirium. RESULTS The study included total 176 patients out of which 20 (12%) developed delirium. The demographic profile of our study population is tabulated as table-i. One hundred and forty one Table-I: Demographics of study population. n=176 Percentage (%) Gender Male Female Age <50 years >50 years CABG surgery Surgery type Valvular surgery Myxoma excision the study. Patients with pre-operative and postoperative CVA or intracranial bleed, preoperative cognitive impairment were excluded from study. Post-operative clinical and cognitive assessment was carried out using confusion assessment method (CAM). The patient was deemed to be in post-operative delirium if CAM score was positive. Risk factors of delirium were recorded and statistically analyzed. Data Analysis The data was analyzed by descriptive statistics (number, percentage, mean and standard deviation) and Chi square was used for analysis of variance. In our study p-value of less than 0.05 was considered as statistically significant. The statistical analysis was done by using SPSS 21. S65 (80.1%) were male and 35 (19.9%) were female. Out of 176 patients, 20 (11.4%) developed postoperative delirium. Risk factor association was calculated by using chi-square test. The 17 out of the 20 (85%) of patients who developed delirium were aged more than 50 years, while 87 out of 156 (49.4%) non delirium patients were aged more than 50 years (p=0.012). Mean mechanical ventilation time in patients who developed delirium was 10.8 hours ± and was 6.47 ± 4.75 hours in patients who did not developed delirium (p=0.000). The 14 (70%) patients who developed delirium were found to be hyperglycemic in our study versus 59 (37.8%) patients who had neither delirium nor hyper-glycemia (p=0.006). ICU stay was prolonged in patients with delirium was 3.52 days ± 5.12 as compared to patients who do not delirium 2.45 ± 3.21 days (p=0.022). Mean Cardiopulmonary bypass time in

69 Delerium After Cardiac Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S64-S68 patients with delirium was min ± and in patients who do not developed delirium was minutes ± (p=0.903). In our study, 15 (75%) patients who had delirium were males, whereas, in delirium free group 126 (80.7%) were males (p= 0.774). The incidence of carotid artery disease in delirium group was 15%, whereas, in non-delirium patients it was 10.6% in non-delirious patients (p=0.586). All patients in both delirium and non-delirium groups suffered from pre-operative com-morbidities including hypertension, diabetes mellitus (p=0.579). In the delirium group, 3 (15%) had peri-operative IABP insertion whereas 100 (63.3%) patients who did hypothesized to occur as a result of the inflammatory response associated with the stress of surgery. Postoperative chemokines have been found to be more elevated in patients who became delirious than in matched controls. This difference was non-significant by forth postoperative day. The mechanism for delirium might include initial leucocytes migration into the central nervous system (CNS) and potentially a breakdown of the blood brain barrier 14. There are several tests for diagnosing and grading of delirium. These include the confusion assessment method (CAM), The Delirium Rating Scale Revised-98, and the delirium symptom Table-II: Clinical variables of study participants. Variable Delirium (n=20) Non delirium (n=156) p-value Age <50 years n=3 n=69 <50 years n=17 n= Gender Male n=15 n=126 Female n=5 n= Carotid artery disease n=3 n=17 O.586 Co-morbidity n=20 n= Intra-aortic balloon pump n=3 n= Inotropes n=18 n= Mean Mechanical ventilation time 10.8 ± hours 6.47 ± 4.75 hours Hyperglycemia n=14 n= Mean cardiopulmonary bypass time ± mins ± mins Mean ICU stay 3.52 days ± ± 3.21 days not develop delirium had IABP insertion, (p=0.216). The postoperative ionotropes were used in 18 (90%) of patients who developed delirium, whereas ionotropes were used in 130 (83.3%) patients in non-delirium group (p= 0.443). The results have been tabulated in table-ii. DISCUSSION Delirium is defined as an acute cognitive impairment and neglect which fluctuates in level of consciousness or altered level of consciousness with unorganized thinking 13. The patients may express hypoactive, hyperactive or mixed psychosocial behaviors. Delirium has been interview 11,12. A recent study from Japan used NEECHAM Confusion Scale and the Estimation of Physiologic Ability and Surgical Stress (E-PASS) for diagnosis and found it useful 15. Although the disorder occurs acutely, but the condition may wax and wane during the course of a day. The diagnosis is further complicated by the presence of pre-existing dementia, psychosis anxiety or depressive disorders. CAM-ICU is a simple and easy diagnostic tool for delirium 15. It has a high sensitivity (93-100%) and specificity (89-100%). It is currently the only validated delirium tool for patients on mechanically ventilator support. It S66

70 Delerium After Cardiac Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S64-S68 was used by us in our study for the diagnosis of delirium. In our study, the 176 patients were studies during their admission to the surgical intensive care unit postoperatively after various cardiac surgeries of these 20 patients (11.4%) developed post-operative delirium. The incidence of post-operative delirium in cardiac surgery was 23% and 31% in studies conducted by Reissmuller and Norkiene respectively 16,17. The incidence of post-operative delirium in our population was found to be higher in patients who had undergone CABG surgery as compared to valvular surgeries (12% vs 10% of cases). In Kazmierski study of 563 patients, the incidence of post-operative delirium according to DSM-IV was 16.3%. Advanced age, pre-operative cognitive impairment, ongoing major depression, anemia, atrial fibrillation, prolonged intubation and post-operative hypoxia were independent risk factors for delirium 18. Advanced age and prolonged intubation and mechanical ventilation as risk factors are in line with our study. However, none of our patients had pre-operative cognitive impairment or major depression. Reissmuller studied 107 patients who had undergone cardiac surgeries. The incidence of post-operative delirium was 23.4%. The risk factors were age over 60 years, longer mechanical ventilation and longer cardiopulmonary bypass time 16. In our study, advanced age and prolonged mechanical ventilation were found to be significant risk factors for delirium. However, we have taken more than 50 years as advanced age, whereas Reisssmuller took more than 60 years as advanced age. Koster review of risk factors for delirium revealed 27 risk factors; 12 predisposing and 15 precipitating factors for delirium after cardiac surgery 6. The most established risk factors were: a trial fibrillation, cognitive impairment, depression, history of stroke, older age and peripheral vascular disease. Our study also established older age as significant risk factor. Whereas, history of stroke, peripheral vascular disease was not found to be associated with delirium. In our study, prolonged mechanical ventilation 10.8 ± 6.13 hours in patients with delirium and 6.47 ± 4.75 hours in non-delirium patients was found to a highly significant risk factor for delirium (p<0.001) but bias may be present in this regard due to the fact that institutional trend towards intubating and mechanically ventilating a patients who has altered sensorium with risk of respiratory compromise. In addition, delays maybe present in extubating a delirious patient. Additionally, none of our patient had pre-operative obvious cognitive impairment nor does an institutional protocol exist for detailed cognitive impairment assessment during pre-anesthesia assessment. Additionally, 176 patients were included in our study. More reliable results would be expected if the study were to be done on a larger sample size. RECOMMENDATIONS Pre-operative identification of patients at high risk of developing post-operative delirium can help in earlier detection of delirium. Postoperatively, daily scoring of patient with CAM- ICU by care giver, which is a simple and quick method that can be helpful in earlier diagnosis and treatment of delirium, thus preventing complication and sequelae of delirium. CONCLUSION Our study has revealed significant risk factors of delirium i.e. advanced age, prolonged mechanical ventilation and hyperglycemia in post cardiac surgery patients. Thus prevention, early detection and timely management of the modifiable risk factors may be helpful in reducing the length of ICU stay, morbidity and mortality. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Diagnostic and statistical manual of mental disorders: DSM-IV. American Psychiatric Association Blachy PH, Starr A. Post-cardiotomy delirium. Am J Psychiatry 1964; 121: Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Falk V, et-al. Predictors of delirium after cardiac surgery delirium: Effect S67

71 Delerium After Cardiac Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S64-S68 of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg 2004; 127(1): McKhann GM, Grega MA, Borowicz LM Jr, Bechamps M, Selnes OA, Baumgartner WA, et al. Encephalopathy and stroke after coronary artery bypass grafting: Incidence, consequences and prediction. Arch Neurol 2002; 59(9): Breitbart W, Gibson C, Tremblay A. The delirium experience: Delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/ caregivers, and their nurses. Psychosomatics 2002; 43(3): Koster S, Hensens AG, Schuurmans MJ, van der Palen J. Risk factors of delirium after cardiac surgery a systemic review. Eur J Cardiovasc Nurs 2011; 10(4): Banerjee A, Wesley Ely E, Pandharipande PP. Agitation and delirium. In: Vincent JL, Abraham E, Moore FA, Kachanek PM, Fink MP. Textbook of critical care. 6th ed. Elsevier Saunders; Deiner and J. H. Silverstein, Postoperative delirium and cognitive dysfunction. Br J Anaesth 2009; 103: Mittal V, Muralee S, Williamson D, McEnerney N, Thomas J, Cash M, et al. Delirium in the elderly: a comprehensive review. Am J Alzheimer s Dis other Demen 2011; 26(2): Miller RR, Ely EW. Delirium and cognitive dysfunction in the intensive care unit. Semin Respir Crit Care Med 2006; 27(3): Neto AS, Nassar AP, Cardoso SO, Manetta JA, Pereira VG, Esposito DC, et al. Delirium screening in critically ill patients: A systematic review and meta-analysis. Crit Care Med 2012; 16(SUPPL-1): Devlin JW, Fong JJ, Fraser GL, Riker RR. Delirium assessment in the critically ill. Intensive Care Med 2007; 33(6): Hattori H, Kamiya J, Shimada H, Akiyama H, Yasui A, Kuroiwa K et al. Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale. Int J Geriatr Psychiatry 2009; 24(11): Rudolph JL, Ramlawi B, Kuchel GA, McElhaney JE, Xie D, Selke FW, et al. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Sci Med Sci 2008; 63(2): Inouye S, vandyck CH, Alessi CA, Balkin S, Siegal AP, Horowitz RI. Clarifying confusion: the confusion assessment method: a new method for detection of delirium. Ann Intern Med 1990; 113(12): Veliz-Reissmüller G, Agüero Torres H, van der Linden J, Lindblom D, Eriksdotter Jönhagen M. Pre-operation mild cognition dysfunction predicts risk for post operation delirium after elective cardiac surgery. Aging Clin Exp Res 2007; 19(3): Norkiene I, Ringaitiene D, Misiuriene I, Samalavicius R, Bubulius R, Bubulis A. Incidence and precipitating factors of coronary artery bypass grafting. Scand Cardiovasc J 2007; 41(3): Kazmierski J, Kowman M, Banch M, Fendler W, Okonski P, Banys A, et al. Incidence and predictors of delirium after cardiac surgery: Results from The IPDACS Study. J Psychosom Res 2010; 69(2): S68

72 Open Access Tissue Plasminogen Activator, Heparin And Streptokinase Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S69-S74 EFFICACY OF TISSUE PLASMINOGEN ACTIVATOR, HEPARIN AND STREPTOKINASE IN PATIENTS WITH SUB MASSIVE PULMONARY EMBOLISM IN A TERTIARY CARE CARDIAC HOSPITAL Imran Ahmed, Ayesha Riaz**, Javeria Kamran*, Abdul Hameed Siddiqui*, Hasnain Yousaf*, Shujja Abbas*, Kamran Abbas*, Farhan Tuyyab*, Tahir Iqbal*, Sohail Aziz* Military Hospital /National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, **Ayub Teaching Hospital, Abbotabad Pakistan ABSTRACT Objective: To determine the clinical characteristics and outcomes of 25 cases of pulmonary embolism in relation to use of thrombolytic and anticoagulants. Study Design: Case series study. Place and Duration of Study: Adult cardiology department of Armed Forces Institute of Cardiology & National Institute of Heart Diseases from Oct 2017 to Jan Material and Methods: Total 25 patients with pulmonary embolism were included in the study using consecutive sampling technique. Clinical characteristics and outcomes of the patients were noted and analyzed. SPSS-23 was used for data analysis. Results: Twenty five cases of acute pulmonary embolism were included in our study and were admitted to the coronary care unit of hospital during the study period. Mean age of patients was 42 ± years with minimum age 20 years and maximum 83 years. There were 19 (76.0%) male patients while 6 (24.0%) female patients. Most common NYHA class with which patients presented was, class-ii 10 (40%) followed by class-iii 8 (32%). The most common CT pulmonary angiogram finding of the patients was bilateral segmental embolism 17 (68.0%). Out of 25 patients, 12 (48.0%) patients received streptokinase and four (16%) received tissue plasminogen activator. Four patients were found to have deep venous thrombosis. Mortality was 20%. Conclusion: Acute pulmonary embolism is a relatively common medical emergency and accurate diagnosis in early period can help institute appropriate thrombolytic therapy to maximally benefit the patients. Keywords:, CT pulmonary angiogram, Deep venous thrombosis, NYHA class, Pulmonary embolism This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Pulmonary embolism (PE) is a relatively common cardiovascular emergency occurring in 60 to 112 of every 100,000 individuals 1. About 430,000 people each year in Europe are affected by pulmonary emboli. In the United States between 300,000 and 600,000 cases occur each year, which results in between 50,000 and 200,000 deaths 2. Rates are similar in males and females. They become more common as people get older. It is the third most common cause of cardiovascular mortality and is responsible for 100,000 to 180,000 deaths annually 1. The prevalence of pulmonary embolism among hospitalized patients in the United States, Correspondence: Dr Imran Ahmed, Military Hospital Rawalpindi Pakistan ( according to data collected between 1979 and 1999, was 0.4% though only per persons were diagnosed with pulmonary embolism per year 3. By occluding the pulmonary arterial bed it may lead to acute life-threatening but potentially reversible right ventricular failure 4. Pulmonary embolism is a difficult diagnosis that may be missed because of nonspecific clinical presentation. However, early diagnosis is fundamental, since immediate treatment is highly effective. PE should be part of differential diagnosis in patients who present with new or worsening dyspnoea, chest pain or hypotension. Based on physician s level of suspicion, the diagnostic workup may include a clinical decision rule, biomarkers (e.g., d-dimers) and/or imaging modalities such as computed tomographic pulmonary angiography (CTPA) or S69

73 Tissue Plasminogen Activator, Heparin And Streptokinase Pak Armed Forces Med J 2018; 68 (Suppl-1): S69-S74 a ventilation perfusion scan. Additional evaluations may be performed with Troponins, B-type natriuretic peptide (BNP) and/or echocardiography. PE is commonly classified as massive (high-risk), submassive (intermediaterisk) and low risk to help determine the required treatment. Massive PE is defined as suspected or confirmed PE in the presence of shock, sustained hypotension, pulselessness or persistent profound bradycardia. Sub- massive PE is defined as suspected or confirmed PE with right ventricular dysfunction in the absence of shock 5. Epidemiology, predisposing factors, natural history, and the pathophysiology of pulmonary embolism have been described more extensively worldwide 4,6,8. Depending on the clinical presentation, initial therapy is primarily aimed either at life- saving restoration of flow through occluded pulmonary arteries (PA) or at the prevention of potentially fatal early recurrences. Both initial treatment and the longterm anticoagulation that is required for secondary prevention must be justified in each patient by the results of an appropriately validated diagnostic strategy 6,7,9. Pulmonary embolism and deep venous thrombosis are two clinical presentations of venous thromboembolism (VTE) and share the same predisposing factors. In most cases pulmonary embolism is a consequence of DVT. Among patients with proximal DVT, about 50% have an associated, usually clinically asymptomatic pulmonary embolism at lung scan 5,7,8. In about 70% of patients with Pulmonary embolism, DVT can be found in the lower limbs if sensitive diagnostic methods are used 10. The risk of death related to the initial acute episode or to recurrent PE is greater in patients who present with pulmonary embolism than in those who present with DVT. According to prospective cohort studies, the acute case fatality rate for Pulmonary embolism ranges from 7 to 11% 11. Although Pulmonary embolism can occur in patients without any identifiable predisposing factors, one or more of these factors are usually identified (secondary pulmonary embolism) The proportion of patients with idiopathic or unprovoked pulmonary embolism was about 20% in the International cooperative pulmonary embolism registry (ICOPER) 15. Patient-related predisposing factors include age, history of previous VTE, active cancer, neurological disease with extremity paresis, medical disorders causing prolonged bed rest, such as heart or acute respiratory failure, and congenital or acquired thrombophilia, hormone replacement therapy and oral contraceptive therapy An association between idiopathic pulmonary embolism and cardiovascular events, including myocardial infarction and stroke, has recently been reported 12,17. Reports of a high risk of pulmonary embolism among obese people, smokers and patients affected by systemic hypertension or metabolic syndrome have renewed interest in the link between arterial thrombo-embolism and VTE 9,10. MATERIAL AND METHODS A Case series study was carried out at Armed forces Institute of Cardiology (AFIC/ NIHD) Rawalpindi from Oct 2017 to Jan A total of 25 patients of pulmonary embolism were included in the study, using consecutive sampling technique. Data collection tool was used to collect the different variables. Data was entered analyzed using SPSS Version 23. RESULTS Twenty five cases of acute pulmonary embolism were included in the study who were admitted in the coronary care unit (CCU) during study period. Mean age of patients was 42 ± 18.3 years with minimum age 20 years and maximum 83 years. There were 19 (76.0%) male patients while 6 (24.0%) female patients. Most common NYHA class with which patients presented was, class-ii 10 (40%) followed by class-iii 8 (32%). The most common CT pulmonary angiogram finding of the patients was bilateral segmental embolism in 17 (68.0%) as shown in table-i. Out of 25 patients, 12 (48.0%) patients received streptokinase. Four patients were found to have deep venous thrombosis. Mortality was 20.0% S70

74 Tissue Plasminogen Activator, Heparin And Streptokinase Pak Armed Forces Med J 2018; 68 (Suppl-1): S69-S74 (n=5). Chi-square test was applied to find out the association between mortality and different variables. Results showed that only NYHA class findings was statistically significant (pvalue<0.05) with mortality as shown in table-ii. DISCUSSION Massive PE was previously defined by anatomical criteria: >50% obstruction of pulmonary vasculature or occlusion of 2 or more S71 lobar arteries. It is now more commonly defined by hemodynamic instability, which is a function of both PE size and underlying cardiopulmonary status. Massive acute pulmonary embolism is now defined as sustained hypotension (systolic Table-I: Frequencies (%) of characteristics of patients with pulmonary embolism. Variables Frequency (%) (n=25) Age (Mean ± SD ) 44 (± 18.52) Outcome Dead 5 (23%) Alive 20 (76%) Gender Male 19 (76%) Female 6 (24%) NYHA I 2 (10%) II 10 (50%) III 4 (20%) IV 4 (20%) ddimers <200 2 (8%) >200< (52%) >400<800 9 (36%) > (4%) Treatment SK 12 (48%) Heparin 9 (36%) tpa 4 (16%) Echo Dilated RA/RV 20 (80%) Normal 5 (20%) DVT Yes 4 (16%) No 21 (84%) CTPA Bil segmental embolism 16 (64%) Saddle Embolus 1 (4%) Bil massive 2 (8%) Lobar embolism 6 (24%) blood pressure <90 mmhg for at least 15 min or requiring inotropic support not due to a cause other than PE such as arrhythmia, hypovolemia, sepsis or LV dysfunction, pulselessness, or persistent profound bradycardia (heart rate <40 bpm with sign and symptoms of shock) 10. Acute

75 Tissue Plasminogen Activator, Heparin And Streptokinase Pak Armed Forces Med J 2018; 68 (Suppl-1): S69-S74 pulmonary embolism leads to an abrupt rise in pulmonary vascular resistance. Right ventricular contractile function is compromised and right ventricular failure ensues. This vicious cycle of cardiogenic shock is augmented by concomitant hypoxia, which inevitably leads to cardiovascular collapse. The interval from the onset of symptoms to death is relatively short. In patients pneumothorax, and an arterial blood gas analysis to strengthen the diagnosis 17. When the diagnosis of massive pulmonary embolism is made, medical or surgical treatment must be initiated immediately. If the patient is in remote area, the decision to perform embolectomy may be made primarily on clinical impression. Thrombolysis is also an established therapy for massive Table-II: Association between outcome and independent variables. Variables Outcome X 2 Results Alive(n=20)(%) Dead (n=5)(%) Gender Male 15 (75%) 4 (80%) p=0.811 Femal 5 (25%) 1 (20%) ddimer <200 1 (5%) 1 (20%) >200 - < (50%) 4 (80%) p=0.184 >400 - <800 8 (40%) (5%) 0 NYHA I 2 (10%) 0 II 10 (50%) 0 p=0.05 III 4 (20%) 4 (80%) IV 4 (20%) 1 (20%) DVT Yes 4 (16%) 1 (20%) p=0.57 No 16 (84%) 4 (80%) Echo Dilated RA/RV 15 (75%) 5 (100%) p=0.75 Normal 5 (25%) 0 Treatment SK 8 (40%) 4 (80%) Heparin 9 (45%) 0 p=0.162 tpa 3 (15%) 1 (20%) with massive pulmonary embolism, 50% died with in 30 minutes, 70% died within 1hour, and more than 85% died within 6 hours of the onset of symptoms. Therefore, the window for obtaining a definitive diagnosis is small. In an optimal setting, the diagnosis of pulmonary embolism can be made on the basis of the history and physical examination along with selective tests, such as electrocardiography (ECG) to rule out myocardial infarction, chest radiography to rule out pulmonary embolism 17,18,28. Definitions of submassive PE vary in literature and intermediate risk PE is sometimes used in preference to submassive. It is defined as acute PE without systemic hypotension (SBP >90 mmhg but with RV dysfunction or myocardial necrosis) 28. In PEITHO trial intermediate risk PE was defined as presence of RV dysfunction or a positive Troponin 17. In MOPPET trial moderate PE was defined as the presence of signs and symptoms of S72

76 Tissue Plasminogen Activator, Heparin And Streptokinase Pak Armed Forces Med J 2018; 68 (Suppl-1): S69-S74 PE plus computed tomographic pulmonary angiographic involvement of >70% involvement of thrombus in >2 lobar or left or right main pulmonary arteries or by a high probability ventilation/perfusion scan showing ventilation/ perfusion mismatch in >2 lobes 12,18. Sub-massive PE accounts for 20% of all PEs with in-hospital mortality of 2-5%. There is evidence from registries data that the short term mortality rate directly attributable to sub-massive PE treated with heparin anticoagulation is probably <3%. It accounts for most deaths from PE, leads to long term morbidity especially chronic pulmonary hypertension and worst functional outcome. Cho JH et al, found that haemodynamically stable patients with PE, 37% have RV dysfunction on echo and also found higher short term mortality in this group (Odds ratio 2.29; 13.7 vs 6.5 without RV dysfunction) 15. RV dysfunction and elevated troponins are also predictors of poor outcome in sub-massive PE 18. As such a smaller PE in a patient with poor cardiopulmonary reserve could produce similar outcomes to a larger PE in a patient without prior cardiopulmonary disease 17. The use of thrombolytic agents for the treatment of sub-massive PE is somewhat debateable the limited documented benefit (e.g. improved hemodynamics, potential for less chronic pulmonary hypertension) must be weighed against the increased risk of lifethreatening hemorrhage and the availability of other therapies (e.g. catheter-directed thrombolysis or clot retrieval) 25. The present study was conducted to document efficacy of thrombolytic and anticoagulant agents in submassive PE. We used Streptokinase and tissue plasminogen activator and heparin and studied their use in terms of efficacy, resolution of symptoms, improvement in haemodynamic profile and echocardiographic parameters. This is an ongoing study and presently data of initial twenty five patients is being analyzed and presented. Streptokinase was used in 12 patients in a dose of 250,000 initial bolus followed by 100,000 units/hour for next 24 hour. Out of these twelve patients, 8 survived and four succumbed to their illness. Tissue plasminogen activator (tpa) was used in four patients in a dose of 100 mg over 2 hours preceded by 10 mg bolus. Out of these four patients, three made an uneventful recovery and one patient died. In the remaining nine patients only heparin was use in a dose of 18 units /Kg/hour preceded by intravenous bolus of 5000 units. Tissue plasminogen activator was used preferentially in young soldiers who developed venous thromboembolism (VTE) at high altitude and later confirmed on CT pulmonary angiogram. The patient who died after tpa administration was because of massive haemoptysis which is in line with higher bleeding risk after thrombolysis 1,15,27. Patients who were given heparin only did reasonably well as no patient died in this group. This was well demonstrated in earlier studies like MAPPET-3 trial which compared heparin with alteplase in sub-massive pulmonary embolism and showed no difference for in-hospital mortality (3.4% versus 2.2%; p=0.71) 27. However, in PEITHO trial which compared Heparin with Tenecteplase, substantial reduction in combined end point of early mortality or haemodynamic collapse was seen but at the cost of significant increase in major haemorrhage (including intracranial haemorrhage) 17. CONCLUSION Cardiologists may be asked to manage patients with massive and sub-massive PE because cardiovascular medical specialists are trained to treat hemodynamic derangements with a variety of interventional and pharma- cological approaches. A rapid and accurate assessment of risk and a decisive treatment plan should be established. Fortunately, fibrinolysis, catheter intervention, and possible col-laboration with cardiac surgeons for desperately sick patients are tools that will assist cardiovascular specialists in maximizing the likelihood of prompt and complete recovery in these seriously ill patients. CONFLICT OF INTEREST This study has no conflict of interest to be declared by any author. S73

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78 Open Access Trans Catheter Pulmonary Balloon Valvuloplasty Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S75-S80 IMMEDIATE THERAPEUTIC OUTCOMES OF TRANS CATHETER PULMONARY BALLOON VALVULOPLASTY FOR CRITICAL PULMONARY STENOSIS Syed Asif Akbar Shah, Mehboob Sultan, Khurram Akhtar, Aziz Ahmed, Nadeem Sadiq, Amjad Mahmood, Ali Nawaz, Kamal Saleem Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To share a single centre experience of percutaneous balloon valvuloplasty for critical pulmonary valve stenosis. Study Design: A retrospective cross sectional study. Place and Duration of study: This study was conducted at AFIC/NIHD Rawalpindi, from Aug 2010 to Dec Materials and Methods: In this study a retrospective analysis of all consecutive infants who underwent BVP for critical PVS was carried out to assess its immediate efficacy and safety. Results: A total of 28 infants diagnosed with critical PVS were enrolled. Male to female ratio was 1.5:1. Pulmonary valve (PV) annulus mean diameter was 12 ± 4.2. Mean age of pulmonary BVP was 6 ± 8 years and average balloon to PV annulus ratio was Immediate success was achieved in 100% by significant reduction of transpulmonary valve peak pressure gradient (p<0.001). One death occurred 5 days after the procedure, 21.4 % had complications and none of our patient needed re-intervention in the immediate post procedure period or before discharge. Conclusion: Percutaneous BVP was found very effective and safe intervention for critical narrowing of pulmonary valve in order to gain time for further intervention needed in a high risk age group for surgery. Balloon pulmonary valvuloplasty is equally successful in neonates as well as in adult subjects and is the treatment of choice for relief of pulmonary valve stenosis. Surgery should be reserved for unsuccessful BVP. Life-long followup to identify the significance of residual pulmonary insufficiency is indicated. Keywords: Critical pulmonary valve stenosis, Percutaneous balloon valvuloplasty, Patent ductus arteriosus This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION PVS has a reported incidence of 0.6 to 0.8 per 1000 live births, and occurs in 50% of all patients with congenital heart disease in association with other CHD s 1,2. Critical pulmonary stenosis with an intact ventricular septum is relatively uncommon but demands urgent intervention because of high risk of mortality. It is defined as very severe pulmonary valve narrowing with some flow across the valve resulting in duct dependant pulmonary circulation and cyanosis or RV dysfunction with supra systemic RV pressures 3-7. Cyanosis is because of right to left shunting at atrial level secondary to decrease RV compliance because of RV hypoplasia or hypertrophy. BPV is a preferred therapeutic alternative to surgical valvotomy in patients with Correspondence: Dr Syed Asif Akbar Shah, Department of PAEDS Cardiology, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan ( Saashah16@hotmail.com) isolated congenital pulmonary valve stenosis 3-6. It results in immediate reduction of the valvular obstruction, it is safe and provides equivalent or better sustained gradient relief when compared to surgical valvotomy 4,5,12. Since the first description of balloon pulmonary valvuloplasty in 1982 by Kan 8, several have applied this technique with great success in all age groups Recommended use of a balloon/annulus ratio of 1.2 to 1.5, should give better results 10. In neonates gradational BVP and balloon annulus ratio not greater than 1.3 can significantly reduce incidence of PR in long term Success rates of balloon pulmonary valvuloplasty in infants with critical PS have been reported to be 55% to 94% Five to ten percent might need surgery to relieve any residual valvular or sub valvular stenosis and 25-30% will need a percutaneous re-intervention in the longterm 17,21,22. Previous surgery and pulmonary valve dysplasia are not contra- S75

79 Trans Catheter Pulmonary Balloon Valvuloplasty Pak Armed Forces Med J 2018; 68 (Suppl-1): S75-S80 indications for balloon valvuloplasty 10,23. Complication can be higher in infants and neonates but are rare in children and adults and also relatively less as compared to other treatment options like PDA stenting 25-27, surgical valvotomy and systemic to PA shunt. Neonatal mortality is approx 3% and morbidity is on average 10% 25,26. Venous injury, myocardial dissection and necrotising enterocolitis (NEC) are leading causes of mortality. RVOT perforation, cardiac tamponade, PV and TV regurgitation, stroke, seizures, endocarditis, septic shock and abrupt closure of ductus are some important complications during BPVP 26. The aim of this study was to assess the immediate results of percutaneous balloon valvuloplasty in all age groups diagnosed with critical pulmonary valve stenosis in a tertiary-care setting. MATERIAL AND METHODS A retrospective cross sectional analysis of all consecutive patients from neonatal to adult age group who underwent percutaneous balloon valvuloplasty for critical pulmonary valve stenosis from Aug 2010 to Dec 2015 at AFIC/NIHD was done. We identified 28 patients who fulfilled the following criteria for critical pulmonary valve stenosis: Severe narrowing of pulmonary valve with some antegrade flow across it resulting in duct dependant pulmonary circulation, cyanosis and RV dysfunction or hypoplastic RV or supra systemic RV pressures as well as those who have undergone percutaneous balloon valvuloplasty within 8 weeks of age. Patients with predominantly subvalvular, supravalvular or branch PS, pulmonary atresia, severe tricuspid annulus hypoplasia (< 4 Z score), coronary circulation dependent on the right ventricle, post surgery critical pulmonary stenosis, patients with any other CHD that needed treatment in the neonatal period and patients with large ASD or VSD (but not PFO or small VSD) were excluded from the study. Clinical records of the selected patients were retrospectively analysed in pre-intervention, intervention, and immediate post intervention period. In the pre-intervention period age, sex, height, weight, symptoms, oxygen saturation in room air and TTE assessment by an experienced cardiologist for existence and direction of shunt across atrial septal defect/ patent foramen ovale, PDA patency and dependancy, tricuspid annulus diameter, right ventricle size, morphology and contraction, pulmonary valve morphology and flow, largest pulmonary annulus diameter measured in systole, maximum peak instantaneous systolic PG across the PV quantified by the modified Bernoulli equation, presence or absence of sub valvular, supra valvular and branch PA s stenosis or any associated cardiac lesions was done. All patients had a well developed right ventricle with a tricuspid annulus size ranging from 9-25 mm (mean ± SD, 11.6 ± 1.8). Patients with severe desaturation were maintained on oral Prostaglandin E2 1 to 2 hrly before, during, and shortly after intervention by a dose of 25 microgram/kg/dose to maintain arterial duct patency. During intervention we recorded age, pre and post percutaneous balloon valvuloplasty pulmonary variables such as trans valvular peak pulmonary gradient, right ventricle pressure, procedural details such as diameter of the largest balloon and ratio of the largest balloon/diameter of the pulmonary annulus, and complications during cardiac catheterisation. Patients were analysed 24 hr after the procedure and on discharge from hospital for oxygen dependance, maximum peak instantaneous systolic PG across the PV, degree of PR, RVF reversal of shunt across PFO and need for percutaneous or surgical intervention. Procedures were performed under general anaesthesia according to the previously described technique 4,5. Venous and arterial accesses were placed by cannulation of the femoral vessels. After cannulation of the femoral vein, right cardiac catheterisation was performed. Pressure gradients were measured, followed by right ventricular angiography in lateral projection to measure the diameter of the pulmonary valve S76

80 Trans Catheter Pulmonary Balloon Valvuloplasty Pak Armed Forces Med J 2018; 68 (Suppl-1): S75-S80 annulus in systole. The valvuloplasty balloon was centred on the annulus valve and inflated until complete resolution of the waist. Finally, pressure measurements were obtained, and a final angiography was performed. Safety of the procedure was assessed by mortality and major complications; success of the procedure was determined by the reduction in pulmonary transvalvular peak gradient after percutaneous balloon valvuloplasty for values 50% of pre ballooning gradient and by the need for percutaneous re-intervention or surgical intervention before hospital discharge. Data Analysis Continuous variables were expressed as pulmonary BVP for critical PVS at our institute. sixteen patients (57.1%) were below 1 year of age. Age of the patients ranged from 1 day to 30 years with a mean age of 6 ± 8 years. There were 17 males (60.7%) and 11 females (39.2%). Weight of the patients ranged from 2.5 to 55 kg with a mean of 17 ± 16 kg. Height of the patients ranged from 51 to 165 cm with a mean of 93 ± 41cm. Calculated body surface area (BSA) ranged from 0.18 to 1.6. The PV annulus measured from the left lateral angiogram had a mean of 12 ± 4.2 (fig-1). The balloon sizes used had a mean of 14 ± 5.7mm with balloon/ annulus ratio ranging from 1.2 to 1.5. Progressive dilatation or gradational BVP of the critical stenosed pulmonary valve was Figure-1: Contrast injection via judkins right catheter at RVOT in LAO 90 degree (Left lateral view) showing a very narrow jet of contrast going across the critically stenosed pulmonary valve. Figure-2: Pre dilatation being done with 12 x 40mm VACS-II balloon over Amplatzer super stiff wire across the critically stenosed pulmonary valve. Figure-3: Final dilatation with a bigger balloon (22 x 40 mm VACS-II) over Amplatzer super stiff wire across critically stenosed pulmonary valve. ranges and Mean ± Standard deviation. Qualitative variables were expressed as percentages. A paired Student t test was used for the comparison of different variables before versus immediately after BVP. All statistical analyses were performed using SPSS (v 20.0; IBM SPSS Software for Predictive Analytics; SPSS, Chicago, IL, United States of America). A p-value <0.05 was considered statistically significant. RESULTS Over the span of 6 years and 5 months from Aug 2010 to Dec 2015, 28pt s underwent done in 5 pt s (17.8%) of neonatal age group by using low profile coronary angioplasty balloons over coronary wires deployed across the pulmonary valve and was also done in one 30 years old by using 12 x 40 mm balloon for pre dilatation (fig-2 & 3) to facilitate passage of catheters and guide wires for definitive BVP. The peak to peak trans valvular PG measured during the procedure dropped significantly from a mean of 98 ± 38 mm Hg before performing the BPV to a mean of 29 ± 14 mmhg after the procedure (p-value<0.001). The immediate S77

81 Trans Catheter Pulmonary Balloon Valvuloplasty Pak Armed Forces Med J 2018; 68 (Suppl-1): S75-S80 success rate defined as the drop in the trans valvular peak to peak PG to more than or equal to 50% of the baseline measurement was achieved in 93% of the cases. Procedural time ranged from min with a mean of 62 ± 42 min s and mean fluoroscopy time was 20 ± 18 min s. There was a highly significant drop in trans valvular pulmonary gradient on trans thoracic echocardiogram from a mean of ± 41mmHg to a mean of 30.6 ± 15.4 mm Hg 24 hrs after BPV (p-value<0.001), this drop in the PG was maintained at discharge. Although incidence of PR significantly increased immediately after the BPV in some of patients (<30%), severity of PR correlated with the increase in balloon/annulus ratio. Regarding complication during BPV, one (3.5%) patient had VT responding to medical treatment, 4 (14.2%) had non fatal cardiac arrest responding to CPR and 2 patients had suboptimal results (<50% reduction in trans valvular peak PG. The intraprocedure mortality rate was zero but one patient died later due to sepsis and DIC needing mechanical ventilation. DISCUSSION Congenital isolated pulmonary valve stenosis is one of the first congenital cardiac defect for which balloon valvuloplasty has become the treatment of choice and preferred therapeutic alternative 3-6 in all age groups regardless of valve morphology 28. Since 1984 when Tynan et al 29 described the results of percutaneous balloon valvuloplasty in neonates with critical pulmonary valve stenosis many have shown its efficacy and success as first-line treatment for critical PS 3,5,6,12,14-17,28. In the present study successful immediate outcome of BPV was reported in 93% of the cases. These results are in close agreement with Loureiro et al 3, Alsawah 7 as well as Luo and and his colleagues 30 who have studied BPV in neonates with CPS with immediate success rates of 91.7%, 94.4% and 100% respectively. The significant immediate reduction of pulmonary trans valvular PG, RVSP and the PG across the RVOT in the current study was consistent with data published by Karagoz et al 31, Saad et al 32, zeevi et al 33 and Loureiro et al 3. Achieving an immediate gradient reduction by using oversized balloons (20 to 40% larger than the annulus) was consistent with results achieved by Benjamin zeevi et al 33. Hundred percent success was achieved by gradational BVP of the critical stenosed pulmonary valve in 5 pts (17.8%) of neonatal age group in contrast to 75% reported by Janusz et al 34 Pre dilatation was necessary in 29.1% cases reported by Alsawah et al 7 and also described by Li and colleagues 35. Contrary to other studies data published by Saad et al 32 who reported immediate post procedure PR in 64% and Werynski et al 36 in 39.5% of children with critical PS, in our patients significant PR (moderate to severe) was observed in less than <30% of cases in the immediate post procedure period and at discharge which is in agreement with the recent findings of Loureiro et al 3 who found moderate PR in 25% and severe in 4.2% post BVP. None of our patients required any additional percutaneous or surgical intervention during or after BVP before discharge contrary to 2.7% requiring PDA stent implantation during the BVP procedure reported by Alsawah et al and also in some by Mortera and assistants 37, Schneider and colleagues 38. Following successful BPV some of our patients were still oxygen or oral PGE2 dependent, to maintain adequate arterial oxygen saturation. This has been reported before by many authors 6,7,39,40 and thought to be secondary to reactive infundibular stenosis as well as impaired RV compliance resulting in right to left shunt across PFO. These patients were treated with propranolol while on oxygen and oral PGE2 with gradual reduction of PGE2 or propranolol only in mild cases. Our experience in that situation was consistent with that of Alsawah et al 7, Buheitel and coworkers 41, Freund and colleagues 42. In our study major complications were observed in 21.4% of patients and only one pt died of complications (3.5%) in the post BVP period,which are almost similar results to what has been reported by Loureiro et al (14 and 31%) S78

82 Trans Catheter Pulmonary Balloon Valvuloplasty Pak Armed Forces Med J 2018; 68 (Suppl-1): S75-S80 (3), Karagoz et al ( 2.7 to 25%) 31 and Alsawah et al 7 respectively. Relatively low mortality rate is because of inclusion of older age groups in our study like reported with almost no mortality by Rao PS 5. CONCLUSION BVP for critical PS was found relatively safe and effective procedure which can be successfully used as primary procedure for critical PS at all ages and a high success rate with low mortality and morbidity can be achieved by careful and sensible attention to various procedural details. Miniaturatization of balloon/catheter systems and refinement of technique can further reduced the complication rate. 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84 Open Access Dyspnea in Pregnancy Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S81-S85 DYSPNEA IN PREGNANCY-INCIDENCE AND COMMON CAUSES Asma Ansari, Fayyaz Hussain, Riffat Sultana*, Hafsa Khalil** Combined Military Hospital Kharian/National University of Medical Sciences (NUMS) Pakistan, *Armed Forces Institute of Radiology & Imaging/ National University of Medical Sciences (NUMS) Rawalpindi Pakistan, **Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine incidence of dyspnea in pregnant patients and major underlying causes in these patients and relation of grade of dyspnea and disease with mortality. Study Design: Prospective cohort study. Place and Duration of Study: Obstetrics and Gynaecology ward of Armed Forces Institute of Cardiology/ National Institute of Heart Disease (AFIC/NIHD) and Obstetrics and Gynaecology department of Military Hospital Rawalpindi, from Jan 2017 to Jun Material and Methods: All patients complaining of dyspnea NYHA II-IV were enrolled from second trimester onwards (>13 weeks). Those undergoing miscarriage, termination of pregnancy and already diagnosed cardiac, pulmonary, thyroid or blood disorders were excluded. Thorough physical examination and laboratory tests to exclude common causes of dyspnea like blood Complete Picture, thyroid function tests, x-ray chest and Echocardiography were done. Patients were followed every month till delivery. Results: Over all incidence of dyspnea was 40% amongst all obstetric patients. In 35% patients no cause was found and 5% had an underlying cause for dyspnea. Mean age 28.5 ± 5 years, Parity 2 ± 1.4, Period of gestation (POG) at diagnosis was 29.5 ± 3.3 weeks, POG at delivery was 36 weeks ± 1.5 weeks, frequency of NYHA class 2,3,4 was 68%, 28% and 4% respectively. Most common cause of dyspnea was anemia 1050 (87.5%), Cardiac disease 87 (7.2%), pulmonary disease 35 (2.9%) thyroid disease 8 (0.66%) and others 20 (1.66%). Mortality ratio was 220/100,000 live births. Out of mortalities 8% were due to cardiac disease compared to 0.3% due to anemia. All the mortalities were in patients who presented with grade 3 and 4 dyspnea. Conclusion: Dyspnea should not be ignored as a normal symptom due to pregnancy changes. It could be the sole manifestation of underlying life threatening disease. Some diseases with a high prevalence like anemia can be identified and treated easily during antenatal period. Early recognition and evaluation can save many precious lives. Keywords: Cardiac disease, Dyspnea, Pregnancy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Dyspnea during pregnancy is quite common, occurring by most estimates in approximately 60% of women with exertion and less than 20% at rest 1. This symptom is so common that it usually is referred to as physiologic dyspnea. Dyspnea during pregnancy can be a result of the pregnancy itself however, other causes of dyspnea should be kept in mind including hematologic, cardiac, and pulmonary etiologies 2. The exact mechanism of dyspnea during pregnancy is not yet known, however, it may be due to increased metabolic needs or mechanical Correspondence: Dr Asma Ansari, Asst Prof, Obstetrics & Gynaecology, Combined Military Hospital Kharian Pakistan asmaansari31@gmail.com causes during pregnancy. Cardiopulmonary signs and symptoms of normal pregnancy may simulate heart disease. These include easy fatigability, palpitations and dyspnea. It has been reported that % of all pregnancies are complicated by cardiovascular disease 3, and although death is rare, cardiovascular disease is the biggest indirect cause of maternal death worldwide, with an attributable rate of two deaths per 100,000 in the UK and a similar rate in other countries 4. Cardiac assessment of the pregnant patient can be difficult as common symptoms of pregnancy, such as breathlessness and fatigue, can mimic cardiac symptoms. Other symptoms mimicking cardiac disease are orthopnea, chest pain, tachycardia and syncope. S81

85 Dyspnea in Pregnancy Pak Armed Forces Med J 2018; 68 (Suppl-1): S81-S85 Signs and symptoms which are abnormal in pregnancy include extreme breathlessness, marked edema, a fourth heart sound, diastolic murmurs, jugular venous pressure of >2 cm and a persistent tachycardia of >100 beats per minute 5. So any one of these should prompt further evaluation. Possible explanations for pregnancyassociated benign dyspnea include changes in chest wall conformation, diaphragm positioning, or altered respiratory center sensitivity 5. Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight babies. The prevalence of anemia among pregnant women living in urban areas is similar, ranging from 29% to 50% among pregnant women attending antenatal clinics in a large private, tertiary hospital in Karachi 6. Anemia has a variety of contributing factors including nutritional, genetic, frequent pregnancies, multiparity, abortions and infectious disease, however, iron deficiency is the cause in 75% of cases 7. The major causes of iron deficiency include insufficient intake of iron-rich foods and poor bioavailability of consumed iron in relation to the need during pregnancy. Prevalence of iron deficiency anemia among women in developing countries was calculated from 40% to 88% 8. The prevalence of hyperthyroidism in pregnancy is about 0.2% to 2.5% 9. The most common cause is Graves' disease. Production of thyroid hormones and iodine requirement both increases by approximately 50% during pregnancy as part of physiology 9. American Thyroid Association recommends >2.5 and >3.0 µiu/ml as cutoff range for diagnosis of hypothyroidism during the first and later part of pregnancy, respectively 10. Chest infections including pneumonia, tuberculosis are common amongst pregnant patients also due to high prevalence in this area. Amniotic fluid embolism is a rare (1 case per ,000 births) but potentially catastrophic complication, with a mortality rate of 10-80% 11. Pulmonary edema may rarely occur in association with 3% of preeclampsia cases. Asthma is one of the most common coexisting medical conditions affecting reproductive-aged woman. Pregnant patients are at risk of developing ARDS from obstetric complications and from nonobstetric conditions. Obstetric complications, such as amniotic fluid embolism, chorioamnionitis, trophoblastic embolism, and placental abruption, can produce acute lung injury 11. There is also anxiety related dyspnea that occurs in a background of emotionally stress which is known as psychogenic dyspnea 12. This study was conducted to determine the incidence of dyspnea amongst pregnant patients which are a vulnerable group, as some signs and symptoms could be ignored considering them due to pregnancy. Life threatening underlying Figure-1: Incidence of dyspnea with a cause. causes which could endanger the life of mother and fetus will remain undiagnosed if their importance in not understood. MATERIAL AND METHODS This was a prospective cohort study conducted at obstetrics and gynecology ward of Armed Forces Institute of Cardiology/National Institute of Heart Disease (AFIC-NIHD) and obstetrics and gynecology department of Military Hospital Rawalpindi from Jan to Jun All the pregnant patients presenting with New York Heart Association Classification class >II dyspnea were included by consecutive non probability sampling technique after informed consent and Institutional Review Board approval, from S82

86 Dyspnea in Pregnancy Pak Armed Forces Med J 2018; 68 (Suppl-1): S81-S85 second trimester (13 weeks) onwards with a live fetus. Those undergoing miscarriage, termination of pregnancy and already diagnosed cardiac, pulmonary, thyroid and blood disorders or past history of cardiac surgery were excluded. Thorough history, physical examination and laboratory tests to exclude common causes of dyspnoea like blood Complete Picture, Thyroid function tests, x-ray chest, ECG and echocardiography were done. For each participant Echocardiography parameters including ejection fraction volume (EF), valvular function, pulmonary pressure and ventricular function were investigated to exclude structural cardiac disease and electrocardiogram was done to exclude rhythm disorders. Blood complete pregnancy, type of delivery, and general condition were recorded and expressed as mean ± SD. Data analysis procedure including frequency and percentage were calculated. After data collection, the relation between dyspnea and mortality was evaluated. RESULTS A Total of 1200 obstetric patients were enrolled during the study period who had dyspnea ranging from NYHA>II. Over all incidence of dyspnea was 40% amongst all obstetric patients. In 35% patients no cause was found and 5% had an underlying cause for dyspnea as shown in fig-1. Mean age 28.5 ± 5 years, Parity 2 ± 1.4, Period of gestation (POG) at Figure-2: Major causes of dyspnea. picture was done to grade Patients into severe anemia (hemoglobin concentration less than 7.0 g/dl), moderate ( g/dl) and mild anemia (10.0 to 11.0 g/dl). Reference ranges for diagnosing thyroid disorders were first trimester, miu/second trimester, miu/land third trimester, miu/l. X-ray chest was done with abdominal shielding only if clinically indicated. Data Analysis Patients were followed every month till delivery or at development of deterioration of NYHA class or fetal or maternal complications. Demographic data including age, parity, Postdelivery data including period of gestation of diagnosis was 29.5 ± 3.3 weeks, POG at delivery was 36 weeks ± 1.5 weeks, frequency of NYHA class 2,3,4 was 68%, 28% and 4% respectively. As shown in fig-2 most common cause of dyspnea was Anemia 1050 (87.5%), Cardiac disease 87 (7.2%), Pulmonary disease 35 (2.9%) Thyroid disease 8 (0.66%) and others 20 (1.66%) as shown in fig-2. Iron deficiency anemia was the cause in 998 (95%), 32 (3%) had thalassemia, 10 (1%) megaloblastic anemia and 10 (1%) had mixed picture. The etiology of maternal cardiac lesions was 96 (57%) acquired, 40 (23%), congenital 25 (15%), arrhythmias and 9 (5%) had cardiomyopathy. Of pulmonary diseases 28 (80%) were asthmatic, 4 (11.6%) infections including S83

87 Dyspnea in Pregnancy Pak Armed Forces Med J 2018; 68 (Suppl-1): S81-S85 tuberculosis and pneumonia, 2 (5.7%) had pulmonary edema and 1 (2.8%) developed acute lung injury secondary to obstetric complications. Less common other causes of dyspnea were sepsis 18 (90%), amniotic fluid embolism 1 (5%) and ruptured gall bladder in 1 (5%) patient. Mode of delivery was 37% LSCS, 52% vaginal delivery, 9.6% instrumental vaginal delivery and 1.4% assisted breech delivery. Mortality ratio was 220/100,000 live births. Out of mortalities 8% were due to cardiac disease compared to 0.3% due to anemia. All the mortalities were in patients who presented with grade 3 and 4 dyspnea. DISCUSSION Dyspnea or breathing discomfort may be a benign symptom of the pregnancy and can exist in the absence of cardiac and pulmonary conditions. Although common during pregnancy dyspnea is almost always limited to the awareness of breathing, rather than the uncomfortable awareness of the necessity for breathing. As in this study 35% patients had physiological dyspnea which is similar to another study by Sahasrabudhe TR 12. It is important to consider the cause of dyspnea, however, because it can herald more severe conditions such as pulmonary edema, pulmonary embolism, pneumothorax, pneumonia, or worsening asthma. The pregnant patient also can suffer cardiac disease, or may have hematologic problems which can produce significant anemia and lead to dyspnea. Ultimately, however, any organic condition which can cause dyspnea in the non-pregnant patient could affect the pregnant patient. In the study by Ruest et al, it was shown that dyspnea is a common finding even in normal pregnancies, while many cardiac and pulmonary diseases manifest with this symptom 13. Weinberger et al stated that dyspnea in a pregnant woman brings up the question whether the patient has certain degrees of an underlying cardiac or pulmonary disease or if is an isolated symptom induced by pregnancy 14. In total, 60-70% of pregnant women experience dyspnea during pregnancy 14, which is most common during the first and second trimesters as compared to this study in which dyspnea was in 35% patients only, as grade 1 dyspnea was excluded. In a study 85% of patients with dyspnea were due to asthma, pneumonia, cardiac ischemia, pulmonary disease, heart failure, obstructive airway disease and psychological problems 15 as compared to this study where anaemia was the leading csuse of dyspnea in 87.5% cases. Regarding the great importance of cardiac diseases and their related morbidity and mortality, mainly during pregnancy and due to unknown nature of many such diseases, the European Cardiac Society Guideline on cardiac disease in pregnancy recommended precise evaluation in pregnant women with dyspnea 16,17. In this study population majority were anemic and a major contributor towards symptoms of breathing difficulty.in another study 90.5% ptients were anemic 18. In Pakistan the prevalence of anemia among pregnant women living in urban areas was reported from 29% to 50%. Some studies have shown that the frequency of Iron deficiency anemia varies in the pregnant women of Karachi (64%), Lahore (73%) and Multan (76%) 19,20. Grades of anemia in these patients were 75.0% mild anemia (hemoglobin from 9.0 to 10.9 g/dl) and 14.8% moderate anemia (hemoglobin from 7.0 to 8.9 g/dl). Only 0.7% were severely anemic (hemoglobin <7.0 g/dl). Pulmonary disease was responsible for dyspnea in 2.9% of patients which is similar to other studies 21. The prevalence of hyperthyroidism in pregnancy is about 0.2% to 2.5% 10 as compared to this study which shows incidence of 0.66%. Other less common causes of dyspnea were responsible for 1.66% cases 22. Out of mortalities 8% were due to cardiac disease compared to 0.3% due to anemia. Global Mortality ratio is 210/100,000 births. In developed world MMR is 14/100,000 and according to demographic survey of Pakistan mortality ratio is 176/100, In this study Mortality ratio was 220/100,000 live births which S84

88 Dyspnea in Pregnancy Pak Armed Forces Med J 2018; 68 (Suppl-1): S81-S85 is high showing that dyspnea is a symptom not to be ignored. Out of mortalities 8% were due to cardiac disease compared to 0.3% due to anemia. Cardiac disease being the leading indirect cause of maternal mortality as shown by other studies 24. Contribution of this study is highlighting the importance of dyspnea as an important symptom in pregnant patients which merits further investigations. Anemia is a public health problem in our country as shown by high incidence in this study but underlying cardiac disease is a major contributor towards maternal mortality and antenatal period is an excellent opportunity to identify and treat these causes for a better maternal and neonatal outcome. Limitation was that study population was subjectively graded and investigated for limited causes. CONCLUSION Dyspnea should not be ignored as a normal symptom due to pregnancy changes. It could be the sole manifestation of underlying life threatening disease. Some diseases with a high prevalence like anemia can be identified and treated easily during antenatal period. Early recognition and evaluation can save many precious lives. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Laviolette L, Laveneziana P, ERS Research Seminar Faculty. Dyspnoea: A multidimensional and multidisciplinary approach. Eur Respir J 2014; 43(6): Dyspnea in pregnancy. Shih-Yi Lee Ding-Kuo Chien Chien-Hsuan Huang Shou-Chuan Shih Wei-Cheng Lee. Taiwan J Obstet Gynecol 2017; 56(4): Ruys TP, Cornette J, Roos-Hesselink JW. Pregnancy and delivery in cardiac disease. J Cardiol 2013; 61(2): Ruys TP, Roos-Hesselink JW, Hall R, Subirana-Domenech MT, Grando-Ting J, Estensen M, et al. Heart failure in pregnant women with cardiac disease: Data from the ROPAC. Heart 2014; 100(3): Choi HS, Han SS, Choi HA, Kim HS, Lee CG, Kim YY, et al. Dyspnea and palpitation during pregnancy. Korean J Intern Med 2001; 16(4): Barroso F, Allard S, Kahan BC, Connolly C, Smethurst H, Choo L, et al. Prevalence of maternal anaemia and its predictors: A multi-centre study. Eur J Obstet Gynecol Reprod Biol 2011; 159(1): Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for : A systematic analysis of population-representative data. Lancet Glob Health 2013; 1(1): e Balarajan Y, Ramakrishnan U, Özaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. Lancet 2011, 378(9809): Thienpont LM, Van Uytfanghe K, Beastall G, Faix JD, Ieiri T, Miller WG, et al. Toussaint B IFCC working group on standardization of thyroid function tests. Report of the IFCC Working Group for Standardization of Thyroid Function Tests; Part 1: Thyroid stimulating hormone. Clin Chem 2010; 56: Krassas GE. Poppe K. Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010; 31: Pereira A, Krieger BP. Pulmonary complications of pregnancy. Clin Chest Med 2004; 25(2): Sahasrabudhe TR. Psychogenic dyspnea. Med J DY Patil Univ 2013; 6: Ruest B, Keller D, Kaplan V, Kunz-Caflisch I. [Dyspnea in pregnancy]. Praxis (Bern 1994). 2011; 100(7): Weinberger SE. Dyspnea during pregnancy: Uptodate; Available from: Bidad K, Heidarnazhad H, Pourpak Z, Ramazanzadeh F, Zendehdel N, Moin M. Frequency of asthma as the cause of dyspnea in pregnancy. Int J Gynaecol Obstet 2010; 111(2): European Society of G, Association for European Paediatric C, German Society for Gender M, Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy: The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011; 32(24): Makino Y, Matsuda Y, Mitani M, Shinohara T, Matsui H. Risk factors associated with preterm delivery in women with cardiac disease. J Cardiol 2012; 59(3): Pushpa OL, Vinod DK, Prakash LG, Ashok PK. A study of prevalance of anemia and socio demographic factors associated with anaemia among pregnant women in Aurangabad city, India. Ann Nigerian Med 2012; 6: Rakhshanda T, Talha BA, Hafiza SA, Saba M, Asif H. Prevalence of anemia and its main determinants among primigravidae in antenatal population of a tertiary care hospital of Lahore. Pak J Med Health Sci 2015; 9(3): Noronha JA, Al Khasawneh E, Seshan V, Ramasubramaniam S, Raman S. Anemia in pregnancy consequences and challenges: A review of literature. J S Asian Fed Obstet Gynecol 2012; 4: Mighty H. Acute respiratory failure in pregnancy. Clin Obstet Gynecol 2010; 53(2): Fong A, Chau CT, Pan D, Ogunyemi DA. Amniotic fluid embolism: Antepartum, intrapartum and demographic factors. J Matern Fetal Neonatal Med 2015; 28(7): Maternal mortality ratio (modeled estimate, per 100,000 live births) WHO, UNICEF, UNFPA, World Bank Group, and the United Nations Population Division. WHO; Trends in Maternal Mortality: 1990 to Geneva, World Health Organization, World Health Organization. Trends in Maternal Mortality: 1990 to Estimates. Developed by WHO, UNICEF, UNFPA and The World Bank. Geneva: WHO; S85

89 Open Access Blood Transfusions in Coronary Artery Bypass Surgery Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 MEDIASTINAL BLEEDING AND BLOOD TRANSFUSIONS IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS SURGERY PERFORMED WITH OR WITHOUT CRDIOPULMONARY BYPASS Muddasar Noor, Farrah Pervaiz, Muhammad Afsheen Iqbal, Muhammad Waseem, Asif Mahmood Janjua, Kanwal Afreen*, Aysha saddiqa, Rehana Javaid Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Combined Military Hospital/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the rate of postoperative bleeding and blood transfusions in patient undergoing coronary artery bypass surgery for coronary artery disease during OPCAB or conventional CABG. Study Design: Comparative cross-sectional study. Place and Duration of Study: Adult Cardiac Surgery Departments of Armed Forces Institute of Cardiology & National Institute of Heart Disease (AFIC/NIHD) Rawalpindi, Pakistan from 1 July 2017 to 31 Dec Material and Methods: Two hundred patients undergoing coronary artery bypass surgeries performed with (Conventional CABG) or without cardiopulmonary bypass. (Off pump CABG /OPCAB) were enrolled in the study and were divided into two equal groups. All procedures were elective. Careful monitoring was carried out on hourly basis. The rate of postoperative chest drainage and number of blood transfusions received were measured in both groups. Results: As compared to the OPCAB group, the patients in CPB group required ion tropic support for a longer duration (29.6 ± 65.1 vs 60.9 ± 71.2, p-value <0.02). Similarly, the rate of chest drainage was significantly higher in conventional CABG Vs OPCAB (45% vs 30% p<0.026). Requirement of blood transfusion (RCC) was significantly higher in conventional CPB vs OPCAB group (1.6 ± 1.6 vs 1.0 ± 1.2, p-value 0.04). Mechanical ventilation time was almost same in both groups with median value of 6 hours. Conclusions: Our study concluded that the main advantages of OPCAB technique are that there is less amount of postoperative chest drainage and it makes it possible to decrease the number of blood transfusions after surgery. Keywords: Blood transfusion, Coronary artery bypass grafting, Cardiopulmonary bypass, Off-pump coronary artery bypass, On-pump coronary artery grafting, Red cell concentrate. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Ischemic heart disease is one the leading causes of death in the world 1,2. Coronary artery bypass grafting (CABG) remains the standard treatment option in patients with extensive coronary artery disease 3. The majority of cardiac procedures are carried out using the cardiopulmonary bypass (CPB), but those performed without, in the recent years, have relatively less rate of complications, as these avoid systemic inflammatory response syndrome (SIRS) produced by the use of extracorporeal Correspondence: Dr Mudassar Noor, Adult Cardic Surgery Dept, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan mudassarnoor82@gmail.com circuit 4-6. This systemic inflammation can involve many organs and is usually self-limiting. There is an ongoing debate regarding the clinical outcomes after on-pump versus off-pump coronary artery bypass (ONCAB versus OPCAB) surgery and postoperative bleeding remains a major concern. The aim of this retrospective study is to compare the effect of CPB, either used or not, on the rates of postoperative bleeding and packed red cell transfusions after coronary surgery, as these are closely related with increased hospital mortality and morbidity, patients survival, blood transfusion reactions, wound infections and sepsis 7-9. S86

90 Blood Transfusions in Coronary Artery Bypass Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 MATERIAL AND METHODS Patients All patients below the age of 70 years who underwent elective isolated CABG surgery using a median sternotomy approach at a tertiary care cardiac facility, between July 2017 and December 2017 were acquired from the adult cardiac surgery database. The decision to perform the operation, either on-pump or off pump was made by the operating surgeon. Patients with age of more than 70 years, redo surgeries, cases who were intended to be operated off-pump but were later converted to on-pump after initiation of coronary grafting, those having difficult coronary anatomy ending up in endarterectomy or venous patch plasty and patients with lateral thoracotomy incisional approaches were excluded. The study was approved by the hospital s institutional ethical review board. This study included 200 patients, 100 patients underwent coronary surgery with CPB (group-1) and 100 cases were subjected to OPCAB grafting (group-2). All patients included in the study were subjected to full history, local and general physical examination, routine laboratory investigations, imaging studies before surgery that included Chest x-rays, 2D-Echoes, Carotid Doppler. The primary endpoints of interest were packed red blood cell transfusions, re-operation rate for bleeding or cardiac tamponade, and 12 h and total postoperative chest tube drainage. Preoperative parameters which were analyzed included age, gender, Body Mass Index (BMI) and co-morbid conditions, whereas operative characteristics included cardiopulmonary bypass time and cross clamp time. Pre-operative Considerations In both groups, patients were using dual antiplatelet therapy in the form of Aspirin and Clopidogrel pre-operatively, which was stopped 3 days and 5 days before operation respectively. No patient received oral or parenteral anticoagulants before surgery. Anesthesia and Anticoagulation Management Patients in both groups, undergoing OPCAB or conventional CPB surgery, received the same anaesthetic regimen. In CABG group, before initiation of CPB, a bolus dose of IU/kg of heparin was given to achieve a kaolin activated clotting time (ACT) of at least 480 seconds. Additional heparin was infused on CPB if required. After termination of CPB, 3-4 mg/kg protamine was given to fully reverse the anticoagulant effect of heparin. In the OPCAB group, 150 IU/kg of heparin was administered before division of the internal mammary artery to maintain an ACT of seconds. On completion of anastomoses in patients undergoing OPCAB, 0.75 mg/kg protamine was given to partially reverse the heparin. Antifibrinolytics in the form of alpha aminocaproic acid were injected at the surgeon s discretion. Operative and Perfusion Procedure OPCAB surgery was performed through a median sternotomy approach. Stabilization of the target coronary artery was achieved by using either a compression device or suction apparatus. Operative blood was aspirated into a blood salvaging system to be concentrated, washed, and transfused if enough was collected. A perfusionist remained on standby for emergency institution of CPB if required. While, surgery in CPB group was performed through a full sternotomy incision using a membrane oxygenator and a roller pump. The circuit was primed with 2200 ml of Hartman solution or 1700 ml Hartman and 500 ml 4% albumin solution with 10,000 units of heparin. An addition of 10 g of mannitol was made while priming the circuit of CPB in patients who had a preoperative creatinine of >0.15 mmol/l. Institution of CPB was achieved by cannulating the ascending aorta and right atrium. After cross-clamping, antegrade or retrograde blood cardioplegia was infused for myocardial protection of the arrested heart. Minimum systemic temperatures ranged from 28 C to 34 C. Perfusionist preference determined whether all or part of the cardiotomy blood was S87

91 Blood Transfusions in Coronary Artery Bypass Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 returned to the CPB circuit or collected in a cellsaving device for subsequent processing. After weaning from CPB, the residual blood in the extracorporeal circuit was salvaged and processed either through a cell-saving device or simply bagged before patient reinfusion. At least two chest drains were inserted in the pericardium and pleura if internal mammary arteries were harvested. These drains were connected to a low Transfusion Protocol For patients in both groups, the decision to transfuse homologous packed RBCs was based on the patient s clinical assessment like pulse, blood pressure, urine output and/or a haematocrit (Hct) level (<20%). Postoperatively, blood transfusions were given when hemoglobin level fell to <10 g/dl. Table-I: Clinical characteristics and demographics (CPB vs OPCAB). Variables CPB n=100 OPCAB n=100 AGE (Mean ± SD) 57.5 ± ± 7.2 Gender n(%) Male Female 85 (84.2%) 16 (15.8%) 76 (76%) 24 (24%) BMI (Mean ± SD) 27.0 ± ± 5.4 NYHA Class I II III IV 28 (28 %) 29 (29%) 43 (43 %) NIL 23 (23%) 34 (34%) 43 (43%) NIL Hypertension 54 (54 %) 52 (52%) Diabetics 46 (46 %) 44 (44%) Smoking Ex-Smokers Current Smokers 21 (21 %) 11 (11%) 25 (25%) 7 (7%) Table-II: Angiographic data (CPB vs OPCAB). Variable CPB n=100 OPCAB n=100 Extent of Coronary artery disease Single vessel Double vessel Triple vessel 2 (2%) 14 (14%) 84 (84%) 5 (5%) 20 (20%) 75 (75%) Left Main stem disease >70% 17 (17%) 15 (15%) suction system (-20 cm H 2O) after closure of the chest. Total chest drainage was recorded as the volume of blood in the collection receptacle from closure of the chest until removal of the chest drains. Postoperative Care Treatment of patients undergoing on-pump or off-pump coronary surgeries followed a standardized care from operation to discharge irrespective of the type of procedure performed. Reoperation Protocol Re-exploration was performed if bleeding exceeded 400 ml/0.5 h, >300 ml/h, or >200 ml/h for 2 hours despite correction of any coagulopathies. Re-operations were also indicated if there were clinical signs of cardiac tamponade such as tachycardia, increasing central venous pressures, or decreasing urine output, usually associated with a sudden reduction in chest tube drainage. S88

92 Blood Transfusions in Coronary Artery Bypass Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 Data Collection and Statistical Analysis Statistical analyses were performed using SPSS version 23 with two tailed tests performed and a p-value<0.05 was considered significant. Data are summarized as the mean ± SD for continuous variables and as frequency and percentages for categorical variables. The two groups (CPB or CABG vs OPCAB) were compared using the Chi-square or Fisher exact test for categorical data and unpaired t tests. group, while 54 (54%) patients were hypertensive in the CPB group. In OPCAB group, 44 patients (44%) were known to be diabetic and the number was 46 (46%) in CPB group. 7 (7%) were smokers in OPCAB patients and there were 11 (11%) smokers in group-2. In OPCAB group, 23 patients (23%) had NYHA class I, 34 patients (34%) had NYHA class II, and 43 (43%) patients were having NYHA class III symptoms. While in CABG group, 28 patients (28%) had NYHA class Table-III: Intra operative data (CPB vs OPCAB). Variable CPB n=100 OPCAB n=100 p-value Ionotropic support (in Hrs) 0.02 (Mean ± SD) 60.9 ± ± 65.1 Chest Drain N (%) Less than 800 ml More than 800 mi 51 (51%) 49 (49%) 70 (70%) 30 (30%) 0.02 Blood Transfusion (RCC) Requirement 0.04 (Mean ± SD) 1.6 ± ± 1.2 Ventilation Time (in hrs) (Mean ± SD) 12.9 ± 25.2 (6) 10.6 ± 23.4 (6) 0.07 Table-IV: Post-operative complication (CPB vs OPCAB). Variable CPB n=100 OPCAB n=100 p-value Re-exploration for bleeding N (%) 12 (12%) 2 (2%) 0.02 ICU Stay Time (in hrs) (Mean ± SD) 67.6 ± ± Mortality N (%) 6 (5.9%) 5 (5%) 0.93 RESULTS Of the total 200 patients, 100 cases were included in each CABG or CPB group. Patients in both groups were similar in terms of demographic features, pre-operative characteristics, re-do operations and incidence of comorbid conditions. In OPCAB group, there were 76 males (76%) and 24 females (24%) with a mean age of 59.1 ± 7.2 years, whereas, in CPB group, there were 85 males (85%) and 16 females (16%), with a mean age of 57.5 ± 8.9 years. Fifty two patients (52%) had hypertension in OPCAB I, 29 patients (29%) had NYHA class II, and 43 (43%) cases were in NYHA class III (table-i). The patients in CPB group had tendency to have multi-vessel disease than those in OPCAB (off pump) group. In CPB group, there were 85 patients (85%) who had triple vessel disease vs 75 (75%) patients in OPCAB group, 20 patients (20%) had double vessel disease in OPCAB vs 14 patients (14%) in CPB; however, there were only 5 patients (5%) who had single vessel disease in OPCAB vs 2 patients (2%) in CPB group. In addition, the left main disease was almost same S89

93 Blood Transfusions in Coronary Artery Bypass Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 among the off pump group 15 (15%) and 17(17%) patients in group-1. Results are shown in table-ii. As compared to the OPCAB group, the patients in the CPB group required ionotropic support for a longer duration (29.6 ± 65.1 vs 60.9 ± 71.2, p-value<0.02). Similarly, the rate of postoperative chest drainage was significantly higher in CPB Vs OPCAB (49% vs 30% p<0.026). Requirement of blood transfusion product (RCC) was significantly higher in CPB group as compared to OPCAB patients (1.6 ± 1.6 vs 1.0 ± 1.2, p-value 0.04). Mechanical ventilation time was almost same in both groups with median value of 6 hours. Results are shown in table-iii & figure. last two decades. It has even become the procedure of choice for some surgeons, who believe that off-pump CABG is associated with lower occurrence of perioperative complications due to avoidance of cardiopulmonary bypass (CPB) and reduced or lack of manipulation of the ascending aorta. A rise in the number of offpump CABG procedures in the late nineties and the earlier half of the first decade of the new millennium set off a never-ending debate regarding the benefits and drawbacks intrinsic to the two techniques of coronary artery grafting. Several randomized controlled trials (RCTs) have been conducted to compare the outcomes of offpump as regards to on-pump CABG Figure: Comparison of OPCAB and coronary surgeries with CPB. There was significantly high incidence of early postoperative complications among patients in CPB compared to those in OPCAB as regards to incidence of complete revascularization (12% vs 2%, p<0.02). Similarly, hospital stay was higher in CPB group as compared to OPCAB group (67.6 ± 74.0 vs 51.0 ± 78.5 hours < p<0.04), respectively. Mortality in both groups was found to be statistically insignificant (5.9% vs 5%, p<0.93). As shown in table-iv and fig. DISCUSSION Off-pump surgery has evolved into the most frequently adopted alternative technique to conventional on-pump coronary artery bypass grafting (CABG) in the treatment of patients with advanced coronary artery disease (CAD) over the S90 procedures 10,11. Most trials demonstrated no difference in immediate outcomes between the two CABG techniques. Nevertheless, the two major RCTs, the Randomized On/ Off Bypass (ROOBY) trial and the Danish On-pump versus Off-pump Randomization Study (DOORS) revealed a significantly higher rate of the primary composite outcome including all-cause mortality, repeat revascularization (RR), or nonfatal myocardial infarction (MI) at 1 year and an inferior graft patency at 6 months following surgery in patients, who underwent off-pump CABG, respectively 12. In contrast, other important RCTs such as the CABG Off- or On-Pump Revascularization Study

94 Blood Transfusions in Coronary Artery Bypass Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 (CORONARY) and the Surgical Management of Arterial Revascularization Therapies (SMART) trial identified no differences in mortality, stroke, MI, RR and quality of life between off-pump and on-pump CABG at a follow-up of 1 year 13. The latter study also showed similar angiographic patency rates. The efficacy of these RCTs to detect and assess differences in clinically important outcome measures between the two operative techniques has been questionable 14. In the present study, there was a reduction in the requirement of blood transfusions in the OPCAB group, as compared to the CPB group. Previous studies have revealed that CPB was associated with increased demand for blood transfusions but did not investigate the contribution of intraoperative hemodilution 15. Other studies have speculated that their observed increased blood transfusion rate for on-pump compared to off-pump patients was caused by an increased postoperative bleeding 16. Our study reported a higher postoperative ICU stay and re-exploration rate in the conventional CABG group as compared to OPCAB group. The evidence in the literature seems to support these findings that Off-pump coronary artery bypass has been associated with a significant reduction in the risk of death, stroke, acute renal failure, mortality or morbidity, and postoperative length of hospital stay compared with on-pump coronary artery bypass surgery CONCLUSION Our study concluded that the main advantages of OPCAB technique are that there is less amount of postoperative chest drainage and it makes it possible to reduce the number of blood transfusions after surgery. LIMITATION OF STUDY This retrospective review failed to show intraoperative haematocrit (Hct) as a marker of hemodilution that provides a more complete understanding of the mechanism of the need for blood transfusions after cardiac surgery. Addressing intraoperative hemodilution is a very important issue in minimizing CPB associated morbidities. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Walczak M, Urbanowicz T K, Tomczyk J. Transfusion of blood products in off-pump coronary artery bypass and conventional coronary artery revascularization. A prospective randomized study. Kardiochir Torakochirurgia Pol 2014; 11(2): Sadowski J, Kapelak B, Wierzbicki K. Coronary artery disease classic and modern surgical treatment. Terapia 2003; 3: Fudulu D, Benedetto U, Pecchinenda GG. Current outcomes of off-pump versus on-pump coronary artery bypass grafting: evidence from randomized controlled trials. J Thorac Dis 2016; 8(Suppl 10): S758-S Wites MM. Zastosowanie krwi i jej preparatów w kardiochirurgii stan aktualny i kierunki rozwoju w oparciu o 20-letnie obserwacje kliniczne. Magazyn Medyczny 1999; 4: Rogowski J, Jarmoszewicz K, Siondalski P, Pawlaczyk R. Opieka pooperacyjna po zabiegach kardiochirurgicznych. Choroby Serca i Naczyń 2006; 3: Raja SG, Husain M, Popescu FL, Chudasama D, Daley S, Amrani M. Does off-pump coronary artery bypass grafting negatively impact long-term survival and freedom from reintervention? Biomed Res Int 2013; 2013: Michalopoulos A, Tzelepis G, Dafni U, Geroulanos S. Determinants of hospital mortality after coronary artery bypass grafting. Chest 1999; 115(6): Engoren MC, Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ. Effect of blood transfusion on long-term survival after cardiac operation. Ann Thorac Surg 2002; 74: Daweirwala PM. Current outcomes of off-pump coronary artery bypass grafting: Evidence from real world practice. J Thorc Dis 2016; 8(Suppl 10): S772-S Shroyer AL, Frederick L, Grover FL, Hattler B, Joseph F, Gerald O, et al. On-pump versus off-pump coronary artery bypass surgery. N Engl J Med 2009; 361: Houlind K, Kjeldsen BJ, Madsen SN, Rasmussen BS, Holme SJ, Nielsen PH, et al. On-pump versus off-pump coronary artery bypass surgery in elderly patients: results from the Danish On- Pump versus Off- Pump Randomization Study. Circulation 2012; 125(20): Lamy A, Devereaux PJ, Prabhakaran D, Davaid P, Hu S, Paolasso E, et al. CORONARY Investigators. Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year. N Engl J Med 2013; 368: Houlind K, Fenger-Grøn M, Holme SJ, Kjeldsen BJ, Madsen SN, Rasmussen BS, et al. Graft patency after off-pump coronary artery bypass surgery is inferior even with identical heparinization protocols. Results from the Danish On-pump Versus Off-pump Randomization Study (DOORS). J Thorac Cardiovasc Surg 2014; 148: Dhurandhar V, Saxena A, Parikh R, Vallely MP, Wilson MK, Butcher JK, et al.outcomes of On-Pump versus Off-Pump coronary artery bypass graft surgery in the High Risk (AusSCORE > 5). Heart Lung Circ 2015; 24(12): Ayman El, Naggar AE, Rania M, Hoseiny E, Mohamed Y. Off pump vs on pump coronary artery bypass grafting: S91

95 Blood Transfusions in Coronary Artery Bypass Surgery Pak Armed Forces Med J 2018; 68 (Suppl-1): S86-S92 Perioperative complications and early clinical outcomes. Egyptian Heart J 2012; 64(1): Shroyer AL, Grover FL, Hattler B, Collins JF, McDonald GO, Kozora E, et al. Veterans Affairs Randomized On/ Off Bypass (ROOBY) Study Group. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med 2009; 361(19): Yousuf-ul-Islam M, Ahmed MU, Khan MS, Bawany FI, Khan A, Arshad MH et al. On Pump coronary artery bypass graft surgery versus Off pump coronary artery bypass graft surgery: A Review. Global J Health Sci 2014; 6(3): Rogers CA, Pike K, Campbell H, Reeves BC, Angelini GD, Gray A, et al. Coronary artery bypass grafting in high-risk patients randomized to off-or on-pump surgery: A randomized controlled trial (the CRISP trial). Health Technol Assess 2014; 18(44): Hlavicka J, Straka Z, Jelinek S, Budera P, Vanek T, Maly M, et al. Off-pump versus on-pump coronary artery bypass grafting surgery in high-risk patients: PRAGUE-6 trial at 30 days and 1 year. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016; 160: Cheng DC, Bainbridge D, Martin JE, Novick RJ. Does offpump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials. Anesthesiology 2005; 102(1): S92

96 Open Access Arrhythmias With Structurally Normal Heart Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S93-S96 ARRHYTHMIAS AMONG YOUNG MALE SOLDIERS UP TO 40 YEARS OF AGE WITH STRUCTURALLY NORMAL HEART Ajab Khan, Imran Ali, Azmat Hayat, Muhammad Shabbir, Rehana Khadim, Ali Nawaz, Hafiz Muhammad Shafiq, Naqib Ullah Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To classify different types of arrhythmias and to study their frequency and presentations among young male soldiers up to 40 years of age who have structurally normal heart. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Inpatient and Outpatient departments of Armed Forces Institute of Cardiology/ National Institute of Heart Diseases (AFIC/NIHD), Rawalpindi, from Jan 2016 to December Materials and Methods: It was a descriptive cross sectional study conducted at inpatient and outpatient departments of AFIC/NIHD, Rawalpindi from Jan 2016 to Dec Male soldiers between 18 to 40 years of age; with no known structured heart disease and presenting with cardiac arrhythmias, not secondary to electrolytes imbalances, hormonal disorders or drugs intake were included in the study through consecutive sampling from hospital record papers. Ethical and institutional approval was taken from IERB committee. Arrhythmias and types were defined as per standard ECG criteria and Holter monitoring. Types of arrhythmias were noted through recorded ECGs and holter reports. Data was entered and analyzed using SPSS version 23. Results: A total of 286 patients were recruited in the study. Mean age of the patients was 34.5 ± 7.6 years. The most common arrhythmia type was found to be supra ventricular tachycardia (SVT) 126 (44%), followed by premature ventricular contractions (PVCs) 80 (28%), early repolarization 34 (11.9%), Atrial Fibrillation (AF) 25 (8.7%), first degree heart block 15 (5.2%), Inappropriate sinus tachycardia (IST) 6 (2.1%). Among SVT common arrhythmias were Atrial Tachycardia (AT) 50 (17.5%) and atrioventricular nodal re-entry tachycardia (AVNRT) 38 (13.2%). Among the recorded symptoms, a palpitation was the most common symptom. No symptoms were recorded for first degree heart block and early repolarization. Conclusion: Common arrhythmias in young male soldiers having structurally normal hearts were PVCs and SVTs. Among SVTs, AT and AVNRT were commonly observed arrhythmias. Dizziness was the common complaint in PVCs. Palpitations was the most commonly observed symptom. Keywords: Arrhythmias, Atrioventricular nodal re-entry tachycardia, Atrial tachycardia, Atrial fibrillation, First degree heart block, Supra ventricular tachycardia This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Cardiac arrhythmias can be benign and can lead to potentially disabling medical conditions or even sudden cardiac death 1,2. Varied causes can lead to arrhythmias in structurally normal or abnormal hearts, including electrolytes abnormalities, channelopathies, hormonal disorders and ischemic cardiac events 3. Common presenting symptoms are dizziness, palpitations, and syncope but in contrast to these ubiquitous complaints, sudden cardiac death Correspondence: Dr Ajab Khan, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan khan_kharotee@gmail.com) remains an important public health concern. statistics from the center for disease control and prevention have estimated sudden cardiac death rates at more than 600, 000 per year in USA 4. Atrial fibrillation is the most common arrhythmia and accounts for the majority of arrhythmiarelated hospitalizations 5. Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common of paroxysmal supraventricular tachycardia (PSVT) in adults 6,7. Idiopathic ventricular tachycardia (VT) account for 10% of all VT diagnoses 8,9. There are community based studies reporting prevalence of different types and common presentations of arrhythmias but, to best S93

97 Arrhythmias With Structurally Normal Heart Pak Armed Forces Med J 2018; 68 (Suppl-1): S93-S96 of our knowledge and search, no study has been done on soldiers. Purpose of this novel study, is to classify different types of arrhythmias, their presentations and frequencies among soldiers up to 40 years of age who have structurally normal heart. MATERIAL AND METHODS It was a descriptive cross sectional study conducted at inpatient and outpatient departments of Armed Forces institute of cardiology and National institute of heart diseases, Rawalpindi from Jan 2016 to Dec Male soldiers between 18 to 40 years of age; with no known coronary artery disease and presenting with cardiac arrhythmias, not secondary to electrolytes imbalances, hormonal disorders or drugs intake were included in the study through consecutive sampling from hospital record papers. Ethical and institutional approval was taken from IERB committee. Arrhythmias and types were defined as per standard ECG criteria and Holter monitoring. Types of arrhythmias were noted through recorded ECGs and Holter reports. Palpitations are defined as an unpleasant awareness of forceful or rapid heartbeats 10. S94 Dizziness and syncope are defined as the sudden transient loss of consciousness with associated loss of postural tone and spontaneous recovery without neurological deficit 11. Data was entered and analyzed using SPSS version 23. RESULTS A total of 286 patients were recruited in the study. Mean age of the patients was 34.5 ± 7.6 years. The most common arrhythmia was found to be Supra ventricular tachycardia (SVT) 126 (44%), followed by premature ventricular contractions (PVCs) 80 (28%), early repolarization 34 (11.9%), Atrial fibrillation (AF) 25(8.7%), first degree heart block 15(5.2%),inappropriate sinus Table-I: Showing types of arrhythmias. Types of Arrhythmias n=286 (%) Supra Ventricular Tachycardia (SVT) AVNRT AVRT Atrial Tachycardia Atrial Flutter 126 (44%) 38 (13.2%) 30 (10.4%) 50 (17.5%) 8 (2.8%) Atrial Fibrillation 25 (8.7%) Premature Ventricular Contractions 80 (28.0%) Inappropriate Sinus Tachycardia 6 (2.1%) First Degree Heart Block 15 (5.2%) Early Repolarization 34 (11.9%) Table-II: Common presentations of arrhythmias. Presenting complaint AVNRT AVRT AT AFL AF PVCs IST Dizziness 1% 10% - 20% - 30% - Palpitation 65% 50% 72% 70% 80% 10% 77% Blackouts Dyspnea 7% - - 5% - - 5% Pre-Syncope % % Syncope tachycardia (IST) 6 (2.1%). Among SVT common arrhythmias were atrial tachycardia (AT) 50 (17.5%) and atrioventricular nodal re-entry tachycardia (AVNRT) 38 (13.2%), while Atrioventricular re-entry tachycardia (AVRT) and atrial flutter (AFL) were less common found in 30 (10.4%) and 8 (2.8%) cases, respectively, as shown in table-i. Among SVTs, AT presented with palpitations (72%) and pre-syncope (18%), while AVNRT, AVRT and AFL commonly presented with palpitations and dizziness (65%

98 Arrhythmias With Structurally Normal Heart Pak Armed Forces Med J 2018; 68 (Suppl-1): S93-S96 and 15%), (50% and 10%) and (70% and 20%), respectively. Among PVCs, common presenting complaints were dizziness (30%) and palpitations (10%). Pre-syncope was common in AT and IST, as shown in table-ii. DISCUSSION There has been significant progress in the understanding of the electrophysiological mechanisms and remodeling processes 12. In present study SVT were the most common arrhythmias in patients with structurally normal hearts present in 44% cases. Among the SVTs most common arrhythmia was noted to be AT (17.5%) followed by AVNRT (13.2%) and AVRT (10.4%). Reported frequency of SVTs in studies conducted by Budhwar et al 13 and Irfan et al 14 is 34% and 38%, respectively. Other common arrhythmias in our study were PVCs present in 28% cases and early repolarization, in 11.9% cases. But in study reported by Abass et al, PVCs were found in 1% and early repolarization in 6% studied male population under 40 years of age with normal hearts 15, while reported frequencies by Liesemer et al 16 were 1.5% and 1.1% for PVCs and early repolarization among male cadets, respectively. In our study, AF was found in 8.7%. Reported incidence of AF was 4.4% among military crew in study by Hunter et al 17. First degree heart block and IST were relatively less frequent, found in 5.2% and 2.1% subjects, respectively. This study has given an account of common clinical presentations for observed arrhythmias. Studies have showed no specific complaint or combination of complaints was likely to predict a disturbance in rhythm 18. Only 40% subjects having PVCs had symptoms, and dizziness was the common complaint (30%). In AT 90% subjects had symptoms where palpitations was the common complaint. Among other arrhythmias, 95% of AFL, 87% of AVNRT and 80% of AF cases were symptomatic. Palpitations was the most common of the symptoms, with variable proportions, related with all types of studied arrhythmias. For first degree heart block and early repolarization no symptoms were noted. In study by Irfan et al, most frequently observed symptom was palpitations, but the mentioned proportions of each symptom was different than our study 14. Nevertheless, it should be kept in mind that the group of subjects analyzed in this study can only be described as selective, since all subjects were young soldiers (less than 40 years of age), it must be assumed that the prevalence revealed by this study is lower than would be the case in an age-matched comparison group from the general population. Furthermore, the major limiting factor was the frequency of symptoms itself, which may be complicated by the fact that the same arrhythmia may occur with different symptoms over a course of time. CONCLUSION Common arrhythmias in young male soldiers having structurally normal hearts were PVCs and SVTs. Among SVTs, AT and AVNRT were commonly observed arrhythmias. Palpitations was the most commonly observed symptom. Significant arrhythmias were detected in both symptomatic and asymptomatic patients, but it is difficult to attribute a symptom to an arrhythmias. Large population study is needed to demonstrate a close temporal relationship between symptoms and types of rhythm disorder. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Tadros R, Ton AT, Fiset C, Nattel S. Sex differences in cardiac electrophysiology and clinical arrhythmias: Epidemiology, therapeutics, and mechanisms. Can J Cardiol 2014; 30(7): Suenari K, Hu YF, Tsao HM, Tai CT, Chiang CE, Lin YJ, et al. Gender differences in the clinical characteristics and atrioventricular nodal conduction properties in patients with atrioventricular nodal reentrant tachycardia. J Cardiovasc Electrophysiol 2010; 21(10): Kurokawa J, Kodama M, Clancy CE, Furukawa T. Sex hormonal regulation of cardiac ion channels in drug-induced QT syndromes. Pharmacol Ther 2016; 168: Odening KE, Koren G. How do sex hormones modify arrhythmogenesis in long QT syndrome,sex hormone effects on arrhythmogenic substrate and triggered activity. Heart Rhythm 2014; 11(11): S95

99 Arrhythmias With Structurally Normal Heart Pak Armed Forces Med J 2018; 68 (Suppl-1): S93-S96 5. Gaborit N, Varro A, Le Bouter S, Szuts V, Escande D, Nattel S, et al. Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts. J Mol Cell Cardiol 2010; 49(4): Dogan M, Yiginer O, Uz O, Kucuk U, Degirmencioglu G, Isilak Z, et al. The effects of female sex hormones on ventricular premature beats and repolarization parameters in physiological menstrual cycle. Pacing Clin Electrophysiol 2016; 39(5): Fischer TH, Herting J, Eiringhaus J, Pabel S, Hartmann NH, Ellenberger D, et al. Sex-dependent alterations of Ca2+ cycling in human cardiac hypertrophy and heart failure. Europace 2016; 18(9): Benjamin EJ, Levy D, Vaziri SM, D Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population- based cohort. The Framingham Heart Study. JAMA 1994; 271(11): Ko D, Rahman F, Schnabel RB, Yin X, Benjamin EJ, Christophersen IE. Atrial fibrillation in women: Epidemiology, pathophysiology, presentation, and prognosis. Nat Rev Cardiol 2016; 13(6): Halaky MA. Approach to the patient with palpitations. In: Braunwald E, Goldman L, editors. Primary cardiology. 2nd ed. Philadelphia: WB Saunders; p Ellis K, Patel VB. Syncope. In: Griffin BP, Topol EJ, editors. Manual of cardiovascular medicine. 2nd ed. Philadelphia: Lippincott & Wilkins; p Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014; 129(8): Badhwar N, Kusumoto F, Goldschlager N. Arrhythmias in the coronary care unit. J Intensive Care Med 2012; 27(5): Irfan G, Ahmad M, Khan AR. Association between symptoms and frequency of arrhythmias on 24-hour Holter monitoring. J Coll Physicians Surg Pak 2009; 19(11): Abass F, Hussain C, Faheem M, Ahmad I, Ahmad J, Qureshi Set al. Electrocardiographic abnormalities in a clinically normal population. J Postgrad Med Inst 2011; 25(2): Liesemer K, Flanagan R, Johnson E, Devenport M, Cartwright V, Puntel R. The Role of Screening Electrocardiograms in the Evaluation of ROTC Cadets Applying for Flight Status. Mil Med 2010; 175(7): Hunter AH, Timperley AC, Reid AN, McLoughlin DC, Nicol E. A 5-Year Review of Atrial Fibrillation in Military Aircrew. Aviat Space Environ Med 2013; 84(12): Zeldis SM, Levine BJ, Michelson EL, Morganroth J. Cardiovascular complaints. Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring. Chest 1980; 78(3): S96

100 Open Access Knowledge of Food Service Staff Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S97-S102 KNOWLEDGE OF FOOD SERVICE STAFF REGARDING FOOD SAFETY AND FOOD HYGIENE IN AFIC & NIHD Maryam Zahid, Hafsa Khalil, Samina Nazir, Sabat Baber, Safdar Abbass Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the knowledge of food service staff regarding food hygiene and food safety. To determine the association between demographic profile and knowledge of food service staff. Study Design: Descriptive cross sectional study. Place and Duration of Study: Armed Forces Institute of Cardiology & National Institute of Heart Diseases Rawalpindi, from Dec 2017 to Jan Material and Methods: A convenient sampling technique was employed to select 45 food service staff members. Food service staff members consisting of cooks, waiters, food delivery boys and cleaner participated in the study. Data collection was done using structured questionnaires. The questionnaire dealing with food safety knowledge comprised 29 close-ended questions. The data were analyzed using the statistical package for social sciences version 22. Results: Among 45 food service staff members who participated in the research, 19 (42%) were cooks, 13 (30%) were waiters, 9 (21%) were food delivery boys and 4 (9%) were cleaners. Twenty three (51%) food service employees were in group of years and 6 (13%) of them were above 50 years of age. Majority of foodhandlers in this study knew the importance of general sanitary practices such as regular hand washing at the work place (98% correct answers), wearing of gloves (100% correct answers), cleaning of workplace (93% correct answers) and detergent use (93%). Education and work activity were significantly associated with food hygiene knowledge, with p-value and 0.021, respectively. Conclusion: In general, the institutional food-handlers have good knowledge of food safety but this does need to be translated into strict hygienic practices during processing and handling food products Keywords: Food hygiene, Food safety, Food service staff. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Food safety is defined as the conditions and measures that are necessary during production, processing, storage, distribution and preparation of food to ensure that it is safe, sound and fit for human consumption 1. When food is cooked on a large scale, it may be handled by many individuals and thus increasing the chances of contamination of the final food. Unintended contamination of food during large scale cooking leads to food-borne disease outbreaks 2-4. The Centre for Disease Control and prevention (CDC) has identified five risk factors relatedto the human factor and preparation methods that contribute to the high prevalence of foodborne Correspondence: Dr Maryam Zahid, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan maryamzahid343@gmail.com illnesses. The five risk factors are improper holding temperatures, inadequate cooking, contaminated equipment, food from unsafe source and poor personal hygiene 5. Food, if not handled hygienically, could be a mode for transmission of hazards 6 and the contaminated food can pose a health threat, a problem that is serious in developing countries due to difficulties in securing optimal hygienic food handling practices. In order to minimize foodborne outbreaks, education must be an integral component of all interventions. Therefore, to plan a successful food safety intervention, obtaining information pertaining to food safety knowledge is of utmost importance. Additionally, making prudent decisions to uproot the problems as early as possible lessens the risk of major foodborne S97

101 Knowledge of Food Service Staff Pak Armed Forces Med J 2018; 68 (Suppl-1): S97-S102 outbreaks. Several studies have posed strong emphasis for educational programs as a way to improve knowledge and control foodborne MATERIAL AND METHODS A convenient sampling technique was employed to select 45 food service staff members. Table: Relation between work activity and educational status with the questions Questions Filtered water is necessary for preparing food. Using gloves while handling food reduces the risk of food contamination. Proper cleaning and sanitization of utensils increase the risk of food contamination. Clean and sanitize work surfaces after each task is important AIDS can be transmitted by food. Bloody diarrhea can be transmitted by food. Microbes are on the skin, in the 1 nose and mouth of healthy food handlers. Clean 1 is the same as sanitized. The correct 2temperature for storing perishable foods is 5 C. During infectious disease of the skin, 2 it is necessary to take leave from work. The ideal place to store raw meat in 2 the refrigerator is on the bottom shelf. Wash raw products 2 before using it is important Work activity Education Status Food Response No Pri Sec Post Cook waiter Delivery cleaner p-value Matric Edu edu Edu Matric Boy Yes No I don t know Yes No const I don t know Yes No I don t know Yes No I don t know Yes No I don t know Yes No I don t know Yes No I don t know Yes No I don t know Yes No I don t know Yes No I don t know Const No I don t know Yes No I don t know Yes No I don t know Conts p- value const Const - Const diseases 7,8 pointed out that food handlers need training and education as a result of their low level of knowledge on microbiological food hazards, temperature control of refrigerators, cross contamination, and personal hygiene 9. Food service staff members consisting of cooks, waiters food delivery boys and cleaner participated in the study. Food service managers and dietitians were excluded from the study as they are more responsible for administration work and for training the food service staff. Data S98

102 Knowledge of Food Service Staff Pak Armed Forces Med J 2018; 68 (Suppl-1): S97-S102 was collected from December 2017 to January Face-to-face interviews were conducted using structured questionnaires in the kitchen of Armed Forces Institute of Cardiology and National Institute of Heart Disease. Demograph the questionnaire dealing with food safety knowledge comprised 29 close-ended questions with three possible answers; true, false, and do not know. These questions specifically dealt with respondents knowledge of personal hygiene, cross contamination, foodborne diseases, microorganisms, temperature control and hygienic practices. A scale ranging between 0 and 29 (representing the total number of questions on food safety knowledge) was used to evaluate the overall knowledge of respondents. Data Analysis years and 6 (13%) of them were above 50 years of age. Thirty four (76%) members were permanently posted in AFIC & NIHD whereas 11 (24%) were temporary employees. Seven (16%) food service employees were serving the hospital for more than 20 years, whereas most of the employees, 24 (53%) had less than 5 years of food service experience. Sixteen (36%) of the members completed 10 years of education and 2 (4.4%) completed 12 years of education, whereas 5 (11%) employees did not receive any proper education. Fourty four (98%) of the food service employees knew the importance of hand washing and use of hair restraint. All the employees knew that using gloves while handling food reduces the risk of food contamination. Forty four (98%) members were aware that cross Figure-1A: Relationship between length of employment and knowledge regarding correct temperature for storing perishable foods. The statistical analysis was carried out using SPSS software version 22 (IBM corporation, USA). Mean ± SD and n (%) was calculated for descriptive variables and chi-square test was applied for comparing various categorical groups. A p-value of <0.05 was taken significant. RESULTS Among 45 food service staff members who participated in the research 19 (42%) were cooks, 13 (30%) were waiters, 9 (21%) were food delivery boys and 4 (9%) were cleaners. All the food service members were male. Twenty three (51%) food service employees were in group of S99 contamination occurs when microorganisms from a contaminated food are transferred by the food handler s hands or kitchen utensils to another food. All employees said its necessary to take leave from work during infectious disease of the skin. Thirteen (30%) didn t know the correct temperature for storing perishable food, where as 22 (49%) knew the right answer. Twenty five (56%) said hot, ready to eat food should be kept at a temperature of 65 C, whereas 6 (13%) didn t knew the answer. Nineteen (42%) employees knew the difference between cleaning and sanitizing. Twenty five (56%) employees said that

103 Knowledge of Food Service Staff Pak Armed Forces Med J 2018; 68 (Suppl-1): S97-S102 AIDS can be transmitted by food and 38 (84%) said typoid fever can be transmitted by food. All employees, 45 (100%) knew that washing of raw products before use is important. Table shows the strong Relationship between work activity and education level with food safety knowledge with the p-value<0.05. In fig-1a health status of workers before employment had p-value of as shown in fig-1c. DISCUSSION Food safety is extremely important to health since it protects against foodborne illnesses. In this study, food safety knowledge of food service workers was carried out to examine the Figure-1B: Relationship between length of employment and knowledge regarding contamination of raw vegetables and undercooked beef. Figure-1C: Relationship between length of employment and knowledge of food service regarding evaluation health status of workers before employment. A p-value relationship of length of employment and knowledge regarding correct temperature for storing perishable foods was shown and it had p-value of While in fig-1b relationship between length of employment and knowledge regarding contamination of raw vegetables and under-cooked beef was highly significant. Relationship between length of employment and knowlwdge of food service regarding evaluation S100 distribution and relationship of food safety knowledge with education level, work activity and length of employment. The largest group 23 (51%) in the study was between the age of years of age. This is similar from other studies where the majority of the participants were also a bit younger aged between 25 to 30 7.

104 Knowledge of Food Service Staff Pak Armed Forces Med J 2018; 68 (Suppl-1): S97-S102 In our study, the food-handlers were knowledgeable about hygiene practices, cleaning and sanitation procedures. Majority of food handlers in this study knew the importance of general sanitary practices such as regular hand washing at the work place, wearing of gloves, cleaning of workplace and detergent use. Similarly in Ghana majority of food-handlers knew the importance of general sanitary practices 4,14. Education and work activity were significantly associated to food hygiene knowledge, with p-value 0.01 and 0.042, respectively specifically regarding proper cleaning and sanitization of utensils. Similar findings were reported in food hygiene knowledge, attitude and practices of food handlers in the Military Hospitals study by Sharif et al (2013) 11, where they reported that practice scores were significantly (p<0.05) affected by the level of education and by the type of work for separating raw from cooked foods. Eighty two percent remember that hepatitis A is a foodborne pathogen. On the other, 84 and 87% of respondents agreed that typhoid fever and bloody diarrhea respectively can be transmitted by food. The majority (56%) of respondents agreed that HIV/AIDS is transmitted by food, which is an indication that public education on HIV/AIDS is not sufficient. These results support recently published work where majority of the respondents did not know if Salmonella, hepatitis A and B viruses, and Staphylococcus caused foodborne diseases 14,15. Over hundred percent (100%) of respondents agreed that taking leave from work in periods of infectious skin disease was necessary Additionally, 91% knew that microorganisms can be found on the skin and in the mouth and nose of healthy looking individuals. They also recognize that the health status of food-handlers should be assessed prior to employment. On the other hand, food-handlers were less familiar with time and temperature abuse and its effect on food safety. Kajagar 9 reported that improper handling of food, including the abuse of time temperature, account for most food-borne disease outbreak. In this study, respondents had insufficient knowledge on time temperature controls. This result is supported by others 10,13,14 whose report show that knowledge of critical temperatures were insufficient amongst food handlers. Similar findings on the lack of adequate knowledge on temperature controls by food handlers have also been reported from different countries. 8,15 CONCLUSION In general, the institutional food handlers have good knowledge in food safety but this does not translate into strict hygienic practices during processing and handling food product. RECOMMENDATIONS Gaungoo and Jeewen 8 in their study for effectiveness of training among food handlers ( A review on the Mauritian Framework ) recommended that it should be mandatory for food handlers to undergo a refresher food safety training course prior to renewal of their Food Handler Certificate after its expiry after three years. Therefore, there is a need for continuous training of food handlers on food hygiene and food safety; this might assist in improve knowledge and maintaining the standard of hygiene practices in food service units. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Clayton DA, Griffith CJ, Price P, Peters AC. Food handlers' beliefs and self-reported practices. Int J Environ Health Res 2002; 12(1): Adams M, Motarjemi Y. Basic food safety for health workers. Geneva: World Health Organization; 1999; Omaye ST. Food and nutritional toxicology. Boca Raton: CRC press; 2004; Annor GA, Baiden EA. Evaluation of food hygiene knowledge attitudes and practices of food handlers in food businesses in Accra, Ghana. Food Nutr Sci 2011; 2(8): Centers for Disease Control and Prevention, Food Safety. Also [online] available from: of food borne Illnesses. S101

105 Knowledge of Food Service Staff Pak Armed Forces Med J 2018; 68 (Suppl-1): S97-S Mensah P, Mwamakamba L, Mohamed C, Nsue M. Public health and food safety in the WHO African Region. Afr J Food Agric Nutr Dev 2012; 12: Abdelhafez AM. Knowledge, attitudes andpractices of food service staff about food hygiene in hospitals in Makkah area, Saudi Arabia. Life Sci 2013; 10(3): Gaungoo Y, Jeewon R. Effectiveness of training among food handlers: A review on the Mauritian Framework. Curr Res Nutr Food Sci 2013; 1(1): Kajagar IA. A study to assess the knowledge regarding practices of food hygiene among food handlers at selected government schools of Belgium City with a view to develop an informational booklet. Doctoral dissertation, KLE University Belgium. Karnataka McIntyre L, Vallaster L, Wilcott L, Henderson SB, Kosatsky T. Evaluation of food safety knowledge, attitudes and selfreported hand washing practices in FOODSAFE trained and untrained food handlers in British Columbia, Canada. Food Control 2013; 30(1): Sharif L, Obaidat MM, Al-Dalalah MR. Food Hygiene Knowledge, Attitudes and Practices of the Food Handlers in the Military Hospitals. Food Nutr Sci 2013; 4(3): Tan SL, Cheng PL, Soon HK, Ghazali H, Mahyudin NA. A qualitative study on personal hygiene knowledge and practices among food handlers at selected primary schools in Klang valley area, Selangor, Malaysia. Food Res Int 2013; 20(1): Tan SL, Abu-Bakar F, Abdul KMS, Yen LH, Mahyudin NA. Hand hygiene knowledge, attitudes and practices among food handlers at primary schools in Hulu Langat district, Selangor (Malaysia). Food Control 2013; 34: Soares LS, Almeida RC, Cerqueira ES, Carvalho JS, Nunes IL. Knowledge, attitudes and practices in food safety and the presence of coagulase positive staphylococci on hands of food handlers in the schools of Camaçari, Brazil. Food Control 2012; 27(1): Ansari-Lari M, Soodbakhsh S, Lakzadeh L. Knowledge, attitudes and practices of workers on food hygienic practices in meat processing plants in Fars, Iran. Food Control 2010; 21(3): S102

106 Open Access Awareness of Health Care Workers Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S103-S108 AWARENESS OF HEALTH CARE WORKERS REGARDING ALCOHAL HAND RUB USAGE AT TERTIARY CARE HOSPITALS Javeria Kamran, Farrah Pervaiz, Safdar Abbas, Suhail Aziz, Muhammad Afsheen Iqbal, Rukhsana Roshan*, Hafiza Zahid, Rabia Atif** Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Combined Military Hospital Gujranwala/National University of Medical Sciences (NUMS) Pakistan, **Armed Forces Postgraduate Medical Institute/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To assess the knowledge, attitude and practices of hand hygiene by using alcohol hand rubs amongst healthcare workers. Study Design: Descriptive cross sectional study. Place and Duration of Study: Military Hospitals of Rawalpindi from Jul 2016 to Dec Material and Methods: Data was collected using a pre-structured questionnaire from 350 healthcare workers using convenience sampling. Results: Statistical analysis showed that 210 (59%) healthcare workers had adequate knowledge about proper Alcohol hand rub usage, 202 (56%) showed positive attitude while good practices were found in 189 (53%) respondents. Strong statistical association exists between socio-demographic characteristics and knowledge and attitude of healthcare workers. Conclusion: The study identified factors responsible for gaps such as: Lack of awareness, work overload, negligence, shortage of time, non-availability of Hand Hygiene facilities, overcrowding of patients and lack of encouragement by seniors in Alcohol Hand Rub usage amongst healthcare workers in tertiary care hospitals. Identified issues can play a pivotal role in determining critical steps required for action to bring about improvement in hand hygiene practices to reduce hospital acquired illnesses and deaths. Keywords: Alcohol hand rub, Hand Hygiene, Hospital acquired infections. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Adoption of hand aseptic techniques to attain hand hygiene (HH) dates back to 19th century which was studied by Semmelweis 1. Association of HH practices and health care associated infections is also a known fact. Multiple studies over the period of time have supported the fact that improved HH practices play an important role in reducing overall length of hospital stays, as well as morbidity and mortality rates 2. Healthcare associated infections (HCAI) undoubtedly portray a grave problem for patient safety and their prevention automatically becomes the first priority of hospitals and Correspondence: Dr Javeria Kamran, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan jk.ny@hotmail.com institutions. Their prevention also remains a major concern worldwide that no hospital, institution or country can claim to have fully attained. In Europe alone, hospital wide prevalence rates of patients affected by healthcare associated infections ranged from 4.6% to 9.3% 3. Prevalence of nosocomial infections is highly dependent on hand hygiene practices of healthcare workers; however, most of these infections can be prevented by simple adoption of WHO recommended My Five Moments of Hand Hygiene Strategy 3. Both, World Health Organization (WHO) and Centre of Disease Control (CDC) recommend guidelines for hand washing with soap and water when visibly dirty but in all other scenarios, alcohol hand rubs are the gold standard for hand hygiene 4. Introducing alcohol hand rubs with multifaceted interventions has S103

107 Awareness of Health Care Workers Pak Armed Forces Med J 2018; 68 (Suppl-1): S103-S108 been reported to increase the compliance rates of healthcare workers 5. Alcohol hand rubs have proven to have better microbiological efficacy, require lesser time to attain preferred effects and a better skin tolerance 6. Despite strong recommendations from WHO as well as CDC to use alcohol hand rub as first line for attainment of hand hygiene in clinical practice, Pakistan is still miles away in attaining the desired goal. In Pakistan, alcohol hand rubs are generally more in practice in Armed Forces Institutes; whereas they are not as prevalent and their availability is also scarce in public sector hospitals. Hence, the rationale of this study was to care workers who were on medical cover, on leave, involved in administrative duties and who did not give the consent for filling out the questionnaire were excluded. Convenience sampling technique was used. The demographic profile of HCW was studied that included age, gender, hospital, profession, education, years of experience and department (ITC, surgical unit etc). A modified, predesigned and pretested questionnaire was used for data collection 7. Data was collected after obtaining ethical clearance from AFIC IERB and AFPGMI IRB. Formal permission was obtained from respective hospitals. All HCWs participated voluntarily in the study after giving verbal informed consent. Participants were guaranteed confidentiality of the information they gave and also had given the Figure: Self-reported hurdles by health care workers in use of alcohol hand rub usage. assess the knowledge, attitude and practices of healthcare workers in those settings where alcohol hand rubs are available. MATERIAL AND METHODS This descriptive cross sectional study was conducted at Military Hospital of Rawalpindi from July 2016 to December 2016 with a view to assess knowledge, attitude and practices of hand hygiene by using alcohol hand rubs amongst healthcare workers. A total of 355 permanently employed Health Care Workers working/ involved in patient care in Tertiary Care Hospitals were included in this study. Health S104 right to refuse or quit participation at any time during their involvement in the study. The questionnaire was pretested on 20 healthcare workers for their understanding of the questionnaire. Data Analysis Data recording, storage, assessment and analysis was done by using SPSS software version 21. Continuous variable data was presented in mean and standard deviation. Categorical variable data is presented in frequencies and percentages. Chi-square test is used to find association between knowledge,

108 Awareness of Health Care Workers Pak Armed Forces Med J 2018; 68 (Suppl-1): S103-S108 attitude, practices and socio-demographic variables. A p-value<0.05 is taken as significant and p-values of different variables are reported. RESULTS Demographic data includes age, gender, hospital, education, profession, years of experience and departments. Majority of HCWs had 7 to 15 year of experience followed by 23 (6%) with >16 years of experience. 153 (43%) respondents belonged to CMH, 51 (14%) to MH, 126 (35%) to AFIC and 25 (7%) to other hospitals. 96 (27%) of HCWs were MBBS, 141 (39%) BSc and 118 (33%) had intermediate level education. Out of 355 respondents 65 (18%) were from ICU, 88 (24%) from medicine, 79 (22%) from surgery, 47 Table-I: Association between demographic characteristics and knowledge of respondents. Demographic Knowledge Characteristics n (%) x 2 Results Adequate Inadequate Gender Male 43 (20) 17 (11) Female 167 (79) 128 (88) p=0.04 Profession Doctor 54(25) 41 (28) Nurse 101(48) 94 (64) p=0.00 Paramedical Staff 55(26) 10 (6) Table-II: Association between demographic characteristics and attitude of respondents. Demographic Attitude Characteristics n (%) x 2 Results Adequate Inadequate Gender Male 26 (12) 34 (22) Female 176 (87) 119 (77) p=0.02 Education MBBS 40 (19) 56 (36) BSc 86 (42) 55 (35) p=0.002 Intermediate 76 (37) 42 (27) Profession Doctor 42 (20) 53 (34) Nurse 121 (59) 74 (48) p=0.014 Paramedical Staff 39 (19) 26 (17) *No statistically significant association is seen between demographic characteristics and practices. 230 (64%) lie between 18 to 26 age bracket whereas 78 (22%) between 26 to 37 and 47 (13%) was >37 years old. Proportion of female to male HCW was 295 (83%) and 60 (16%) respectively. Female HCWs were by far in majority. The difference in proportion is due to the fact that males belonged mostly to paramedical staff whereas doctors and nurses were mostly females. Most of the respondents had 1 to 6 years of experience 285 (80%) followed by 47 (13%) who (13%) from pediatrics and 76 (21%) from other departments. Majority of respondents 195 (54%) belonged to nurses followed by 95 (26%) of doctors followed by 65 (18%) of paramedical staff. Mean age of HCWs was (± 7.52) years, ranging between 18 to 47 years. Mean years of experience was 4.79 (± 5.4), ranging between 1 to 25 years. S105

109 Awareness of Health Care Workers Pak Armed Forces Med J 2018; 68 (Suppl-1): S103-S108 Regarding mode of spread of nosocomial infections, 144 (40%) responded correctly by answering that it is transmitted by hands whereas 211 (59.4%) thought that common utensils and patients poor hygiene was responsible for its spread. As regards effectiveness of alcohol hand rubs, 351 (98%) had the correct knowledge that alcohol hand rubs reduced transmission of infections, 324 (94%) were aware of WHOs recommendations for routine use of alcohol hand rub, 218 (61%) said AHR was less rapid than soap and water, 264 (74%) stated that AHR caused skin dryness and 271 (76%) knew that AHR was more effective mode of attaining hand hygiene. About 203 (57%) HCWs had the knowledge about the appropriate time that should be given for AHR to kill the germs and have effective level of reduction of microbes on hands. Hurdles reported by HCWs during HH practices by use of AHR usage are mentionbes as shown in figure. About 337 (94%) HCWs correctly reported that alcohol hand rubs should be used before touching a patient, only 130 (36%) practiced hand hygien after exposure to the body fluids whereas 312 (87%) correctly performed hand hygiene immediately before an aseptic technique. Three hundred and twenty seven (92%) performed hand hygiene after exiting patients environment. As regards attitude of HCWs showing positive association with increased likelihood of colonization of hands with harmful germs, 272 (76%) had positive attitude of not wearing jewelry, 322 (90%) had the attitude to avoid damaged skin, 315 (88%) with attitude to avoid use of artificial nails and 102 (28%) had the attitude of regular use of hand cream to avoid colonization of hands with germs due to damaged skin. Table-I shows significant association between gender, profession and knowledge whereas Table-II shows significant association between gender, education, profession and attitude. DISCUSSION The study was conducted in multiple departments of military hospitals to assess knowledge, attitude and practices of HCWs regarding use of alcohol hand rub for attaining hand hygiene. Health care workers hands are the most usual type of vehicle for transmission of health care associated infections. Pathogenic micro-organisms have the ability to survive for 2-60 minutes on health care workers hands. So, in order to provide optimal care health care, workers should follow recommended guidelines to get their hands rid of micro-organisms 8. A systematic review comprising 96 studies was published which reported that overall compliance rate was 32% in doctors; much lower than 48% in nurses. Also, they practiced HH 21% of times before touching the patient and 47% after coming in contact with the patient 9, whereas in our study 46% of doctors and 58% of nurses showed compliance with HH practices. A similar study conducted in Spain showed compliance rate of 56% in acute wards 10 and yet another study conducted in ICU of a tertiary care hospital in India reported the compliance rate of 43%. It did not differ much between physicians and nurses being 41% and 40% respectively 11. A study conducted in Iran also showed shockingly low compliance of HH practices. Overall compliance was 6.4% (teaching hospital: 7.4%, public hospital: 6.2%, private hospital: 1.4%). Nurses (8.4%) had the highest rates of compliance 12. A multi-centered study conducted in multiple departments in Pakistan concluded that out of 3243 respondents, 87% had knowledge about hand washing techniques but only 69% practiced hand hygiene procedures adequately. Out of those who performed HH, 58% performed HH for more than 20 seconds as per WHO guidelines. Majority preferred soap and water over alcohol hand rubs 13. In our study 67% preferred alcohol hand rub usage and 73% reported to be performing HH for over 20 seconds. However, 76% of the HCWs agreed that S106

110 Awareness of Health Care Workers Pak Armed Forces Med J 2018; 68 (Suppl-1): S103-S108 hand rubs were more effective for hand hygiene and 67% reported to be using alcohol hand rub as preferred means of acquiring hand hygiene in comparison to 32% which used soap and water. In our study 98% of HCWs had the knowledge that AHR usage reduces the transfer of infections from one person to another, 61% had the correct knowledge that AHR is faster acting HH product and 76% knew that hand rubs are more effective than hand washing. The difference in the study was attributed to non-availability of AHR at the patient care points, poor quality of AHR, skin irritation and allergies. An observational study conducted in Istanbul in Pediatric ICU on the compliance of HH for the five World Health Organization (WHO) indications revealed HCWs were more likely to use soap and water (63.6%) compared to waterless alcohol based hand hygiene (36.3%). Adherence to hand hygiene practice and use of alcohol-based disinfectant was found to be very low because of the unpleasant irritation effects on the hands and lack of knowledge concerning its benefits 14. In our study, we observed that rate of HH practices vary with different healthcare departments which is supported by a study conducted in Kuwait by Batool Al-Wazzan et al. which concluded thatcompliance varied in departments i.e. 17% in emergency, 55% in medical wards, 43% in ICU, 40% in Surgical wards 15. A study conducted in Saudi Arabia, notified the hurdles faced in attaining HH by AHR usage as: less encouragement by seniors, inaccessibility to HH products, lack of knowledge, forgetfulness, more work load and irritating effect of AHR on hands which are the similar hurdles mentioned in a study conducted by Al-Tawfiq and pittet for improving HH compliance in healthcare setting 16. Similar hurdles were also reported in our study. The limitation of our study is that to quantify the practices was not possible and mixed method should have been used to overcome this hurdle. There is also the issue of generalizability as external factors vary from place to place. CONCLUSION This study shows that HCWs display adequate knowledge and attitude but there is a gap between practices which is attributed to multiple hurdles. A WHO recommended multi-faceted, multi-dimensional approach involving individual and organization is required to bring about improvement in HH practices 3. This study should be followed by an observational study involving multiple conductors to confirm the reported facts by HCWs. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Hardy J. Dr. Semmelweis, The Savior of Mothers Barahona-Guzman N, Rodriguez-Calderon ME, Rosenthal VD, Olarte N, Villamil-Gomez W, Rojas C, et al. Impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene approach in three cities of Colombia. Int J Infect Dis 2014; 19: WHO. WHO Guidelines on Hand Hygiene in Health Care: A Summary Boyce JM, Pittet D. Healthcare Infection Control Practices Advisory Committee, and HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force, Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America, MMWR Recommendations and Reports Allegranzi B, Pittet D. Role of hand hygiene in healthcareassociated infection prevention. J Hosp Infect 2009; 73(4): Babeluk R, Jutz S, Mertlitz S, Matiasek J, Klaus C. Hand hygiene evaluation of three disinfectant hand sanitizers in a community setting. PloS one 2014; 9(11): e Rao MH, Arain GM, Khan MI, Taseer I-u-H, Talreja KL, Ali G, et al. Assessment of knowledge, attitude and practices pattern of hand washing in some major public sector hospitals of Pakistan (A Multi-Center Study). Pak J Med Res 2012; 51(3): Sax H, Allegranzi B, Uçkay I, Larson E, Boyce J, Pittet D. My five moments for hand hygiene : A user-centred design approach to understand, train, monitor and report hand hygiene. J Hosp Infect 2007; 67(1): Erasmus V, Daha TJ, Brug H, Richardus JH, Behrendt MD, Vos MC et al. Systematic review of studies on compliance with hand hygiene guidelines in hospital care. Infect Control Hosp Epidemiol 2010; 31(3): S107

111 Awareness of Health Care Workers Pak Armed Forces Med J 2018; 68 (Suppl-1): S103-S Sobrequés J, Espuñes J, Bañeres J. Intervention to improve hand hygiene compliance in Catalonia, Spain. Med clin 2014; 143(1): Sharma S, Sharma S, Puri S, Whig J. Hand hygiene compliance in the intensive care units of a tertiary care hospital. Indian J Community Med 2011; 36(3): Baghaei R, Sharifian E, Kamran A. Can theoretical intervention improve hand hygiene behavior among nurses? Psychol Res Behav Manag 2016; 9: Rao MH, Arian GM, Khan MI, Taseer I-u-H, Talreja KL, Ali G, et al. Assessment of knowledge, attitude and practices pattern of hand washing in some major public sector hospitals of Pakistan. A Multi-Center Study. Pak J Med Res 2012; 51(3): Karaaslan A, Kepenekli KE, Atici S, Sili U, Soysal A, Culha G, et al. Compliance of healthcare workers with hand hygiene practices in neonatal and pediatric intensive care units: Overt observation. Interdiscip Perspect Infect Dis 2014; Al-Wazzan B, Salmeen Y, Bouhaimed M, Al-Taiar A. Hand hygiene practices among nursing staff in public secondary care hospitals in Kuwait: Med Princ Pract 2011; 20(4): Al-Tawfiq JA, Pittet D. Improving hand hygiene compliance in healthcare settings using behavior change theories: reflections. Teach Learn Med 2013; 25(4): S108

112 Open Access Stent Thrombosis in Patient Undergoing Primary PCI Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 FREQUENCY AND PREDICTORS OF STENT THROMBOSIS IN PRIMARY PCI PATIENTS AT AFIC Hafiz Muhammad Shafique, Sohail Aziz, Sarfaraz ali zahid, Rehana Khadim, Mubarra Nasir Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the frequency and predictors of early stent thrombosis in primary Primary Percutaneous Intervention patients. Study Design: Cross sectional study. Place and Duration of Study: Department of Cardiology AFIC/NIHD Rawalpindi, from Jan 2016 to Dec Material and Methods: Non probability consecutive sampling technique was used to enroll 960 patients with ST segment elevation myocardial infarction and underwent Primary percutaneous coronary intervention in the prescribed duration satisfying inclusion/exclusion criteria. Data regarding type of myocardial infarction, risk factor like diabetes mellitus (DM), hypertension, smoking and family history was recorded followed by analysis using SPSS version 21. Results: Total 960 patients included with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, 883 (92%) were male and 77 (8%) were female, with male female ratio of 11.4: 1. Mean age of presentation was ± 7.84 years in males and ± 8.99 years in females respectively. Stents were implanted in 937 (97.6%) out of 960 patients, including 738 (76.9%) who received drug-eluting stents and 95 (9.89%) who received only bare metal stents, 81 (8.43%) patients received both BMS and DES and POBA was done in 23 (2.3%) patients. Definite stent thrombosis occurred in 16 (1.7%), and 3 (0.32%) patients receiving DES and BMS respectively. Probable stent thrombosis occurred in 3 (0.32%) patients receiving DES and 1 (0.1%) patient receiving BMS. Total frequency of early stent thrombosis is 2.35%. Early stent thrombosis was associated with higher in hospital mortality (p=0.03) Conclusion: Early stent thrombosis has multifactorial causes in primary PCI patents, and is associated with diabetes mellitus, late presentation to hospital, length of stent, high thrombus burden and small stent diameter. Keywords: Stent thrombosis, St Segment elevation myocardial infarction, Primary Percutaneous Coronary Intervention. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Primary percutaneous coronary intervention (PPCI) is the treatment of choice in patients with ST segment elevation myocardial infarction (STEMI). These patients are at increased risk of acute and sub-acute risk of stent thrombosis when compared with stable coronary disease 1-3. Stent thrombosis is a serious and dreadful complication of PCI which can lead to death and myocardial infarction 6-7. Early ST following primary PCI is almost 3 to 4 times higher when compared with elective PCI 26 Swedish Registry revealed the rate of ST in STEMI cohort about 2.5 times greater than the non-stemi cohort 27. Correspondence: Dr Hafiz Muhammad Shafique, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan shafique176@gmail.com Hence, STEMI cohort remains a unique group that poses a higher risk of early ST and worse outcomes There are multifocal etiologies of early stent thrombosis (ST) and are associated with clinical features of patient, lesion-related, procedural, and post-procedural factors, including type of stent and thrombus burden 3-5. Platelet aggregation adhesion and activation play pivitol role in the beginning of intracoronary thrombosis that leads to acute coronary syndromes (ACS) and ischemic complications after coronary artery interventions, including recurrent myocardial. The present study was undertaken to identify the frequency of early stent thrombosis in PPCI patients and associated clinical and angiographic risk factors. Infarction (MI) and stent thrombosis (ST). Indeed, the most S109

113 Stent Thrombosis in Patient Undergoing Primary PCI Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 feared complication related to coronary stent placement is ST. Stent thrombosis can occur after implantation of either a bare metal stent (BMS) or a drug-eluting stent (DES) 10,11. The reported incidence of early stent thrombosis ranges from % 12,13. The risk of early ST is similar between BMS and DES, but very late ST might occur more frequently in patients receiving firstgeneration DES. Stent thrombosis is associated with high risk of MI and death although the frequency of event is low 9. PATIENTS AND METHODS This descriptive cross sectional study was conducted at the Department of Cardiology, AFIC/NIHD, Rawalpindi. We used WHO calculator for sample size and included consecutive 960 patients with ST segment elevation Myocardial infarction presented in emergency department for one year from Jan 2016 to Dec All patients with ST segment elevation MI (25-80 years) of both gender presented in emergency were included in the study. Patients with Patients with Chronic Kidney disease (CKD), previous history of early stent thrombosis (EST) and cardiogenic shock were excluded from study. Acute STEMI was diagnosed on the basis of history of chest pain lasting >30 minutes associated with an STelevation of 1 mm in 2 contiguous leads or new left bundle branch block plus time from symptom onset to presentation 24 hours. The main objective of the study was to analyze predictors of early ST in STEMI patients treated with primary PCI. Early ST was defined as ST within 30 days of coronary stent deployment. Diagnosis of ST was made according to the definition proposed by the Academic Research Consortium 28. Only patients with early (0-30 days post stent deployment) ST were analyzed. Definite ST was defined as symptoms suggestive of an ACS along with angiographic or pathologic confirmation of ST. Probable ST was defined as unexplained death within 30 days or target vessel myocardial infarction without angiographic confirmation of ST. Patients were further subdivided into acute (<24 hrs of stent deployment) and subacute ST (>24 hours of stent deployment). Patients were followed up at 30 days post discharge. Stroke was defined as a focal neurologic deficit resulting from a cerebrovascular cause, lasting >24 hr, that was not due to an obvious identifiable cause. After confirmation of STEMI and brief history was taken to rule out any contraindication to dual antiplatelet treatment. After obtaining informed consent all patients were loaded with 300 mg of aspirin, 600 mg of clopidogrel and mg of atorvastatin and transferred to the catheterization laboratory as early as possible. Procedure was performed either through radial or femoral route although the vast majority of interventions were performed via the radial route. I/V 70 to 100 U/kg heparin was administered to maintain the activated clotting time (ACT) between 200 and 250s. Glycoprotein IIb/IIIa inhibitors were given in the form of two I/V boluses during the procedure and as an intravenous infusion post procedurally to all patients in the absence of contraindications. Infarct related artery (IRA) was engaged with an appropriate sized guiding catheter and the culprit lesion was crossed with non-hydrophilic soft guide wire. After lesion crossing, the TIMI flow and thrombus burden were assessed. If TIMI flow was grade III and thrombus burden was low, the lesion was stented directly. Conversely, when there was large thrombus burden, aspiration thrombectomy was performed and balloon dilatation was done if the lesion was too tight to allow the passage of the stent or when it was difficult to assess the size of the distal vessel. Non-infarct related artery was imaged at the end with a diagnostic catheter to rule out any critical lesions with compromised blood flow As per the hospital protocol, bare metal stents (BMS) and drug-eluting stents (DES) were used. In case of multi-vessel disease, PCI was limited to Infarct Related Artery (IRA) unless patients had significant stenosis with less than TIMI III flow in a non-ira. Coronary flow of the infarct related artery was assessed visually by the operator and S110

114 Stent Thrombosis in Patient Undergoing Primary PCI Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 classified according to the TIMI grading system on a scale of 0 3 both before and after the PCI. Procedural success was defined as achievement of vessel patency to a residual stenosis <30% with TIMI 3 flow. Hemodynamically stable patients discharged on the third day. At the time of discharge, all the patients were continued on dual antiplatelet, statin, beta-blocker and ACE inhibitor if not contraindicated. Patient s record were follow up for month on electronic system. Those who didn t follow up were telephonically contacted and asked for complications. Data Analysis The relevant data were collected on a structured proforma. Procedural data was assessed from the database at the time of the PPCI, and hospital outcomes was be assessed from chart reviews in the previous records. Follow-up events were obtained from reviews of medical records and telephone contact. Statistical analysis was performed using statistical software SPSS 23. Mean and standard deviation was calculated for quantitative variable age. Other list of variables included : age in years, sex, diabetes, hypertension, hyperlipidemia, smoker, previous PCI, previous myocardial infarction, or coronary artery bypass graft (CABG) surgery; multivessel disease; access site (femoral vs. radial); drugeluting stents; Target lesion Length (mm), Reference Diameter of artery (mm), thrombus burden (low, moderate, high). Statistical analysis was done with Chi-square test for categorical S111 variable and Independent Kruskal Wallis test was used for dependant categorical and independent numerical variables. The statistically significant p-value in all these tests was assumed at a value <0.05. From the list of variables, diabetes mellitus, late presentation to hospital, length of stent, high thrombus burden and Small stent diameter at PPCI were found to be significant. RESULTS Total 960 patients included with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, 883 (92%) were male and 77 (8%) were female, with male female ratio of 11.4: 1. Mean age of presentation was ± 7.84 years in males and Table-I: Stent Thrombosis in different types of stents. Types of Stent DES BMS POBA DES + BMS Definite stent thrombosis 19 (1.97%) 16 (1.7%) 3 (0.32%) 0 0 Probabale stent thrombosis 4 (0.41%) 3 (0.31%) 1 (0.1%) 0 0 No stent thrombosis 937 (97.6%) 738 (76.9%) 95 (9.89%) 23 (2.3%) 81 (8.43%) Total Table-II : Frequency of stent thrombosis. Early stent thrombosis Frequency Percentage (%) Acute stent thrombosis 10 1 Subacute stent thrombosis No stent thrombosis Total ± 8.99 years in females respectively. Stents were implanted in 937 (97.6%) out of 960 patients, including 738 (76.9%) who received drug-eluting stents and 95 (9.89%) who received only bare metal stents, 81 (8.43%) patients received both BMS and DES and POBA was done in 23 (2.3%) patients as shown in table-i. Definite stent thrombosis occurred in 16 (1.7%), and 3 (0.32%) patients receiving DES and BMS respectively. Probable stent thrombosis occurred in 3 (0.32%) patients receiving DES and 1 (0.1%) patient receiving BMS as shown in table-i. Total frequency of early stent thrombosis was 2.35% as shown in table-ii. Early stent thrombosis is associated with higher in hospital mortality. Frequency of acute stent thrombosis was 1% and 1.35% of subacute thrombosis. Stent thrombosis

115 Stent Thrombosis in Patient Undergoing Primary PCI Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 in PPCI patient in our study was increased in frequency in age between 58 to 75 years but it is not statistically significant. Early Stent thrombosis developed in 13 (8.2%) of diabetic patients which is statistically significant (p=0.0001, There were no significant association of early stent thrombosis in patients seen in stent thrombosis vs non stent thrombosis group as 47.8% vs 5.8%, 39.1% vs 38.8%, 8.6% vs 8.3% respectively. Radial approach was used in 30 (90.9%) patients of stent thrombosis group and 891 (92.8%) of non stent thrombosis group and femoral approach was used in 3 (9%) and 35 (3.65%) patients of both groups respectively. Left Table-III: Comparison of risk factors between two groups. Stent thrombosis No stent thrombosis Definite ST Probable ST (n=19) (n=4) (n=937) p-value Diabetes / (Non diabetic) 11(8) 2 (2) 145 (792) Hyperlipidemia/ (normal lipid profile) 2 (17) 1 (3) 123 (814) 0.78 Hypertensive / (Normotensive) 3 (16) 1 (3) 239 (698) 0.88 Smoker/(Nonsmoker) 6 (13) 2 (2) 255 (682) 0.67 Previous PCI/(No PCI) 2 (17) 0 (4) 43 (894) 0.65 Previous CABG/ (No previous CABG) 2 (17) 0 (4) 28 (909) 0.29 Previous MI/ (No previous MI) 0 (28) 1 (3) 23 (914) 0.57 Family history of IHD/ (No family history of IHD) 1 (18) 0 (4) 121 (816) Systolic Blood pressure ± ± 19.8 (by Independent samples Kruskal Wallis test) Duration of symptoms 7.8 ± ± (by Independent samples Kruskal Wallis test) with hypertension, smoking, previous history of PCI, CABG and MI as shown in table-iii. Family history of ischemic heart disease. Drop in systolic blood pressure (100.5 ± 15.7) at presentation and long duration of symptoms (7.8 ± 2.6 hours) is a risk factor for stent thrombosis as shown in table-iii. About 48.8% of patients with stent thrombosis vs 14.3% of nonstent thrombosis have high thrombus burden which is statistically significant. Anterior, inferior and lateral myocardial infarction was anterior descending (LAD) was the commonest infarct related artery accounting for culprit artery followed by right coronary artery (RCA) and left circumflex artery (LCX) as shown in table-iv. Patients with early ST had higher in-hospital mortality, 21.7 versus 6%, (p 0.03) and 30-day mortality versus 5%, (p 0.05). Furthermore, the rate of cardiogenic shock (p ) and cerebrovascular accident (p 0.006) was higher in the early ST group. S112

116 Stent Thrombosis in Patient Undergoing Primary PCI Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 DISCUSSION In this study, we studied the frequency, predictors and outcomes of early Stent thrombosis in patinets with STEMI who were managed with primary PCI. Males were predominant in this cohort, their preponderance was around 91%, 8.3% were female while in 15 days of stent deployment respectively. In our study DES and BMS had no significant difference for early stent thrombosis and the results were consistent with the ACUITY trial 17. The baseline characteristics of the patients are shown in table. Diabetic patients were found to have increased stent thrombosis which is statistically significant Table-IV: Procedural characteristics of two groups and their short term outcome. Stent thrombosis No stent thrombosis group group (n=23) (n=937) p-value IRA 0.68 LAD % % RCA % % LCx 2 8.6% % Target lesion Length (mm) 28 ± ± 5.8 Reference Diameter of artery (mm) 2.75 ± ± 0.5 Initial TIMI flow in the IRA % % % % % % % % 0.34 Thrombus Burden Low % % Moderate % % High % % Acces site radial % % femoral % % Outcome In-hospital mortality 5 (21.7%) 56 (6%) day mortality 3 (13.04%) 47 (5%) 0.05 Cardiogenic shock 8 (34%) 112 (12%) Stroke 1 (4.3%) 9 (0.96%) EUROMAX trial 76% were female and 24% were male. Stent thrombosis in our study is frequently encountered in 58 to 75 years of age group of patients (table-iii). The frequency of early ST was 2.35% in our study. Definite stent thrombosis and probable stent thrombosis occurred in 19 and 4 patients, respectively. Acute stent thrombosis and subacute stent thrombosis occurred in 10 (1%) and 13(1.35%) cases within 24 hours and within S113 as compared to non-diabetic. These results are consistent with previously published study 22. Similarly low blood pressure and increased duration of symptoms or prolong ischemic time is statistically significant independent risk factor for stent thrombosis in this study. The procedural and angiographic results are shown in table. Stent in left anterior descending artery is clinicaly significant but statiscally insignificant factor for early stent thrombosis. Longer stent length and

117 Stent Thrombosis in Patient Undergoing Primary PCI Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 relatively smaller stent diameter were significant risk factor for early stent thrombosis in our study. These result are similar to results from the multicenter Spanish registry ESTROFA (Estudio Espanol sobre TR Ombosis de stents F Armacoactivos) 12. Theoretically, STEMI patients have high coronary thrombus burden, hemodynamic changes, and coronary inflammation which can lead to the highest risk of early ST in patients of ACS. However, it is noted that the incidence of early ST in the primary PCI patients was similar to the non-stemi group 16,17. However, acute and subacute stent thrombosis risk raised to 3 to 4 times in patients undergoing PCI for ACS when compared to patients with stable ischemic heart disease undergoing PCI 18,19. Data from various randomized trials has revealed diversity in the incidence of early ST. The rate of early stent thrombosis has ranged from roughly 0.6% in the EUROMAX registry 20, 1% in the MATRIX 14 trial, 1.4% in the ACUITY 17 trial, 2% in the HORIZONSAMI 21 to as high as 3.4% in the bivalirudin arm of the HEATPPCI study 15. In contrast, the incidence of early ST in our primary PCI study was 2.35%, which is on the upper end of previously published data. It is found that early ST was associated with significantly higher in hospital mortality, when compared with previously published studies 23,24. Mortality was more common in patients with subacute stent thrombosis as it was associated with other systemic illnesses such as shock or metabolic acidosis and at the same time acute ST was rapidly diagnosed and treated. This was initialy observed by by Ioannis Iakovou et al 25. Incidence of cardiogenic shock and stroke in patients with early ST was higher (table-ii(b)). Higher events of stroke could be secondary to hypotension related hypoperfusion and a increased risk of mural thrombus in ST patients. Our study has some limitations; The small number of patients with early ST can lead to type II error and because of relatively small number of events we were unable to perform a multiple logistic regression and therefore incapable to execute a propensity score match. Secondly, we analyzed data by using clopidogrel as the preferred antiplatelet agent, and novel antiplatelet agents were not available in our setup. It is difficult to comment if the use of novel antiplatelet agents has reduced the incidence of ST, specifically in light of results of MATRIX and HEAT-PPCI trials where significant patients were on novel antiplatelet agents. CONCLUSION Early ST remains a rare but an important complication following primary PCI. Diabetes mellitus, increased total ischemic time, length of stent, high thrombus burden and Small stent diameter are associated with early ST. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Dangas GD, Caixeta A, Mehran R, Parise H, Lansky AJ, Cristea E, et al. Frequency and predictors of stent thrombosis after percutaneous coronary intervention in acute myocardial infarction. Circulation 2011; 123(16): Kukreja N, Onuma Y, Garcia-Garcia HM, Daemen J, Van- Domburg R, Serruys PW. For the Interventional Cardiologists of the Thoraxcenter (2000 to 2005). The risk of stent thrombosis in patients with acute coronary syndromes treated with bare-metal and drug-eluting stents. J Am Coll Cardiol Intv 2009; 2(6): Luscher TF, Steffel J, Eberli FR, Joner M, Nakazawa G, Tanner FC. Drugeluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation 2007; 115(8): Nakano M, Yahagi K, Otsuka F, Sakakura K, Finn AV, Kutys R et al. Causes of early stent thrombosis in patients presenting with acute coronary syndrome: An ex vivo human autopsy study. J Am Coll Cardiol 2014; 63(23): Dangas GD, Claessen BE, Mehran R, Xu K, Fahy M, Parise H, et al. Development and validation of a stent thrombosis risk score in patients with acute coronary syndromes. J Am Coll Cardiol Intv 2012; 5(11): D Ascenzo F, Bollati M, Clementi F. Incidence and predictors of coronary stent thrombosis: evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thrombosis. Int J Cardiol 2013; 167: Armstrong EJ, Feldman DN, Wang TY. Clinical presentation, management and outcomes of angiographically documented early, late, and very late stent thrombosis. J Am Coll Cardiol Intv 2012; 5: Valensi P, Lorgis L, Cottin Y. Prevalence, incidence, predictive factors and prognosis of silent myocardial infarction: A review of the literature. Arch Cardiovasc Dis March 2011: 104(3): S114

118 Stent Thrombosis in Patient Undergoing Primary PCI Pak Armed Forces Med J 2018; 68 (Suppl-1): S109-S15 9. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293: Cutlip DE, Baim DS, Ho KK, Popma JJ, Lansky AJ, Cohen DJ et al. Stent thrombosis in the modern era: A pooled analysis of multicenter coronary stent clinical trials. Circulation 2001; 103(15): Iakovou I, Schmidt T, Bonizonne E, Ge L, Sangiorgi GM, Stankovic G et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293(17): De la Torre-Hernandez JM, Alfonso F, Hernandez F, Elizaga J, Sanmartin M, Pinar E, et al. Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpanol sobre TROmbosis de stents FArmacoactivos). J Am Coll Cardiol 2008; 51(10): Beinart R, Abu Sham'a R, Segev A, Hod H, Guetta V, Shechter M et al. The incidence and clinical predictors of early stent thrombosis in patients with acute coronary syndrome. Am Heart J 2010; 159(1): Valgimigli M, Frigoli E, Leonardi S, Rothenbuhler M, Gagnor A, Calabro P, et al. Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes. N Engl J Med 2015; 373: Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R,et al. Investigators H-Pt Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEATPPCI): An open-label, single centre, randomised controlled trial. Lancet 2014; 384: Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT, et al. Angiographic stent 6 SINGH ET AL. Thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction. The Importance of Thrombus Burden. J Am Coll Cardiol 2007; 50(7): Aoki J, Lansky AJ, Mehran R, Moses J, Bertrand ME, McLaurin BT, et al. Early stent thrombosis in patients with acute coronary syndromes treated with drug-eluting and bare metal stents: The Acute Catheterization and Urgent Intervention Triage Strategy trial. Circulation 2009; 119: Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus and paclitaxel-eluting coronary stents. N Engl J Med 2007; 356(10): Clemmensen P, Wiberg S, Van t Hof A, Deliargyris EN, Coste P, Ten Berg J, et al. Acute stent thrombosis after primary percutaneous coronary intervention: Insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography). JACC Cardiovasc Interven 2015; 8(1): Dangas GD, Caixeta A, Mehran R, Parise H, Lansky AJ, Cristea E, et al. Harmonizing Outcomes with R, Stents in AMI, Trial I. Frequency and predictors of stent thrombosis after percutaneous coronary intervention in acute myocardial infarction. Circulation 2011; 123(16): Raffaele P, Anna F, Koskinas LR, Thomas P, Marco V, Stefan S, et al. Effect of diabetes mellitus on frequency of adverse events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Am J Cardiol 2016; 118: Secemsky EA, Matteau A, Yeh RW, Steg PG, Camenzind E, Wijns W, et al. Comparison of Short and Long Term Cardiac Mortality in Early Versus Late Stent Thrombosis (from Pooled PROTECT Trials). Am J Cardiol 2015; 115(12): Balaguer-Malfagon JR, Pomar-Domingo F, Vilar-Herrero JV, Planasdel Viejo AM, Perez FE. Stent thrombosis in the modern era: Incidence, outcome and predictive factors. Rev Esp Cardiol 2006; 59(8): Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293(17): Brodie B, Pokharel Y, Garg A, Kissling G, Hansen C, Milks S, et al. Predictors of early, late, and very late stent thrombosis after primary percutaneous coronary intervention with bare-metal and drug-eluting stents for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 2012; 5(10): Lagerqvist B, Carlsson J, Frobert O, Lindback J, Schersten F, Stenestrand U, et al. Stent thrombosis in Sweden: A report from the Swedish Coronary Angiography and Angioplasty Registry. Circ Cardiovasc Interv 2009; 2: Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, et al. Clinical end points in coronary stent trials: A case for standardized definitions. Circulation 2007; 115(17): S115

119 Open Access Cardiac Surgery Associated Acute Kidney Injury Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S116-S19 CARDIAC SURGERY ASSOCIATED ACUTE KIDNEY INJURY IN RELATION TO CARDIOPULMONARY BYPASS TIME AND AORTIC CROSS CLAMP TIME Amna, Etizaz Haider Kazmi*, Rashad Siddiqi, Karam Iqbal, Iftikhar Ahmad Zaidi, Rehana Javaid Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Bahria Hospital Islamabad Pakistan ABSTRACT Objective: To identify the frequency of cardiac surgery associated acute kidney injury and its association with cardio pulmonary bypass time and aortic cross clamp time. Study Design: Descriptive cross sectional study. Place and Duration of Study: Six months duration in Adult cardiac anesthesia department of Armed Forces Institute of Cardiology, Rawalpindi. Material and Methods: A total of 340 patients undergoing cardiac surgery were evaluated for CSA AKI as per the Akin Kidney Injury Network (AKIN) criteria over a period of 6 months for 5 postoperative days (POD). The chi-square test was used find the relationship of different durations of CPB and aortic cross clamp time with CSA-AKI. Results: A total of 340 patients (269 male, 71 female; mean age of ± years, and baseline mean serum creatinine 0.97 ± 0.23 mg%) patients undergone mostly coronary artery bypass grafting, and valvular heart disease correction was evaluated. Nearly 69.7% suffered CSA-AKI. The incidence of acute kidney injury was significantly increased by increase in cardiopulmonary bypass time and aortic cross clamp time with p-values <0.01 and <0.01 respectively. Conclusion: CSA-AKI is common complication, mostly of AKIN Class-I and increases with increasing CPB and cross clamp time. The AKIN can be identified earlier and can be prevented by decreasing cardiopulmonary bypass time and aortic cross clamp time. Keywords: Aortic cross clamp time, Cardiac surgery associated acute kidney injury, Cardio pulmonary bypass time. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Cardiac surgery associated acute kidney injury (CSA-AKI) is one of the common and serious postoperative complication after cardiac surgery that employs cardiopulmonary bypass (CPB) 1. Clinically relevant kidney injury occurs in about 30% of cardiac surgery patients and 1% to 2% require dialysis 2. Even modest kidney injury is independently associated with markedly increased morbidity and mortality 3. Cardiac surgery associated kidney injury is caused by a variety mechanisms, including exogenous and endogenous toxins, metabolic abnormalities, ischemia and reperfusion injury, neuro-hormonal activation, inflammation, and oxidative stress 4. Several risk factors have baeen identified for post Correspondence: Dr Amna, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan. amna.amc@gmail.com operative kidney injury such as diabetes mellitus, preexisting kidney disease, and left ventricular dysfunction, cardiopulmonary bypass time (CPB), Intra aortic balloon pump, preoperative anemia, peri-operative red blood cell transfusions, and postoperative exploration 5-7. Some of these risk factors such as cardiopulmonary bypass time, and aortic cross clamp time are modifiable 8. Development of AKI is associated with the use of cardiopulmonary bypass and the, with combined surgical procedures (valve replacement and coronary artery bypass) and prolonged cardiopulmonary bypass times increasing the incidence of AKI in adults 9. Cardiac surgery associated acute kidney injury increases with increasing CPB time and cross clamp time 10. The development of AKI In adults undergoing cardiac surgery, is associated with prolonged ICU stay and an increased risk of S116

120 Cardiac Surgery Associated Acute Kidney Injury Pak Armed Forces Med J 2018; 68 (Suppl-1): S116-S19 death 11,12. Our purpose of study was to identify the incidence of cardiac Surgery associated acute kidney injury and its association with cardiopulmonary bypass time and cross clamp time and this will help in detecting the potential risk of kidney injury in our setup. MATERIAL AND METHODS After approval by the ethical committee of our institute; consecutive patients undergoing cardiac surgery were studied in our descriptivecross sectional study lasting 06 months after approval of abstract/synopsis. Preoperative evaluation, premedication, anesthesia and surgery was performed according to institutional protocols; no adjustments were made for study participants. Demographic data and preoperative serum creatinine cardiopulmonary bypass time and aortic cross clamp time were noted. After the surgery patients were immediately transported to and cross clamp time i-e <70, , >140 minutes and <50, 50-80, >80minutes. The data was analyzed by descriptive statistics (number, percentage, mean and standard deviation) and Chi square was used for analysis of variance. A p-value<0.05 was taken as significant. Operational Definition Acute Kidney Injury Network was formed in September It described Acute kidney injury in terms of three stages using serum creatinine and urine output criteria 13 (table-i). RESULTS Two hundred and sixty nine (79.1%) were male and 71 (20.9%) were female. Also mean ± standard deviation (SD) for age and weight were evaluated and found to be of ± years and ± kg respectively. The mean ± SD Table-I: Serum creatinine criteria. Stage Serum creatinine criteria Urine out criteria 1 Creatinine from baseline OR: Creatinine increased by at least 26.4μmol/L <0.5ml/kg/hr 6 hours 2 Creatinine <0.5ml/kg/hr 12 hours 3 Creatinine OR Creatinine over 354μmol/L, <0.3ml/kg/hr 24 hours OR with an acute increase by at least 44 μmol/lor: The Anuria for 12 hours initiation of RRT the ICU. Serum creatinine was recorded daily in post operative period for five days. CSA-AKI was determined using acute kidney injury network (AKIN) Criteria. All the patients were assessed for risk stratification and diagnosis of post-operative acute kidney injury by the investigators. Data Analysis Data was analyzed using statistical package for social science (SPSS) version 20. CSA-AKI incidence and severity was determined using AKIN criteria and expressed in absolute number and percentages. The serum creatinine levels was noted and analyzed in positive and negative cases. Cardiopulmonary bypass time and aortic cross clamp time was recorded and stratified further based on different durations of CPB time preoperative serum creatinine was 0.97 ± 0.23 mg%, and creatinine clearance was ± ml/1.73 m 2 BSA. The mean ± SD duration of CPB was About 19 ± min while aortic cross clamp duration was ± min (table-i). The predominant diseases requiring surgeries were coronary artery disease (81.2%) (table-ii). Out of 340 patients 8 (2.35%) patients developed acute kidney injury class 3, 50(14.7%) patients develop class 2 kidney injury. The incidence of acute kidney injury was significantly increased by increase in cardiopulmonary bypass time and aortic cross clamp time, with 42.6% of cases occurring in patients with time between minutes (table III). A p-value was also highly significant <0.01 for both cardiopulmonary bypass time and aortic cross clamp time. About 69.7% of the patients developed acute kidney S117

121 Cardiac Surgery Associated Acute Kidney Injury Pak Armed Forces Med J 2018; 68 (Suppl-1): S116-S19 injury according to acute kidney injury network criteria. Increasing Cardiopulmonary bypass time and aortic cross clamp time was also found to be significantly increasing icu stay p-value <0.01and <0.01 respectively, mortality with p-value of 0.02 and 0.42, and acute kidney injury p-value <0.01 and 0.01 respectively. Acute kidney injury was significantly associated with increase in mortality and ICU stay with p-value <0.01. DISCUSSION In Our observational study, it was tried to evaluate the incidence of CSA-AKI with an bypass grafting (CABG) surgeries (81.2%) as compared to valve replacement surgeries in which is also an independent risk factor for postoperative acute renal failure 10,16. Patients with CSA-AKI progressing to renal failure requiring HD varies from 1% to 3% 17,18. In our study 2.35% patients required renal replacement therapy. The CPB and cross clamp time has got deleterious effect on kidney leading to acute kidney injury, they are among modifiable risk factors 10,19 and attention should be paid to reduce CPB time and aortic cross clamp time. Elena Mancini and colleagues found that time on CPB was associated with increase in acute renal failure Table-II: The predominant cardiac diseases requiring surgeries. Disease Frequency Percentage Valid Cumulative percentage percentage Coronary arterydisease Mitral valve disease Valid Aortic valve disease Double valvedisease Coronary plus valve disease Total Table-III: The association of acute kidney injury with cardiopulmonary bypass time. AKIN class Total < 70 mins cpbtime mins >140 mins Total intention to get more insight so that more appropriate risk stratification can be done. In the present study, 69.7% of the patients were found to develop acute kidney injury by definition of CSA-AKI which is relatively higher as compared to the findings of other studies and reviews 7,14 This is probably because we used AKIN criteria used in our study which categorizes even 0.3 mg% absolute rise of serum creatinine as Class-I acute kidney injury (AKI). The AKIN criteria have shown to diagnose significantly more patients as having AKI as compared to risk, injury, failure, loss of kidney function, and end stage renal failure 15. The predominant surgery performed in the present study was Coronary requiring dialysis 20. In our study significantly increased CSA-AKI numbers (p<0.01) was found with increasing trend of CPB durations. The cross clamp time has also shown similar and significant impact on CSA-AKI (p<0.01). Off- pump or beating heart surgery was developed to avoid post operative complications like kidney injury and pulmonary complications. Kidney injury requiring renal replacement is less common in cardiac surgery without CPB 21. A meta-analysis of 22 randomized trials was evaluated to compare off-pump and on-pump cardiac surgery with respect to kidney injury off pump patients got benefit 22. Coronary a very S118

122 Cardiac Surgery Associated Acute Kidney Injury Pak Armed Forces Med J 2018; 68 (Suppl-1): S116-S19 large randomized controlled trial also compare off-pump and on pump CABG surgery 23 to find long term effect on kidneys. Our study is a single centre prospective study and patients without cardiopulmonary bypass have not been identified. CONCLUSION CSA-AKI is very common complication, mostly of AKIN Class-I and increases with increasing CPB and cross clamp time. The AKIN can be identified earlier and can be prevented by decreasing cardiopulmonary bypass time and aortic cross clamp time. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Beginning, Ending Supportive Therapy for the Kidney I: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 2 94: Lagny MG, Jouret F, Koch JN, Blaffart F, Donneau AF, Albert A, et al. Incidence and outcomes of acute kidney injury after cardiac surgery using either criteria of the RIFLE classification. BMC Nephrol 2015; 16: Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, et al. Minimal changesof serum creatinine predict prognosis in patients aftercardiothoracic surgery: A prospective cohort study. J Am Soc Nephrol 2004; 15(6): Bellomo R, Auriemma S, Fabbri A, D Onofrio A, Katz N, McCullough PA, et al. The pathophysiology of cardiac surgeryassociated acute kidney injury (CSA-AKI). Int J Artif Organs 2008; 31(2): Wijeysundera DN, Karkouti K, Dupuis JY, Rao V, Chan CT, Granton JT, et al. Derivation and validation of a simplified predictive index for renalreplacement therapy after cardiac surgery. JAMA 2007; 297(16): Provenchere S, Plantefeve G, Hufnagel G, Vicaut E, de Vaumas C, Lecharny JB, et al. Renal dysfunction after cardiac surgery with normothermic cardiopulmonary bypass: incidence, risk factors, and effect on clinical outcome. AnesthAnalg 2003; 96: Rosner MH, Okusa MD: Acute kidney injury associated with cardiac surgery. Clin J Am SocNephrol 2006; 1(1): Machado MN, Nakazone MA, Maia LN. Prognostic value of acute kidney after cardiac surgery according to kidney disease: Improving global outcomes definition and staging ( KIGDO) criteria. PLoS One 2014; 9(5): e Rosner MH, Portilla D, Okusa MD: Cardiac surgery as a cause of acute kidney injury: Pathogenesis and potential therapies. J Intensive Care Med 2008; 23(1): Karim HM, Yunus M, Saikia MK, Kalita JP, Mandal M. Incidence and progression of cardiac surgery associated acute kidney injury and its relationship with bypass and cross clamp time. Ann Card Anaesth 2017; 20(1): Robert AM, Kramer RS, Dacey LJ, Charlesworth DC, Leavitt BJ, Helm RE, et al Cardiac surgery-associated acute kidney injury: A comparison of two consensus criteria. Ann Thorac Surg 2010; 90(6): Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V. Acuterenal failure after cardiac surgery: Evaluation of the RIFLE classification. Ann Thorac Surg 2006; 81(2): Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11(2): R Karkouti K, Wijeysundera DN, Yau TM, Callum JL, Cheng DC, Crowther M, et al. Acute kidney injury after cardiac surgery: Focus on modifiable risk factors. Circulation 2009; 119(4): Englberger L, Suri RM, Li Z, Casey ET, Daly RC, Dearani JA, et al. Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery. Crit Care 2011; 15(1): R Grayson AD, Khater M, Jackson M, Fox MA. Valvular heart operation is an independent risk factor for acute renal failure. Ann Thorac Surg 2003; 75(6): Vives M, Wijeysundera D, Marczin N, Monedero P, Rao V. Cardiac surgery associated acute kidney injury. Interact Cardiovasc Thorac Surg 2014; 18(5): Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2: De Mendonça Filho HT, Pereira KC, Fontes M, Vieira DA, De Mendonça ML, Campos LA, et al. Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: A prospective observational study. Crit Care 2006; 10(2): R Mancini E, Caramelli F, Ranucci M, Sangiorgi D, Reggiani LB, Frascaroli G, et al. Is time on cardiopulmonary bypass during cardiac surgery associated with acute kidney injury requiring dialysis. Hemodial Int 2012; 16(2): Bucerius J, Gummert JF, Walther T, Schmitt DV, Doll N, Falk V, et al. On pump versus off pump coronary artery bypass grafting: Impact on postoperative renal failure requiring renal replacement therapy. Ann Thorac Surg 2004; 77: Seabra VF, Alobaidi S, Balk EM, Poon AH, Jaber BL. Off-pump coronary artery bypass surgery and acute kidney injury: A metaanalysis of randomized controlled trials. Clin J Am Soc Nephrol 2010; 5(10): Garg AX, Devereaux PJ, Yusuf S, Cuerden MS, Parikh CR, Coca SG, et al. Coronary Artery Bypass Grafting Surgery Off- or Onpump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial. BMJ Open 2012; 2(2): e S119

123 Open Access Acute Anterior Wall ST-Elevated Myocardial Infarction Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S120-S23 PATTERNS OF LAD INVOLVEMENT IN INDIVIDUALS TILL 40 YEARS OF AGE PRESENTING AS ACUTE ANTERIOR WALL ST-ELEVATED MYOCARDIAL INFARCTION AND UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION Azhar Ali Chaudhry, Imran Ali, Sarfaraz Ali Zahid, Tariq Hussain Khattak, Rehana Khadim, Hazfiz Muhammad Shafique, Asma Shabbir, Tahir Naqqash, Kumail Giskikari, Atif Altaf Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To study the patterns of left anterior descending artery (LAD) involvement in individuals till 40 years of age presenting as acute anterior wall ST elevation myocardial Infarction (AW-STEMI) undergoing primary percutaneous coronary intervention. Study Design: Descriptive cross-sectional study. Place and Duration of study: Armed Forces institute of cardiology and National institute of heart diseases from, Jan 2014 to Oct 2017 Material and Methods: Using non probability consecutive sampling technique 223 patients were included in study according to inclusion and exclusion criteria. Results: Out of 223 patients 205 (91.9%) were male and 18 (8%) were female. Common site for CAD lesion was mid LAD, present in 136 (61.2%) cases followed by proximal, osteal and distal LAD in 66 (29.3%) patients, 11 (5.1%) and 9(4.4%) cases, respectively. Smoking was the most common risk factor for coronary artery disease (CAD) present in 76 (34.5%) cases, hypertension was the second common prevailing risk factor present in 54 (24.2%) patients. Other less common risk factors were family history of CAD, Diabetes Mellitus present in 43 (19.2%) and 32 (14.3%) cases, respectively. Pulmonary edema was the most common complication seen with osteal and proximal LAD lesions in 1 (9%) and 3 (4.5%) cases, respectively. Other complications were cardiogenic shock, arrhythmias and in hospital deaths. Conclusion: Most common site for coronary artery disease in young with Ant Wall -STEMI is the mid LAD followed by proximal lesions. Larger studies are needed to study the risk factors, firmly establish the association of coronary lesion site and rate of complications in young patients presenting with acute myocardial infarction and further compare it with older age group population. Keywords: Anterior wall myocardial infarction, LAD, Primary Percutanous Coronary Intervention, STEMI, Young. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Coronary artery disease (CAD) is the leading cause of morbidity and mortality, both in developing as well as developed countries 1. About 17.7 million people died from Cardiovascular Diseases (CVDs) in 2015, representing 31% of all global deaths 2. By 2030 global projected annual mortality due to CVDs is estimated to rise to 23.3 million 3. Prevalence of CAD in young is relatively uncommon. Reported incidence of myocardial infarction (MI) in young adults varies Correspondence: Dr Azhar Ali Chaudhry, Armed Force Institute of Cardiology/NHID Rawalpindi Pakistan azharalichaudhry@gmail.com between 2% and 10%, according to different studies 4-6. Consequences of MI in young, particularly, can be overwhelming due the fact that they provide the workforce and positive impact in every field of life and MI can have potential devastating effects on patient s mental health and socioeconomic integrity. Moreover there are differences in risk factors and angiographic characteristics of coronary artery lesions in young comparing old patients 7. Present study was planned to provide an insight into common patterns for left anterior descending artery (LAD) involvement and related complications in individuals till 40 years S120

124 Acute Anterior Wall ST-Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S120-S23 age presenting as acute Anterior Wall ST Elevation MI (AW-STEMI) who underwent primary Percutaneous coronary Intervention (PCI) to LAD at our clinical setup. MATERIAL AND METHODS This descriptive cross sectional study was carried out at Armed Forces Institute of Cardiology and National Institute of Heart Disease (AFIC and NIHD) Rawalpindi from Jan 2014 to Oct Study was approved by the institutional review board. Informed consent of patients was taken. Patients included till 40 years of age of both gender who presented to emergency reception (ER) with typical chest pain of cardiac origin of investigations. Data for patterns of LAD involvement is known through angiographic recordings. Patients were closely monitored in intensive coronary care unit for 48 hours following primary PCI for possible complications. Data Analysis Data analysis was done using statistical package for the social sciences (SPSS) ver 20. Data was presented in frequencies and proportions. RESULTS Total number of patients included in our study were 223, out of which 205 (91.9%) were male and 18 (8%) were female. Most common site for CAD lesion was mid LAD, present in 137 (61.2%) cases. while proximal, osteal and distal Table-I: Demograhics and risk factors for coronary artery disease. Risk Factors n=223 Percentage (%) Smoking History Hypertension Family History Diabetes Mellitus No risk factors Table-II: Patterns of LAD involvement in anterior wall myocardial infarction. Site of Lesion n=223 Percentage (%) Osteal Proximal Mid Distal Table-III: Complications in STEMI patients with site of lesion. Complications Osteal (n=11) Proximal (n=66) Mid (n=137) Distal (n=9) Pulmonary Edema 1 (9.0%) 3 (4.5%) 4 (2.9%) - Cardiogenic Shock 2 (18.1%) - 1 (0.7%) - Arrhythmias - 1 (1.5%) - 1 (11.1%) Stroke Mortality 2 (18.1%) 2 (3.0%) 4 (2.9%) - less than 12 hours duration, Electrocardiograph (ECG) showing ST elevation of at least 0.2 mv in more than one precordial leads and underwent primary PCI to LAD. Patients who had previous history of CAD or PCI and the patients presenting after 12 hours of onset of chest pain were excluded. The demographic data was noted down. Risk factors for CADs were recorded through relevant history and laboratory S121 LAD were involved in 66 (29.3%), 11 (5.1%) and 9 (4.4%) cases respectively as shown in table-i. Among the risk factors for CADs, smoking was the most common one present in 77 (34.5%) cases, while hypertension was the second common prevailing risk factor present in 54 (24.2%) subjects. Other less prevailing risk factors were family history of CAD present in 43 (19.2%) and diabetes mellitus in 32 (14.3%) cases. In 17 (7.6%)

125 Acute Anterior Wall ST-Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S120-S23 patients no risk factors were known for CAD as shown in table-ii. Pulmonary edema was the most common complication associated with osteal and proximal LAD lesions present in 1 (9%) and 3(4.5%) cases, respectively. Cardiogenic shock was mainly seen with osteal LAD occlusions. Mortality was 18.1% in osteal LAD disease as shown in table-iii. DISCUSSION Taking into account that the early onset of ischemic heart disease is not so rare, the evaluation of its risk profile, clinical features and prognosis may have a relevant clinical impact for risk factors modification and for the improvement of primary and secondary prevention. In our study 91.9% patients were male same as studies reported by Incalcaterra et al 8 and Hosseini et al 9 While reported proportions were 84% and 86% in studies reported by Saghir et al 10 and Maroszyńska-Dmoch et al 11, respectively. Mid LAD was the most common site for coronary artery lesion involved in 61.2% cases. Proximal LAD coronary artery lesion was present in 29.3% cases. Osteal and Distal LAD coronary artery lesions were relatively rare, present in 5.1% and 4.4% cases respectively. These results are consistent with findings of TIMI study Group which showed that mid LAD was the most common site of involvement in young patients with Anterior Myocardial Infarction 12. In our study complications were most commonly found with osteal and Proximal LAD disease. Recorded complications were cardiogenic shock, pulmonary edema, and Arrhythmias. Overall mortality was 3.0%. These findings were also consistent with the findings of TIMI study group. No local studies were found on the subject even after careful online search to compare our results and the only study available was very old publication of TIMI study group. Identifying and addressing risk factors for CAD in young population is of utmost importance for primordial and primary prevention of CAD. In this study risk factor profile was comparable to national and international studies with smoking being the most common, followed by HTN and Diabetes Mellitus respectively 10,13. CONCLUSION Most common site for coronary artery disease in young with Ant Wall -STEMI was found to be the mid LAD followed by proximal lesions. Larger studies are needed to study the risk factors, firmly establish the association of coronary lesion site and rate of complications in young patients presenting with acute myocardial infarction and further compare it with older age group population. LIMITATION OF STUDY This was just an observational study and not a randomized trial for documentation of patterns of LAD involvement in AW-STEMI undergoing PPCI in young patients. Larger studies are needed to assess the risk factor profiles, establish association of site of lesion with complications in young individuals undergoing PPCI for AW-STEMI. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author REFERENCES 1. Menees DS, Peterson ED, Wang Y, Curtis JP, Messenger JC, Rumsfeld JS, et al. Door to balloon time and mortality among patients undergoing primary PCI. N Engl J Med 2013; 369(10): Hata J, Kiyohara Y. Epidemiology of stroke and coronary artery disease in Asia Circ J 2013; 77(8): Badimon L, Padro T, Vilahur G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur Heart J Acute Cardiovasc Care 2012; 1(1): Kushner FG, Hand M, Smith SC Jr, King SB, Anderson JL, Antman EM, et al. American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines 2009 Focused Updates: ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on percutaneous coronary intervention (updating the 2005 Guideline and2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009; 120(22): Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. Task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), ESC Guidelines for the management of acute S122

126 Acute Anterior Wall ST-Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S120-S23 myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33(20): Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review of 23 randomized trials. Lancet. 2003; 361(9351): Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med ; 349(8): Widimsky P, Wijns W, Fajadet J, de Belder M, Knot J, Aaberge L. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur Heart J 2010; 31(8): Lassen JF, Botker HE, Terkelsen CJ. Timely and optimal treatment of patients with STEMI. Nat Rev Cardiol 2013; 10(1): Thorsted Sorensen J, Steengaard C, Holmvang L, Okkels Jensen L, Terkelsen CJ. Primary percutaneous coronary intervention as anational Danish reperfusion strategy of STelevation myocardial infarction. Ugeskr Laeger 2013; 175(4): Rao SV, Cohen MG, Kandzari DE, Bertrand OF, Gilchrist IC. The transradial approach to percutaneous coronary intervention: historical perspective, current concepts, and future directions. J Am Coll Cardiol 2010; 55: Jang JS, Jin HY, Seo JS, Yang TH, Kim DK, KIM DK, et al. Transradial versus transfemoral approach for primary percutaneous coronary intervention in patients with acute myocardial infarction: a systematic review and meta-analysis. Euro-Intervention 2012; 8(4): Swaminathan RV, Wang TY, Kaltenbach LA, Kim LK, Minutello RM, Bergman G, et al. Non system Reasons for Delay in Doorto-Balloon Time and Associated In-Hospital Mortality, A Report From the National Cardiovascular Data Registry. J Am Coll Cardiol 2013; 61(16): S123

127 Open Access Tilt-Table Testing in Patients With Unexplained Syncope Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S124-S28 COMPARISON OF DIFFERENT TYPES OF RESPONSES TO TILT-TABLE TESTING IN PATIENTS OF BOTH GENDERS WITH UNEXPLAINED SYNCOPE Ayesha Riaz, Azmat Hayat*, Zahoor Khattak*, Sadaf Shabbir Kiani*, Mubarra Nasir*, Samra Rehmat*, Hassan Kamal*, Muhammad Shabbir*, Abdul Hameed Siddiqui*, Fatima Qayyum Ayub Teaching Hospital Abbottabad Pakistan, *Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To compare the frequency of various types of responses in both genders undergoing tilt table test with unexplained syncope. Study Design: A comparative cross-sectional study. Place and Duration of Study: Department of EP studies, Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from Aug 2017 to Jan Material and Methods: Patients were recruited through non-probability consecutive sampling. Patients of all age groups of both genders who had syncope as per operational definition were included in our study. Patients who were excluded from the study were, newly diagnosed or previously established history of arrhythmias, coronary artery disease, cardiomyopathies and structural heart disease e.g. HOCM, aortic stenosis, mitral stenosis. Patients who had history of epilepsy on medical record and history of anemia on medical record were also excluded from the study. Base line demographic information of patients (age, gender, duration of complain) and types of responses were recorded on especially designed proforma. Results: Total 294 patients were recruited for the study. Mean age of the patients was 46.7 ± 8.1 years, with minimum age 12 years and maximum age 85 years. Male patients were found to be 244 (82.4%) while female patients were 50 (16.9%). Mean duration of complaints was 1.5 ± 1.7 months. Our study showed that the most common type of response in male and females were mixed type (88.1%) and (84%) respectively, with the p-value of while, cardioinhibitory type response was (2.8%) but found in male gender only. Next most common type was vasodepressor type response common in females than males with 6% and 2.4% respectively. Subsequently, less frequent type of response was showed with classic type of orthrostatic hypotension (2%) while type Initial orthrostatic hypotension was not recoreded in the study. Females were more frequent than males in Progressive orthrostatic hypotension with (5%) and (0.4%) in males. POTS response was not present in either gender. Conclusion: As our study showed, among type of responses, mixed type of response has a significantly high positive rate being more common in male gender, while vasodepressive type and progressive orthostatic hypotension type being more common in female gender. Tilt-table testing plays a major role during the evaluation of syncope patients, helps to differentiate syncope subtypes and could be useful in guiding treatment. however, the need for using another protocol with a similar diagnostic accuracy in gender specificity is necessary. Keywords: Tilt-table testing, Syncope, Arrhythmia, Cardiomyopathy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Syncope is a clinical syndrome defined as a relatively brief and self-limited transient loss of consciousness (TLOC) caused by a period of in Correspondence: Dr Ayesha Riaz, Ayub Teaching Hospital (ATH) Abbottabad Pakistan doc.aysh@gmail.com adequate cerebral nutrient flow. Most often the trigger is an abrupt drop of systemic blood pressure 1. True syncope must be distinguished from other common non-syncope conditions in which real TLOC may have occurred such as seizures or concussions, or in which TLOC may seem to have occurred such as with accidental falls or psychogenic pseudosyncope 1. S124

128 Tilt-Table Testing in Patients With Unexplained Syncope Pak Armed Forces Med J 2018; 68 (Suppl-1): S124-S28 The tilt table test (TTT) was initially described by Kenny et al 2, in 1986 as a tool to diagnose syncope of unknown origin. Since then various protocols have been developed. The cornerstone of the test is an orthostatic challenge which is done with the upright tilt. Apart from its main use in the syncope workup, use of the test was described in the evaluation of the presence of autonomic neuropathy in a variety of conditions 3. The main idea behind the test is that reflex syncope is due to the abnormal cardiac autonomic reflexes, which lead to inappropriate vasodilatation (vaso-depressive reflex syncope), inappropriate bradycardia (cardioinhibitory reflex syncope) or a mixed response 4. A prolonged upright position is a known trigger of reflex syncope, where, after an initial normal adaptation to standing, inappropriate vasodilatation or bradycardia appears, leading to symptoms. This is different from the orthostatic hypotension, where the initial response to standing is abnormal 1. These are benign conditions without any associated increase in mortality and are characterized by vasodilatation or vagally driven bradycardia or asystole, which causes profound systemic hypotension and consequent dizziness, presyncope, and finally, syncope. Older people are at a high risk for syncope due to the physiological changes of aging and the presence of more comorbid conditions and, thereby, more medications, which may predispose them to hypotension 5,6. However, a definite relationship between age and type of syncope has yet to be fully documented, particularly in the elderly, whose clinical conditions need further clarification 7. No such study has been done before in our local population. Results of international studies cannot be generalized on our population due to different genetic makeup and confounding variables. Therefore we planned to determine the frequency of different types of responses in patients with syncope undergoing tilt table test in our local population. Results of our study would help to generate local evidence for further research in this subject. Syncope Defined as a sudden transient loss of consciousness with associated loss of postural tone and spontaneous recovery without neurologic deficit and without requiring electrical or chemical cardioversion 3. Types of Responses to Tilt-Table Testing Mixed type: The heart rate falls at the time of syncope, but it does not fall to under 40 beats per minute (bpm), or reaches <40 beats per minute for less than 10 seconds, with or without asystole <3sec. The blood pressure falls before the heart rate falls 5. Cardio-inhibitory type: Defined as any one of following: a) Cardioinhibition without asystole occurs when the heart rate falls to a ventricular rate below 40 bpm for longer than 10 seconds but asystole of shorter than 3 seconds. The blood pressure drops prior to the fall of the heart rate. b)cardioinhibition with asystole is defined as when the heart rate falls to a ventricular rate below 40 bpm for longer than 10 secondsbut with occurrence of asystole for more than 3 seconds. The heart rate fall coincides with or precedes the blood pressure fall 6. Vasodepressor type: BP falls to systolic value of <60mmHg. The heart rate does not fall by more than 10% from its peak value at the time of syncope 7. Initial orthostatic hypotension: Decrease in BP >40mmHg at standing with spontaneous and fast normalization, so that hypotension and symptoms last <30secs 8. Classic orthostatic hypotension: Decrease in systolic Bp 20mmHg and diastolic BP 10mmHg during the first 03 minutes after standing 9. Progressive orthostatic hypotension: Slow and progressive systolic BP decline after the 3rd minute of standing 10. Postural orthostatic tachycardia syndrome (POTS): Increase in heart rate >30 beats per minute or heart rate >120 beats per minute S125

129 Tilt-Table Testing in Patients With Unexplained Syncope Pak Armed Forces Med J 2018; 68 (Suppl-1): S124-S28 after standing, accompanied by symptoms (e.g. fatigue, dyspnea, light headedness) 11. MATERIAL AND METHODS A descriptive cross sectional study was carried out at the department of EP studies, Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from Aug 2017 to Jan Patients were recruited through non-probability consecutive sampling. Patients of all age groups of both genders who had syncope as per operational definition were included in our study. Patients who were excluded from the study were, newly diagnosed or previously established history of arrhythmias, coronary artery disease, cardiomyopathies and structural heart disease e.g. HOCM, aortic stenosis, mitral stenosis. Patients who had history of epilepsy on medical record and history of anemia on medical record after an initial observation with the patient in the supine position for 10 minutes. The test consisted of 2 consecutive stages. In stage-i, the patient was tilted at 70 degrees for 20 minutes without medication and with control of the heart rate and 3-lead electrocardiography. The blood pressure was continuously and non-invasively monitored during the test. If syncope (or limiting symptoms) developed, the test would be halted and the patient was returned into the supine position. Otherwise, the patient would be taken into stage-ii, where 500 micrograms of sublingual TNG was administered and tilting was continued for another 20 minutes. If syncope (or limiting symptoms) occurred during the active phase, the tilt table was rapidly reversed to return the patient to the supine position, and the study was terminated. Data was entered and analyzed with IBM-SPSS version-22. Table: Comparison of type of responses to tilt-table testing in both genders. Type of responses to tilttable testing Male patients n(%) Female patients n(%) p-value Mixed Type 215 (88.0%) 42 (84.0%) Cardioinhibitory type with asystole Without Asystole 1 (0.4%) 6 (2.4%) - - Vasodepressor Type 6 (2.4%) 3 (6.0%) Initial orthostatic hypotension - Classic orthostatic hypotension 5 (1.7%) - Progressive orthostatic hypotension 1 (0.4%) 5 (10.0%) Postural orthostatic tachycardia syndrome (POTS) - were also excluded from the study. Base line demographic information of patients (age, gender, duration of complain) and types of responses were recorded on especially designed proforma. The tilt table test was performed using an electrically controlled tilt table with a foot board for weight bearing, using a Task Force hemodynamic monitor 3040i. The blood pressure, heart rate, and rhythm was continuously monitored and recorded according to a 2-stage tilt protocol with nitroglycerin (TNG) provocation. The tilt table test was conducted S126 RESULTS Total 294 patients were recruited for the study. Mean age of the patients was 46.7 ± 8.1 years with minimum age 12 years and maximum age 85 years. Male patients were found to be 244 (82.4%) while female patients were 50 (16.9%). Mean duration of complaints was 1.5 ± 1.7 months as shown in table-i. Our study showed that the most common type of response in male and females were mixed type (88.1%) and (84%) respectively, with the p-value of while,

130 Tilt-Table Testing in Patients With Unexplained Syncope Pak Armed Forces Med J 2018; 68 (Suppl-1): S124-S28 cardio inhibitory type response was (2.8%) but found in male gender only. Next most common type was vasodepressor type response common in females than males with 6% and 2.4% respectively. Subsequently, less frequent type of response was showed with classic type of orthrostatic hypotension (2%) while type Initial orthrostatic hypotension was not recorded in the study. Females were more frequent than males in Progressive orthrostatic hypotension with (5%) and (0.4%) in males. POTS response was not present in either gender. DISCUSSION Tilt-testing enables the reproduction of reflex syncope. Positive responses in patients with neu rally mediated syncope are 61-69% and specificity is high (92-94%) 5. The most commonly used protocol includes tilting to 70, a passive unmedicated phase of 20 minutes, application of μg sublingual nitroglycerine at the 20th minute and an additional 20 minutes of standing 12. The most common indication for TTT is to confirm a diagnosis of reflex syncope in patients in whom this diagnosis has been suspected but not confirmed by the initial evaluation. This includes cases with a single unexplained syncope in a high-risk setting or those with multiple recurrent episodes when a cardiovascular cause has been reasonably excluded 13. TTT is also recommended when it is of clinical value to demonstrate susceptibility to reflex syncope to the patient. Other indications for tilt-testing are discrimination between reflex syncope and orthostatic hypotension or falls, between TLOC with jerking movements and epilepsy, and in patients with frequent episodes of TLOC and suspicion of psychiatric problems 14. Performing tilt-testing according to ESC guidelines could have a high diagnostic yield (higher than most of the other tests). Occurrence and recurrence of TLOC could have a major impact on a patient s wellbeing and social adaptation 15. Most of the tests initially performed on these patients (mostly in general practices and not in dedicated syncope units) do not yield any positive results. It is still widespread practice to refer such cases to a neurologist who will perform different tests to exclude epilepsy, which can be additionally frustrating for the patient. Generally, these tests have a much lower diagnostic yield compared to tilt-testing. In such a situation the ability to apply a simple and noninvasive test (like TTT) which could confirm the diagnosis of the most common syncope type reflex syncope is of great value. The type of response to tilt-testing could guide patient management 16. Patients with vasodepressor and mixed syncope and those with orthostatic hypotension most of all need reassurance regarding the benign nature of the condition. Education plays a key role in this setting and includes avoidance of triggering factors, increase in fluid intake, physical counter pressure maneuvers and tilt-training 10,17. The proper management for patients with cardioinhibitory syncope with asystole has been the subject of much debate 5,8. Several randomized controlled trials 4,6,10 based on tilt-testing response have given conflicting results. The International study on syncope of uncertain etiology-2 trial 10 showed a striking reduction in the recurrence of syncope with pacing in patients with documented asystole during spontaneous syncope (implantable loop recorder monitoring). International study on syncope of uncertain etiology-2 was a nonrandomized trial, but recently its results were confirmed by the randomized International study on syncope of uncertain etiology-3 trial 10. In a study by Noormand et a l7 has showed that frequency of mixed type syncope was 36.7%, cardioinhibitory 35.3% and 27.4% was vasodepressive in patients underwent tilt table test 7. Our study showed that the most common type of response in male and females were mixed type (88.1%) and (84%) respectively, with the p-value of while, cardioinhibitory type response was (2.8%) but found in male gender only. Next most common type was vasodepressor type response common in females than males with 6% and 2.4% respectively. Subsequently, less frequent type of response was showed with classic type of orthrostatic hypotension (2%) S127

131 Tilt-Table Testing in Patients With Unexplained Syncope Pak Armed Forces Med J 2018; 68 (Suppl-1): S124-S28 while type Initial orthrostatic hypotension was not recoreded in the study. Females were more frequent than males in Progressive orthrostatic hypotension with (5%) and (0.4%) in males. POTS response was not present in either gender. At present, the issue regarding the appropriateness of pacing patients with TTTinduced asystole during syncope is not fully resolved. The decision to implant a pacemaker (an invasive procedure) should be taken in the clinical context of a benign (in terms of mortality) condition that usually affects young individuals and often children. CONCLUSION As our study showed, among type of responses, mixed type of response has a significantly high positive rate being more common in male gender, while vasodepressive type and progressive orthostatic hypotension type being more common in female gender. Tilt-table testing plays a major role during the evaluation of syncope patients, helps to differentiate syncope subtypes and could be useful in guiding treatment. However, the need for using another protocol with a similar diagnostic accuracy in gender specificity is necessary. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Koene RJ, Adkisson WO, Benditt DJ. Syncope and the risk of sudden cardiac death: evaluation, management, and prevention. J Arrhythm 2017; 33(6): Teodorovich N, Swissa M. Tilt table test today-state of the art. World J Cardiol 2016; 8(3): Chelimsky G, McCabe NP, Janata J, Elston R, Zhang L, Ialacci S, et al. Autonomic testing of women with interstitial cystitis/ bladder pain syndrome. ClinAuton Res 2014; 24(4): Da-Silva RMFL. The current indication for pacemaker in patients with cardioinhibitory vasovagal syncope. Open Cardiovasc Med J 2016; 10: Goyal P, Maurer MS. Syncope in older adults. J Geriatr Cardiol 2016; 13(5): Shafiee A, van Bodegom D. The necessity for research on the elderly in Iran. J Tehran Heart Cent 2012; 7(1): Noormand R, Shafiee A, Davoodi G, Tavakoli F, Gheini A, Yaminisharif A, et al. Age and the head-up tilt test outcome in syncope patients. Res Cardiovasc Med 2015; 4(4): e Brignole M, Ungar A, Casagranda I, Gulizia M, Lunati M, Ammirati F, et al. Prospective multicentre systematic guidelinebased management of patients referred to the syncope units of general hospitals Europace 2010; 12(1): Sutton R, Brignole M. Twenty-eight years of research permit reinterpretation of tilt-testing: hypotensive susceptibility rather than diagnosis. Eur Heart J 2014; 35(33): Van Dijk N, Quartieri F, Blanc JJ, Garcia-Civera R, Brignole M, Moya A. Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: The Physical Counterpressure Manoeuvres Trial. J Am Coll Cardiol 2016; 48(8): Duygu H, Zoghi M, Turk U, Akyuz S, Ozerkan F, Akilli A, et al. The role of tilt training in preventing recurrent syncope in patients with vasovagal syncope: A prospective and randomized study. Pacing Clin Electrophysiol 2008; 31(5): Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P, et al. Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope: pacemaker versus no therapy: A multicenter randomized study. The vasovagal syncope International study (VASIS) Investigators. Circulation 2010; 102(3): Connolly SJ, Sheldon R, Thorpe KE, Roberts RS, Ellenbogen KA, Wilkoff BL, et al. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. JAMA 2003; 289(17): Raviele A, Giada F, Menozzi C, Speca G, Orazi S, Gasparini G, et al. A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tiltinduced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE). Eur Heart J 2004; 25(19): Brignole M, Menozzi C, Moya A, Andresen D, Blanc JJ, Krahn AD, et al. Pacemaker therapy in patients with neurally-mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation 2012; 125(21): Simova I, Katova T, Zerdeva E, Dasheva A, Levunlieva E, Kuneva A. Syncope in children and adolescents. Role of tilt-table testing. Bulgarian Cardiology 2014; 3(XX): Simova I, Katova T. Tilt-table testing in patients with syncope. Bulgarian Cardiology 2012; XVIII (suppl-2): p-57. S128

132 Open Access Gait Speed A Clinical Maker of Frailty Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S129-S33 GAIT SPEED A CLINICAL MAKER OF FRAILTY AS A PREDICTOR OF CARDIAC SURGERY-RELATED COMPLICATIONS AND IN HOSPITAL MORBIDITY IN PATIENTS UNDERGOING CARDIAC SURGERY Shiza Ali Khan, Safdar Abbas, Muhammad Waseem, Hafsa Khalil Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To use gait speed as a frailty marker to predict the adverse outcomes after cardiac surgery and in hospital morbidity of elderly patients undergoing the cardiac surgery. Study Design: Comparative cross-sectional study. Place and Duration of study: Department of Cardiac Surgery Armed forces Institute of Cardiology and National Institute of Heart Disease, from Oct 2017 to Feb Materials and Methods: This study was conducted on 100 adult patients undergoing the cardiac surgery at AFIC/NIHD, over 5 months from Oct 2017 to Feb Patients included if they were 55 years or older; undergoing coronary artery bypass graft (CABG) surgery, aortic valve surgery, mitral valve surgery, or CABG combined with aortic or mitral valve surgery. The primary predictor was slow gait speed, 5-meter walk in 6 seconds or longer. The primary end point was a composite of post-operative complications and in hospital morbidity Results: Comparative cross-sectional study consisted of hundred patients out of which 81 (81%) were male and (19) 19% were female patients. Ninety two (92%) with a mean age of 62.5 ± 5.3 years. The post-operative complications like prolonged ventilation with p-value (p<0.001), deep sternal wound infection (p=0.41), Pulmonary complications (p=0.002) and prolonged post-operative length of stay (p<0.001) were more in patient with slow and slowest walking speed and differences were highly significant. There was no significant different in stroke (p=0.771), reoperation (p=0.342) and readmission (p=0.451) with slow and slowest gait speed. Conclusion: Gait speed is most economical and independent predictor of adverse outcomes and morbidity after cardiac surgery. Gait speed as a frailty marker may help to identify, screen and subset the adult population at high risk of adverse outcomes of cardiac surgery that could benefit from further assessment. Keywords: Cardiac surgery, Coronary artery bypass graft, Gait speed test. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Walk is a basic and necessary component of functional mobility so a person can move around and complete their everyday tasks. Slowness of movement with aging is a complete biological phenomena that involves integrity of physiological system like nervous system, skeletal system, muscular system, respiratory system and the circulatory system 1. In medicine, frailty is used to defineas older adults with impaired resistance to stressors due to a decline in physiologic reserve 2. In older adults, the prevalence of frailty is 10% 3. Slow walking speed is a reliable and valid source to measure frailty Correspondence: Dr Shiza Ali Khan, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan shizaalikhann@gmail.com and found to be associated with adverse outcomes of cardiovascular disease 4-6. Gait speed test measured as the time required to walk a short distance (usually 5m) at a comfortable pace and one of the most commonly used tests to screen for frailty and identify high-risk adults thatneed further evaluation 7. Gait speed test is found most promising especially in cardiac surgery, where an aging and heterogeneity of older adults make clinical decision making very challenging and also inherent stress to surgery. Prediction of morbidity is particularly relevant to the older adults because they have less resiliency to complications and complications are a noteworthy driver of increase hospital billing, adverse outcomes can affect the quality of life, and prolongs the stay in hospital 8. Numerous S129

133 Gait Speed A Clinical Maker of Frailty Pak Armed Forces Med J 2018; 68 (Suppl-1): S129-S33 cross-sectional and randomized studies have shown adverse outcomes of cardiac surgery are fairly large, older adults undergoing cardiac surgery has already presented with many comorbid illnesses which make them frail so they present with adverse outcome after surgery that make effect their hospital stay longer with adverse outcomes of post-operative complications The frailty assessment before cardiac surgery (Frailty ABCs) study measured gait speed in 131 patients undergoing cardiac surgery and found that slow gait speed (<0.83 m/s) was associated with an odds ratio (OR) of 3.05 (95% CI, ) for in-hospital mortality or major morbidity 12. As walking speed is a clinical maker of frailty and gait speed is very simple and can help to identify, screen and subset the adult population at high risk of adverse out comes of cardiac surgerythus: The purpose of this study was to use gait speed as a frailty marker to predict the adverse outcomes after cardiac surgery and morbidity of elderly patients undergoing the cardiac surgery. MATERIAL AND METHODS A comparative cross-sectional study was conducted on hundred patients undergoing the cardiac surgery at AFIC/NIHD, over 5 months from Oct 2017 to Feb Eligible patients were approached. Based on this 5-m gait speed test, walking speed more than or equal to 6sec considered as slow and less than 6sec as normal which served as the primary predictor variable for this study. The treating physicians and patients were blinded to the gait speed test results so as not to influence their decision to proceed with the surgery or their post-operative management. No patient lost follow up till discharge. Participants Patients included if they were 55 years or older undergoing coronary artery bypass graft (CABG) surgery, aortic valve surgery, mitral valve surgery, or CABG combined with aortic or mitral valve surgery. Exclusion Criteria Emergent surgery, defined as a surgery for which there should be no delay due to ongoing refractory cardiac compromise, Clinical instability, defined as active coronary ischemia, decompensated heart failure not yet stabilized, or any acute process causing significant symptoms or abnormal vital signs. Patient having any respiratory disease preoperatively. Any neurological condition (CVA, spinal cord injury effecting walking speed). Severe neuropsychiatric condition causing inability to cooperate with the study procedures. Patient reported dyspnea at NYHAIV. Patient having angina at CCS Grade-III. Predictor Variable, Gait Speed Test The primary predictor variable was 5-m gait speed. Based on this 5-m gait speed test, walking speed more than 6 sec is consider as slowest and equal to 6 sec considered as slow and less than 6 sec as normal. Timed measured by a stopwatch over a short distance (5 meter). Patients were permitted to use any mobility aid. Measured straight walk on a level indoor surface without turns (excluding walking on treadmill). Test begins on the word go ; start the timer with the first footfall on the 0-m line; and stop the timer with the first foot fall on the 5-m line. To take average, this test was repeated 3 times, for accurate measurement. Although speed is typically measured in m/s, it was elected to report it in seconds (taken to walk 5 m) to facilitate subsequent bedside application and interpretation of this test in clinical practice without any calculations 13. Outcome variables The primary end point was in-hospital morbidity and post-operative complications increasing the length of stay. These complications were stroke (central neurologic deficit persisting >72 h), prolonged ventilation (>24 h), deep S130

134 Gait Speed A Clinical Maker of Frailty Pak Armed Forces Med J 2018; 68 (Suppl-1): S129-S33 sternal wound infection (requirement for operative intervention and antibiotic therapy, with positive culture), pulmonary complications (pleural effusions and atelectasis), readmission, need for reoperation (for any reason) and prolonged post-operative length of hospital stay (>10 days after surgery). Statistical Analysis The statistical analysis was carried out using SPSS 23 (Statistical package for social sciences) software. Statistical test applied was chi-square and descriptive statistics was applied to calculate mean, standard deviation and frequencies. RESULTS This comparative cross sectional study consisted of 100 patients with a mean age of 62.5 ± 5.3 years; 81 (81%) were male and (19) 19% Table: Association of Gait speed test with outcome variables. Outcome Variables Normal Gait Speed (n=8) were female patients. No patients were lost to follow-up. Out of these patients, Body mass index (calculated as weight in kilograms divided by height in meters squared), thirty eight (38%) were withnormal weight, twenty three (23%) were overweight, seven (7%) were under weight and thirty two (32%) were obese patients. Among comorbid conditions, hypertension was most common condition in fifty six (56%) patients and the frequency of other comorbidities like diabetes was in thirty four (34%) patients, dyslipidemia 3 (3%) and twenty seven (27%) were active smokers. The mean and standard deviation of LVEF in percentage 53.9 ± Prior to surgery eighty (80%) patients reported dyspnea at NYHA class-ii, sixteen (16%) were at NYHA class- I, 4 (4%) were at NYHA class-iii. The surgery performed wasisolated CABG in ninety two (92%) Patients, four (4%) had AV replacement, two (2%) had MV replacement only and two (2%) AVreplacement+CABG. Among Post-operative complications 52 patient went on prolonged ventilation, there was a significant association (p=0.000) that slowest walker had prolonged ventilation (n=50) than slow walkers (n=2), eleven patients had deep sternal wound infection are slowest walkers (p=0.41), twenty patients had pulmonary complications were slowest walker (p=0.002), There was no significant association between stroke and slow gait speed or slowest gait speed (p=0.771), reoperation (p=0.342) and readmission (p=0.451). There was a significant association between prolonged post-operative length of stay (>10 days). Among 39 patients with Slow gait speed (n=26) Frail prolonged stay n=33 with slowest gait speed, n=1 with slow gait speed and n= 5 was with normal gait speed (p<0.001) as shown in table. DISCUSSION Slowest gait speed (n=66) High Risk Frailty p-value Prolonged ventilation - 2 (3.8%) 50 (96%) <0.001 Deep sternal wound infection (100%) Pulmonary complications (100%) Reoperation (100%) Stroke (100%) Prolonged post-operative length of stay (>10 days) 5 (12.9%) 1 (2.5%) 33 (84.6%) <0.001 Readmission (100%) The finding of this study was to use gait speed as a frailty marker to predict the adverse outcomes after cardiac surgery and in hospital morbidity of elderly patients undergoing the cardiac surgery. The 5-m gait speed test was successfully implemented at 109 centers in more than patients during a 3-year time frame. Slow gait speed was independently predictive of operative mortality and, to a lesser extent of major morbidity and adverse outcomes of cardiac surgery. This result was observed across a spectrum of the most commonly performed S131

135 Gait Speed A Clinical Maker of Frailty Pak Armed Forces Med J 2018; 68 (Suppl-1): S129-S33 cardiac surgical procedures used to treat ischemic and valvular heart disease. Overall, for each 0.1- m/s decrease in gait speed (eg, taking 6 seconds as opposed to 7 seconds to walk the 5-m course at a comfortable pace), there was an 11% relative increase in operative mortality after adjusting for STS-PROM 12,13. Afilalo et al, reported that an impaired gait speed (a simple measure of frailty) can be used to identify elderly patients at high risk of major in-hospital events after cardiac surgery. They defined the primary predictor slow gait speed as the time taken to walk 5 m in more than 6s, consistent with our findings patients that participants presented with slow walking speed had adverse outcomes and increased length of stay after cardiac surgery 13. Patients undergoing cardiac surgery had twice incidence of stroke and renal failure post-operatively 14, 15 but in this study there was no significant association between stroke and slow gait speed or slowest gait speed (p=0.771), reoperation (p=0.342) and readmission (p=0.451). Although it is clear that frailty portends adverse outcomes, its subjective nature has inhibited the application of this knowledge. This study supports the use of the 5-m gait speed test as an objective measure of frailty and should help overcome this barrier. Gait speed can play an influential role in defining the appropriate treatment plan for the older patient. In addition to signaling for further evaluation and support at the slow end of gait speed, it can be reassuring at the high end of gait speed despite a patient s advanced chronological age. Prediction of operative risk, particularly in the complex clinical case of a patient with multiple chronic conditions, can help the care team and patient arrive at the most informed decision aligned with values and goals for both survival and quality of life. This shared decision may on occasion be for a less-invasive option, such as percutaneous intervention, medical management, or comfort care. When cardiac surgery is the treatment of choice, this real-world study reaffirms that older adults have the potential for excellent outcomes with low overall rates of mortality and major morbidity. To further improve outcomes, comparative effectiveness studies are needed to determine whether the risks of cardiac surgery are modulated by patient frailty, as are randomized clinical trials to determine whether the benefits of cardiac surgery are maximized by concomitant interventions, such as exercise training, nutritional supplementation, multidimensional programs, home-based services, and drug therapies 16 17,18,20,21. CONCLUSION This study adds to the growing body of literature that has shown that slow gait speed is prevalent in patients with cardiovascular disease and predictive of adverse outcomes 16. To our knowledge, this study test the value of gait speed as frailty marker in patients undergoing cardiac surgery. As gait speed is most economical, and independent predictor of adverse outcomes and morbidity after cardiac surgery. It may be useful to identify, screen and subset the elderly population at high risk of adverse out comes of cardiac surgery that could benefit from further assessment. Additional research is needed to examine the effect of gait speed on long-term hazards and patient-centered outcomes, and to develop targeted interventions that can offset the negative impact of frailty. LIMITATION OF STUDY There are a number of limitations in this study. The primary end point was measured inhospital as opposed to long term, and events occurring after discharge or transfer were not captured. This is particularly relevant for deep sternal wound infections that typically occur weeks after surgery, once patients have been discharged. This study conducted at single center with relatively small sample size and male patient were more than female patient so we suggest that multicenter study required with large sample size representing gender equality around Pakistan for more examination. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. S132

136 Gait Speed A Clinical Maker of Frailty Pak Armed Forces Med J 2018; 68 (Suppl-1): S129-S33 REFERENCES 1. Ferrucci L, Bandinelli S, Benvenuti E,, Di Iorio A, Macchi C, Harris TB, et al. Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the In CHIANTI study. J Am Geriatr Soc 2000; 48(12): Bergman H, Ferrucci L, Guralnik J, Hogan DB, Hummel S, Karunananthan S, et al. Frailty: an emerging research and clinical paradigm issues and controversies. J Gerontol A Biol Sci Med Sci 2007; 62(7): Collard RM, Boter H, Schoevers RA, Oude Voshaar. RC. Prevalence of frailty in community-dwelling older persons: A systematic review. J Am Geriatr Soc 2012; 60(8): Purser JL, Kuchibhatla MN, Fillenbaum GG, Harding T, Peterson ED, Alexander KP. Identifying frailty in hospitalized older adults with significant coronary artery disease. J Am Geriatr Soc 2006; 54(11): Cesari M1, Kritchevsky SB, Penninx BW, Nicklas BJ, Simonsick EM, Newman AB, et al. Prognostic value of usual gait speed in well-functioning older people--results from the Health, Aging and Body Composition Study. J Am Geriatr Soc 2005; 53(10): Dumurgier J, Elbaz A, Ducimetière P, Tavernier B, Alpérovitch A, Tzourio C. Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study. BMJ 2009; 339: b Abellan van Kan G, Rolland Y, Andrieu S, Bauer J, Beauchet O, Bonnefoy M, et al. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging 2009; 13(10): Geissler HJ, Hölzl P, Marohl S, Kuhn-Régnier F, Mehlhorn U, Südkamp M, et al. Risk stratification in heart surgery: comparison of six score systems. Eur J Cardiothorac Surg 2000; 17(4): TIME Investigators. Trial of Invasive versus Medical therapy in Elderly patients with chronic symptomatic coronary-artery disease (TIME): A randomised trial. Lancet 2001; 358(9286): Pfisterer M, Buser P, Osswald S, Allemann U, Amann W, Angehrn W, et al. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs optimized medical treatment strategy: one-year results of the randomized TIME trial. JAMA 2003; 289(9): Alexander KP1, Anstrom KJ, Muhlbaier LH, Grosswald RD, Smith PK, Jones RH, et al. Outcomes of cardiac surgery in patients 80 years: results from the National cardiovascular network. J Am Coll Cardiol 2000; 35(3): Afilalo J, Bergman H, Perrault LP, Dendukuri N, Robichaud S. Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery. J Am Coll Cardiol 2010; 56(20): Cesari M, Kritchevsky SB, Penninx BW, Nicklas BJ, Simonsick EM, Newman AB, et al. Prognostic value of usual gait speed in well-functioning older people results from the Health, Aging and Body Composition Study. J Am Geriatr Soc 2005; 53(10): Pfisterer M, Buser P, Osswald S, Alleman U, Amman W, Angehrn W, et al. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs optimized medical treatment strategy: one-year results of the randomized TIME trial JAMA 2003; 289(9): Alexander KP, Anstrom KJ, Muhlbaier LH, Grosswald RD, Smith PK, Jones RH, et al.outcomes of cardiac surgery in patients 80 years: Results from the National Cardiovascular Network. J Am Coll Cardiol 2000; 35(3): Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA, et al. Frailty assessment in the cardiovascular care of older adults. J Am CollCardiol 2014; 63(8): Kircher TT, Wormstall H, Müller PH, Schwärzler F, Buchkremer G, Wild K, et al. A randomised trial of a geriatric evaluation and management consultation services in frail hospitalisedpatients. Age Ageing 2007; 36(1): Needham DM. Mobilizing patients in the intensive care unit: improving neuromuscular weakness and physical function JAMA 2008; 300(14): Binder EF, Yarasheski KE, Steger-May K, Sinacore DR, Brown M, Schechtman KB. Effects of progressive resistance training on body composition in frail older adults: Results of a randomized, controlled trial. J Gerontol A Biol Sci Med Sci 2005; 60(11): Bibas L, Levi M, Bendayan M, Mullie L, Forman DE, Afilalo J. Therapeutic interventions for frail elderly patients: part I: published randomized trials. ProgCardiovasc Dis. 2014; 57(2): Bendayan M, Bibas L, Levi M, Mullie L, Forman DE, Afilalo J. Therapeutic interventions for frail elderly patients: part II: ongoing and unpublished randomized trials. ProgCardiovasc Dis 2014; 57(2): S133

137 Open Access Original Article Gebapentin And Lorazepam As Premedication Pak Armed Forces Med J 2018; 68 (Suppl-1): S COMPARISON OF GABAPENTIN AND LORAZEPAM AS PREMEDICATION TO ATTENUATE THE PRESSOR RESPONSE TO INTUBATION IN CARDIAC PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFT SURGERY; A RANDOMIZED CONTROLLED TRIAL Muhammad Adnan Akram, Safdar Abbas, Rehana Javaid, Rashad Siddiqi, Sheza Iftikhar*, Javeria Kamran Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Holy Family Hospital Rawalpindi Pakistan ABSTRACT Objective: To determine the efficacy of Gabapentin and Lorazepam as premedication to reduce the presser response to intubation in cardiac patients undergoing CABG surgery. Study Design: Randomized control trial. Place and Duration of Study: Adult cardiac anesthesia department of Armed Forces Institute of Cardiology, Rawalpindi, from Nov 2017 to Feb Material and Methods: This double blinded randomized clinical trial was carried out on 110 patients scheduled for elective CABG under general anesthesia with endotracheal intubation. Patients were divided into two equal groups, where group A patients received 300mg of Gabapentin (Gabix) R in one dosage and group B received 2mg of Lorazepam (Ativan) R in one dosage, 4 hours before shifting to OT. Patient s hemodynamic parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were recorded before induction of anaesthesia (baseline) and at 1, 5 and 10 minutes after tracheal intubation. Results: There was no significant difference in the baseline hemodynamic parameters of the patients in two groups, the inter-group comparison showed significantly higher HR, SBP, DBP and MAP at 1, 5 and 10 minutes after tracheal intubation in group B (lorazepam) patients (p<0.05). Conclusion: Premedication with 300 mg of oral Gabapentin four hour before surgery better attenuates the hemodynamic response to laryngoscopy & intubation in comparison to 2mg of oral Lorazepam. Keywords: CABG, Endotracheal intubation, Premedication. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Hypertension and tachycardia, accompanied by increased sympathetic nervous system activity, may guide to an imbalance between myocardial oxygen demand and supply. This may lead to myocardial ischemia in patients who have coronary artery disease or in those with risk of ischemic heart diseases 1,2. Myocardial ischemia increases the risk of myocardial infarction, which is a serious peri operative complication with an associated mortality rate of 17 42% 3 and may compromise patients functional status 1,4. Perioperative myocardial ischemia during elective coronary artery bypass Correspondence: Dr Muhammad Adnan Akram, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan dr_adnanakram@yahoo.com graft (CABG) can occur in the pre bypass period, during bypass and in the post bypass period. Reperfusion of the myocardium after an ischemia stimulates myocardial apoptosis and resultant increase in infarct size through the reperfusion injury, despite the restoration of coronary blood flow 5,6. To minimize the myocardial ischemia during CABG, multiple strategies are often employed by the perioperative team. Myocardial protection is an area which is being widely researched currently to prevent or reduce the incidence of PMI. Laryngoscopy & intubation are related with cardiovascular changes like hypertension, tachycardia, dysrhythmia and even myocardial ischemia. These responses may be hazardous in individuals with coronary artery insufficiency, vascular anomalies or intracranial disease 4. Variety of medications have been S134

138 Gebapentin And Lorazepam As Premedication Pak Armed Forces Med J 2018; 68 (Suppl-1): S suggested to control these hemodynamic responses and prevent hemodynamic instabilities 7,8. Gabapentin, a structural analogue of gamma-amino butyric acid, has revealed to have multi-modal effects which make it a potentially useful drug for premedication in adults, providing postoperative analgesia and preoperative anxiolysis while preventing chronic postsurgical pain, postoperative nausea and vomiting and delirium 9. In addition, the drug has also been reported to successfully attenuate the cardiovascular responses to tracheal intubation. This beneficial effect of Gabapentin is probably due to inhibition of membrane voltage gated calcium channels, an action similar to calcium channel blockers. Two recent randomized controlled trials have shown that oral Gabapentin premedication attenuated the hemodynamic changes following tracheal intubation 10,11. On the Lorazepam (Ativan) 2mg in patients undergoing coronary artery bypass grafting (CABG) surgery. MATERIAL AND METHODS This study was double blind randomized control trial conducted at Armed Forces Institute of Cardiology/NIHD from between November 2017 and February After approval of the hospital ethics committee, consecutive 110 patients scheduled for elective CABG, were randomly allocated in two groups A and B using computer generated random number tables. After taking informed consent from the patient and a day before surgery, when the patients were listed up for surgery, the in-charge nurse of the preoperative ward was informed by the investigator to allocate the patient in either of the two groups. Neither the patient nor the anaesthetist planned to be conducting the surgery next day, did not know what premedication the patient had Table-I: Patient s characteristics of both groups. Variable Gebapentin Lorazepam (N=55) (N=55) p-value Age (Mean ± SD) 59.1 ± ± BMI (Mean ± SD) 24.3 ± ± Gender Male Female 42 (76.3%) 13 (23.6%) 33 (60.0%) 22 (40.0%) 0.10 Hypertension 46 (83.6%) 51 (92.7%) 0.11 Diabetes 33 (60.0%) 35 (63.6%) 0.84 Smokers 20 (36.3%) 14 (25.4%) 0.30 other hand, benzodiazepines used as sedative and anxiolytic medications, are routinely administered to mechanically ventilated (MV) patients 12 in ICU but have been associated with prolonged mechanical ventilation and ICU length of stay (LOS). As there is no contemporary data documenting the comparison of the effects of Gabapentin and Lorazepam on reduction of presser response in cardiac surgical patients, we conducted this study to evaluate the effects of premedication dose of oral Gabapentin (Gabix) 300 mg and premedication dose of oral received, Patients in group A (n=55) received 300mg of Gabapentin, 4 hours before shifting to OT with a sip of water, and patients in group B (n=55) received 2mg of Lorazepam, 4 hours before shifting to OT with a sip of water. All patients were induced with standard intravenous induction drugs including propofol 1mg/kg, fentanyl 3ug/kg, midazolam 2mg and sevoflurane 4%. An anesthesiology resident who was blinded to the study recorded baseline parameters of patients including heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP), mean arterial pressure (MAP) immediately before intubation (baseline), and at S135

139 Gebapentin And Lorazepam As Premedication Pak Armed Forces Med J 2018; 68 (Suppl-1): S , 5 and 10 minutes after tracheal intubation. Patients of both genders and age between 25 to 65 years, undergoing elective CABG surgery were included in the study. Patients with emergency CABG, uncontrolled hypertension, patients with missed dose of beta blockers and with severe renal dysfunction with serum creatinine level >2micromole/L and/or Creatinine clearance <40ml/min. were excluded from our study. RESULTS The results were available for all 110 patients. There was no significant difference between the demographics including age, gender, body mass index (BMI) and co-morbids like hypertension and diabetes in the patients of two groups, except the Gabapentin group had more smokers than the Lorazepam group (table-i). The baseline hemodynamic variables including SBP, DBP, MAP, and HR were all similar in the two groups (p>0.05). Although, there were similar trend in the hemodynamic response to tracheal intubation in both groups, i.e. a rise in SBP and DBP at 1 and 5 minutes interval, post-intubation and returning towards baseline at 10 minutes, these hemodynamic changes were significantly pronounced in patients of group B (receiving Lorazepam) as shown in tables-ii & III. DISCUSSION Hemodynamic response to tracheal intubation remains a sore point for the practicing anaesthesiologists all across the world. A lot of work has been done in patients undergoing Table-II: Comparing mean arterial pressure and Heart rate between the Gebapentin and Lorazepam groups at different time points of intubation. Variable Gebapentin Lorazepam (n=55) (n=55) p-value MAP baseline ± ± MAP after 1minute of intubation ± ± 10.1 <0.001 MAP after 5 minute of intubation 89.5 ± ± 10.3 <0.001 MAP after 10 minute of intubation 84.9 ± ± 10.0 <0.001 HR baseline 83.6 ± ± 11.2 <0.001 HR after 1minute of intubation 78.6 ± ± HR after 5 minute of intubation 71.6 ± ± HR after 10 minute of intubation 68.8 ± ± Table-III: Comparing systolic and diastolic blood pressure between the Gebapentin and Lorazepam groups at different time points of intubation. Variable Gebapentin Lorazepam (n=55) (n=55) p-value Systolic BP baseline ± ± Systolic BP after 1 minute of intubation ± ± 15.5 <0.001 Systolic BP after 5 minute of intubation ± ± 15.6 <0.001 Systolic BP after 10 minute of intubation ± ± 14.8 <0.001 Diastolic BP baseline 89.1 ± ± Diastolic BP after 1minute of intubation 81.8 ± ± 9.7 <0.001 Diastolic BP after 5 minute of intubation 73.8 ± ± 9.9 <0.001 Diastolic BP after 10 minute of intubation 70.1 ± ± cardiac as well as non-cardiac surgeries using different drugs and comparing their effects on patients. In our study it was found that the changes in hemodynamic variables (i.e. the rise in HR, SBP, MAP and DBP) were present in both groups, but the measures of these indicators were significantly lower in Gabapentin group at all time points. Review of recent literature had S136

140 Gebapentin And Lorazepam As Premedication Pak Armed Forces Med J 2018; 68 (Suppl-1): S similar results and is comparable with our study. The hemodynamic presser response during laryngoscopy and intubation occurs frequently 14. Shribman et al reported that laryngoscopy increases the blood pressure and catecholamine levels, while intubation significantly increases heart rate which could lead to dangerous sequelae 13,14. Though various agents have been used to prevent these pressure responses, but still the search for ideal agent continues Our study shows that the presser response to intubation does occur after premedication with Gabapentin, but the severity is much less as compared to the patients receiving Lorazepam. Our study concurs with the study conducted by Rastogi et al who found that 150 mg of pregabalin successfully attenuated the hemodynamic response to airway instrumen-tation 19. However, unlike other studies our study did not note any significant difference in the heart rate between the two groups following intubation. The probable reason could be the dose and type of different premedication and induction agents used in other studies. Our study also confers to the study done by Chaudhary et al who did a comparative study between pregabalin and clonidine. They observed that pregabalin was equally efficacious in stabilizing the hemodynamics during laryngoscopy. However, pregabalin premedication was associated with higher mean heart rate values after intubation as compared to the clonidine group In another comparative study, Raichurkar et al concluded that 200μg clonidine and 150mg pregabalin given 90 minutes before surgery and noted that pregabalin was better in attenuating hypertensive response to airway instrumentation while heart rate was better attenuated by clonidine premedication 25. The present study is comparable with other similar studies that has obtained some powerful evidence indicating that the use of oral gabapentin, even hours before tracheal intubation can be successful for attenuation of the hemodynamic response to laryngoscopy and intubation The mechanism of hemodynamic response attenuation following preoperative gabapentin administration is already unknown. One of the anticipated mechanisms is inhibition of membrane voltage-gated calcium channels that is similarly identified following use of calcium channels blockers. In fact the non strychnine site of NMDA receptor and two subunits of voltagesensitive calcium channels have been indicated as the binding sites of gabapentin, thus can mediate hemodynamic indices stability by gabapentin In another study, decreasing the synthesis of some neurotransmitters such as glutamate has been suggested as the mechanism of hemodynamic stability following gabapentin administration 29. Besides, it has been shown that the change in arterial pressure usually occurs the following laryngoscopy while the maximum increase in heart rate can occur during endotracheal intubation 31. On the other hand, gabapentin mechanism of action in attenuating heart rate and blood pressure response to tracheal intubation might be different 32, and more studies in this field are needed. CONCLUSION We conclude that premedication with 300 mg of oral gabapentin four hours before surgery better attenuates hemodynamic response to laryngoscopy & intubation along with acceptable levels of sedation in comparison of 2mg of lorazepam. ACKNOWLEDGEMENT We thank research and develpoment department AFIC/NIHD staff specially Shahzaib Arshad and Nazma Latif for helping in data collection and entry. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Fleisher LA: Preoperative evaluation, Clinical Anesthesia, 3rd edition. Edited by Barash PG, Cullen BF, Stoelting RK. Philadelphia, Lippincott Raven Publishers, 1997, pp S137

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142 Open Access Original Article Balloon Atrial Septostomy Pak Armed Forces Med J 2018; 68 (Suppl-1): S BALLOON ATRIAL SEPTOSTOMY: IS BEDSIDE PROCEDURE SAFE AND EFFECTIVE UNDER TRANSTHORACIC ECHOCARDIOGRAPHIC GUIDANCE? Nadia Quddus, Mehboob Sultan*, Maad Ullah*, Khurram Akhtar*, Nadeem Sadiq*, Amjad Mahmood*, Kamal Saleem*, Asif Akbar Shah*, Aziz Ahmed*, Muhammad Zahid* Shifa International Hospital, Islamabad Pakistan, *Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To evaluate the safety and efficacy of balloon atrial septostomy under transthoracic Echocardiographic guidance in ward setting in patients with transposition of great arteries. Study Design: Comparative cross-sectional study. Place and Duration of Study: Armed Forces Institute of Cardiology Rawalpindi from Jan 2012 to Dec Material and Method: It was a comparative cross-sectional study of all consecutive young infants with transposition of the great arteries that underwent balloon atrial septostomy for restrictive inter-atrial communication and cyanosis from January 2012 to December In group 1, balloon atrial septostomy was performed under local anesthesia in ward setting successfully. The cases who were shifted to catheterization lab for completion of procedure assigned as group 2 (procedure started in ward but couldn t be completed). Results: A total of 49 patients with transposition of the great arteries underwent balloon atrial septostomy during study period, 77.6% (n=38) of these were male and 22.4% (n=11) were female. A total of 44.8% (n=22) patients presented in 1st week with significant p-value <0.05. Balloon atrial septostomy was successfully performed in ward in 42 cases (group 1), while seven cases (group 2) were shifted to cath lab for completion of procedure. There was significant improvement in Oxygen saturation post-procedure with p-value of <0.05 in both groups and there was positive correlation between post-procedural Patent foramen ovale size and post-procedural oxygen saturation. Independent t-test was applied to compare both groups and there was no significant statistical difference between two groups. Conclusion: Balloon atrial septostomy was found to be safely performed in ward setting under transthoracic guidance, provided expertise of technique are available. However facilities of catheterization lab should also be available for backup. Keywords: Balloon atrial septostomy, Transposition of great vessels. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Congenital heart diseases occur in approximately 6 in 1,000 live births and transposition of the great arteries (TGA) is the most commonly diagnosed cyanotic congenital heart disease presenting in the neonatal period 1,2. In TGA, the aorta and pulmonary arteries do not arise from their respective ventricles, resulting in ventriculo-arterial discordance and thus parallel pulmonary and systemic circulation. In the patients with un-repaired TGA, delivery of oxygen to tissues, including the brain, is dependent on mixing between the systemic and Correspondence: Dr Nadia Quddus, Department of Pediatric, Shifa International Hospital, Islamabad Pakistan drmehboobsultan@gmail.com pulmonary circulations. An adequate inter-atrial communication along with prostaglandin infusion to keep patent ductus arteriosus open, are the two very important components of initial stabilization of young infants with unrepaired TGA 3. Balloon atrial septostomy (BAS) was introduced by Rashkind and Miller in 1966 and is an effective palliative procedure in children with transposition of the great arteries and poor inter-circulatory mixing 4. The non-restrictive atrial communication improves systemic oxygen saturations and helps in preoperative stabilization prior to definitive arterial switch operation (ASO) 5-7. BAS can be performed in catheterization lab as conventional manner or can be done in S139

143 Balloon Atrial Septostomy Pak Armed Forces Med J 2018; 68 (Suppl-1): S intensive care/ward settings under transthoracic echocardiography guidance. In fluoroscopic guided cardiac catheterization, there is exposure to radiation 8 and involves shifting of young infants to cath lab which may increases the risks of destabilization and hypothermia. Moreover as a bedside procedure it is cost effective too. We are reporting our three years experience of BAS in young infants done in ward setting under transthoracic guidance in department of paediatric cardiology. MATERIAL AND METHODS It was a comparative cross-sectional study of all consecutive young infants with transposition of the great arteries that underwent BAS for restrictive inter-atrial communication, from January 2012 to December 2014 Armed Forces Institute of Cardiology Rawalpindi. Balloon septostomy was performed under local anesthesia in ward setting successfully, allotted as group 1. Those who failed in ward were taken to Informed consent was taken before procedure. Neonates were kept warm throughout the procedure by warmers. Femoral vein was preferred mode of access in both groups. After establishing venous line (confirmed by transthoracic echo by visualizing wire in IVC or Fig-1: Genderwise distribution of patients with TGA underwent BAS. by injecting saline in IVC), 1.8 ml septostomy balloon advanced from IVC to right atrium across the PFO to left atrium. The standard subcostal Figure-2: Access site shows the type of vein being use during the procedure. catheterization lab and assigned as group 2. A detailed proforma was filled for each patient. Detailed maternal, patient history and examination including gender, gestational age, birth weight, postnatal age of admission, oxygen saturation levels before and after procedure, presenting complaints and complications were recorded. Baseline investigations including complete blood count, infective markers and biochemistry were also recorded. Pre-procedural echocardiographic findings were also recorded. view was mainly used to delineate the inter-atrial septum and to guide the balloon catheter. In all cases, 6F short sheaths were used. After confirming position in left atrium, balloon inflated and pulled back to right atrium with quick yet precise force to create an adequate inter-atrial communication. Procedure repeated till desired results achieved. In group 2, we could not cross the PFO with echo guidance and thus shifted to cath lab and procedure was completed under fluoroscopy guidance. S140

144 Balloon Atrial Septostomy Pak Armed Forces Med J 2018; 68 (Suppl-1): S Post procedural care included intravenous fluids, two doses of antibiotics and keeping baby dry and warm. Post-procedural echo was done for size of PFO and for ventricular functions and pericardial effusion. Post procedural saturations were recorded. Data was analyzed in SPSS 16. Data Analysis Descriptive statistics including means, standard deviations and percentages for variables like degree of hypoxia, complications and outcome were calculated. A p-values calculated for quantitative analysis. Group 1 and cath lab for completion of procedure as shown in table-i. In group 2, mean fluoroscopy time was 2.2 ± 1.4 minutes. One patient had respiratory arrest which was managed with positive pressure ventilation and another one developed minimal pericardial effusion in group 1 which was managed conservatively and dissolved itself over next two days as mentioned in table-ii. There was significant improvement in Oxygen saturation post- procedure with p-value of <0.05 in both groups. There was positive correlation (r=+0.613, p-value 0.00) between post-procedural Table-I: Parameters of both groups are compared as follows Parameter Group 1 (mean ± SD) Group 2 (mean ± SD) Weight (kilogram) 3.05 ± ± 0.39 Length (cm) 52.4 ± ± 3.3 Mean age of presentation (days) 15.2 ± ± 31.3 Pre-procedural saturation % 56.2 ± ± 6 Post-procedural saturation % ± ± 3.69 Pre-procedural PFO (mm) 1.96 ± ± 0.36 Post-procedural PFO (mm) 4.7 ± ± 0.68 Time of Procedure (minutes) ± ± Table-II: Comparison of safety parameter between two groups Safety Parameter No. of patients Group 1 Respiratory arrest 1 0 Pericardial effusion 1 0 Cross over rate 7 0 No. of patients Group 2 group 2 were compared by independent t-test. RESULTS A total of 49 patients with TGA underwent BAS during study period, 77.6% (n=38) of these were male and 22.4% (n=11) were female (fig-i). A total of 44.8% (n=22) patients presented in 1st week with significant p-value<0.05 and 37% patients were severely cyanosed with oxygen saturation <50%. In 83.7% (n=41) cases via right femoral vein, 14.3% (n=7) via left femoral vein and in 2% (n=1) cases umbilical vein was utilized as mentioned in fig 2. Balloon atrial septostomy was successfully performed in ward in 42 (86%) cases (group 1), while seven (14%) cases (group 2) were shifted to PFO size and post-procedural oxygen saturation. Independent t-test was applied to compare both groups and there was no significant statistical difference between two group. DISCUSSION TGA is the most common cyanotic congenital heart disease in neonatal period and mostly presents in first week of life 9,10. In developing country like ours, presentation of these cases can be delayed due to lack of adequate health facilities and early recognition. In our study population only 44.8% presented during first week of life. TGA is more common in males as reported by many studies, and in accordance 77.6% of our study population was male 11. To maintain adequate oxygen saturations, it s mandatory to S141

145 Balloon Atrial Septostomy Pak Armed Forces Med J 2018; 68 (Suppl-1): S have some form of free mixing between systemic and pulmonary circulation. It can be either achieved at atrial level or by having unrestricted large VSD or PDA. In neonates with small restrictive inter atrial communications, even presence of VSD/PDA may not allow adequate mixing of blood, thus necessitating creation of ASD with the help of balloon atrial septostomy. Rashkind and Miller, in 1966 gave description of the BAS and thus open door for interventional cardiology 12,13. BAS is of established value in the management of many congenital heart diseases in the neonatal period and most important of all is TGA. BAS can be performed in cath lab under fluoroscopic monitoring, ITC or in paediatric wards under echocardiographic control at bedside 14. In ward, it is easy to maintain body temperature of young infant and also avoids potential destabilization while shifting the baby to cath lab and moreover we can prevent child from undue exposure of radiations. We offered BAS in ward setting to 49 patients and were completely done in ward in 85.7% of the patient. However, in only 14.2% septostomy balloon could not be advanced to left atrium under echo guidance and procedure was completed under fluoroscopy guidance. In almost all patients (98%) percutaneous femoral vein was used to access central line which carry lowest post-op complications as discussed in another study by Porter et al 15 There was significant improvement in Oxygen saturation postprocedure with p-value of <0.05 in both groups. The diameter of the foramen ovale was the most important factor influencing arterial oxygenation 16,17. We found no statistical difference when both groups were compared. In many centers, with trained specialists, it is performed at bedside and considered safe and cost-effective 18. CONCLUSION Bedside BAS was found and effective procedure and also helped in prevention risk of radiation exposure without a change in efficacy. However facilities of catheterization lab should be available as a standby. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Al-Mukhaini KS, Mohamed AM. Transposition of the great arteries and coarctation of the aorta in an infant presenting with bronchiolitis: An incidental finding. Sultan Qaboos Univ Med J 2017; 17: e348-e Talemal L, Donofrio MT. Hemodynamic consequences of a restrictive ductus arteriosus and foramen ovale in fetal transposition of the great arteries. J Neonatal Perinatal Med 2016; 9: Sivakumar K. Atrial septal stenting - How I do it? Ann Pediatr Cardiol 2015; 8: Martins P, Castela E. Transposition of the great arteries. Orphanet J Rare Dis 2008; 3: Gopalakrishnan A, Sasidharan B, Krishnamoorthy KM, Sivasubramonian S, Dharan BS, Mathew T et al. Left ventricular regression after balloon atrial septostomy in d-transposition of the great arteries. Eur J Cardiothorac Surg 2016; 50: Polito A, Ricci Z, Fragasso T, Cogo PE. Balloon atrial septostomy and pre-operative brain injury in neonates with transposition of the great arteries: A systematic review and a meta-analysis. Cardiol Young 2012; 22: Khoury M, Sandoval JP, Grosse-Wortmann L, Jaeggi E, Chaturvedi RR. Catheter-Based palliation in an infant with obstructed cor triatriatum. Can J Cardiol 2016; 32: Harbron RW, Chapple CL, O'Sullivan JJ, Lee C, McHugh K. Cancer incidence among children and young adults who have undergone x-ray guided cardiac catheterization procedures. Eur J Epidemiol McMahon CJ, Snyder CS, Rivenes SM, Sang CJ, Fraser CD. Neonatal arterial switch operation for transposition of the great arteries in a patient with mirror image dextrocardia and situs inversus totalis. Tex Heart Inst J 2000; 27(2): Konuma T, Shimpo H. Transposition of Great Artery. Kyobu Geka 2015; 688: Bianca S, Ettore G. Sex ratio imbalance in transposition of the great arteries and possible agricultural environmental risk factors. Images Paediatr Cardiol 2001; 3: Boehm W, Emmel M, Sreeram N. Balloon atrial septostomy: History and technique. Images Paediatr Cardiol 2006; 8(1): Mullins CE. History of pediatric interventional catheterization: pediatric therapeutic cardiac catheterizations. Pediatr Cardiol 1998; 19(1): Guarnera S, Contarini M, Sciacca P, Patanè L, Parisi MG, Pulvirenti A, et al. Indications for percutaneous atrioseptostomy. Comparison of echocardiographic and fluoroscopic monitoring. Pediatr Med Chir 1997; 19(4): Porter CJ, Gillette PC, Mullins CE, McNamara DG. Cardiac catheterization in the neonate. A comparison of three techniques. J Pediatr 1978; 93(1): Baylen BG, Grzeszczak M, Gleason ME, Cyran SE, Weber HS, Myers J, et al. Role of balloon atrial septostomy before early arterial switch repair of transposition of the great arteries. J Am Coll Cardiol 1992; 19(5): Chantepie A, Schleich JM, Gournay V, Blaysat G, Maragnes P. Preoperative mortality in transposition of the great vessels. Arch Pediatr 2000; 7(1): Matter M, Almarsafawy H, Hafez M, Attia G, Elkhier M. Balloon atrial septostomy: The oldest cardiac interventional procedure in Mansoura. Egyptian Heart J 2011; 63: S142

146 Open Access Acute Left Ventricular Failure Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S143-S46 FREQUENCY AND OUTCOME OF ACUTE LEFT VENTRICULAR FAILURE IN PATIENTS UNDERGOING PRIMARY PERCUTANOUS CORONARY INTERVENTION FOR ST- SEGMENT ELEVATION ANTERIOR WALL MYOCARDIAL INFARCTION Tahir Naqqash, Tariq Hussain Khattak, Sohail Aziz, Rehana Khadim, Aiza Qayyum, Tahir Iqbal, Farhan Tayyub, Waheed Akhter, Muhammad Yasin Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the frequency and outcomes of acute left ventricular failure in patients undergoing primary PCI for ST segment elevation anterior wall myocardial infarction. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Adult cardiology department, Armed Forces Institute of Cardiology & National Institute of Heart Diseases Rawalpindi, Pakistan from Jan 2017 to Jun Material and Methods: One hundred and twenty patients of both genders between 20 to 90 years of age meeting the inclusion criteria were recruited in the study. ECG was done for every patient for diagnosis of acute anterior wall myocardial infarction. Blood test including cardiac biomarkers was sent. Patients with acute anterior wall MI, their outcomes like acute left ventricular failure, pre or post primary PCI outcomes and in-hospital mortality were documented for every patient. Results: Out of 120 patients who underwent primary PCI for acute anterior wall MI. 101 (84.4%) patients were males while 19 (15.6%) patients were female patients. Mean age of the patients was 54.6 ± 7.5 years. Forty (33.3%) patients had single vessel coronary artery disease, 48 (40%) had double vessels coronary disease and 32 (26.7%) patients were with triple vessels coronary artery disease. Forty five (37.5%) patients had peri-procedural acute LVF. One hundred and ten (91.7%) patients improved and were discharged from hospital. In-hospital mortality was 8.3%. Conclusion: It is concluded from our study that primary PCI is first choice and best reperfusion strategy because it improves acute LVF and its outcome in patient with acute anterior wall MI and hence reduce morbidity and mortality. Keywords: Anterior wall MI, Primary PCI, Acute LVF This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Acute left ventricular failure is a serious condition. It affects 38 million patients worldwide. The development of heart failure has a negative effect on the outcome of Acute MI patient. It is accordingly considered as a warning sign for death among them 1. Its prevalence is 10-40% in acute MI patients 2. The most common mechanical complication of acute myocardial infarction is acute left ventricular failure 3. The factors like recurrent myocardial ischemia, size of infarct, remodeling of the ventricles, stunning myocardium, mechanical complications, and hibernation of myocardium Correspondence: Dr Tahir Naqqash, Armed Forces Institute of Cardiology Rawalpindi Pakistan tahirnaqqash1980@gmail.com influence the left ventricular systolic dysfunction after acute myocardial infarction 4,5. The presence of acute LVF after acute myocardial infarction increases the mortality by at least 3 to 4 times. It is the common complication after acute ST segment elevation MI mostly associated with acute anterior wall myocardial infarction 6. Previous myocardial infarction, advaced age, female gender, anterior wall myocardial infarction and diabetes mellitus are risk factors which play a major role in the development of cardiogenic shock 7. Aging of the population and longevity in the lives of cardiac patients by modern therapeutic intervention has resulted in an increase in prevalence of left heart failure 8,9. The mortality rate in patients with left heart failure has remained unacceptably high despite S143

147 Acute Left Ventricular Failure Pak Armed Forces Med J 2018; 68 (Suppl-1): S143-S46 improvements in therapy 10, early detection of susceptible persons and intervention would benefit from preventive measures 11. In Hospital mortality is 5% to 8% with acute LVF. Primary PCI is first choice reperfusion strategy because it improves outcome in patient with acute ST elevation MI especially acute anterior wall MI in term of morbidity and mortality 12,13. Coronary artery disease is the leading cause of heart failure in patients with reduced LV ejection fraction which is more associated with anterior wall 14,15. This study was carried out to determine the from Jan to Jun All the patients with acute anterior wall myocardial infarction undergoing Primary PCI were included in the study. Patients with COPD, valvular heart disease, LRTI, old myocardial infarction, acute ST elevation, MI thrombolysed with streptokinase prior to PCI and patients with prior CCF were excluded from the study. Informed written consent was taken from the family of the patients for participation in the study, after informing the purpose of study. History of co-morbids and chest pain was taken and clinical examination was performed. The Table: Clinical characteristics of the patients Variables n (%) Age (mean ± SD) 54.6 ± 7.5 years Gender Male 101 (84.2%) Female 19 (15.8%) Risk Factors Diabetes Mellitus Hypertension Smoking History Hyperlipiemia Coronary Artery Disease Single Vessel CAD Double Vessel CAD Triple Vessel CAD KILLIP Class KILLIP Class-I KILLIP Class-II KILLIP Class-III KILLIP Class-IV frequency and outcomes of acute left ventricular failure in the patients and to see whether early diagnosis of heart failure and treating it by identifying risk factors can prevent recurrent attacks and frequent hospital admissions. MATERIAL AND METHODS This descriptive cross-sectional study was carried out at Armed Forces Institute of Cardiology & National Institute of Heart Diseases after approval from hospital ethical committee S (17.5%) 61 (50.8%) 30 (25.0%) 7 (5.8%) 40 (33.3%) 48 (40.0%) 32 (26.7%) 75 (62.5%) 36 (30.0%) 6 (5.0%) 3 (2.5%) Peri- Procedural Acute LVF 45 (37.5%) Mortality 10 (8.3%) diagnosis of acute ST-segment elevation anterior wall MI was based on the presence of chest pain lasting 20 minutes or longer combined with typical electrocardiographic changes (ST-segment elevation 2 mv in 2 contiguous precordial anterior leads, presumed new complete left bundle branch block). Patients with at least one of the following criteria were labeled with acute left ventricular failure; a) KILLIP Class 2 on admission, b) KILLIP Class 2 at any time of hospitalization.

148 Acute Left Ventricular Failure Pak Armed Forces Med J 2018; 68 (Suppl-1): S143-S46 Data Analysis All the data was analyzed on SPSS-21. Mean ± Standard Deviation was calculated for quantitative variables e.g. Age. Frequency and percentages was calculated for qualitative variables e.g. gender, risk factors, severity of disease, left ventricular failure and outcomes. RESULTS Out of 120 patients who underwent primary PCI for acute anterior wall MI. One hundred and one (84.4%) patients were males while 19 (15.6%) patients were female patients. Mean age of the patients was 54.6 ± 7.5 years. 40 (33.3%) patients had single vessel coronary artery disease, 48 (40%) had double vessels coronary disease and 32 (26.7%) patients were with triple vessels coronary artery disease. 45 (37.5%) patients had peri-procedural acute LVF. 110 (91.7%) patients improved and were discharged from hospital. Inhospital mortality was 8.3% as shown in table. DISCUSSION Acute myocardial infarction is the major killer in the modern world. Approximately 450,000 people in USA dies from coronary artery disease per year. The survival rate in hospitalized patients in U.S is approximately 95%. There are two types of acute MI, acute Non ST segment elevation MI and acute ST segment elevation MI. Acute LVF is the common complication of Acute MI, mainly associated with STEMI of the STEMI, anterior wall MI is the mainly complicated by acute LVF which may lead to death if not promptly diagnosed and managed. Primary PCI is first choice reperfusion strategy because it improves outcome in patient with acute ST elevation MI in term of morbidity and mortality 4,5. It reduces morbidity and mortality in patients with acute LVF at presentation or post procedure as compared to streptokinase. A study conducted in Germany on 312 patients undergoing primary PCI, 16.9% developed periprocedural acute left ventricular failure. All-cause in-hospital mortality was 10% patients, out of which 87% was associated with acute LVF 9. Cardiovascular risk factors play a major role in the occurrence of MI and its complication like LVF. In our study hypertension, smoking and diabetes were major risk factor for MI. Out of 120 patients who underwent primary PCI for acute anterior wall MI, 16 (13.3%) were of years age group and 104 (86.7%) were of years age group, 101 (84.4%) were male and 19 (15.6%) were female. Forty (33.3%) patients had single vessel coronary artery disease, 48 (40%) had double vessels coronary disease and 32 (26.7%) patients were with triple vessels coronary artery disease. Seventy five (62.5%) were in KILLIP class-i of heart failure. Thirty six patients (30.0%) developed KILLIP class-ii left ventricular failure, 6 (5%) were with KILLIP class-iii and 3 (2.5%) were with KILLIP class-iv. Fourty five (37.5%) patients had peri-procedural acute LVF. One hundred and ten (91.7%) patients improved and were discharged from hospital. In-hospital mortality was 8.3% which is in accordance with developed countries of the world 10,11. CONCLUSION It is concluded from our study that primary PCI is first choice and best reperfusion strategy because it improves acute LVF and outcome in patient with acute Anterior wall MI and hence reduce morbidity and mortality. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure N Engl J Med 2005; 352: Rivero-Ayerza M, Theuns DA, Garcia-Garcia HM, Boersma E, Simoons M, Jordaens LJ. Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials. Eur Heart J 2006; 27: de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail 2009; 11(9): Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: Insights from the randomized aldactone evaluation study (RALES). RALES investigators. Circulation 2000; 102(22): S145

149 Acute Left Ventricular Failure Pak Armed Forces Med J 2018; 68 (Suppl-1): S143-S46 5. Alla F, Kearney-Schwartz A, Radauceanu A, DoresS Das, Dousset B, Zannad F. Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes Eur J Heart Fail 2006; 8(2); Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem 1994; 269: Sharma UC, Pokharel S, van-brakel TJ, van-berlo JH, Cleutjens JP, Schroen B et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation 2004; 110: Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP et al. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol 2008; 172(2); Kimmenade RR, Januzzi JL Jr, Ellinor PT, Sharma UC, Bakker JA, Low AF, et al. Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure. J Am Coll Cardiol 2006; 48(6): Milting H, Ellinghaus P, Seewald M, Cakar H, Bohms B, Kassner A, et al. Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices. J Heart Lung Transplant 2008; 27(6): Shah RV, Chen-Tournoux AA, Picard MH, van Kimmenade RR, Januzzi JL. Galectin-3, cardiac structure and function, and longterm mortality in patients with acutely decompensated heart failure. Eur J Heart Fail 2010; 12(8): Lok DJ, Van Der Meer P, De la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, et al. Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol 2010; 99; De Boer RA, Lok DJ, Jaarsma T, van der Meer P, Voors AA, Hillege HL, et al. Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction. Ann Med 2011; 43(1); Lainsca KM, Coletta AP, Sherwi N, Cleland JG. Clinical trials update from the Heart Failure Society of America meeting 2009: Fast, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF, and MARVEL-1. Eur J Heart Fail 2010; 12(2); D'Ascia C, Cittadini A, Monti MG, Riccio G, Sacca L. Effects of biventricular pacing on interstitial remodelling, tumor necrosis factor-alpha expression, and apoptotic death in failing human myocardium. Eur Heart J 2006; 27(2): S146

150 Open Access Duke Treadmill Score in Patients Presenting With Angina Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S147-S52 ROLE OF DUKE TREADMILL SCORE IN ASSESSING THE SEVERITY OF CORONARY ARTERY DISEASE IN PATIENTS PRESENTING WITH ANGINA Muhammad Asad, Rehana Khadim, Tahir Iqbal, Hafiz Muhammad Shafique, Mir Waqas Baloch, Samra Rehmat, Hasnain Iqbal, Sibtain Iqbal, Mohsin Hayat Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To evaluate the role of duke treadmill score in assessing the severity of coronary artery disease in patients presenting with angina. Study Design: A descriptive cross-sectional study. Place and Duration of Study: Adult Cardiology department of AFIC and NIHD Rawalpindi, from Sep 2017 to Dec Material and Methods: Patients of both genders above the age of 30 years who presented first time with angina were included in the study. Patients excluded from the study were those who had previous myocardial infarction, patients with severe valve disease (severe stenosis and/or regurgitation of heart valves), patients with prosthetic valve, heart failure (ejection fraction <50), acute coronary syndrome (unstable angina pectoris), hematological disorders, previous revascularization procedures (whether percutaneous transluminal coronary angioplasty or coronary artery bypass grafting [CABG]), congenital heart disease, patients taking digoxin therapy and having chronic kidney disease. Results: There were 100 patients included in the study. The mean age of the patients was ± 6.74 years, with minimum age 31 years and maximum age 55 years. About 68 (68.0%) patients were males and 32 were females (32.0%). The main risk factors for CAD among study participants were diabetes mellitus 55 (55.0%) hypertension 24 (24.0%) and smoking 13 (13.0%). Association between Duke Treadmill Score and SYNTAX score was found out by using ANOVA (Analysis of variance) and it showed statistically significant result between two variables with p= Association between Duke Treadmill score and coronary arteries involvement was found by using chisquare test, the result of which was statistically significant with p= Conclusion: It is concluded from our study that Duke treadmill score is a significant prognostic tool for coronary artery disease. There is significant association between DTS and SYNTAX score. DTS also had a significant association with extensive and significant CAD. Keywords: Coronary Artery Disease, Duke treadmill score (DTS), SYNTAX score. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Cardiovascular disease is considered to be one of the leading cause of death among human race 1 Ischemic heart disease (IHD) is one of the common manifestation of this disease 2. Stable angina is one of the presenting features of IHD 2. Worldwide 50% of all deaths have been attributed to coronary artery disease 3. Instable angina, blood and oxygen supply to the myocardial tissue is diminished because of obstructive atherosclerosis and ischemia occurs Correspondence: Dr Muhammad Asad, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan masad12880@gmail.com when the demand increases, such as during exercise 4. The diagnosis of coronary heart disease (CHD) as the cause of chest pain requires the use of a careful clinical history as well as additional investigations. Coronary angiography is the gold standard test for identifying the presence and extent of atherosclerotic coronary artery disease (CAD) 5,6. Exercise stress testing is a widely used and inexpensive method for initial evaluation of patients with suspected CAD 7. Exercise tolerance test has been used to assess patients who present with chest pain and intermediate pre-test probability of ischemic heart disease 8. The limited sensitivity and specificity of standard exercise ECG testing for S147

151 Duke Treadmill Score in Patients Presenting With Angina Pak Armed Forces Med J 2018; 68 (Suppl-1): S147-S52 detection of coronary artery disease have stimulated increased use and development of noninvasive stress imaging technologies 9. However, the added diagnostic accuracy of stress imaging tests is associated with substantially higher cost. An alternative to the use of more expensive tests is the more efficient use of available low-cost data. Diagnostic and prognostic predictive accuracy increases when multiple pieces of information from the patient s clinical history and the treadmill test are integrated 10,11. Duke Treadmill Score (DTS) is a composite index that is based on the results from the exercise test, including ST-segment depression, chest pain and exercise duration, and provides more accurate prognostic information for the evaluation of patients with clinically-suspected ischemic heart disease 12,13. SYNTAX score (SS) is an angiographic scoring system that is widely used to evaluate the severity and complexity of CAD. It is used in the estimation of long-term outcomes of CAD and in the selection of the treatment modality. Its efficacy has been demonstrated in various studies 14,15. Some studies 5,9 have suggested that DTS score helps in assessing the severity of the disease. Therefore in this article we investigated the role of DTS in prediction of severity (SYNTAX score) of CAD. MATERIAL AND METHODS This descriptive cross sectional study was conducted at Cardiology Department of AFIC & NIHD Rawalpindi, from September 2017 till December Patients were recruited through non-probability purposive sampling. Patients of both genders above the age of 30 years who presented first time with angina were included in the study. Patients excluded from the study were those who had previous myocardial infarction, patients with severe valve disease (severe stenosis and/or regurgitation of one or more heart valves), patients with prosthetic valve disease, heart failure (ejection fraction <50), acute coronary syndrome (unstable angina pectoris), hematological disorders, Revascularization procedures (whether percutaneous transluminal coronary angioplasty or coronary artery bypass grafting [CABG]), congenital heart disease, patients taking digoxin therapy and chronic kidney disease were excluded from the study. Permission of study was sought from hospital ethical committee. Patients without a history of prior CAD, admitted to the outpatient clinic with chest pain (typical angina, atypical angina, nonangina chest pain) were included. Pre test probabilities (PTP) of all patients were calculated. Patients with low (<15%) and high (>85%) probability were excluded from the study. Only the patients with intermediate PTP (15 85%) performed exercise stress testing, and DTS was calculated in each subject. Patients with 1 mm or more horizontal or down-sloping ST depression (80 ms after the J point) due to effort were considered to have a positive stress test and underwent coronary angiography (CAG). These patients composed the study population. All the patients underwent symptom-limited exercise testing according to the standard Bruce protocol test with standard ECG, blood pressure and heart rate measurements performed at prespecified time points as per relevant guidelines and were exercised to the endpoints described in the original duke treadmill score (DTS) study by Mark et al 7. Resting heart rate, blood pressure and 12-lead ECGs were recorded in the supine and upright positions before exercise. The target heart rate was determined according to the formula 0.85x (220-age). During each minute of exercise, heart rate, blood pressure and ECG were recorded. Exercise testing was discontinued if exertional hypotension, malignant ventricular arrhythmias or limiting chest pain was reported. An abnormal exercise ST response was defined as 1 mm or more of horizontal or down sloping ST depression (J point ± 80 ms). The equation for calculating the Duke treadmill score is as follows: DTS= exercise time-(5 x ST deviation)-(4 exercise angina). Exercise angina was assessed as one of three levels: S148

152 Duke Treadmill Score in Patients Presenting With Angina Pak Armed Forces Med J 2018; 68 (Suppl-1): S147-S52 0= none, 1= non-limiting and 2= exercise-limiting. The DTS was grouped into low-risk (with a score of +5), moderate-risk (with scores ranging from -10 to +4), and high-risk (with a score of -11) categories. Coronary angiography was performed by the Judkins technique, using the standard Seldinger technique through a percutaneous femoral or radial artery puncture. Each angiogram was analyzed independently by experienced interventional cardiologist who was blinded to the patient clinical data. Those patients whose angiogram was normal were excluded from the study. Coronary lesion was considered subtypes, and mean ST changes. Chi square test was used to assess the significance of associations between variables. Level of significance (p-value) 0.05 was considered significant. RESULTS There were 100 patients included in the study. The mean age of the patients was ± 6.74 years with minimum age 31 years and maximum age 55 years. About 68 (68.0%) patients were males and 32 were females (32.0%). The main risk factors for CAD among study participants were diabetes mellitus 55 (55%) then 24 hypertension (24%) and smoking 13 (13.0%). Patients who had one risk factor were 54 (54.0%), those who had two risk factors were 25 (25.0%), those who had no risk factors were 8 (8.0%) and those who had three risk factors were 13 (13.0%). Table-I: Characteristics of angiographic findings in various DTS groups. Significant stenosis All patients n=100 Low risk +5 n=20 Moderate risk -10 to +4 n=58 High risk -11 n=22 p-value LAD RCA LCX LMS Table-II: Association between Duke Treadmill Score and SYNTAX score. DTS DTS DTS to p-value SYNTAX Score (Mean ± SD) 19 ± ± ± hemodynamically significant when stenosis of coronary artery was 70% and stenosis of the left main stem was 50%. Each coronary lesion producing 50% diameter stenosis in vessels 1.5 mm was scored separately and added together to provide the overall Syntax Score, which was calculated prospectively using the Syntax Score algorithm. Data Analysis Data was entered and analyzed in SPSS version 23. The mean and standard deviation was calculated for quantitative variables. The frequency and percentage was calculated for qualitative variable. Student s t-test was used to compare DTS risk groups, coronary artery lesions The mean St changes seen in exercise tolerance test was 1.61mm The mean syntax score of all the patients under study was 23.1 ± 8.65 with minimum score of 7 and maximum 46. There were 22 patients in Low risk group, 58 patients in intermediate and 20 patients in high risk group. The frequency of various angiographic findings in DTS groups is given in table-i. Association between Duke treadmill score and SYNTAX score was found out by using ANOVA (Analysis of variance) which showed statistically significant result between two variables, with p=0.04 as shown in table-ii. Association between Duke treadmill score and coronary arteries involvement was found out by using chi-square S149

153 Duke Treadmill Score in Patients Presenting With Angina Pak Armed Forces Med J 2018; 68 (Suppl-1): S147-S52 test. The result was statistically significant with p=0.001 as shown in table-iii. DISCUSSION Exercise testing is the most widely performed test for prognostic assessment of ischemic heart disease in patients who are able to with stand exercise and who have no substantial abnormalities in the resting electrocardiogram. It is assumed that the patients with suspicion of ischemic heart disease and a low risk exercise test result have a favorable prognosis 16,17. Demographic presentation of the present study revealed that males were more than females The SYNTAX score presents information about prognosis. Moreover, DTS is also known to provide information about prognosis. While DTS is expected to be low and SS to be high in patients with severe CAD, the number of studies demonstrating a comprehensive evaluation of both these two risk stratification methods is limited 20. Acar et al 21 found the average DTS value to be 2.5 ± 7 while it was in our study. Our study population had lower DTS values. The difference in the number of patients may also be the reason for this inequality. In the present study the no of vessels involved was Table-III: Association between Duke treadmill score and coronary arteries involvement. Coronary Arteries DTS DTS DTS Involvement to p-value LAD 3 (15.8%) 7 (16.7%) 4 (10.3%) LAD, LCX 4 (21.1%) 6 (14.3%) 7 (17.9) LAD, LCX, RCA 3 (15.8%) 13 (31.1%) 15 (38.5%) LAD, RCA 5 (26.3%) 6 (14.3%) 6 (15.4%) LAD, RCA, LCX - 3 (7.1%) - LAD, LCX, RCA 1 (5.3%) - - LCX, RCA (7.7%) LMS, LAD, LCX, RCA - 1 (2.4%) - LMS, LCX, LAD - 1 (2.4%) - RCA - 2 (4.8%) - RCA, LAD - 1 (2.4%) - RCA, LCX 2 (10.5%) - 2 (5.1%) although no significant difference was observed, in age groups and mean age, between males and females (p>0.05). This finding is consistent with results of Saeed et al study in Iraq 18 and Assiri 19. The SYNTAX score, which is used in the evaluation of angiographic severity of coronary lesions, has already been shown to predict mortality in addition to its role in the decisionmaking process of intervention procedure (percutaneous coronary intervention [PCI] or CABG). DTS is a risk stratification index that was developed by Mark et al 7 and Shaw et al 13. DTS is widely used in the prediction of CAD. DTS includes non-invasive clinical information, while SYNTAX score (SS) exhibits information about the severity and complexity of coronary lesions. more in intermediate group and high risk DTS score group patients as compared to low group. This picture is close to the results of other study in USA; Kwok et al study 22, in regard to three vessels involvement. The sex in the present study did not significantly affect the outcome of DTS (p=0.79). This finding is inconsistent with that found in other study carried out by Jang et al study in South Korea 23 and an earlier study conducted by Shaw et al in USA 13 that found significant association between sex and DTS, the inconsistency with these studies might be attributed to the small number of females compared to males in our study. The present study revealed a significant association between high risk DTS and the extent CAD (p<0.001). This S150

154 Duke Treadmill Score in Patients Presenting With Angina Pak Armed Forces Med J 2018; 68 (Suppl-1): S147-S52 finding is consistent with results of Acar et al 21 who concluded that there is strong correlation between high risk DTS and coronary lesion complexity. Shaw et al 13 also found a significant association between high risk DTS with extensive and significant CAD. They regarded CAD severity as the number of diseased arteries rather than the degree of stenosis of coronary arteries. In a study done on stable angina patients by Banerjee et al comparing DTS with single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) showed that exercise treadmill test using DTS score was satisfactorily correlated with SPECT-MPI scanning in low DTS subsets of patients. They inferred that the patients with low DTS score do not need an MPI study and should undergo CAG for further evaluation 24. In another similar study it was suggested that patients with low DTS score can be referred to CAG without SPECT-MPI and patients with high DTS can be followed on medical management 25. At the present time, physicians usually ignore DTS results while making a decision about CAG. DTS can provide information about the potential outcomes of coronary angiography such as requirement of CABG and PCI and therefore we believe that it should be used more often in clinical practice. Our results also support the evidence that DTS can be used more often in clinical cardiology practice instead of CT coronary angiography to avoid radiation exposure, especially in patients with high DTS. CONCLUSION It is concluded from our study that Duke treadmill score is a significant prognostic tool for coronary artery disease. There is significant association between DTS and SYNTAX score. DTS also had a significant association with extensive and significant CAD so it might play a role in diagnosis as well as guiding management strategy. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author REFERENCES 1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics-2012 update: A report from the American Heart Association. Circulation (1): e National Board of Health and Welfare. Causes of death Sweden: National Board of Health and Welfare; Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352(16): Boden WE. Angina pectoris and stable ischemic heart disease. In: Goldman L, Schafer AI, editors. Cecil Medicine. 24 ed. Philadelphia: Saunders Elsevier; Liu JL, Maniadakis N, Gray A, Rayner M. The economic burden of coronary heart disease in the UK Heart 2002; 88(6): Stewart S, Murphy N, Walker A, McGuire A, McMurray JJ. The current cost of angina pectoris to the National Health Service in the UK. Heart 2003; 89(8): Mark DB, Hlatky MA, Harrell FE Jr, Lee KL, Califf RM, Pryor DB. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med 1987; 106(6): Ali SN, Shehzad A, Qureshi BA, Hashmi KA. pattern of angiographic findings in patients with stable angina having high risk duke score on exercise testing. Pak Heart J 2016; 49(04): Yanagisawa S, Miki K, Yasuda N. The prognostic value of treadmill exercise testing in very elderly patients: heart rate recovery as a predictor of mortality in octogenarians. Europace 2011; 13(1): Gulati M, Shaw LJ, Thisted RA, Black HR, Bairey Merz CN, Arnsdorf MF. Heart rate response to exercise stress testing in asymptomatic women: the ST. James women take heart project. Circulation 2010; 122(2): Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, et al. ACC/AHA 2002 guidelines update for exercise testing: Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2002; 106(14): Eryol NK, Başar E, Ozdoğru I, Ciçek Y, Abaci A, Oğuzhan A et al. Should troponin-t be assessed during exercise stress testing in patients with stable angina pectoris Anadolu Kardiyol Derg, 2002; 2(2): Shaw LJ, Peterson ED, Shaw LK, Kesler KL, DeLong ER, Harrell FE J. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation, 1998; 98(16): Aksakal E, Tanboğa IH, Kurt M, Kaya A, Topcu S. Predictors of coronary lesions complexity in patients with stable coronary artery disease. Angiology 2013; 64(4): Uçar H, Gür M, Börekçi A, Yıldırım A, Baykan AO, Kalkan GY. Relationship between extent and complexity of coronary artery disease and different left ventricular geometric patterns in patients with coronary artery disease and hypertension. Anadolu Kardiyol Derg 2015; 15(10): Mark DB, Hlatky MA, Harrell FE Jr, Lee KL, Califf RM, Pryor DB. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med 1987; 106(6): Mark DB, Shaw L, Harrell FE Jr, Hlatky MA, Lee KL Bengtson JR, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med 1991; 325(12): S151

155 Duke Treadmill Score in Patients Presenting With Angina Pak Armed Forces Med J 2018; 68 (Suppl-1): S147-S Saeed ID, Abdulmajeed MA. Gender effect on coronary angiographic findings in evaluation of chest pain. Ann Coll Med Mosul 2013; 39 (2): Assiri AS. Gender differences in clinical presentation and management of patients with acute coronary syndrome in Southwest of Saudi Arabia. J Saudi Heart Assoc 2011; 23(3): Günaydın ZY, Bektaş O, Gürel YE, Karagöz A, Kaya A, Kırış T, et al. The value of the Duke treadmill score in predicting the presence and severity of coronary artery disease. Kardiologia Polska 2016; 74(2): Acar Z, Korkmaz L, Agac MT, Erkan H, Dursun I, Kalaycioglu E, et al. Relationship between Duke Treadmill Score and coronary artery lesion complexity. Clin Invest Med 2012; 35(6): Kwok JM, Miller TD, Hodge DO, Gibbons RJ. Prognostic value of the Duke treadmill score in the elderly. J Am Coll Cardiol 2002; 39(9): Jang JY, Sohn IS, Kim JN, RN, Park JH, Park CB, et al. Treadmill exercise stress echocardiography in patients with no history of coronary artery disease: A single-center experience in Korean population. Korean Circ J 2011; 41(9): Banerjee SK, Haque KM, Sharma AK, Ahmed CM, Iqbal AT, Nisa L. Role of exercise tolerance test (ETT) and gated single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) in predicting severity of ischemia in patients with chest pain. Bangladesh Med Res Counc Bull 2005; 31(1): Shaikh AH, Hanif B, Hassan K. Correlation of Duke s treadmill score with gated myocardial perfusion imaging in patients referred for chest pain evaluation. J Pak Med Assoc 2011; 61: S152

156 Open Access Coronary Arteriovenous Fistula Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S153-S56 TRANSCATHETER MANAGEMENT OF CORONARY ARTERIOVENOUS FISTULA - SEVEN YEAR EXPERIENCE Mehboob Sultan, Khurram Akhtar, Maad Ullah, Nadeem Sadiq, Amjad Mehmood, Kamal Saleem, Syed Asif Akbar Shah, Aziz Ahmed Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To measure efficacy and immediate complications of percutaneous device closure of coronary artery fistula (CAF). Study Design: Retrospective study. Place and Duration of Study: Armed Forces Institute of Cardiology and National Institute of Heart Diseases, (AFIC/NIHD) Rawalpindi, from Jan 2011 to Dec Material and Methods: Consecutive eight patients, who underwent attempted CAF device closure were included in the study. Device closure was attempted in isolated CAF (Coronary artery fistula) with significant shunt and with body weight of at least 10 kgs. Results: Total 8 cases of attempted CAF device closure were included with mean age of 13 years and male to female ratio of 1:1. In 7 cases (87.5%), CAF were successfully occluded. There was no mortality, thrombosis, residual leak or peripheral vascular injuries in the study population. We used three ductal occluders and four septal device occluders to achieve complete closure of CAFs in seven cases. Conclusion: Transcatheter occlusion of CAF by various occluder devices is an effective therapeutic option with high success rate. Complication rate is low in the hands of skilled operators. Keywords: Coronary fistula, Device closure, Occluder device. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Isolated Coronary artery fistula (CAF) are one of least common cases encountered in pediatric catheterization laboratory and defined as an abnormal linking between one or more coronary arteries and an adjacent cardiac chamber or vascular structure 1-3. First described by Krause in , CAF is a rare anomaly found in approximately 0.2% of patients undergoing diagnostic coronary angiography and accounts for about 0.2%-0.4% of all congenital cardiac defects but is most common paediatric coronary anomalies 5,6. The true incidence of CAFs cannot be accurately estimated as the small fistulas are usually asymptomatic and may not come to medical attention. CAFs are divided into two types, either a coronary-cameral fistula ending in any of the Correspondence: Dr Mehboob Sultan, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan drmehboobsultan@gmail.com cardiac chambers or a coronary arteriovenous fistula ending in either a systemic or pulmonary vein. CAF arise most commonly from the RCA (>50%), the rest arising from the left coronary artery or both coronary arteries 7. The vast majority terminate in the right side of the heart (>90%), primarily the right ventricle, right atrium, pulmonary trunk, coronary sinus and, rarely, in the left atrium or left ventricle 5-8. The natural history of coronary artery fistula is vastly unpredictable as some patients report no symptoms throughout life. In the absence of symptoms, a continuous murmur may be the only positive clinical sign 6,9. The symptoms are mainly dependent on the severity of the shunt, with small shunts being asymptomatic and such patients can be monitored periodically to make sure the condition is not progressing. Reported pediatric fistula-related complications include congestive heart failure, myocardial infarction, bacterial endocarditis, rupture and death The aim of this audit was to share our experience S153

157 Coronary Arteriovenous Fistula Pak Armed Forces Med J 2018; 68 (Suppl-1): S153-S56 regarding device closure of CAFs in last seven years at AFIC/NIHD, with especial emphasis on immediate complications and problems encountered during these procedures. MATERIAL AND METHODS This retrospective study analyzed the CAF device closure done from January 2011 to December 2017 by reviewing the clinical records including catheterization data, echocardiography reports and follow up record. Total 08 patients with attempted percutaneous CAF device closure were included in the study. Device closure was attempted in isolated CAF with significant shunt and with body weight of at least 10 kgs. All patients were under went detailed pre procedural assessment including history & physical examination, 12 Lead ECG, chest x-ray, blood complete picture and echocardiography (fig-1). After taking informed consent, patients were taken to the catheterization lab. Both femoral vein and artery entered with short sheaths. Aortogram was performed with pigtail to delineate the anatomy of fistula, exit point, narrowest least beyond narrowest point. In one case, wire retaining technique was used. The appropriate device was advanced through the delivery sheath and the larger disk was deployed beyond narrowest point of interest and then sheath and the retention disk were pulled back as a single unit. The rest of the device was then peeled off by pulling back the delivery sheath. Post procedural Figure-1: 2D Echocardiogram showing large Left Coronary Artery to Right Atrial coronary fistula. aortogram was performed to confirm device position and to evaluate residual leak and device Figure-2: Large RCA to RA fistula being closed with ductal device. diameter, coronary arteries and their branches. In seven cases, fistula crossed from aorta and snared from venous side to make an Arterio-venous loop. As shown in fig-2 & 3, in one case (LCA to LV fistula) after Trans-septal puncture wire crossed from LV to fistula to Aorta and snared from arterial side. Appropriate delivery sheath advanced from venous side across the fistula, at S154 Figure-3: Large LCA to LV fistula after device occlusion. was released only if correct positioning was ascertained. Post procedural care included two doses of antibiotics, vital signs monitoring, examination & echo-cardiography after 4 hours and discharge echocardiography in next morning. Data was entered in SPSS 23 and descriptive analysis done; Student s t or chisquare tests were used as appropriate.

158 Coronary Arteriovenous Fistula Pak Armed Forces Med J 2018; 68 (Suppl-1): S153-S56 RESULTS There were 8 cases (4 male & 4 female) of CAF underwent attempted device closure from 2011 to The details of all patients are shown in table 1. Mean age was 12.9 ± 12 years and mean weight was 34.5 ± 22 kgs and mean height was 128 ± 36 cms. Among eight cases, 5 (62.5%) were done under general anaesthesia. Both femoral vein and artery were entered with short sheaths. The procedure was successful in seven while in one case, fistula anatomy was considered not suitable for device closure due to more than one narrow tortuous exit points. There was no Table: Details of patients, Coronary artery fistula and devices used. Age in Weight Gender CAF details Device used years in Kgs 10/8 Ductal 6 19 Female RCA to RA Occluder residual flow after device closure. In three cases, PDA occluder was used whereas in another three VSD septal occluder was used to completely occlude the flow. In one patient (41-year old male), CAF was occluded with 12 mm ASD device. During early follow-up there were no complications or evidence of coronary arterial insufficiency. DISCUSSION S155 CAFs are rare but very important clinical entity and represent abnormal connection between one or more coronary arteries and an adjacent cardiac chamber or vascular structure. In our study, the most common site of origin was RCA to RA as documented in literature 5,6,8. The treatments options include surgical, transcatheter or hybrid approach 2,12. The goal of treatment for symptomatic patients is to completely stop the flow across the fistulous track without compromising the coronary arteries flow 9. Although CAF complications are more common in older children over time, there is still no consensus in terms of treatment indications in children with asymptomatic fistula 1. Surgery was the only choice to treat CAFS, prior to the availability of occlusive devices. Cheung DL etal reported surgical results of 41 patients with no operative mortality and more than 96% of the patients were asymptomatic at a mean follow-up duration of 09 years 13. Fluoroscopy time in min Procedural time in min Male RCA to RA 8 VSD device Female LCA to RV 16/14 Ductal Occluder Female RCA to RA 16 VSD device Male RCA to RA 12 ASD device Male LCA to LV 14/12 Ductal Occluder Male RCA to RA Female LCA to RA 8 VSD device The first successful percutaneous transcatheter coil embolization was performed in 1983, has therefore become the procedure of choice in many centers in order to avoid surgical risk 9. Depending upon morphology, variety of devices are being reported for trans-catheter occlusion of CAFs including coils, ductal occlusion devices, septal occlusion devices, vascular plugs, detachable balloons etc 1,3,8, Factors to consider in deciding between surgery and device occlusion include the size of the fistula, its location and drainage pattern and the associated cardiac lesions 9. Transcatheter treatment is proving to be an important mode of treatment in CAFs cases as acceptable immediate results and by avoiding surgical risks. A recent study from Switzerland, shared their experience of six

159 Coronary Arteriovenous Fistula Pak Armed Forces Med J 2018; 68 (Suppl-1): S153-S56 patients with CAFs, treated by catheter interventions with 83% immediate success and good results at seven years follow up 2. One of their patient had significant residual flow and required surgery 2. We did not use coils in our patients, rather all seven cases were closed with devices (3 ductal, 3 VSD occluders & one ASD device Occluder), largely because of anatomy of fistula and operators preferences. One out of eight procedures was unsuccessful as anatomy of RCA to RV fistula was not favorable for device closure. There were more than one narrow and tortuous exit points to inlet area of RV and guide wire could not be negotiated across the fistula. In our small cohort, there were no immediate complications and patient remained asymptomatic in early follow-up period. Complications after CAF occlusion are rare but may include transient T-wave inversions, transient arrhythmias, coil or device migration/ embolization, coronary artery trauma or rupture, or total occlusion of a coronary artery. In view of possibility of coronary complications, longterm follow up is mandatory 17. Low-dose aspirin therapy (3 to 5 mg/kg per day) is recommended until coronary normalization occurs. Warfarin may be added if the dilatation is severe (>10 mm), particularly when coronary flow is sluggish 18. We used aspirin or warfarin for about one year in almost all the cases followed by recatheter study. CONCLUSION Transcatheter closure of the CAF was found safe and effective percutaneous intervention with high success rate and good safety profile in hands of skilled operators. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Gulgun M, Slack M. Percutaneous closure of a coronary fistula with single Amplatzer Vascular Plug II in a five-month-old female: The youngest case report. Rev Port Cardiol 2016; 35(2): Christmann M, Hoop R, Dave H, Quandt D, Knirsch W, Kretschmar O. Closure of coronary artery fistula in childhood: Treatment techniques and long-term follow-up. Clin Res Cardiol 2017; 106: Lee SN, Lee J, Ji EY, Jang BH, Lee HH, Moon KW. Percutaneous management of coronary artery-to-pulmonary artery fistula using an amplatzer vascular plug with the trans-radial approach. Intern Med 2016; 55(8): Karuse Wueber den Ursprung einer accessorishen A. Coronaria cordis aus der A. pulmonalis Z Ratl Med 1865; 24: Said SA, Lam J, van der Werf T. Solitary coronary artery fistula: A congenital anomaly in children and adults: a contemporary review. Congenit Heart Dis 2006; 1(3): Sherwood MC, Rockenmacher S, Colan SD, Geva T. Prognostic significance of clinically silent coronary artery fistulas. Am J Cardiol 1999; 83(3): Saito A, Shiono M, Yamamoto T, Inoue T, Hata M, Sezai A, et al. Surgical treatment for innominate artery aneurysm with a coronary pulmonary artery fistula: A case report. Ann Thorac Cardiovasc Surg 2005; 11(1): Carminati M, Giugno L, Chessa M, Butera G, Piazza L, Bussadori C. Coronary-cameral fistulas: Indications and methods for closure. Euro Intervention 2016; 12 Suppl X: X28- X Meng-Hung Chi, Ming-Ren Chen, Haw-Kwei H, Yu-Ching L. Transcatheter coil embolization of a huge right coronary artery to right ventricle fistula. Acta Cardiol Sin 2007; 23: Mishra RC, Barik R, Patnaik AN. Infective endocarditis of the left main to right atrial coronary cameral fistula. J Cardiovasc Echogr 2016; 26: Khanna R, Raja D, Goel PK. An elephant trunk appearance what is the diagnosis? Echocardiography 2016; 33: Jia Y, Hongxin L, Wenbin G, Zhang H, Zou C. Peratrial Device Closure of a Congenital Coronary Artery Fistula through a Right Parasternal Approach: Innovative Use of Available Technology. Heart Surg Forum. 2016; 19(1): e Cheung DL, Au WK, Cheung HH, Chiu CS, Lee WT. Coronary artery fistulas: Long-term results of surgical correction. Ann Thorac Surg 2001; 71: Sadiq M, Latif F, Shafi T, Wilkinson JL, Qureshi SA. Management of coronary arteriovenous fistula by device. Pak Heart J 2000; 33: Regazzoli D, Giglio M, Besana F, Leone PP, Tanaka A, Ancona MB, et al. Multimodality evaluation of percutaneous closure of coronary fistula using AMPLATZER Vascular Plug IV. Int J Cardiol 2016; 225: Zhang ZG, Xu XD, Bai Y, Zhang XL, Tan HW, Zhu YF. Transcatheter closure of medium and large congenital coronary artery fistula using wire-maintaining technique. J Cardiol 2015; 66(6): Wang SS, Zhang ZW, Qian MY, Zhuang J, Zeng GH. Transcatheter closure of coronary arterial fistula in children and adolescents. Pediatr Int 2014; 56: Colin JM, Michael RN, John PK, Charles EM, Ronald GG. Coronary artery fistula management and intermediate term outcome after transcatheter coil occlusion. Tex Heart Inst J 2001; 28(1): S156

160 Open Access Recombinant Factor Seven To For Congenital Heart Disease Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S157-S60 SINGLE CENTER EXPERIENCE ON USE OF RECOMBINANT FACTOR SEVEN FOR BLEEDING AFTER CONGENITAL HEART SURGERY Amna, Etizaz Haider Kazmi, Kamal Saleem, Rehana Javaid, Iftikhar Ahmad Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: The objective of our study is to review the use of recombinant factor seven to control bleeding in non hemophilic patients undergoing cardiac surgery for congenital heart disease. Study Design: Retrospective case series. Place and Duration of Study: Peads cardiac anesthesia department of Armed Forces Institute of Cardiology, Rawalpindi, from Jan 2017 to Jan Material and Methods: Data was collected from ICU daily monitoring and treatment charts. Patients who received rfviia to limit post surgical bleeding were sorted out. Gender, Age, weight, disease, date of surgery, dose of factor seven, thrombotic evidence and mortality of patients who were given factor seven to control bleeding were recorded. Results: Total 19 patients received factor seven from Jan 2017 to Jan Mean age at surgery was 6.99 years. Nine patients (47.4%) underwent total correction for Tetrollogy of fellot, three patients (15.8%) had surgical patch closure for ventricle septal defect and two patients (10.5%) had arterial switch operation for transposition of great arteries. Fourteen patients (73.7%) survived to hospital discharge. Nine patients (47.4%) received 40mcg/kg or less of rfviia while the remaining ten patients received up to 80mcg/kg total dose of rfviia post operatively. None of the patients was found to have evidence of thrombosis. Conclusion: Post operative bleeding was found very common and challenging problem in cardiac surgery. Further prospective study over large number of patients should be done and rfviia should be compared with tranexamic acid transfusion and desmopressin. Keywords: Congenital, Non-haemophilic factor, Tetrollogy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Severe post operative bleeding is one of the major causes of morbidity in pediatric patients with congenital heart disease undergoing open heart surgeries. Bleeding requiring exploration occurs in 1% of pediatric cardiac surgery patients, and transfusion may exceed 100 ml per Kg 1. Several factors are responsible for coagulation disturbances and bleeding following cardiopulmonary bypass in patients with congenital heart disease. This includes dilution during priming of pump, platelet disorder and dysfunction, premature haemostatic system in neonates, fibrinolysis, residual heparin and disseminated intravascular coagulation (DIC) 2. Abnormal homeostasis and bleeding disorder is Correspondence: Dr Amna, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan amna.amc@gmail.com well known in children with cyanotic heart disease. These children in hypo-coagulable state related to impaired fibrinogen function 3. In 1999 Recombinant factor seven was approved for treatment of bleeding in patients with hemophilia and inhibitors of factor VIII or IX 4. Activated factor VIIa plays important role in homeostasis mechanism by forming complex with tissue factor, this complex then activates factor X which induces thrombin formation 5. It has been increasing because of usage of off-label in controlling excessive bleeding following trauma, surgery and extracorporeal membrane oxygenation (ECMO) support 6. In cardiac surgery patients factor seven has been found to reduce transfusion requirements and chest drain output 7. The use of recombinant factor seven has less widely been reported in pediatric patients than adults. In children different non hemophilic S157

161 Recombinant Factor Seven To For Congenital Heart Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S157-S60 conditions has been described that may benefit from rfviia to control bleeding associated with cardiac surgery, neurosurgery, DIC, liver failure and transplantation 8, rfviia has also got some adverse effects like, the potential to cause limb ischemia, as well as pathologic thrombosis and related major neurological events 9. The main objective of this study is to review the use of rfviia for the treatment of bleeding in nonhemophiliac pediatric patients undergoing cardiac surgery for congenital heart disease in our setup and to recommend its use in future. The objective of our study was to review the use of recombinant factor seven to control bleeding in non hemophilic patients undergoing cardiac surgery for congenital heart disease. MATERIAL AND METHODS A retrospective cases series conducted at Pediatric cardiac surgery operation theatre and intensive care unit Armed Forces Instititute of Cardiology (AFIC) from January 2017 to January After approval from ethical committee, we reviewed retrospectively medical record of patients undergoing congenital heart surgeries requiring cardiopulmonary bypass from Jan, 2017 to Jan 2018 in pediatric cardiac surgery ICU. Data was collected from ICU daily monitoring and treatment charts. Patients who received rfviia to limit post surgical bleeding were sorted out. Gender, Age, weight, disease, date of surgery, dose of factor seven, thrombotic evidence and mortality of patients who were given factor seven to control bleeding were recorded. Total 19 patients were found to receive rfviia. Conduct and management of cardio pulmonary bypass S158 (CPB), surgical procedure was according to institutional guidelines and surgeon practice. Data Analysis The data was analyzed by descriptive statistics (frequency, percentage, mean and standard deviation) and chi square test was used for analysis of variance. In our study p-value of less than 0.05 was considered as statistically significant. The statistical analysis was done by using SPSS version 21. RESULTS For the 19 patients in our study, the demographics, congenital heart defects, dose of factor seven used, thrombotic evidence and mortality was analyzed. Mean age at surgery was 6.99 years with standard deviation of 6.16 (range: 2 months 20 years) as shown in table. Nine patients (47.4%) underwent total correction for Table: Clinical variables of study participants. S. No Variables Variable value 1. Age (mean ± SD) years 6.99 ± 6.16 Procedure type. Total correction for tetrollogy of fellot. 9 (47.4%) Surgical patch closure for ventricle septal 2. 3(15.8%) defect. Arterial switch operation for transposition of great arteries 2(10.5%) 3. rfviia dose <40 mcg/kg 9 (47.4%) Tetrollogy of fellot, three patients (15.8%) had surgical patch closure for ventricle septal defect and two patients (10.5%) had arterial switch operation for transposition of great arteries. Fourteen patients 73.7%) survived to hospital discharge and five (26.3%) died. Nine patients (47.4%) received 40mcg/kg or less of rfviia while the remaining ten patients received up to 80 mcg/kg total dose of rfviia postoperatively. None of the patients was found to have evidence of thrombosis. A p-value was found insignificant when two doses of factor seven were compared as related to mortality. A p-value was also found to be insignificant when effect of type of congenital heart defect was studied on mortality.

162 Recombinant Factor Seven To For Congenital Heart Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S157-S60 DISCUSSION Post operative bleeding requiring massive transfusion and re-exploration is one of the major problems in patients undergoing cardiac surgery. Re-exploration and multiple transfusions are associated with increase in mortality and end organ injury 10. Blood products are most commonly used for management of bleeding. Antifibrinolytic agents like tranexamic acid, has been used in our setup in cardiac surgery to reduce blood loss and need for transfusions. Factor concentrates and pharmacologic agents such as Desmopressin have been studied for control of bleeding after surgery 11. In 1999 recombinant factor seven was licensed for management of bleeding in hemophilia patients with inhibitors. In these patients the standard bolus dosing varies from 90 to 120mcg/kg and repeated every two to three hours until cessation of bleeding 12 and rfviia has been used as off label in controlling surgical bleeding. Its first off-label use was reported in 2001 as rescue treatment of uncontrolled postoperative bleeding 13. Since then there have been increasing number of cases that report off label use of rfviia in various clinical situations where bleeding was difficult to control such as cardiac surgery, massive trauma and obstretetrical uncontrolled bleeding The congenital cardiac anesthesia society task force recommends rfvii for refractory post CPB bleeding 16. In our center use of rfviia occurred just few years back. It is not being frequently used in our centre to control bleeding because of limited supply and resources. The half life of rfviia is 2.9 hours; therefore the frequency of rfviia dose is every two to three hours 17. In our institute rfviia is given at dose of mcg/kg and repeated after one hour as required. The dose of rfviia in non hemophilia patients to control bleeding has not been determined; low doses have been studied and found effective. Friederich et al found that 20mcg/kg was effective to control bleeding 18. Karsies et al. noted that mcg/kg per dose every two to three hours was effective 19. In our study 47.4% of the patients received 40 mcg/kg or less and remaining received up to 80 mcg/kg. The use of rfviia is associated with thrombotic events. Chuansumrit et al. studied the use of rfviia pediatric patients for control of hemorrhage and noted adverse events. He found the total number of doses given was directly related to thrombo-embolic events 20. In our study no patient had thrombosis. Our study was a retrospective with small number of patients. In future we plan to conduct study which would be prospective control trial. CONCLUSION Post operative bleeding was found common and challenging problem in cardiac surgery. Further prospective study over large number of patients should be done and rfviia should be compared with tranexamic acid transfusion and desmopressin. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author REFERENCES 1. Razon Y, Erez E, Vidne B, Birk E, Katz J, Tamari H, et al. Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease. Paediatr Anaesth 2005; 15(3): Warren OJ, Rogers PL, Watret AL, de Wit KL, Darzi AW, Gill R, et al. Defining the role of recombinant activated factor VII in pediatric cardiac surgery: where should we go from here? Pediatr Crit Care Med 2009; 10(5): Jenkins KJ, Gauvreau K, Newburger JW, Spray TL, Moller JH, Iezzoni LI. Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg 2002; 123(1): Weisko RB.Intraoperative use of recombinant activated coagulation factor VII. Anesthesiology 2002; 96: Barua A, Rao VP, Ramesh B. Barua B, El- Shafei H. Salvage use of activated recombinant factor VII in the management of refractory bleeding following cardiac surgery. J Blood Med 2011; 2: Wittenstein B, Ng C, Ravn H, Goldman A. Recombinant factor VII for severe bleeding during extracorporeal membrane oxygenation following open heart surgery. Pediatr Crit Care Med 2005; 6: AlGahtani FH, Alshaikh M, AlDiab A. Recombinant activated factor VII in controlling bleeding in non-hemophiliac patients. Annals of Saudi Medicine 2010; 30(3): Tang Y, Wu Q, Wu X, Qiu H,Sun A, Ruan C, et al. Use of recombinant factor VIIa in uncontrolled gastrointestinal bleeding after hematopoietic stem cell transplantation among patients with thrombocytopenia. Pak J Med Sci 2015; 31(6): S159

163 Recombinant Factor Seven To For Congenital Heart Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S157-S60 9. Karsies TJ, Nicol KK, Galantowicz ME, Stephens JA, Kerlin BA. Thrombotic risk of recombinant factor seven in pediatric cardiac surgery: A single institution experience. Ann Thorac Surg 2010; 89(2): Despotis G, Eby C, Lublin DM. A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery. Transfusion 2008; 48(suppl-1): 2S 30S 11. Crescenzi G, Landoni G, Biondi-Zoccai G, Pappalardo F, Nuzzi M, Bignami E, et al. Desmopressin reduces transfusion needs after surgery. Anesthesiology 2008; 109(6): Seremetis S. Dose optimization of recombinant factor VIIain the treatment of acute bleeding in haemophilia-associated inhibitors. Blood Coagul Fibrinolysis 2003; 14(1 suppl):s Lindley CM1, Sawyer WT, Macik BG, Lusher J, Harrison JF, Baird-Cox K, et al. Pharmacokinetics and pharmacodynamics of recombinant factor VIIa. Clin Pharmacol Ther 1994; 55(6): Yao D, Li Y, Wang J, yu W, Li J. Effects of recombinant activated factor VIIa on abdominal trauma patients. Blood Coagul Fribrinolysis 2014; 25: Zatta A, Mcquilten Z, Kandane-Rathnayake R, Isbister J, Dunkley S, Mcneil J, et al. The Australian and New Zealand Haemostasis Registery: ten years of data on off-licence use of recombinant activated factor VII. Blood Transfus 2015; 13: Guzzetta NA, Russell IA, Williams GD. Review of off-label use of recombinant activated factor VII in pediatric cardiac surgery patients. Anesth Analg 2012; 115(2): Al Douri M, Shafi T, Al Khudairi D, Al Bokhari E, Black L, Akinwale N, et al. Effect of the administration of recombinant activated factor VII (rfviia; NovoSeven) in the management of severe uncontrolled bleeding in patients undergoing heart valve replacement surgery. Blood Coagul Fibrinolysis 2000; 11 (Suppl- 1): S Friederich PW, Henny CP, Messelink EJ, Geerdink MG, Keller T, Kurth KH, et al. Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a doubleblind placebo-controlled randomized trial. Lancet 2003; 361(19353): Karsies TJ, Nicol KK, Galantowicz ME, Stephens JA, Kerlin BA. Thrombotic risk of recombinant factor seven in pediatric cardiac surgery: a single institution experience. Ann Thorac Surg 2010; 89(2): Chuansumrit A, Teeraratkul S, Wanichkul S, Treepongkaruna S, Sirachainan N, Pakakasama S, et al. Recombinant-activated factor vii for control and prevention of hemorrhage in nonhemophilic pediatric patients. Blood Coagul Fibrinolysis 2010; 21: S160

164 Open Access Reciprocal Electrocardiographic With Acute Inferior Wall Myocardial Infarction Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S161-S65 IN-HOSPITAL OUTCOMES OF PATIENTS WITH OR WITHOUT RECIPROCAL ELECTROCARDIOGRAPHIC CHANGES PRESENTING WITH ACUTE INFERIOR WALL MYOCARDIAL INFARCTION Hafiz Muhammad Shafique, Tahir Iqbal, Hassan Kamal, Tariq Hussain, Ajab Khan, Hassan Shabeer Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the in-hospital outcome in patients with and without reciprocal electrocardiographic changes presenting with acute inferior wall myocardial infarction. Study Design: Descriptive cohort study. Place and Duration of Study: Cardiology department of AFIC & NIHD, Rawalpindi from Jan 2017 to Dec Material and Methods: Patients of both genders, who had acute inferior wall myocardial infarction were included in the study. While Patients with previous myocardial infarction, CABG assessed by history, left ventricular hypertrophy assessed by electrocardiography by sokolow criteria were excluded from the study. Results: Two hundred and fifty patients were recruited in our study who presented with inferior wall infarction through consecutive sampling. Age of patients ranged from 35 to 85 years with mean age of ± 9.7 years and 219 (87.6%) patients were males while 31 (12.4%) patients were females. Out of 250 patients 161 (64.4%) of patients were with reciprocal changes and 89 (35.6%) were without reciprocal changes and 12(7.2%) patients had cardiogenic shock while 17 (6.8%) patients had ventricular arrhythmias and 44 (17.4%) patients were with atrioventricular block. Mortality rate was 10 (6.6%). Conclusion: It is concluded from our study that reciprocal ST depression in acute inferior wall myocardial infarction reflects ischemia in territory distant from the site of infarction and is associated with a high risk of fatal arrhythmias and late morbidity. Keywords: Reciprocal echocardiography changes, Inferior wall MI, Cardiogenic shock, Atrioventricular shock This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Inferior wall myocardial infarction accounts for nearly 40-50% of all acute myocardial infarction 1,2,16. The presence of ST segment depression (reciprocal changes) in precordial leads during acute inferior wall myocardial infarction is associated with greater myocardial necrosis hence left ventricular dysfunction and more frequent left coronary artery disease. Thus identifying a subset of high risk group with poor outcome 3,4. When ST segment elevation occurs in two continuous leads and ST segment depression occur in other leads, ST elevation is considered primary changes and ST depression considered as reciprocal changes. This reciprocal change may also represent remote ischemia in a distant territory in patient with multi-vessel coronary Correspondence: Dr Hafiz Muhammad Shafique, Armed Forces Institute of Cardiology /NHID Rawalpindi Pakistan Shafique76@gmail.com disease or may represent simply a benign electrical phenomenon 5,6. Various forms of ST depression in STEMI 17 have different implications. In patients with inferior myocardial infarction, ST segment depression in lead avl is a reciprocal change and is usually present in nearly all patients 18, while ST depression in leads V1-V3 most likely does not represent ischemia at different region rather reciprocal changes 19. Interestingly, among patients with inferior STEMI, ST segment depression in leads V4-V6 is usually associated with left anterior descending coronary stenosis or three vessel disease representing ischemic changes at distant zone 20. There is huge ever growing burden of coronary artery disease in Pakistan and most of the patient often seek care in emergency department with myocardial infarction demanding strenuous workup. This study would help emergency department staff to identify high risk patient S161

165 Reciprocal Electrocardiographic With Acute Inferior Wall Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S161-S65 (those with reciprocal changes) who benefit more from invasive approach like percutaneous coronary intervention at priority bases and hence there would be reduction in mortality and complications in this high risk group. MATERIAL AND METHODS It was a descriptive cohort study, conducted at cardiology department of AFIC/NIHD, Rawalpindi from Jan 2017 to Dec Patients were recruited through non-probability consecutive sampling. Patients of both genders, who had acute inferior wall myocardial infarction were included in the study. While Patients with previous myocardial infarction, by-pass surgery assessed by history, left ventricular hypertrophy assessed by electrocardiography by Sokolow criteria were excluded from the study. Patients who had ST elevation in anterior or anterolateral leads in addition to ST-segment elevation in inferior leads on electrocardiography, with serum creatinine more than 1.5mg/dl, with right ventricular infarction assessed by electrocardiography and ST elevation in right sided chest leads and with posterior wall MI in combination as assessed by tall R wave in 1st pre-cordial lead were also excluded from the study. A shift of more than 1mm; in two or more leads were taken as, evidence of ST depression or elevation. Patients without reciprocal changes i.e. ST depression <1.0 mm in chest leads were taken as group-i and those with reciprocal changes >1.0 mm were taken as group-ii. The diagnosis of acute inferior myocardial infarction was then confirmed during coronary angiography by identifying the causative lesion (the thrombotically occluded infarct-related vessel) S162 that was then revascularized during the primary percutaneous coronary intervention or was given injection streptokinase if patient was unwilling for PPCI or lesion was not crossed. Electrocardiographic monitoring for initial 24 hours using three chest leads to record Atrio-ventricular blocks and Ventricular arrhythmias was carried out. Patients underwent echocardiography to record remote regional wall motion abnormality. Patients were observed during period of hospitalization for mortality. Data Analysis Data was analyzed by SPSS Version-21. Mean and SD were used for continous variables while frequency (%) for categorical variables and chi-square test was applied to compare the groups. RESULTS Two hundred and fifty patients recruited in our study, who presented with inferior wall infarction. Age of patients ranged from 35 to 85 Table-I: Distribution of Reciprocal Echocardiographical changes between two groups. Groups N (%) Group-I Without Reciprocal Changes 89 (35.6%) Group-II With Reciprocal Changes 161 (64.4%) Table-II: Distribution and comparison of remote regional wall motion abnormality in study groups. Groups Remote Regional Wall Motion Abnormality (n=142) p-value Group-I Without Reciprocal Changes 19 (21.3%) Group II With Reciprocal Changes 123 (76.4%) years with mean age of ± 9.7 years. 219 (87.6%) patients were males while 31(12.4%) patients were females. Out of 250 patients 161 (64.4%) of patients were with reciprocal changes and 89 (35.6%) were without reciprocal changes, shown in table-i and 142 (56.8%) of patients were with remote regional wall motion abnormalities and 108 (43.2%) patients were, without remote regional wall motion abnormality. Out of 161 (64.4%) patients with reciprocal changes 123 (76.4%) were with remote regional wall motion abnormality and 38(23.6%) were without remote regional wall motion abnormality. Out of 89 (35.6%) patients without reciprocal changes 19 (21.3%) were with remote regional wall motion

166 Reciprocal Electrocardiographic With Acute Inferior Wall Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S161-S65 abnormality and 70 (78.7%) were without remote regional wall motion abnormality as shown in table-ii. Complications were found to be cardiogenic shock, ventricular arrhythmias and atrio-ventricular block. Twelve (7.2%) were with cardiogenic shock. In patients with reciprocal changes 9 (5.3%) suffered with cardiogenic shock. In patients without reciprocal changes 3 (3.4%) suffered with cardiogenic shock. Seventeen (6.8%) had episode of ventricular arrhythmias. Patients with reciprocal changes 16 (9.9%) had ventricular arrhythmias. Patients without reciprocal changes 1 (1.1%) had between two groups. Statistically significant association was found between presence of remote regional wall motion abnormality and reciprocal changes. Presence of cardiogenic shock was statistically insignificant in between two groups: p-value=0.32. In case of ventricular arrhythmias difference was statistically significant between two groups (p=0.007). Presence of Atrioventricular block was statistically significant in between two groups, p-value= Mortality was not statistically significant between two groups, shown in table-iii (a) & table-iii (b). Table-III (a): Distribution and comparison of complications among study groups. Complications Group-I with Group-II without reciprocal changes reciprocal changes p-value Cardiogenic Shock 3 (3.4%) 9 (5.4%) 0.32 Ventricular Arrhythmias 1 (1.1%) 16 (9.9%) Atrioventricular Block 3 (3.4%) 41 (25.5%) Mortality 1 (1.12%) 5 (3.1%) 0.30 Table-III (b): Clinical characteristics of study population. Variables Group-I Without Reciprocal Changes Group II With Reciprocal Changes p-value (n=89) (n=161) Diabetes Mellitus 11 (12.3%) 34 (21.1%) 0.08 Hypertension 31 (34.8%) 55 (34.1%) 0.51 Smokers 27 (30.3%) 50 (31.0%) 0.67 Family history of IHD 7 (7.8%) 19 (11.8%) 0.22 Systolic Blood pressure ± 31.0 mm Hg ± 27.8 mm Hg 0.39 Diastolic Blood pressure 79.8 ± ± Door to balloon time ± 30.4 min 59.1 ± 32.6 min 0.08 ventricular arrhythmias. Forty four (17.4%) patients developed atrioventricular block. In patients with reciprocal changes 41 (25.5%) had atrioventricular block. In patients without reciprocal changes 3 (3.4%) were with atrioventricular block. Out of 250 patients 10 (6.6%) died. In patients with reciprocal changes 1 (1.12%) died while 5 (3.1%) died patients without reciprocal changes. Chi-square test was used to determine the significance level of difference in patients with reciprocal changes and without reciprocal changes. Demographic variables were similar DISCUSSION Acute myocardial infarction is common not only in developed countries but is also a raising epidemic in developing countries. It is still one of major killer of mankind 7,8. Pakistanis are part of an ethnic group which suffers from the highest prevalence rates of coronary artery disease 9. According to the most carful estimates based on sound scientific studies nearly one hundred thousand individuals suffered an acute myocardial infarction in Pakistan in calendar year Inferior wall myocardial infarction occurred in 64.4% in this study while a study S163

167 Reciprocal Electrocardiographic With Acute Inferior Wall Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S161-S65 conducted by Abbase AH it was 62.5% of patients. In another study conducted by GP parate et al it was 80% 8. It is generally agreed that presence of precordial ST depression identifies a sub group of patients with inferior wall myocardial infarction with lower ejection fraction reflecting larger infarction and more severe remote regional wall motion abnormalities 11. In this study Remote regional wall motion abnormalities were present in 76.4% of patients with reciprocal changes and 21.3% of patients without reciprocal changes 12. In a study conducted by Abbase AH Remote regional wall motion abnormality was present in 80% of patients with reciprocal changes and 15% of patients without reciprocal changes 8. In study done by Shah et al found abnormal regional wall motion abnormality in patients with ST depression was 50% vs 15% in patients without ST depression 13. The two leading explanations for anterior ST depression that are believed to explain the larger infarction with more Remote regional wall motion abnormalities and more complicated courses observed in these patients are anterior ischemia due to concomitant LAD disease or more extensive infero-posterior infarction which produces ST elevation manifested as anterior ST depression on surface electrocardiography 14. Some studies mentioned that complications in patients with reciprocal changes occurred in 72% compared with 31% in patients without ST depression. In study by Abbase AH complications occurred were 44.4% of patients with Reciprocal changes and 7% of patients without Reciprocal changes 8. In present study complications occurred in 42.9% of patients with reciprocal changes and 7% of patients without Reciprocal changes. Also in our study we mentioned complications in terms of cardiogenic shock, ventricular arrhythmias, atrioventricular block, which was not done in previous studies 11,14. Cardiogenic shock occurred in 8.6% of patients with Reciprocal changes and 3.4% of patients without reciprocal changes. There was significant difference of occurrence of cardiogenic shock in patients with and without reciprocal changes. Ventricular arrhytmias occurred in 9.9% of patients with Reciprocal Changes and 1.1% of patients without reciprocal changes 10. There was no statistically significant difference of occurrence of ventricular arrhythmias in patients with and without reciprocal changes. atrioventricular block occurred in 25.5% of patients with reciprocal changes and 3.4% of patients without reciprocal changes. There was significant difference of occurrence of atrioventricular block in patients with and without reciprocal changes. Mortality rates among patients with inferior myocardial infarction is generally 2-9% 9 but it differs according to ST depression. Some studies compared the mortality in patients without ST depression versus with precordial ST depression without stating maximum ST depression was 4%, 4% vs 31%, and 28% 7,11,12. In a study done by Abbase AH mortality was 13.3% in patients with Reciprocal changes and 4% in patients without Reciprocal Changes 8. In this study mortality in patients with Reciprocal changes was 3.4% and in patients without reciprocal changes was 4.1% the difference between groups was not significant. ST depression in precordial leads reflects more than single vessel disease and this occurs more in patients with ST depression and thus explain the lower ejection fraction, Remote regional wall motion abnormality and higher incidence of complications and mortality 5,9. It is thought that in patients with ST depression and single vessel disease a branch of the right coronary artery often supplies the apex that it did in patients without anterior ST depression. So ST depression is either a reflect of larger infarction due to multivessel disease or greater amount of myocardium supplied by infarct related artery 11. It is recognized from work of Shroder et al and others 5,13 that extent of ST segment elevation plus depression defines territory at risk and its overall resolution is prognostically relevant. LIMITATION OF STUDY The sample size in both group is not large enough to implement on the general population S164

168 Reciprocal Electrocardiographic With Acute Inferior Wall Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S161-S65 and it is recommended to conduct prospective study with large sample size. CONCLUSION It was concluded from our study that Reciprocal ST depression in acute inferior wall myocardial infarction reflects ischemia in territory distant from the site of infarction and is associated with a high risk of fatal arrhythmias and late morbidity. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics 2016 update: A report from the American Heart Association. Circulation 2016; 133(4): e Hafeez S, Javed A, Kayani AM. Clinical profile of patients presenting with acute ST elevation Myocardial infarction J Pak Assoc 2010; 60(3): Noriega FJ, Vives-Borrás M, Solé-González E, García-Picart J, Arzamendi D, Cinca J. Influence of the extent of coronary atherosclerotic disease on ST-segment changes induced by ST elevation myocardial infarction. Am J Cardiol 2014; 113(5): Berry C, Carrick D, Carberry J, Mcentegart M, Petrie M, Eteiba H, et al. Current smoking, microvascular pathology and adverse outcome after acute st-segment elevation myocardial infarction: new pathophysiological insights. J Am Coll Cardiol 2017; 69 (11 supplement): Elias B. ST-segment depression and T-wave inversion: classification, diagnosis and caveats. cleveland clin J Med 2011; 78 (6): Toma M, Fu Y, Wagner G, Goodman SG, Granger C, Wallentin L, et al. Risk stratification in ST elevation myocardial infarction is enhanced by combining baseline ST deviation and subsequent ST segment resolution. Heart 2008; 94(3): e6. 7. Shah N, Kelly AM, Cox N,woong C, Soon K. Myocardial Infarction in the Young : Risk Factors, Presentation, Management and Prognosis. Heart Lung Circ 2016; 25(10): Abbase AH. Significance of Reciprocal ST Segment Depression in Acute Inferior Myocardial Infarction. Med J Babylon 2010; 7(4-3): Rumboldt Z, Rumboldt M, Pesenti S, Polic S, Miric D. Peculiarities of myocardial infarction at young age in Southern Croatia. Cardiologia 1995; 40(6): Jamshed D, Hiremath MS, Das MK, Desai DM, Chpra VK, Biswas AD. Vascular Disease in Young Indians (20-40 Years): Role of Ischemic Heart Disease J Clin Diagn Res 2016; 10(9): OE08-OE Ishaq M, Beg MS, Ansari SA, Hakeem A, Ali S. Coronary artery disease risk profiles at a specialized tertiary care centre in Pakistan. Pak J Cardiol 2003; 14: Malik R, Begum S, Afridi MN. Acute myocardial infarction, frequency of modifiable risk factors. Professional Med J 2016; 23(3): Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol 1989; 14(1): Masina SC, Sartorius B, Ranjith N. Risk factor assessment in South African Black patients presenting with acute myocardial infarction at RK Khan Hospital, Durban: risk factor assessment. SA Heart 2016; 13(1): Khan MS, Jafary FH, Faruqui AM, Rasool SI, Hatcher J, Chaturvedi N, et al. High prevalence of lack of knowledge of symptoms of acute myocardial infarction in Pakistan and its contribution to delayed presentation to the hospital. BMC Public Health 2007; 7: Reddy K, Khaliq A, Henning RJ. Recent advances in the diagnosis and treatment of acute myocardial infarction. World J Cardiol 2015; 7(5): Nour MK, Significance of reciprocal ST segment depression in ST elevation myocardial infarction, Egypt J Crit Care Med 2017; 5(1): Birnbaum Y, Sclarovsky S, Mager A, Strasberg B, Rechavia E. Segment depression in avl: a sensitive marker for acute inferior myocardial infarction. Eur Heart J 1993; 14(1): Peterson ED, Hathaway WR, Zabel KM, Pieper KS, Granger CB, Wagner GS, et al. Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the throbmoyltic era: results in 16; 521 patients. J Am Coll Cardiol 1996; 28: Birnbaum Y1, Wagner GS, Barbash GI, Gates K, Criger DA, Sclarovsky S,et al.correlation of angiographic findings and right (V1 to V3) versus left (V4 to V6) precordial ST segment depression in inferior wall acute myocardial infarction. Am J Cardiol 1999; 83(2): S165

169 Open Access Acute ST-Segment Elevated Myocardial Infarction Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S166-S71 EVALUATION OF ROLE OF SERUM URIC ACID AS AN INDICATOR OF PROGNOSIS IN PATIENTS PRESENTING WITH ACUTE ST-SEGMENT ELEVATED MYOCARDIAL INFARCTION Muhammad Asad, Tahir Iqbal, Waheed Ur Rehman*, Hafiz Muhammad Shafique, Mir Waqas baloch, Sadaf Shabbir Kiani, Rehana Khadim, Tahir Naqash, Aatika Kamran Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Combined Military Hospital Multan Pakistan ABSTRACT Objective: To evaluate the role of serum uric acid as an indicator of prognosis in patients presenting with Acute ST segment elevated myocardial infarction. Study Design: Descriptive cross sectional study. Place and Duration of Study: Adult Cardiology Department, Armed Forces Institute of Cardiology & National Institute of Heart Diseases Rawalpindi Pakistan, from Sep 2017 to Jan Material and Methods: Patients were recruited through non-probability purposive sampling. Patients of both gender between 25 to 70 years of age with acute ST elevation myocardial infarction, were included in the study. Patients who were excluded from the study were those who had NSTEMI, Old myocardial infarctions in any territory, pacemaker implantation, liver disease, kidney disease (creatinine >1.5 mg/dl), patients having gout, hypothyroidism, malignancy, valvular heart disease, alcoholics, on diuretics, ACE inhibitors, ARB s or drugs that increase uric acid levels. Results: Total 200 patients were included in the study according to the inclusion criteria of the study. Mean age was 49.7 ± 7.96 years which ranges from 35 to 71 years. There were 151 (75.5%) male and 49 (24.5%) female patients. Male to female ratio was Patients were divided into two groups according to their serum uric acid level. Regarding the types of myocardial infarction, anterior MI was most common among high uric acid patients but location of MI was not statistically significant with p-value=0.6. Out of 200 patients who presented with STEMI, 156 (78.0%) underwent primary PCI, 2 (1.0%) were thrombolysed and 42 (21.0%) patients were late for thrombolysis. 31 (15.5%) patients in PPCI group had high uric acid levels (p-value=0.001) as compared to 35 (17.5%) patients (p-value=0.001) in late for thrombolysis group. Conclusion: In conclusion, it is suggested that uric acid level on admission is not only closely related but also a predictor of cardiovascular mortality in patients presenting with STEMI during the in-hospital period. Keywords: Acute ST elevated myocardial infarction, NSTEMI, Serum uric acid. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION One of the most common causes of death worldwide is attributed to acute myocardial infarction (AMI) and patients with AMI are shown to have a high rate of mortality during the first month following an event, especially during in-hospital stay 1. In myocardial infarction there is formation of thrombus in coronary artery which leads to the occlusion of blood flow in it. If the occlusion persists for more than 20 minutes then this results in irreversible damage to the heart Correspondence: Dr Muhammad Asad, Armed Forces Institute of Cardiology / NIHD Rawalpindi Pakistan masad1288@gmail.com muscles and cell death would occur 2. Cardiac myocytes produce a compound called Adenosine and the role of this compound is to cause vasodilation of arteries. Some conditions like hypoxia and tissue ischemia cause an increase in the levels of this compound 3. This adenosine when produced is broken down by a structure called Endothelium. As a result of degradation adenosine is converted to uric acid (UA) rapidly; so this results in the increase in concentration of UA which leads to the decrease in the intracellular PH. As a consequence there is rapid UA efflux to the vascular lumen 4. Under stressful condition like in ischemia, activity of enzymes S166

170 Acute ST-Segment Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S166-S71 involved in the synthesis of Xanthine oxidase activity and uric acid is increased, therefore elevated serum uric acid may act as a marker of underlying tissue ischaemia 5. In myocardial infarction (MI) there is release of some proteins and enzymes known as cardiac markers (CPK, MB/ Troponin T & I and myoglobin) into the blood stream and the area which is the most necrotic releases the largest amount. It has been demonstrated that there exists a temporal relationship of these cardiac biomarkers with MI however they do not correlate with myocardial function 6. Epidemiological studies have recently shown that serum uric acid may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients 6. It has been still not clear that how does uric acid produce pathological effects on our bodily functions including cardiovascular systems and studies are still ongoing, but it has been revealed that hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, haemorrheology and aggregation 5. There is ample proof that increased levels of uric acid is a bad prognostic factor in those patients who have mild to severe heart failure and the development of hyperuricemia is linked almost always with the worsening of renal failure in these patients 7. Akpek M and his colleagues studied association of serum uric acid levels on coronary flow in patients undergoing primary PCI. They showed that among patients with STEMI plasma uric acid level on admission was an independent and powerful predictor of poor coronary blood flow after primary PCI and also in hospital major adverse cardiac events (MACE) 20. A Japan based study (Japanese Acute Coronary Syndrome Study) showed a close collaboration between serum uric acid concentration and Killip s classification in patients of acute myocardial infarction and those types of patients who have high uric acid concentration develop large number of short term adverse effects 8. Long term mortality is closely associated with serum uric acid level, Killip s class, age and peak creatinine phosphokinase level and they have been related as significant predictors of long-term mortality. Patients with angiographically confirmed coronary artery disease with serum uric acid levels in the upper quartile are five times more likely to die than those in the lowest quartile. 1 mg/dl increase in serum acid levels was associated with a 26% increase in mortality 9. Another study done by Chen et al in STEMI patients showed a relationship between serum UA and adverse events 10. Kroll et al showed that in patients with higher on admission serum UA short term and long term mortality was increased 11. Akpek et al. reported that hyperuricemia is associated with endothelial dysfunction and microvascular disease in patients with STEMI and they concluded that free radicals may be responsible for the no-reflow phenomenon during reperfusion therapy 18,19. Furthermore, hyperuricemia may decrease nitric oxide production in vascular endothelium, which plays an important role in the regulation of coronary blood flow 20. This study is being done to evaluate the role of serum uric acid in predicting cardiovascular events in patients presenting with acute ST elevation myocardial infarction, showing its association with Killip s class of heart failure and assessing the relationship of raised serum uric acid levels with in hospital mortality. MATERIAL AND METHODS This study was descriptive cross-sectional study conducted at AFIC/NIHD Rawalpindi from September 2017 to January Patients were recruited through non-probability purposive sampling. Patients of both gender between 25 to 70 years of age with acute St elevation myocardial infarction, were included in the study. Patients who were excluded from the study were those who had NSTEMI, Old S167

171 Acute ST-Segment Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S166-S71 myocardial infarctions in any territory, pacemaker implantation, liver disease, kidney disease (creatinine > 1.5 mg/dl), patients having gout, hypothyroidism, malignancy, valvular heart disease, alcoholics, on diuretics, ACE inhibitors, ARB s or drugs that increase uric acid levels. Permission was sought from hospital ethical committee. Patients presenting with acute St elevation myocardial infarction were selected based on inclusion criteria. A detailed cardiovascular history and examination with special reference to KILLIP class was done. Risk factors like diabetes mellitus, hypertension, hyperlipidemia and smoking were taken into account. Hypertension was interpreted as blood pressure 140/90 or taking anti-hypertensive medications. Patients having fasting blood glucose level higher than 126 mg/dl or having a random blood glucose test level of 200 mg/dl or higher as well as those taking medications for S168 hyperglycemia were defined as having diabetes. Blood sample for uric acid was drawn 24 hours after admission. Normal levels of uric acid were defined mg/dl in women and mg/dl in men according to our reference laboratory. The study population was divided into normal and hyperuricemic groups according to baseline levels. Hyperuricemia was defined as serum uric acid levels as >6 mg/dl in women and >7 mg/dl in men. The patients underwent coronary angiography and revascularization according to current guidelines. Coronary angiography was Table-I: Clinical data, Risk factors and Location of MI of the patients. Variables Hyperuricemic Normouricemic (n=68) (n=132) p-value Age 48.6 ± 7.3 years ± 8.2 years 0.19 Gender Male 48 (70.5%) 103 (78.0%) Female 20 (29.4%) 29 (21.9%) DM 34 (50.0%) 49 (37.12%) 0.05 HTN 20 (29.4%) 33 (25%) 0.30 Smokers 18 (26.4%) 37 (28%) 0.47 Anterior Wall MI 40 (58.8%) 73 (55.3%) Inferior wall MI 26 (38.2%) 52 (39.3%) Posterior wall MI 1 (1.4%) 6 (4.5%) 0.6 Lateral wall MI 1 (1.4%) 2 (1.5%) Table-II: Management of patient, KILLIP class and complications of St elevation myocardial infarction. Variables Hyperurecemic Normourecemic (n=68) (n=132) p-value Death 16 (16.1%) 12 (0.9%) 0.06 Ventricular Tachycardia 3 (0.4%) 5 (0.3%) 0.55 Primary PCI 31 (45.5%) 125 (94.6%) Late for thrombolysis 35 (51.4%) 7 (0.5%) KILLIP 1 39 (63.2%) 118 (89.3%) KILLIP 2 15 (22.1%) 7 (0.5%) KILLIP 3 10 (14.7%) 5 (0.3%) KILLIP 4 4 (0.2%) 2 (0.1 %) done through radial or femoral route using Judkin s technique and on Philips machines in catheterization laboratory. Data was analyzed in SPSS version 23. RESULTS Total 200 patients were included in the study according to the inclusion criteria of the study. Mean age was 49.7 ± 7.96 years which ranges

172 Acute ST-Segment Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S166-S71 from 35 to 71 years. There were 151 (75.5%) male and 49 (24.5%) female patients. Male to female ratio was Patients were divided into two groups according to their serum uric acid level. Table-I shows the demographic, risk factors and location of MI of patients according to their serum uric acid level. Regarding the types of myocardial infarction, anterior MI was most common among high uric acid patients but location of MI was not statistically significant with p-value =0.6. Out of 200 patients who presented with STEMI, 156 (78.0%) underwent primary PCI, 2 (1.0%) were thrombolysed and 42 (21.0%) were found hyperuricemic and this was significant with p-value= Ventricular tachycardia occurred in 8 (4.0%) patients, 5 (2.5%) of them had high uric acid levels (p-value=0.55) as shown below. DISCUSSION Uric acid (UA) has long been known to be a cardiovascular risk factor. Clinical and epidemiological studies have shown that there is an association between high levels of UA and the severity of coronary artery disease. Increased serum UA levels were independently and significantly associated with cardiovascular Figure: KILLIP class of patients according to their uric acid level. patients were late for thrombolysis. 31 (15.5%) patients in PPCI group had high uric acid levels (p-value=0.001) as compared to 35 (17.5%) patients (p-value=0.001) in late for thrombolysis group. Taking risk factors of STEMI into account smoking and hypertension were more common in normal UA group but diabetes was more commonly found in high UA group (p=0.05). Figure shows the KILLIP class differences in two groups. Out of 200 patients most of the patients were in KILLIP class 1 and hyperuricemia occurred more commonly with higher KILLIP class (p-value=0.001) as shown in table-ii. Death occurred in 28 (14.0%) patients in whom 16 (8.0%) S169 mortality over a long-term period. These findings suggest a relationship between high serum UA levels and coronary artery disease, although the underlying mechanisms remain unclear 12. Our study showed that mean age of patients in high and normal uric acid groups was not significant. Furthermore there was no statistical significance between male and female patients in both groups. Regarding risk factors diabetes mellitus was significantly associated with the rise of uric acid post myocardial infarction but other risk factors of hypertension and smoking were not.a study by Safi et al also showed a significant association between hyperuricemia and type 2 diabetes mellitus 13.

173 Acute ST-Segment Elevated Myocardial Infarction Pak Armed Forces Med J 2018; 68 (Suppl-1): S166-S71 The aim in the management of acute myocardial infarction is early restoration of myocardial blood flow because early reperfusion decreases mortality rates. In patients who had myocardial infarction those who were having higher UA concentration were in high Killip s class. A failing heart due to AMI may cause tissue hypo perfusion and hypoxia, which results as a trigger factor for xanthine oxidase activation and oxidative stress production. Xanthine oxidase and oxidative stress as reflected by UA may form a vicious cycle that promotes severe heart failure. Therefore, UA may not be only a bystander marker but also a causative marker of mortality in patients who have AMI. In view of this fact improvement of coronary reperfusion alone may be less effective in decreasing heart failure and reducing mortality rate in patients who have acute myocardial infarction and high UA level and are in a high Killip s class 8. Supporting this fact some studies have shown that in patients with MI, high serum UA level can increase the mortality rate. Our study also supported the above findings with higher no of death in hyperuricemic patients. A study done by Kaya et al showed that raised levels of UA are significantly related to lower thrombolysis in myocardial infarction (TIMI) flows in infarct- related artery and adverse events and in-hospital mortality are higher in patients with STEMI who had undergone primary percutaneous coronary intervention (PCI) 19. Our study also showed that no of patients who had underwent primary pci had lower rates of high uric acid levels 31 (45.5%) vs 125 (94.6%) p-value compared to those who were late for thrombolysis 35 (51.4%) vs 7 (0.5%) p-value as per the guidelines. In this study we also found out that frequency of ventricular tachycardia was not statistically significant among the two groups (p-value 0.5). According to a study by Siniša Car1 and et al A total of 621 patients (age years, 64.7% men, 77.5% AMI with ST elevation, SUA μmol/l) were included. Higher SUA on admission was independently associated with higher in-hospital mortality (p 0.043) and higher thirty-day mortality (p 0.018). Higher serum uric acid determined on admission is associated with higher in-hospital mortality and poorer long-term survival after AMI 15. Nadkar and Jain concluded that SUA levels were higher in patients with acute MI and were correlated with killip s class 16. In a recent systematic review, it was shown that increased risk of incident heart failure can be associated with hyperuricemia and also cardiovascular mortality, composite of death or cardiac events and risk of all other mortality cause. In this regard, for every 1 mg/dl increase in serum uric acid, the odds of development of heart failure increased by 19% and the risk of total mortality and the combined endpoint in patients with heart failure increased by 4% 13. Our study showed that death occurred in 16 out of 68 patients having raised uric acid which was statistically significant (p-value 0.06) which correlates with the above studies. CONCLUSION In conclusion, it is suggested that uric acid level on admission is not only closely related but also a predictor of cardiovascular mortality in patients presenting with STEMI during the inhospital period. Heart failure is also linked to hyperuricemia. The majority of deaths in St elevation myocardial infarction occur during hospital admission. Uric Acid being a readily available laboratory test can be used as a biomarker for risk stratification. STEMI patients having hyperuricemia should be monitored closely for cardiovascular events during the inhospital period. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al. Disorders of the cardiovascular system. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison s principle of internal medicine. 17th ed. McGraw-Hill 2016; p Soukoulis V, Boden WE, Smith SC, O Gara PT. Nonantithrombotic medical options in acute coronary S170

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175 Open Access Left Main Stem Disease Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S172-S75 FREQUENCY AND PATTERN OF LEFT MAIN STEM DISEASE IN PATIENTS REPORTING AT AFIC & NIHD, RAWALPINDI Hassan Shabeer, Sohail Aziz, Tahir Iqbal, Rehana Khadim, Hafiz Muhammad Shafique, Bilal Sidique*, Azhar Ali Chaudhry Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Combined Military Hospital Peshawar Pakistan ABSTRACT Objective: To determine the frequency and pattern of left main stem disease in patients reporting at AFIC & NIHD, Rawalpindi Study Design: A single center, descriptive cross-sectional study. Place and Duration of Study: Adult Cardiology department of AFIC & NIHD from 1 st Jul 2017 to 31 st Dec Material and Methods: Patients were recruited through consecutive non- probability sampling. All the Patients of either gender who underwent for coronary angiography were included in the study. Patients excluded were either known case of coronary artery disease or Post CABG or Post PCI patients. All patients were assessed for eligibility and enrolled in study according to inclusion & exclusion criteria after informed consent. History of diabetes, hypertension, dyslipidemia, obesity, and smoking were recorded. Coronary angiographic findings of patients were noted. Data was entered and analyzed in SPSS version-21. Results: A total of 6136 patients underwent coronary angiography during study period out of which there were 538 (8.7%) patients with LMS disease. Mean Age of the patients was ± 2.2 years with minimum age 27 years and maximum 75 years. There were 487 (90.5%) male patients while 51 (9.5%) female patients. Hypertension was found to be the most prevalent risk factor 280 (52.0%) followed by Obesity (BMI 30), smoking history, diabetes mellitus and dyslipidemia. About 282 (52.4%) patients had TVCAD. Forty three (8.0%) had bifurcation LMS disease, 15 (2.8%) patients had shaft LMS disease while one patient had ostial LMS disease. Conclusion: The frequency of Left main coronary artery is quite high in our patient population (8.9%), which leads to increase morbidity and mortality in these patients Keywords: Coronary angiography, Coronary artery disease, Left main stem disease. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Coronary artery disease (CAD) is the leading cause of death in the world 1. CAD burden is on rise in developing countries despite of recent advancements in diagnostic and therapeutic approaches owing to life style changes because of rapid urbanization 2. Every 5th middle aged person in Pakistan is having CAD 3. A good number of those patients present with left main stem disease defined as >50% luminal diameter narrowing of left main stem which carries 50% mortality at 3 years with medical management and requires early intervention 4,5. When left main stem disease is present, it is associated with multivessel CAD in about 70% of the patients 6-8. LMS disease with concomitant TVCAD carries a Correspondence: Dr Hassan Shabeer, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan hasanshabeer@gmail.com S172 high risk of death and adverse outcomes. Isolated left main coronary artery stenosis is not uncommon 9. Most common site for left main stenosis is distal left main bifurcation followed by ostial left main while shaft of left main has least incidence of left main stenosis in western population 10. Significant LMS disease (>50% narrowing) is reported in approximately 5% of patients who underwent coronary angiography, while total occlusion of LMS is quite uncommon almost incompatible with life and is very rarely seen in general routine day-to-day practice. Review by DE Ward 11 showed that 6 patients (0.04%) out of 11,900 patients undergoing angiography had complete left main occlusion 12. Significant LMS disease occurs in upto 7% of patients who under went coronary angiography 9,10. But these are international

176 Left Main Stem Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S172-S75 studies 11,12 and local burden of left main stem disease is not known and data regarding this subject is scanty. MATERIAL AND METHODS It was descriptive cross sectional study, conducted at Department of Cardiology AFIC & NIHD, Rawalpindi from 1st July 2017 to 31 st December All consecutive patients undergoing coronary angiography during this study period were included in the study. Patients excluded were either known case of pattern of disease was noted. Data was entered and analyzed in SPSS version-21. Continuous variables such as age, height, weight and BMI were reported as mean ± standard deviation while categorical variables such as gender, diabetes, hypertension, dyslipi-demia and smoking were reported as frequency and percentages. Frequency of LMS disease and type of disease like one involving ostium, shaft or bifurcation were presented as percentages. Confounding factors and interactions were addressed by stratification for variables such as Table-I: Showing baseline and risk factors profile. Variables n (%) Age Gender Male Female (mean ± S.D) ± 0.2 years (Range) years 487 (90.5%) 51 (9.5%) Hypertension 280 (52.0%) Obesity(BMI 30) 273 (50.7%) Smoking History 265 (47.2%) Diabetes Mellitus 207 (38.7%) Dyslipidemia 188 (30.8%) LMS Disease Normal Ostial Shaft Bifurcation 479 (89.0%) 1 (0.2%) 15 (2.8%) 43 (8.0%) TVCAD 282 (52.4%) Table-II: Association between LMS disease and TVCAD. LMS Disease TVCAD No TVCAD p-value Total 236 (43.9%) 243 (45.2%) Osteal - 1 (0.2%) Shaft 15 (2.8%) - Bifurcation 31 (5.8%) 12 (2.2%) 0.02 CAD or Post CABG or Post PCI patients. All patients were assessed for eligibility and enrolled in study according to inclusion / exclusion criteria after informed consent. Permission from the institutional ethical committee was taken before the commencement of study. History of diabetes, hypertension, dyslipidemia, obesity, and smoking were recorded. Angiographic findings of patients with age, gender, smoking and diabetes. Chi Square test was used for association of variables. RESULTS A total of 6136 patients underwent coronary angiography during study period out of which there were 538 (8.7%) patients with LMS disease. Mean Age of the patients was ± 2.2 years with minimum age 27 years and maximum 75 S173

177 Left Main Stem Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S172-S75 years. There were 487 (90.5%) male patients while 51 (9.5%) female patients. Hypertension was found to be the most prevalent risk factor 280 (52.0%) followed by Obesity (BMI 30), smoking history, diabetes mellitus and dyslipidemia. About 282 (52.4%) patients had TVCAD. 43 (8.0%) had bifurcation LMS disease, 15 (2.8%) patients had shaft LMS disease while one patient had ostial LMS disease as shown in table-i. Association between TVCAD and LMS disease was found to be statistically significant with p-value=0.02 as shown in table-ii. DISCUSSION Coronary artery disease is the most important cause of mortality in the developed countries and is one of the leading causes of disease burden in developing countries 11. CAD is the epidemic of this era worldwide 12, LMS disease remains an independent risk factor for increased mortality and morbidity during all stages of management of coronary artery disease 13. LMS disease is often silent with unpredictable presentation and as such poses a certain diagnostic and management challenge 14. Significant (defined as a greater than 50 percent angiographic narrowing) LMS disease is found in 8.9% of our study patient population which is higher as compared to 4% to 6% of all patients who underwent coronary angiography 15, most likely because of late presentation to tertiary care in our study population. It is associated with multivessel coronary artery disease in around 70% of cases 16, Identification of significant left main disease is not always easy. Coronary Angiography may sometimes under or overestimate the degree of left main narrowing. This is particularly true for ostial or distal bifurcation, or in the presence of dense calcium or eccentric disease which requires other modalities for objective assessment of disease severity 17. On the other hand Left main stem disease is a relatively infrequent cause of symptomatic coronary artery disease 15, so patient most of the time come to medical attention very late in our part of the world. There are limited number of cath labs available in very few centers and most patient are taken to those cath labs quite late with advanced disease when they are having class III and Class IV angina, so the chance of picking the LMS disease earlier is further reduced. Coronary anomalies and coronary heart disease together contribute about 24% to Sudden cardiac death 10. However about 40% of sudden deaths can be unwitnessed 20. There is another 3 to 5% of cases which remain unexplained 12. During our study, we came across 538 (8.9%) cases of significant left main disease. The possible cause we presume of higher rate as compare to the international data 13 is that, our patient s presentation is very late to the cath lab and during this delay there disease gets worse. The average age was ± 0.2 years in our study population and people get coronary involvement very early so there has to to be an early screening for CAD here. There were 487 (90.5%) male while 51 (9.5%) female patients, The possible reason can be increased prevalence of coronary artery disease in male population 14, secondly there is a trend of females presenting very late to tertiary care as compared to males in developing countries like pakistan likely because of societal taboos, Diabetics were 207 (38.5%) out of 538 patients with left main stem disease. Non diabetics were 331. Although diabetes is a major risk factor but mortality is only 2 to 4% higher 15 in diabetics. The possible cause of getting the low figure in them can be the same custom of late presentation and in the age group they came to us we lost a significant number of cases. Patients who were hypertensive with left main disease were 280 (52.0%). This is interesting as hypertension is a late presentation as compare to diabeties 6. About 7.9% patients who were having significant Left Main CAD were in class I angina, whereas class II angina patients with significant disease were 73%, and 14.28% were in class III and 4.7% were in CLASS IV angina. Again, if we look at the cohorts 10,13 more patients were found in the class of angina where angiography might not have been done routinely and by the time they reach the catheterization laboratory we have lost most of them. S174

178 Left Main Stem Disease Pak Armed Forces Med J 2018; 68 (Suppl-1): S172-S75 CONCLUSION There is a high frequency of left main disease in our population with comparatively younger patients presenting with significant LMS disease which is an independent risk factor for high mortality and morbidity so there is a need for devising some measures to recognize those patients earlier for avoiding any catastrophe on patient and family. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Leal J, Luengo-Fernández R, Gray A, Petersen S, Rayner M. Economic burden of cardiovascular diseases in the enlarged European Union. Eur Heart J 2006; 27(13): TanmayN; Arnab G. Cardiovascular disease risk factors in Asian Indian population: A systematic review. J Cardiovasc Dis Res 2013; 4(4): Faheem M, Shah I, Noor L, Adil M, Hameedullah, Hafizullah M. Effect of cholesterol level on plateletaggregability in normal individuals. J Pak Med Inst 2013; 27(03): Taylor H, Deumite N, Chaitman B, Davis K, Killip J, Rogers W. Asymptomatic leftmain coronary artery disease in the Coronary Artery Surgery Study (CASS) registry. Circulation 1989; 79(6): Cohen M, Gorlin R. Main left coronary artery disease: Clinical experience from Circulation 1975; 52(2): Karabulut A, Cakmak M. Treatment strategies in the left main coronary artery disease associated with acute coronary syndromes. J Saudi Heart Assoc 2015; 27(4): Gagnor A, Tomassini F, Romagnoli E, Infantino V, Rosa-Brusin MC, Maria C. Percutaneous left main coronary disease treatment without on site surgery back up in patients with acute coronary syndromes: Immediate and 2-year outcomes. Catheter Cardiovasc Interv 2012; 79(6): Lee MS, Sillano D, Latib A, Chieffo A, Zoccai GB, Bhatia R. Multicenter international registry of unprotected left main coronary artery percutaneous coronary intervention with drugeluting stents in patients with myocardial infarction. Catheter Cardiovasc Interv 2009; 73(1): Stone P, Goldschlager N. Left main coronary artery disease: Review and appraisal. Cardiovasc Med 1979; 4(2): DeMots H, Rosch J, McAnulty J. Left main coronary artery disease.cardiovasc Clin 1977; 8(2): Joanna C, Michael K, Andrew B. Goldstone, Arzhang F, Thanos A. Current diagnosis and management of left main coronary disease. Eur J Cardiothorac Surg 2010; 38(4): Ragosta M, Dee S, Sarembock IJ, Lipson LC, Gimple LW, Powers ER, et al. Prevalence of unfavorable angiographic characteristics for percutaneous intervention in patients with unprotected left main coronary artery disease. Catheter Cardiovasc Interv 2006; 68(3): Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009; 360(10): Botman CJ, Schonberger J, Koolen S, Penn O, Botman H, Dib N, et al. Does stenosis severity of native vessels influence bypass graft patency? A prospective fractional flow reserve guided study. Ann Thorac Surg 2007; 83(6): Sciagra R, Tebbe U, Vogt A, Wiegand V, Kreuzer H, Neuhaus KL. Occlusion of the common trunk of the left coronary artery. Physiopathological features and clinical findings [in Italian]. G Ital Cardiol 2006; 16(11): Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics: A report from the American Heart Association. Circulation 2015; 131(4): e Conti CR. When should patients with chest pain be referred for coronary angiography. Clin Cardiol 2004; 27(2): S175

179 Open Access Gender And Coronary Artery Bypass Grafting Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S82 EFFECT OF GENDER ON OPERATIVE AND EARLY RESULTS OF CORONARY ARTERY BYPASS GRAFTING Iftikhar Paras, Ghulam Hussain, Mirza Ahmad Raza Baig, Sehrish Khalid, Sara Zaheer*, Khaliq Mahmood Chaudhary Parvaiz Elahi Institute of Cardiology Multan Pakistan, *Civil Hospital Multan Pakistan ABSTRACT Objective: To evaluate the effect of gender on early morbidity and mortality after coronary artery bypass grafting. Study Design: Retrospective comparative study. Place and Duration of Study: Cardiac surgery unit of Chaudhary Pervaiz Elahi Institute of Cardiology Multan Pakistan, from Jun 2013 to Dec Material and Methods: Two thousand and one (2001) patients were included in this study, out of which 1445 were men and 556 women. SPSS V20 was used for data analysis. Independent sample t-test was used to compare quantitative variables, while qualitative variables were compared using Chi-square or Fisher s exact test. A p-value <0.05 was considered as statistically significant. Results: Out of two thousand and one patients 1445 (72.30%) were men and 556 (27.70%) were women. Women were more obese, hypertensive and diabetics as compared to men. Pre-op ejection fraction was high in female group (p-value 0.003). Cardiopulmonary bypass time and cross clamp time was significantly high in male gender (p-value <0.001 and <0.001 respectively). The need of inotropic and circulatory support on weaning from bypass and in ICU stay was high in female gender (p-value <0.001 and <0.001 respectively). Mechanical ventilation support time and hospital stay time was significantly high in women population (p-value 0.01 and <0.001 respectively). Incidence of renal complications was significantly high in female gender, 30 (2.7%) in female versus 12 (0.8%) in male population (p-value 0.001). In-hospital mortality was 17 (3.1%) in female and 11 (0.8%) in male group with highly significant p-value of < There was no significant effect of hypertension and diabetes on operative outcomes of female gender. Conclusion: Female gender is associated with higher incidence of mortality and morbidity after coronary artery bypass grafting. Keywords: Coronary artery bypass grafting, Female gender, Morbidity. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION In the recent years, there has been a tremendous increase in the number of coronary artery bypass graft (CABG) surgery as it is considered an effective method for patients suffering from severe coronary artery disease for both male and female gender 1. But women are reported to have higher incidence of perioperative mortality and morbidity after coronary artery bypass grafting 2. According to European system for cardiac risk evaluation female gender is an independent risk factor for CABG surgery 3. According to some researches difference in Correspondence: Dr Ghulam Hussain, Cardic Surgery Department, CPE Institute of Cardiology Multan Pakistan hussain.surgery@gmail.com Received: 16 May 2016; revised received: 05 Feb 2017; accepted: 10 May 2017 variables in men and women is responsible for this variation as women who referred to CABG are older than men 4, smaller coronary arteries 5, more advanced disease, less utilization of internal thoracic artery graft 6,7, and higher rate co-morbid conditions e.g. diabetes mellitus, higher rates of Pulmonary Hypertension and heart failure 8. Despite huge number of researches on this issue it is still unclear whether it is gender or the co-morbid conditions that are responsible for poor outcome in female patients as compared to males. But almost all authors are agreeing that female patients have poor outcome after surgery. On the other hand, some researchers have found similar post-operative outcomes in female gender as compared to male 9,10. The purpose of this study is to see the difference in pre-operative risk S176

180 Gender And Coronary Artery Bypass Grafting Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S82 factors and post-operative outcomes in patients undergoing CABG surgery at a tertiary care cardiac center. PATIENTS AND METHODS It was a retrospective comparative study conducted in the cardiac surgery unit of Ch. Pervaiz Elahi Institute of Cardiology Multan, Pakistan. The demographic, echocardiographic, angiographic and per-operative data of patients operated from January 2013 to September 2015 was retrieved from the cardiac surgery database of the hospital. All patients undergoing coronary Table-I: Comparison of pre-operative characteristics. Variable Male Gender Female Gender p-value Number 1445 (72.30) 556 (27.70) Age (Y) ± ± Body Mass Index ± ± 5.19 <0.001 Hypertension (%) 592 (41.0) 348 (62.5) <0.001 Diabetic History (%) 452(31.3) 293 (52.7) <0.001 Smoking History (%) 631 (43.7) 21 (3.8) <0.001 Family History (%) 300 (20.8) 144 (25.9) Pre-op EF ± ± Pre-op Creatinine Levels 1.02 ± ± 0.25 <0.001 Parsonnet Score 3.88 ± ± 3.4 <0.001 Severity of the Disease (%) SVD 69 (4.8) 22 (4.0) DVD 256 (17.7) 96 (17.3) TVD 803 (55.6) 310 (55.8) 0.83 LMS 317 (21.9) 128 (23.0) Angina Class CCS (%) Class I 183 (12.7) 62 (11.2) Class II 25 (8.7) 40 (7.2) Class III 1071 (74.1) 431 (77.5) Class IV 66 (4.6) 23(4.1) LV Function Grades (%) Grade I 953 (66.0) 402 (72.3) Grade II 306 (21.2) 104 (18.7) Grade III 186 (12.9) 50 (9.0) Priority Status (%) Elective 1371 (94.9) 537 (96.6) Urgent 63 (4.4) 19 (3.4) Emergency 9 (0.6) 0 (0.0) 0.16 Salvage 2 (0.1) 0 (0.0) EF=Ejection Fraction, CCS=Canadian Cardiovascular society. artery bypass grafting (CABG) were selected for the study. Patients undergoing concomitant surgery along with CABG were excluded from the study. Total number of 2001 patients was included in this study. The patients were divided into two groups depending upon the gender of patients. Sample size for this study was calculated by using the incidence of Perioperative MI. In the study of Yazdanian et al, there were 1.9% males who developed perioperative MI during surgery while none of the females developed peri-operative MI 14. Using the results of this study the calculated sample size S177

181 Gender And Coronary Artery Bypass Grafting Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S82 was 420 individuals in each group. In our study, there were 1445 men and 556 women. In all patients anesthesia were induced and maintained by low doses of midazolam (2-3 mg), fentanyl (10-15mg/kg), propofol ( mg/kg min) and isoflurane ( %). In all patients standard cardiopulmonary bypass was established through median sternotomy using straight tip aortic cannula and a cavo-atrial venous cannula. Moderate hypothermia (28-32 C) was used in all patients. After clamping the aorta, cardiac arrest was achieved and maintained by using cold blood cardioplegia delivered through the aortic root at the aortic root pressures of mmhg. Internal thoracic and sephanous vein grafts were used as conduits in all patients. In ICU, frequency of major complications e.g. myocardial infarction, respiratory complications, renal failure and neurologic complications, ventilation time, inotropic support and hospital mortality were noted. Myocardial infarction was defined as a fivefold increase in CK-MB levels from the borderline value post-operatively. Increase in post-operative creatinine more than 1mg/dl from the pre-op value was recognized as renal failure. Pulmonary complications were Table-II: Comparison of operative and early post-operative variables. Variable Male Gender Female Gender p-value Bypass Time 108 ± ± <0.001 Clamp Time ± ± <0.001 Number of Grafts 2.83 ± ± Post-op CKMB* Levels (IU) ± Peri-op MI** (%) 52 (3.6) 40 (7.2) Duration of Support (hours) ± ± Ventilation time (hours) 7.66 ± ± ICU Stay (hours) ± ± Hospital stay (days) 7.02 ± ± 3.29 <0.001 Inotropic Support (%) Mild 880 (60.9) 323 (58.1) Moderate 339 (23.5) 137 (24.6) High Dose 38 (2.6) 48 (8.6) <0.001 Nil 188 (13.0) 48 (8.6) Neurologic complications (%) Brain death 3 (0.2) 1(0.2) Permanent Local Paralysis 1 (0.1) 5 (0.9) Acute Confusional State 12 (0.8) 6 (1.1) 0.07 TIA 2 (0.1) 1 (0.2) Renal Complications (%) 12 ( (2.7) Pulmonary Complications (%) 60 (4.2) 30 (5.4) (0.23) IABP*** (%) 47 (3.3) 43 (7.7) <0.001 Operative Mortality (%) 11 (0.8) 17 (3.1) <0.001 *CKMB=Creatinine Kinase Myocardial Band, **MI=Myocardial Infarction, ***IABP=Intra-aortic Balloon Pump. defined as; pleural effusion requiring drainage, pneumonia, prolonged ventilation more than 48 hours and development of ARDS. Any death that occurred during or after surgery within the hospital was categorized as In-hospital mortality. Emergency surgery was defined as need of surgery on next routinely available operative day, if operative time was given on routine OPD visit is was defined as elective surgery, if surgery was S178

182 Gender And Coronary Artery Bypass Grafting Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S82 performed on immediate available list it as defined as urgent surgery. SPSS V20 was used for data analysis. Independent sample t-test was used to compare quantitative variables, while qualitative variables were compared using Chi-square or Fisher s exact test. Quantitative variables were presented as mean and standard deviation while qualitative variables were presented as frequency and percentage. A p-value<0.05 was considered as statistically significant. having history of hypertension and diabetes. The incidence of hypertension was 592 (41.0%) versus 348 (62.5%) and 452 (31.3%) versus 293 (52.7%) in male and female group and this difference was statistically significant (p-value <0.001 and <0.001 respectively). Pre-op ejection fractions were also higher in female group (0.003). There were more patients in LV Grade II and III in male group (p-value 0.013). Numbers of grafts applied were same in both groups (table-i). Cardiopulmonary bypass time and cross Table-III: Comparison of post-operative characteristics and complications between diabetics and non-diabetics in female gender. Variable Diabetic Non-Diabetics p-value Post-op CKMB Levels (IU) ± ± Peri-op MI (%) 12 (4.1) 28 (10.6) Duration of Support (hours) ± ± Ventilation time (hours) ± ± ICU Stay (hours) ± ± Hospital stay (days) 7.58 ± ± Inotropic Support (%) Mild 172 (58.7) 151 (57.4) Moderate 76 (25.9) 61 (23.2) High Dose 22 (7.5) 26 (9.9) 0.61 Nil 23 (7.8) 25 (9.5) Neurologic complications (%) Brain death 0 (0.00) 1 (0.0) Permanent Local Paralysis 3 (1.0) 2 (0.8) Acute Confusional State 4 (1.4) 2 (0.8) TIA 1 (0.3) 0 (0.0) Renal Complications (%) 6 (2.0) 9 (3.4) 0.32 Pulmonary Complications (%) 15 (5.1) 15 (5.7) 0.76 IABP (%) 17 (5.8) 26 (9.9) 0.07 Operative Mortality (%) 8 (2.7) 9 (3.4) RESULTS Out of two thousand and one (2001) patients, there were 1445 (72.30%) males and 556 (27.70%) females. There was no significant difference between baseline characteristics between the groups except females were more obese as compared to males. Mean body mass index in female group was ± 5.19 versus ± 4.48 in male group (p-value <0.001). Regarding risk factors there were more females clamp time was significantly high in male gender. Post-op Creatinine Kinase Myocardial Band (CK-MB) levels were high in female group but this difference was not significant. Duration of ventilation support and inotropic support was significantly high in female group with highly significant p-values 0.01 and 0.02 respectively. Similarly hospital stay time was also high in female group. There were more patients in female group who required high inotropic support S179

183 Gender And Coronary Artery Bypass Grafting Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S82 post-operatively, there were 48 (8.6%) patients in female group who required high inotropic support as compared to 38 (2.6%) patients in male group (p-value <0.001). incidence of neurologic complications and renal complications was also high in female group. The need of inotropic support on weaning from cardiopulmonary bypass time was also higher in female group (pvalue <0.001). Similarly operative mortality was also higher in female group. There were 17 (3.1%) Table-IV: Comparison of post-operative characteristics and complications between hypertensive and non-hypertensive population in female gender. Variable Hypertensive Non-hypertensive p-value Number of Patients Post-op CKMB Levels (IU) ± ± Peri-op MI (%) 27 (7.8) 13 (6.2) 0.51 Duration of Support (hours) ± ± Ventilation time (hours) 9.99 ± ± ICU Stay (hours) ± ± Hospital stay (days) 7.74 ± ± Inotropic Support (%) Mild 209 (60.1) 114 (54.8) Moderate 80 (23.0) 57 (27.4) High Dose 26 (7.5) 22 (10.6) 0.27 Nil 33 (9.5) 15 (7.2) Neurologic complications (%) Brain death 1 (0.3) 0 (0.0) Permanent Local Paralysis 1 (0.3) 4 (1.9) Acute Confusional State 6 (1.7) 0 (0.0) TIA 0 (0.0) 1 (0.5) Renal Complications (%) 8 (2.3) 7 (3.4) 0.45 Pulmonary Complications (%) 16 (4.6) 14 (6.7) 0.28 IABP (%) 27 (7.8) 16 (7.7) 0.97 Operative Mortality (%) 13 (3.7) 4 (1.9) 0.23 mortalities in female gender versus only 11 (0.8%) mortalities in male group with p-value <0.001 (table-ii). So we found that female gender was associated with higher incidence of morbidity and mortality in patients undergoing coronary artery bypass graft surgery. We stratified the patients on the basis of gender and see the effect of major co-morbid pathologies that were significantly high in female population. We analyze the patients on S180 the basis of hypertensive and non-hypertensive and diabetics and non-diabetics. Regarding Diabetics and non-diabetics there was no significant difference in postoperative outcomes and complications except the incidence of perioperative MI was significantly high in nondiabetic group. Requirement of IABP was also high in non-diabetic group but this difference was not statistically significant (table-iii). On comparison of women on the basis of hypertensives and non-hypertensives, no significant difference was found between the postoperative outcomes and complications (table-iv). So we do not found any significant effect of co-morbidities on operative outcomes of female gender. DISCUSSION 0.06 Coronary artery bypass grafting is associated with the risk of mortality and morbidity but according to several studies the risk of postoperative complications and mortality is more

184 Gender And Coronary Artery Bypass Grafting Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S82 in women population 2,11. Many studies has concluded that female gender is an independent predictor of mortality after CABG surgery 12,13. Some studies have concluded that it is not gender but actually these are comorbid risk factors which are associated with higher mortality in female gender 14,15. According to the Australian Society of Cardiac and Thoracic Surgeons cardiac surgery database, women carry a higher risk of 30 day operative mortality as compared to men, operative mortality in female gender was 2.2 vs 1.5 percent in male gender 16. In our study, the operative morality in women was 3.1% versus 0.8% in men. The need and duration of inotropic support and Intra-aortic balloon pump counterpulsation support on weaning from cardiopulmonary bypass was also high in women population. In our study the women were younger as compared to men and have larger body surface area ± 5.19 versus ± 4.48 in male population. But according to many studies the women who undergo CABG were older having small body surface area 4,16. The reason for this difference is not known. But we found a higher incidence of diabetes and hypertension in female population as compared to men. In this study hypertension was 22.5% more common in women. Similarly incidence of diabetes was also 21.4% high in women population. There were more men in LV Grade II and III in this study. And more men underwent urgent emergency and salvage surgeries unlike previous studies. Advanced age, smaller body surface area, Low LV grade, urgent surgery and incomplete revascularization were considered as contributing factors of mortality and morbidity in previous studies. But in this study, there were no such factor available. And there was no difference in number of grafts in men and women. We also found a higher incidence of post-operative complications in women population. The incidence of renal complications and neurologic complications was high in women population in this study. And we did not find any significant effect of co-morbidities like diabetes and hypertension on postoperative outcomes and complications in female gender. So we found that female gender is associated with higher incidence of morbidity and mortality after coronary artery bypass graft surgery. CONCLUSION Female gender is associated with higher incidence of mortality and morbidity after coronary artery bypass grafting. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004; 110(14): e Edwards FH, Carey JS, Grover FL, Bero JW, Hartz RS. Impact of gender on coronary bypass operative mortality. The Annals of Thoracic Surgery 1998; 66(1): Roques F, Nashef S, Michel P, Gauducheau E, De Vincentiis C, Baudet E, et al. Risk factors and outcome in European cardiac surgery: analysis of the Euro SCORE multinational database of patients. Eur J Cardiothorac Surg 1999; 15(6): Khan SS, Nessim S, Gray R, Czer LS, Chaux A, Matloff J. Increased mortality of women in coronary artery bypass surgery: evidence for referral bias. Ann Intern Med 1990; 112(8): Golino A, Panza A, Jannelli G, Vigorito C, Giordano A, Persico S, et al. Myocardial revascularization in women. Tex Heart Inst J 1991; 18(3): Leavitt BJ, O Connor GT, Olmstead EM, Morton JR, Maloney CT, Dacey LJ, et al. Use of the internal mammary artery graft and in-hospital mortality and other adverse outcomes associated with coronary artery bypass surgery. Circulation 2001; 103(4): O'connor G, Morton J, Diehl M, Olmstead E, Coffin L, Levy D, et al. Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group. Circulation 1993; 88(5): Aldea GS, Gaudiani JM, Shapira OM, Jacobs AK, Weinberg J, Cupples AL, et al. Effect of gender on postoperative outcomes and hospital stays after coronary artery bypass grafting. The Annals of thoracic surgery 1999; 67(4): Herlitz J, Brandrup-Wognsen G, Karlson B, Sjöland H, Karlsson T, Caidahl K, et al. Mortality, risk indicators of death, mode of death and symptoms of angina pectoris during 5 years after coronary artery bypass grafting in men and women. J Intern Med 2000; 247(4): Loop FD, Golding LR, Macmillan JP, Cosgrove DM, Lytle BW, Sheldon WC. Coronary artery surgery in women compared with men: analyses of risks and long-term results. J Am Coll Cardiol 1983; 1(2s1): S181

185 Gender And Coronary Artery Bypass Grafting Pak Armed Forces Med J 2018; 68 (Suppl-1): S176-S Jones RH, Hannan EL, Hammermeister KE, DeLong ER, O'Connor GT, Luepker RV, et al. Identification of preoperative variables needed for risk adjustment of short-term mortality after coronary artery bypass graft surgery. J Am Coll Cardiol 1996; 28(6): Blankstein R, Ward RP, Arnsdorf M, Jones B, Lou Y-B, Pine M. Female gender is an independent predictor of operative mortality after coronary artery bypass graft surgery contemporary analysis of 31 midwestern hospitals. Circulation 2005; 112(9 suppl): I-323-I Bukkapatnam RN, Yeo KK, Li Z, Amsterdam EA. Operative mortality in women and men undergoing coronary artery bypass grafting (from the California Coronary Artery Bypass Grafting Outcomes Reporting Program). Am J Cardiol 2010; 105(3): Yazdanian F, Azarfarin R, Aghdaii N, Motlagh SJ, Faritous Z, Alavi M, et al. Relationship Between Gender and In-Hospital Morbidity and Mortality After Coronary Artery Bypass Grafting Surgery in an Iranian Population. Research in Cardiovascular Medicine 2012; 1(1): Koch CG, Weng Y-s, Zhou SX, Savino JS, Mathew JP, Hsu PH, et al. Prevalence of risk factors, and not gender per se, determines short-and long-term survival after coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2003; 17(5): Saxena A, Dinh D, Smith JA, Shardey G, Reid CM, Newcomb AE. Sex differences in outcomes following isolated coronary artery bypass graft surgery in Australian patients: analysis of the Australasian Society of Cardiac and Thoracic Surgeons cardiac surgery database. Eur J Cardiothorac Surg 2012; 41(4): S182

186 Open Access Original Article Grafts And MSCT Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S PATENCY OF BYPASS GRAFTS ON MSCT ANGIOGRAPHY, AFIC EXPERIENCE Muhammad Nadir Khan, Muhammad Adil*, Syed Shahid Abbas, Sohail Aziz, Jahanzab Ali, Abdullah Hamid Gondal*, Muhammad Hamza Jahangeer*, Arslan Mehmood* Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan, *Army Medical Collage/ National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To determine the patency of coronary artery bypass grafts (CABG) in patients presenting with recurrent angina. Study Design: Descriptive study. Place and Duration of Study: Cardiac Catheterization Lab AFIC/NIHD, Rawalpindi, from Jan 2011 to Jan 2014 over a time period of about 3 years. Material and Methods: A total of 955 patients who presented with recurrent angina or atypical chest pain or newly developed ECG changes after prior bypass surgery were included in study. Patients with chest pain at rest, cardiac arrhythmias and history of allergy to contrast, renal failure, hemodynamically unstable patients and pregnant females were not enrolled in study. All 955 patients were selected by non-probability consecutive sampling. Patient s demographic and multi-slice computer tomography (MSCT) angiography findings were recorded. Finally data was analyzed by using SPSS version 21. Result: Out of 955 patients 863 (90.4%) were male while remaining 92 (9.6%) were female. Age range was years. LIMA was the most frequently implanted graft i.e. 861 (90.16%). RIMA is the least implanted graft. Out of 861 LIMA grafts 788 (91.5%) were patent as visualized by MSCT, 55 (6.4%) were occluded while 18 (2.1%) were atretic. A total of 2001 saphenous venous grafts were implanted out of which 1234 (61.66%) were patent, 682 (34.08%) were occluded while 85 (4.3%) were diseased. In case of RADIAL a total of 33 (91.7%) grafts were patent, 3 (8.3%) were occluded and in case of RIMA 19 (82.6%) grafts were patent and 4 (17.4%) were occluded. Overall 91.30% of arterial grafts were patent. In case of both RADIAL and RIMA no graft was diseased. Conclusion: SVG were patent in 61.66% of the grafts while arterial grafts had a patency rate of 91.30%. Thus arterial grafts have high patency rate as compared to others. Keywords: CABG, Graft patency, MSCT angiography. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION With the commencement of digital era and industrialization coronary artery disease has become one of the most common causes of hospital admission and mortality. As a result coronary artery bypass graft surgery (CABG) is most often frequently performed surgical procedure in advanced countries 1. In USA, around patients undergo CABG annually 2. CABG has emerged as an effective treatment for patients with intractable angina and in patients having stable coronary artery disease 3. However its long term results are limited by Correspondence: Dr Muhammad Nadir Khan, Armed Forces Institute of Cardiology & NIHD Rawalpindi Pakistan yesnadirkhan@gmail.com Received: 20 May 2015; revised received: 07 Mar 2017; accepted: 11 May 2017 failure of grafts 4. Generally speaking graft occlusion occurs in 10-15% of patients shortly after surgery or during first year and in 25% patients in 5 years 5. Venous graft patency is reduced to 50% at 10 years after surgery, and at 15 years about 80% of the venous grafts become occluded while 90% of the arterial grafts remain patent even after 10 years of surgery. LIMA have much improved survival rates 6,7. Recurrent angina after CABG has become an important issue in cardiology, as reflected by increasing number of patients presenting with thoracic discomfort raising a question of bypass graft stenosis. Therefore evaluation of the bypass graft as well as native arteries is indispensable. Coronary interventional angiography is the gold standard technique in the evaluation of bypass S183

187 Grafts And MSCT Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S graft patency and stenosis. As it is invasive and complicated technique, therefore both immediate and follow up control of graft patency are not performed 8. Therefore since the early 1980s, CT and MRI were in use as an alternative to invasive techniques to visualize bypass grafts. However both techniques cannot judge graft stenosis and distal graft anastamosis 9. Similarly electron beam tomography on the other hand is limited by three dimensional resolutions, cost and its availability. With advancement in technology, both temporal and spatial resolution could be substantially increased by use of Multi-detector row spiral computed tomography (MSCT). MSCT with retrospective ECG gating has partly overcome the limitations of EBCT and MRI and show high accuracy in the detection of graft diseases 10,11. Many studies have demonstrated good diagnostic accuracy of MSCT for the detection of significant stenosis in grafts with high diagnostic accuracy (sensitivity 96% to 99%, specificity 95% to 100%) 12,13. In current study we analyze bypass graft patency by using 64 slice MSCT in patients who has underwent CABG and presented with recurrent chest discomfort at Armed Forces Institute of Cardiology, Rawalpindi. MATERIAL AND METHODS This descriptive study was performed at Catherization laboratory, Armed Forces Institute of Cardiology, from Jan 2011 to Jan 2014 over a time period of about 3 years. All 955 consecutive patients who were scheduled for invasive coronary angiography (ICA) were included in the study. Patients with chest pain at rest, cardiac arrhythmias and history of allergy to contrast, renal failure, hemodynamically unstable patients and pregnant females were not enrolled in study. All 955 patients were selected by nonprobability consecutive sampling. Written informed consent was taken from all the patients. In all patients 64 slice MSCT angiography was performed within 15 days before ICA. Patients were given metoprolol 100mg orally 3 hours before the procedure to bring heart rate below 65beats/min. Heart rate, electrocardiogram, and blood pressure were monitored; and additional intravenous metoprolol (10-15mg) was administered if necessary to achieve the target heart rate. Sublingual nitroglycerin 0.5mg was given 1 minute before image acquisition. Computerized tomography angiography (CTA) images were taken using 64 slice MSCT scanner. During scan ml of contrast agent usually iopamidol was injected continuously at infusion rate of 4.5 ml/s through antecubital vein for MSCT images. Contrast was followed by injection of 30-50ml saline chasing bolus. Scanning was initiated in craniocaudal direction. This was done during a single inspiratory breath hold for an acquisition time of sec. For an optimal heart phase selection, retrospective ECG gating was used. Retrospective reconstruction of the image data was performed for acquisition of phase images starting from early systole (10% of the R-R interval) and ending at late diastole (90% of the R-R interval) using 10% increments. All images were reconstructed with a display field of view of 25cm, a standard soft tissue filter as suggested by the manufacturer and an effective slice thickness of 0.625mm with an increment of 0.625mm. The best phase was selected for analysis of grafts and native vessels. After scan images were reformatted and were analyzed by two experts and findings were agreed upon. Only excellent (with no motion or gating artifacts present), good (with minor motion artifacts present) and diagnostic (with substantial motion artifacts present, but luminal assessment of significant stenosis still possible) images were selected for graft evaluation.all the grafts were assessed for the origin, the body, the distal anastamosis and the native recipient coronary arteries after the grafts. Patient s demographic data and MSCT angiography findings were recorded. Finally data was analyzed by using SPSS version 21. Various descriptive statistics were used to calculate frequencies, percentages and standard deviation. The numerical data such as age were expressed S184

188 Grafts And MSCT Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S as Mean ± Standard deviation while the categorical data were expressed as frequency and percentages. RESULTS Out of 955 patients 863 (90.4%) were male while remaining 92 (9.6%) were female. Age range was years with mean of ± Hypertension was most common risk factors followed by smoking, diabetes mellitius and hyperlipidemia. Maximum number of grafts DISCUSSION MSCT is the latest breakthrough in CT technology. It is in use since 1992 in the form of dual spiral scanning, while first 4 slice unit was introduced in Systems with 8, 10, 16, 32 and 64 detector arrays have become available over the last few years. Compared with previous generations, 64 slice MSCT scanner provides improve temporal and spatial resolution Although promising results have been Table-I: Frequency of grafts implanted. Grafts Characteristics LIMA 861 (90.16%) SVG to LAD 90 (9.42%) SVG to DIAG 389 (40.73%) SVG to OM1 732 (76.65%) SVG to OM2 75 (7.85%) SVG to RCA 715 (75.87%) RADIAL 36 (3.77%) RIMA 23 (2.41%) LIMA (Left Internal Mammary Artery), RIMA (Right Internal Mammary Artery), SVG (Saphenous Venous Graft), LAD (Left Anterior Descending), DIAG (Diagonal), RCA (Right Coronary Artery), OM (Obtuse Marginal). Table-II: MSCT findings. Patent Occluded Diseased LIMA 788 (91.5%) 55 (6.4%) 18 (2.1%) SVG to LAD 60 (66.7%) 23 (25.6%) 7 (7.8%) SVG to DIAG 243 (62.5%) 132 (33.9%) 14 (3.6%) SVG to OM1 438 (59.8%) 251 (34.3%) 43 (5.9%) SVG to OM2 54 (72%) 18 (24%) 3 (4%) SVG to RCA 439 (61.4%) 253 (35.4%) 23 (3.2%) RADIAL 33 (91.7%) 3 (8.3%) 0 (0.0%) RIMA 19 (82.6%) 4 (17.4%) 0 (0.0%) implanted in a patient was 4 while minimum of 1 graft was implanted in a patient. A total of 2001 saphenous venous grafts were implanted out of which 1234 (61.66%) were patent, 682 (34.08%) were occluded while 85 (4.3%) were diseased. In case of RADIAL a total of 33 (91.7%) grafts were patent, 3 (8.3%) were occluded and in case of RIMA 19 (82.6%) grafts were patent and 4 (17.4%) were occluded. Overall 91.30% of arterial grafts were patent. In case of both RADIAL and RIMA no graft was diseased. Frequency and type of graft implanted and MSCT angiography findings are shown in table-i & II. S185 reported for MRI recently. Langerak et al evaluated 56 venous grafts with the help of MRI 17. Similarly in another study, patients who presented with recurrent chest pain were assessed by MRI to detect stenosis. A sensitivity and specificity of 94% and 63% were observed for the detection of single vein grafts with stenosis 50%; sensitivity and specificity rose to 96 and 92%, respectively, when stenosis 70% was considered. Other non-invasive techniques like exercise ECG, stress myocardial imaging and stress echo are also available for the assessment of post CBAG patients however they lack the

189 Grafts And MSCT Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S anatomical details of the grafts and native vessels. In present study we assess the patency of arterial and venous graft in patients who presented with recurrent chest pain. In our study the overall patency rate of saphenous venous grafts was 61.66%, however it depends upon the grafted vessel ( %), similarly patency rate of arterial graft ranges from 82.6%-91.7%. These results are consistent with the results described by Basri et al 18. He stated a patency rate of % for saphenous venous grafts while patency rate for arterial grafts was 95% including 97.3% for the LIMA grafts, 50% for the RA grafts, and 50% for the RIMA grafts. These results are also confirmed by another study in which a patency rate of >90% was stated 18. Naveed et al 19 conducted a study on 64 post CABG patients to evaluate the patency of bypass grafts. He showed a patency rate of 66% for SVG and 92% for arterial grafts. Various studies have shown that year post CABG graft patency is % for venous grafts and 85 % for the arterial grafts 20,21. The best quality images are always obtained in patients with low heart rate. However recent study has demonstrated that heart rate is not a crucial determinant of image quality 22. However temporal resolution varies with patient heart rate. Therefore we gave beta blockers in cases to lower the heart rate. MSCT can not be called as risk free investigation because of radiation exposure and contrast administration. Compared with ordinary coronary CT, the scan range was extended by 37% which results in high radiation dose 23. Although 64 slice MSCT has become gold standard for evaluation of post CABG grafts, still development of new generation scanners are still under way. Cardiac freeze frame technique, dualsource CT, flat-panel CT will help to improve further temporal resolution, abolishes the problem of breadth holding further reduces motion artifacts and artifacts related to variations of heart rate during the scan. CONCLUSION MSCT in our setup has comparable results to the data available from other cardiology facilities around the world and it has become a standard care for the evaluation of graft disease. Our data showed that 61.66% SVG were patent while arterial grafts were patent in 91.30% of the grafts. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Weiss AJ, Elixhauser A, Andrews RA. Characteristics of operating room procedures in US Hospitals, Statistical brief Naveed T, Ayub M, Nazeer M, Mallick NH, Mohydin BS, Ali Z, et al. Role of 64-slice multi detector computed tomography for non-invasive visualisation of coronary artery bypass grafts for follow up in post CABG patients. JAMC 2010; 22(2): Motevali M, Ghanaati H, Bassri H, Abdi S, Salari F, Noohi F, et al. Evaluation of early coronary graft patency after coronary artery bypass graft surgery using multislice computed tomography angiography 2009: Bassri H, Salari F, Noohi F, Motevali M, Abdi S, Givtaj N,et al. Evaluation of early coronary graft patency after coronary artery bypass graft surgery using multislice computed tomography angiography. BMC Cardiovascular Disorders Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR et al. Coronary bypass graft fate and patient outcome: Angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am CollCardiol 1996; 28: Julian MA. Patient education: Coronary artery bypass graft surgery (Beyond the Basics). Up To Date, Parissis H. Alan W Soo and Bassel Al-Alao. Is there any further advantage of using more than one internal mammary artery? Literature review and analysis. Asian Cardiovascular and Thoracic Annals 2012; 21(1): Sherif A Khedra, Mohamed A Hassaana, Mohamed H Allamb. Diagnostic value of MDCT angiography in assessment of coronary artery bypass graft. The Egyptian Journal of Radiology and Nuclear Medicine 2013; 44(2): Engelmann MG, Knez A, Von Smekal A, Wintersperger BJ, Huehns TY, Hofling B et al. Non-invasive coronary bypass graft imaging after multivessel revascularization. Int JCardiol 2000; 76: Cibis M, Potters WV, Gijsen FJ, Marquering H, Van Ooij P, Van Bavel E, et al. The effect of spatial and temporal resolution of cine phase contrast MRI on wall shear stress and oscillatory shear index assessment. PLoS ONE 2016; 11(9): e Schlosser T, Konorza T, Hunold P, Kühl H, Schmermund A, Barkhausen et al. Noninvasive visualization of coronary artery bypass grafts using 16-detector row computed tomography. J Am Coll Cardiol 2004; 44: Sherif A. Khedr, Mohamed A. Hassaan, Mohamed H. Allam. Diagnostic value of MDCT angiography in assessment of coronary artery bypass graft. The Egyptian Journal of Radiology and Nuclear Medicine 2013: 44: S186

190 Grafts And MSCT Angiography Pak Armed Forces Med J 2018; 68 (Suppl-1): S Anders K, Baumr S, Schmid M. Coronary artery bypass graft (CABG) patency: assessment with high resolution submillimeter 16-slice multidetector-row computed tomography (MDTC) versus coronary angiography. Eur J Radiol 2006; 57: Hu H, He HD, Foley WD, Fox SH. Four multidetector-row helical CT: image quality and volume coverage speed. Radiology 2000; 215: Mollet N, Cademartiri F, van Mieghem CA, Runza G, McFadden EP, Baks T, et al. High-resolution spiral computed tomography coronary angiography in patients referred for diagnostic conventional coronary angiography. Circulation 2005; 112: Leber AW, Knez A, von Ziegler F, Becker A, Nikolaou K, Paul S, et al. Quantification of obstructive and non obstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 2005; 46: Langerak SE, Vliegen HW, Jukema JW, Knuz P, Zwinderman AH, Lamb HJ. Value of magnetic resonance imaging for the non invasive detection of stenosis in coronary artery bypass grafts and recipients coronary arteries. Circulation 2003; 107: Bassri H, Salari F, Noohi F, M Motevali, Seifollah A, NGivtaj, K Raissi et al. Evaluation of early coronary graft patency after coronary artery bypass graft surgery using multislice computed tomography angiography. BMC Cardiovascular Disorders 2009: 9: Naveed T, Ayub M, Nazeer M, Mallick NH, Bilal S, Ali MS. Role of 64 slice multi detector computrized tomography for non invasive visualization of coronary artery bypass grafts for follow up in post CABG patients. JAMC 2010; 22(2) 20. Motwani JG, Topol E J. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition and prevention. Circulation 1998; 97: Van Domburg RT, Foley DP, Breeman A, Van Herwerden LA, Serruys PW. Coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty: Twenty-year clinical outcome. Eur Heart J 2002; 23: Jones CM, Athanasiou T, Dunne N, Kirby J, Aziz O, Haq A, et al. Multi-detector computed tomography in coronary artery bypass graft assessment: A meta-analysis. Ann Thorac Surg 2007; 83: Hausleiter J, Meyer T, Hadamitzky M, Huber E, Zankl M, Martinoff S, et al. Radiation dose estimates from cardiac multislice computed tomography in daily practice: Impact of different scanning protocols on effective dose estimates. Circulation 2006; 113: S187

191 Open Access Outcome of Pericardial Effusion Original Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S188-S93 EVALUATION OF ETIOLOGY, CLINICO-PATHOLOGICAL PRESENTATION AND OUTCOME OF PERICARDIAL EFFUSION Muhammad Kashif, Tanvir Ahmad Raja, Adeel Ur Rehman, Azhar Mehmood Kiyani, Faizania Shabbir*, Tausif Ahmed Rajput** Rawalpindi Institute of Cardiology Rawalpindi Pakistan, *Rawalpindi Medical College Rawalpindi Pakistan, **Shifa Tameer-e-Millat University Islamabad Pakistan ABSTRACT Objective: To quantify the common causes and clinical presentation of pericardial effusion and its outcome. Study Design: Descriptive study. Place and duration of study: Rawalpindi Institute of Cardiology, Rawalpindi for a period of one year. Material and Methods: A total of 63 cases of pericardial effusion confirmed by clinical complaints and echocardiography were enrolled. Etiology of disease, clinical presentation and management outcome were observed. The patients were consented for participation in the study. Consent was taken from patients. SPSS 17.0 was used to analyze data. Results: The mean age of patients was 43.9 years with male predominance (61.9%). Leading cause of disease was infectious tuberculous 47 (74.6%), followed by malignant cause 5 (7.9%). Fever 33 (52.3%), shortness of breath 38 (60.3%) and chest pain were main complaints. Conservative management with ATT was given in 38 (60.3%) whereas majority of the patients were managed with pericardiocentesis 53 (84.1%). Majority 59 (93.6%) improved and discharge whereas 3 (4.6%) died and 1 (1.5%) patient suffered recurrence. Conclusions: The leading cause of pericardial effusion was infectious tuberculous in this study. Breathing difficulty, chest pain, fever and cough were the common presenting complaints. Majority of patients were managed with ATT + pericardiocentesis and they improved and got discharged. Keywords: Clinical complaints, Etiology, Outcome, Pericardial effusion. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Pericardial effusion presents relatively commonly in clinical practice 1. It is a significant cause of cardiac malfunction and could lead to tamponade due to accumulation of fluid in cardiac sac. Its effect on heart depends on the size of effusion and fluid volume. Pericardial effusion is attributed to underlying diseases like tuberculosis, malignancy or other viral conditions, however, in many instances the cause is unknown and thus, present as idiopathic pericardial effusion 2. In the western world malignancy is the major cause of pericardial effusion whereas in the developing and under developed world infectious causes like TB are still common underlying condition 2,3. Correspondence: Dr Muhammad Kashif, Resident Cardiologist Rawalpindi Institute of Cardiology Rawalpindi Pakistan kashifbbh@gmail.com Received: 24 Oct 2017; revised received: 01 Dec 2017; accepted: 27 Dec 2017 Thoracic x-ray shows the presence of an enlarged cardiac silhouette with clear lungs and at times is non-specific. Echocardiography is the baseline investigation to determine the presence of pericardial effusion, it is also prioritized due to its distinctive strength to measure the size and volume of fluid 4. In cases of mild pericardial effusion (<10 mm space in sac) is though very frequent specially in women, it is at times misjudged and can be accurately screened for its nature and intensity by a CT scan or a more indepth MR imaging 4,5. There are numerous management strategies for pericardial effusion; conservative management, pericardiocentesis and surgical options. The outcome of any treatment lies on the intensity of effusion and any specific co-morbid condition 6. Pakistan being a lower middle income developing country has plenty of infectious risk S188

192 Outcome of Pericardial Effusion Pak Armed Forces Med J 2018; 68 (Suppl-1): S188-S93 attributable social and environmental conditions. Pericardial effusion is a frequent presentation but its observation and study has been a neglected affair so far, specially, in the underdeveloped world. There is no or very few pervious data regarding this topic from national and local level settings. Thus, we aimed to determine the etiological background of pericardial effusion and outcome of its management in an exclusive cardiac facility of the country. MATERIAL AND METHODS A descriptive study was conducted in the Rawalpindi Institute of Cardiology, Rawalpindi for a period of one year from April 2016 to April A total of 63 pericardial effusion patients were selected and enrolled. An informed consent was administered to those fulfilling the study inclusion criteria. The etiological background and clinical presentation of patients was noted. The status of pericardial effusion on the basis of ECHO and biochemical parameters was also noted. The management strategies and their final outcome in terms of improvement, recurrence and death were also noted. The patients comprised of adult cases above 15 years of age and both genders. Patients with Table-I: Demographic characteristics of study patients (n=63). Demographic characteristics No. of cases Percentage (%) Age (years) 15 to to to to to or above Mean ± SD 43.9 ± 18.8 Gender Male Female Table-II: Etiology of disease in study patients (n=63). Etiological factors & Comorbidities No. of cases Percentage (%) Infectious Malignancy CRF SLE Post PCI TPM Co-morbidities Hypertension/AF Hypothyroidism VSD signs and symptoms of pericardial effusion confirmed on echocardiogram were included. Those below the age of 15 years and having any associated cardiac co-morbidity were excluded from the study. The study sample was 59 calculated through WHO sample size calculator; based on 95% confidence level, alpha error of 5% and anticipated population with pericardia effusion of 4% (ref), after including a 5% non-response S189

193 Outcome of Pericardial Effusion Pak Armed Forces Med J 2018; 68 (Suppl-1): S188-S93 rate. Sampling was done through non-probability consecutive sampling. The data was analyzed using SPSS software version Descriptive statistics was applied to measure frequency and percentages from categorical variables like etiology, clinical presentation and management outcome and mean and standard deviation from quantitative numerical variables like age of patients and biochemical laboratory parameters like ESR, hemoglobin and TLC levels. RESULTS The mean age of stud patients was 43.9 ± 18.8 years with almost equal distribution in all decades of life ranging from 15 years to up to 80 moderate size whereas size was normal in 17 (26.9%) patients. The location of the pericardial effusion was almost circumferential in all study cases. The average ESR was 44.5 ± 12.1 and hemoglobin level was 11.7 ± 2.7 mg/dl. In 19 (30.1%) cases the pericardial fluid was exudative lymphocytic, in 5 (7.9%) cases it was bacterial while in 2 (3.1%) patients it was transudative lymphocytic. Medical ATT + pericardiocentesis was given to 38 (60.3%), Antibiotics + pericardiocentesis given to 15 (23.8%) whereas 12 (19.0%) patients were managed with pericardiocentesis alone (table-iii). The majority of the patients 59 (93.6%) Figure: Frequency of presenting complaints (n=63). years. Male gender was in majority with (61.9%) proportion (table-i). In most of the patients the etiology of disease was infectious tuberculous 47 (74.6%), followed by malignant in 5 (7.9%), CRF in 4 (6.2%) and other frequent causes were SLE 2 (3.1%) and comorbidities like hypertension, hypothyroidism and VSD in 1 (1.5%) patient each (table-ii). The most frequent signs and symptoms in patients were fever 33 (52.3%), shortness of breath 38 (60.3%) and chest pain in 20 (31.7%) patients. The other presenting complaints noted in the study were cough 17 (26.9%) and cardiac tamponade seen in 4 (6.3%) cases (figure). The size of pericardial effusion was found large in 37 (58.7%) patients, in 9 (14.2%) it was S190 improved and were discharged from hospital, however, there were 3 (4.6%) deaths and 1 (1.5%) patient had recurrence of pericardial effusion (table-iv). DISCUSSION To date this is one of the earliest observations of pericardial effusion from Pakistan in terms of etiology, clinco-pathological presentation and management outcome. The scientific literature on this topic is not commonly available internationally. A total of 63 patients were analyzed in this trial and the main cause of pericardial effusion was infectious tuberculous (up to 80.0%) and malignant in (8.0%) cases. A study from India on children witnessed a similar trend where tuberculosis was the main cause of

194 Outcome of Pericardial Effusion Pak Armed Forces Med J 2018; 68 (Suppl-1): S188-S93 pericardial effusion 7. Similarly, Guven et al from Turkey reported tubercular etiology in 30% of their cases 8. However, most of previous reports from developed world have in contrast finding and the current study clearly shows a deviation from those reports. Studies by Corey et al and These etiologic findings are in contrast to our study results where the main reasons were infectious TB whereas malignancy and others appeared to be less significant causative agents. The final etiology of pericardial effusion should be based on specific data, in this regard simple Table-III: Findings on investigations and management strategy in the study (n=63). Findings No. of cases Percentage (%) Findings on echo Size Large Moderate Normal Location Circumferential pericardial effusion Circumferential effusion with tamponade Signs of tamponade Lab findings ESR 44.5 ± 12.1 Hemoglobin 11.7 ± 2.7 Pericardial fluid analysis Exudative lymphocytic Bacterial Transudative lymphocytic Management Medical ATT + Pericardiocentesis % Antibiotics + Pericardiocentesis % Pericardiocentesis alone % Table-IV: Outcome of patients (n=63). Outcome No. of cases Percentage (%) Improved and discharge % Death % Recurrence % Colombo et al witnessed idiopathic and neoplasm causes as the main factors of pericardial effusion in their patients followed by less frequent cause like uremia and TB 9,10. Similarly, Sagristà-Sauleda et al also witnessed neoplasm and idiopathic nature as the most frequent causes of pericardial effusion followed by uremia, TB and other factors 11. clinical complaints may be useful. A previous report observed that hemodynamic compromise, cardiomegaly, pleural effusion, and a large pericardial effusion were significantly found in patients with tuberculous or malignant pericardial disease 12. The difference in etiology is attributed to the geographic, socioeconomic and environmental S191

195 Outcome of Pericardial Effusion Pak Armed Forces Med J 2018; 68 (Suppl-1): S188-S93 factors. The causes are viral or noncommunicable in developed world and TB in the developing and under developed world. The etiology in current study is not surprising as Pakistan is still one of the few countries where Tuberculosis is epidemic. In the present study the clinical findings are continuous with previous literature in terms of patients having breathlessness, fever and chest pain, however, cough was also noted as a main complaint. Previous reports also establish these complaints commonly associated with pericardial effusion 7,13. In the current study, most patients had large size of pleural effusion and location was circumferential in almost all. Similarly, the biochemical investigation of hemogloblin was found in normal range, whereas TLC and ESR were found raised indicative of infection. A previous study by Ilan Y found similar findings of hemoglobin and hematocrit in their pericardial effusion patients. It is natural that the disease brings biochemical derangement in majority of patients 13. Medical treatment + pericardiocenteris was given to (60.0%) cases in this study, however, almost one fifth were given antibiotic + pericardiocentesis and one fifth were managed with pericardiocentesis alone. We noted treatment success in (93.6%) study cases, recurrence occurred in 1 (1.5%) case whereas there were 3 (4.6%) deaths which were attributed to underlying medical condition like malignancy and CRF whereas one patient died due to post PCI effusion in the present study. Bastian reported from his series of cardiac tamponade patients undergoing primary pericardiocentesis, had a success rate of 81% and a recurrence rate of 19% 14. A high mortality (8.3%) and complication (16.6%) rates were witnessed by Önem et al after percutaneous catheter drainage in the management of cardiac tamponade 15. In patients with massive idiopathic chronic pericardial effusion, pericardiocentesis is recommended because of the chances of unexpected overt tamponade. Moreover, simple pericardiocentesis alleviates symptoms in majority of patients, however, pericardial effusion could recur in as many as 40%-50% cases 16. It has been suggested by many that pericardiocentesis or percutaneous tube drainage could be a useful management for patients with acute tamponade 17. Conservative management in tuberculous infectious pericardial effusion has its own merits for the underlying condition and patients had significant improvement. The prognosis of pericardial effusion depends on underlying etiology, in cases with malignant causes and involvement of lungs and other closely located abdominal parts there is a risk of poor outcome. The cases with tuberculous infectious pericardial effusion the outcome is better with first conservative management and then drainage of effusion. In recurrent cases surgical options like pericardectomy can deal best. CONCLUSION As per our findings the leading cause of pericardial effusion was infectious tuberculous in this study. Breathing difficulty, chest pain, fever and cough were the common presenting complaints in our study. Majority of patients were managed with medical ATT + pericardiocentesis. Most of the patients improved and were discharged in recovered state whereas 3 patients died not mainly due to pericardial procedure but underlying malignancy and renal failure. Keeping the lethal nature of pericardial effusion, there is a need to observe these patients and intervene in time so that the risk of mortality can be averted. ACKNOWLDEGEMENT We are thankful to the hospital management and patients for their cooperation and provision of data to carry out this study. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. S192

196 Outcome of Pericardial Effusion Pak Armed Forces Med J 2018; 68 (Suppl-1): S188-S93 REFERENCES 1. Sagristà-Sauleda J, Mercé AS, Soler-Soler J. Diagnosis and management of pericardial effusion. World J Cardiol 2011; 3(5): Shabetai R. Pericardial effusion: Haemodynamic spectrum. Heart 2004; 90(3): Yıldız A, Yılmaz R. Kalp tamponad. Türkiye Klinikleri J Surg Med Sci 2007; 3: Jneid H, Ziskind A, Palacios IF. Pericardial interventions. In: Topol EJ, Teirstein, eds. Textbook of Interventional Cardiology. 6th ed. Philadelphia, PA: Saunders; Nunziata A, Catalano O, Cusati B, et al; for European Society of Radiology. Two signs of hemodynamic disturbance: contrast material reflux within the azygos vein (AV) and within the inferior vena cava (IVC) [abstract]. Presented at: Proceedings of the European Congress of Radiology 2000; Vienna, Austria. Presentation Yüksel V, Hüseyin S, Okyay A, Gürkan SC, Gür O, Canbaz S et al. Management of pericardial effusion by subxiphoidal pericardiostomy in adults. Türk Göğüs Kalp Damar Cerrahisi Dergisi 2012; 20(3): Bagri NK, Yadav DK, Agarwal S, Aier T, Gupta V. Pericardial effusion in children: Experience from tertiary care center in northern india. Indian Pediatrics 2014; 51(3): Guven H, Bakiler AR, Ulger Z, Iseri B, Kozan M, Dorak C. Evaluation of children with a large pericardial effusion and cardiac tamponade. Acta Cardiol 2007; 62(2): Colombo A, Olson HG, Egan J, Gardin JM. Etiology and prognostic implications of a large pericardial effusion in men. Clin Cardiol 1988; 11(6): Levy PY, Fournier PE, Charrel R, Metras D, Habib G, Raoult D. Molecular analysis of pericardial fluid: A 7-year experience. Eur Heart J 2006; 27: Sagristà-Sauleda J, Mercé J, Permanyer-Miralda G, Soler- Soler J. Clinical clues to the causes of large pericardial effusions. Am J Med 2000; 109(2): George TJ, Arnaoutakis GJ, Beaty CA, Kilic A, Baugartner WA, Conte JV. Contemporary etiologies, risk factors, and outcomes after pericardiectomy. Ann Thorac Surg 2012; 94(2): Ilan Y, Orm R, Ben-Chetrit E. Etiology, treatment, and prognosis of large pericarc:lial effusions. A study of 34 patients. Claat 1991; 100: Bastian A, Meissner A, Lins M, Siegel EG, Möller F, Simon R. Pericardiocentesis: Differential aspects of a common procedure. Intensive Care Med 2000; 26: Önem G, Baltalarlı A, Özcan AV, Evrengül H, Gökşin İ, Saçar M, et al. Kardiyak tamponad tedavisinde subksifoid perikardiyal pencere ve perkütan kateter ile drenaj. Turk Gogus Kalp Dama 2006; 14: Vaitkus PT, Herrmann HC, LeWinter MM. Treatment of malignant pericardial effusion. JAMA 1994; 272: Jneid H, Maree AO, Palacios IF. Acute pericardial disease: Pericardiocentesis and Percutaneous Pericardiotomy. In: Mebazaa A, Gheorghiade M, Zannad FM, Parrillo JE. (eds) Acute Heart Failure. Springer, London S193

197 Open Access Left Main Coronary Artery Stenting Review Article Pak Armed Forces Med J 2018; 68 (Suppl-1): S194-S97 REVIEW ARTICLE LEFT MAIN CORONARY ARTERY STENTING Muhammad Nadir Khan, Tahira Muqaddas Army Cardiac Center, Lahore Pakistan ABSTRACT Coronary artery bypass surgery is considered as the gold standard treatment of unprotected left main coronary artery (ULMCA) disease. Over the last 2 decades, improvement in stent technology and operators experience explained the increased number of reports on the results of percutaneous coronary interventions (PCIs) for the treatment of left main (LM) coronary artery lesion. The recent data which compared efficacy and safety of PCIs using drug-eluting stent and coronary artery bypass surgery showed comparable results and a lesser need for repeat revascularization for coronary artery bypass surgery. Keywords: Coronary artery bypasses graft, Left main coronary artery, Percutaneous coronary intervention. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Patients who undergo coronary angiography, significant unprotected left main coronary artery (ULMCA) disease found to occur occurs in 5-7% of cases and 3 years mortality of the patients with ULMCA disease who were treated medically was 60% 1. CABG has been the gold standard therapy for LM disease but with the advent of newer drug-eluting stents (DES), better intravascular imaging modalities and careful patient selection, the use of PCI in this set of patients is expanding. Management of LMCA Disease Medical Treatment Versus CABG Most studies which were conducted 3 decades ago in small numbers of patients for treatment of LMCA disease showed survival benefit of CABG when compared to medical treatment 1. CABG Taggart et al 2 reported a review based on a series of studies, all of which showed an inhospital mortality of between 2 and 3% after CABG for Left main artery stenosis and 5-6% mortality at 5 years as per studies which did not Correspondence: Dr Muhammad Nadir Khan, Associate Professor, Army Cardiac Center, Lahore Pakistan yesnadirkhan@gmail.com report on long-term outcomes. PCI with Stent Implantation Bare-Metal Stents vs DES Initially ULM stenting with the use of baremetal stents produced results similar to those of bypass surgery depending on the patient cohort 3. However, high restenosis rates associated with their use, often resulted in sudden cardiac death which resulted in limitation of ULM stenting advancement during that time period. With the advent of DES in 2002 and its dramatic reduction in rates of restenosis, registry data from multiple centers worldwide showed major adverse cardiovascular event rates similar to those of CABG 4. Comparison of PCI vs CABG According to Ganesh et al 5 PCI with DES is a safe and durable alternative to CABG for the revascularization of UPLM stenosis in select patients at long-term follow-up. Several observational, non-randomized registries have shown similar major adverse cardiovascular events (MACCE) between patients treated with DES and CABG in the subset of patients up to 5 years of clinical follow-up. Randomized controlled trials (RCTs) which compared PCI With CABG for the Treatment of Unprotected Left Main coronary artery disease (CAD) are shown in table-i. S194

198 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S194-S97 The SYNTAX 7 (synergy between percutaneous intervention with taxus and cardiac surgery) provides the largest data regarding early and late outcomes of PCI of LMS. The primary end point of death, stroke, MI and repeat revascularization favored CABG. The secondary end point of death, stroke and MI was not different between those who undergo PCI or CABG. Primary end point favoring CABG was driven by increased rate of repeat revascularization in PCI group (26.7% vs 15.5%), though notably rate of stroke was also significantly lower in PCI group (1.5% VS 4.3%). Calculating SYNTAX score is a class I indication for left main stem disease or multi vessel disease as per recent AHA/ ACC PCI guidelines. Patients with low (0-22) and intermediate score (23-32) can be treated with PCI or CABG with equal results. Those with high score (>32) do better with CABG. In a subgroup analysis it was found that MACCE rates were significantly higher in the paclitaxel eluting stent (PES) arm compared with the CABG arm in diabetic patients and directionally higher (but non-significant) in nondiabetic patients. SYNTAX score II 8 (SSII) provides 4-year mortality after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in order to facilitate decision-making between these two methods. SSII has robust prognostic accuracy, both in CABG and in PCI patient groups and was more accurate in stratifying patients for late mortality when compared with SS. The recent EXCEL trial 9 (evaluation of Xience Prime or Xience V-eluting stent vs CABG for effectiveness of LM revascularization) evaluated the safety and efficacy of PCI with Xience Prime or Xience V EES vs. CABG in patients with ULMCA disease with a low or intermediate SYNTAX score (<33). This trial concluded that PCI with everolimus eluting stents was non inferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. Society Guidelines Table-I: RCTs comparing PCI vs CABG for unprotected left main CAD. Event rate for Event rate for Event rate for primary end primary end secondary Trial name p-value points points end points PCI CABG PCI Recommendations Pertaining to Unprotected Left Main Intervention in the American College of Cardiology Foundation / American Heart Association / Society of Cardiovascular Angiography and Intervention 2011 Guidelines for PCI are given in table-ii. European Society of Cardiology Guidelines 2014 Recommendations for the type of revascularization in left main stem disease are shown in table-iii. Procedural Consideration Severity of Obstruction Event rate for secondary end points CABG p-value LE MANS ± 8.3% 49.8 ± % 64.4% % (SS<32) 32.1% (SS<32) SYNTAX 36.9% 31.0% % (SS>32) 29.7% (SS>32) EXCEL 15.4% 14.7% 0.02 for Noninferiorit y 0.98 for superiority 23.1% 19.1% 0.01 for noninferioriy 0.10 for superiority For lesions of indeterminate severity on coronary angiography, intra vascular ultrasound (IVUS) is used. Significant obstruction of LMS, minimal luminal area (MLA) of <6mm 2 has been shown to be highly sensitive and specific to predict fractional flow reserve(ffr)<0.75. Post S195

199 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S194-S97 PCI, minimal stent area (MSA) <8 mm 2 in the proximal LMS, <7 mm 2 in the LMS bifurcation, <6 mm 2 in ostial LAD and <5 mm 2 in ostial LCx is associated with under expanded stent and ISR 10. Drug-Eluting Stent Choices Intracoronary Stenting and Angiographic Results: Drug-eluting Stents for Unprotected LM Lesions (ISAR-LM2) 11 evaluated the safety and efficacy of everolimus EES vs zotarolimus eluting In the ERACI IV study, patients treated with second generation DES as compared to the firstgeneration DES in patients with multiple vessel disease and unprotected left main stenosis had lower incidence of MACCE. Bio resorbable vascular scaffolds (BVS) in ostial LM lesions has the advantage of avoiding permanent metal struts protruding into the aorta. Techniques of Left Main PCI Table-II: Recommendations pertaining to left main intervention. Classification Level of Evidence Recommendations IIa B PCI 1) Low SYNTAX score [ 22], ostial or trunk left main CAD 2) Increased risk of adverse surgical outcomes IIa B PCI 1) UA/NSTEMI with unprotected left main coronary artery is the culprit. 2) Patient is not a candidate for CABG IIa C PCI 1) STEMI with unprotected left main coronary artery is the culprit 2) TIMI flow grade <3 3) PCI can be performed more rapidly and safely than CABG IIb B PCI 1) Low-intermediate SYNTAX score of <33, bifurcation left main CAD 2) Increased risk of adverse surgical outcomes III (HARM) B PCI shouldn t be performed 1) Unfavorable anatomy for PCI 2) Good candidates for CABG Table-III: Recommendations for the type of revascularization in left main stem disease. CABG PCI LMS disease with SYNTAX score >22 IB I B LMS disease with SYNTAX score IB IIa B LMS disease with SYNTAX score >32 IB III B stent (ZES) and provided comparable clinical and angiographic outcomes at 1-year follow-up. Using the results of the French Left Main Taxus and the LEft MAin Xience registries, EES was compared to PES. After 2-year follow-up, there was a reduction by 53% in target lesion failure with EES 12. NEST 13 registry 154 patients with left main coronary disease were treated with everolimus- (44.2%), zotarolimus- (29.9%) and biolimus A9- eluting (25.9%) stents were followed up for 2 years. The MACE rate was 18.8% and no case of MI or definite stent thrombosis was reported. Ostial And Mid Vessel Lesions These lesions can be stented with a singlestent strategy. Szabo technique or the passage of a second coronary guide wire into the aortic root to are techniques for proper ostial stent placement. Distal Left Main Lesions In more than half of all patients, distal left main stem is involved. In case of LMCA lesions involving bifurcation, PCI is complicated by plaque shift. True distal bifurcation lesions may either be treated by a single or two-stent strategy. Certain lesion characteristics like plaque S196

200 Left Main Coronary Artery Stenting Pak Armed Forces Med J 2018; 68 (Suppl-1): S194-S97 distribution, the diameter of the branches, the angle between them, anatomy of the side branches along with operator experience decide the treatment strategy Final KBPD (kissing balloon post dilatation is mandatory while using 2 stent strategy. A number of 2-stent techniques like T- stenting, crush stenting, culotte stenting, and simultaneous kissing stenting or Y-stenting ca be used with various levels of complexities and indications. Recently, dedicated bifurcation stents or selfexpandable stents (TRYTON, AXXESS, BiOSS, STENTYS) were used for the treatment of distal LMS stenosis. Early results are encouraging, but definite conclusions are still awaited 10. Role of FFR And OCT A final minimal stent area >9.6mm sq has been associated with a very low rate of revascularization after LMS PCI. FFR help the operator decide to provisionally stent the pinched LCx artery because the degree of angiographic stenosis of LCx is frequently mismatched with functional severity according to FFR. 3D-OCT (optical coherence tomography) can be used in identifying about carina or plaque shift, side branch compromise and floating struts at the side branch ostium. Dual Anti-Platelet Therapy According to the current guidelines of AHA 2016, long-term aspirin administration and at least 6 months dual anti-platelet therapy (DAT) should be used in patients receiving a DES (Class: I); however, this is not specific for ULMCA stenting. Although the risk benefit ratio of long-term DAT is not well defined, many clinicians favor prolonged DAT after ULMCA stenting with DES. CONCLUSION Stenting of ULMCA stenosis requires careful patient selection after medical-surgical consultation (Heart Team concept) and ethics of information. Patients with less complex LMS disease can be treated by PCI and more complex LMS lesions by CABG. With the results of ongoing trails, current guidelines can be modified. Financial Disclosure Authors have no financial interests related to the material in the manuscript. CONFLICT OF INTEREST The authors report no relationships that could be construed as a conflict of interest. REFERENCES 1. Eugene B. Left main coronary artery disease. N Engl J Med 2016; 375: Taggart D, Kaul S, Boden WE, Ferguson TB, Guyton RA, Mack MJ et al. Revascularisation for unprotected left main stem coronary artery stenosis: Stenting or surgery. J Am Coll Cardiol 2008; 51: Tan WA, Tamai H, Park SJ, Plokker HW, Nobuyoshi M, Suzuki T, et al. Long-term clinical outcomes after unprotected left main trunk percutaneous revascularization in 279 patients. Circulation 2001; 104(14): Park SJ, Kim YH, Lee BK, Lee SW, Lee CW, Hong MK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis: comparison with bare metal stent implantation. J Am Coll Cardiol 2005; 45(3): GaneshA, Eshan P, Murat ET, Stephen E, Patrick W, Samir R, et al. JACC: Cardiovasc Interv 2013; 6(12): Paul S. Teirstein MD, Matthew J. Price, MD Left Main Percutaneous Coronary; J Am Coll Cardiol 2012; 1: Marie-Claude M, Patrick WS, A. Pieter K, Ted EF, Elisabeth S, Antonio C et al. Five-Year Outcomes in Patients with Left Main Disease Treated with Either Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting in the SYNTAX Trial. Circulation 2014; 137(4): Gregg WS, Joseph FS, Patrick WS, Charles AS, Philippe G, Puskas J et al. Everolimus-eluting stents or bypass Surgery for left main coronary artery disease. N Engl J Med 2016; 375: Lucian MP, Lucian Z, Pavel P, Marin P, Adrian B, Marian C, et al. Current treatment of left main coronary artery disease. Cor et Vasa 2016; 58(3): e328-e Mehilli J, Richardt G, Valgimigli M, Schulz S, Singh A, Abdel- Wahab M et al. Zotarolimus- versus everolimus-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2013; 62(22): Moynagh A, Salvatella N, Harb T, Olivier D, Nicolas D,Thierry L et al. Two-year outcomes of everolimus vs. paclitaxel-eluting stent for the treatment of unprotected left main lesions: A propensity score matching comparison of patients included in the French Left Main Taxus (FLM Taxus) and the LEft MAin Xience (LEMAX) registries. Euro Intervention 2013; 9: Bernelli C, Chieffo A, Buchanan GL, Montorfano M, Latib A, Figini F, et al. New-generation drug-eluting stent experience in the percutaneous treatment of unprotected left main coronary artery disease: The NEST registry. J Invasive Cardiol 2013; 25: S197

201 Open Access Short Communication Levels of High Sensitivity Troponin-I Pak Armed Forces Med J 2018; 68 (Suppl-1): S EFFECT OF RECENTRIFUGATION ON THE LEVELS OF HIGH SENSITIVITY TROPONIN I Sumbal Nida, Raja Kamran Afzal, Mohammad Zaheer Us Saeed Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT Objective: To compare the levels of high sensitivity troponin I in plasma after specimen re-centrifugation in patients presenting with acute coronary syndrome. Study Design: Cross sectional study. Place and Duration of study: Department of Pathology, Armed Forces Institute of Cardiology, Rawalpindi, from Sep to Nov Material and Methods: Seventy five patients plasma samples of high sensitivity troponin I levels, exceeding the value of 0.06ng/ml were analyzed. Blood was collected in K/EDTA evacuated tubes and plasma was separated after an initial centrifugation (2000 g, 10 min; not refrigerated). The samples were recentrifuged after first analysis. High sensitivity troponin I was measured through the chemiluminescence technique on ADVIA CENTAUR XP immunoassay analyzer. Normally distributed continuous variables were presented as Mean ± SD and the others as median. Two-tailed Wilcoxon analysis was applied to determine the difference in high sensitivity troponin I specimens before and after recentrifugation. A p-value <0.05 was considered as statistically significant. Results: Median value of high sensitivity troponin I was 4.051ng/ml before re-centrifugation and ng/ml after recentrifugation. About 2.5 th to 97.5 th percentile interval was and ng/ml, before and after recentrifugation, respectively. Difference between the two samples were statistically analyzed by using twotailed Wilcoxon analysis that showed a statistically significant difference (p-value<0.01). Conclusion: Recentrifugation of specimens is followed by a significant reduction in high sensitivity troponin I levels which may result in misdiagnosis and treatment of the patients. Keywords: High sensitivity troponin I, Recentrifugation. SHORT COMMUNICATION This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Cardiac troponins (ctn) have a major role in the diagnosis of myocardial infarction. Analytical performance of these assays is thus critical in diagnosis of patients with acute coronary syndrome (ACS) 1. International consensus guidelines define acute myocardial infarction (AMI) in terms of rise and fall of cardiac troponins 2. However since the time troponins have been introduced, problem of false positive results arose. Particulate matter such as fibrin strands were thought to be responsible for such results, therefore many researchers suggested the process of Correspondence: Dr Sumbal Nida, Armed Forces Institute of Cardiology/ NIHD Rawalpindi Pakistan docsumbalnida@gmail.com recentrifugation of the samples with high results 3. Various pre-analytical factors such as specimen type, hemolysis, lipemia, icterus, microclots and debris have been reported to affect the results of cardiac troponins 1. Lipids and proteins have been reported to interfere with troponin assay 4. Relative centrifugation force (RCF) has been studied to see its effect on these interferants revealing that low RCF of >300 for 30 min does have an effect on high sensitivity troponin assay. However recentrifugation was recommended for pooled patient based quality controls or samples that have been stored for some time 5. Researchers further argued that if recentrifugation is carried out for all specimens it may also result in false negative results which increases the chance of missing patients with S198

202 Levels of High Sensitivity Troponin-I Pak Armed Forces Med J 2018; 68 (Suppl-1): S ACS 6. High speed centrifugation can cause adherence of troponins to the walls of the test tube resulting in lower values. A study carried out by Canovi et al in 2015 compared the results of conventional troponin in plasma before and after recentrifugation, concluding a significant reduction in the levels of the troponin 7. However the question for high sensitivity troponin regarding this problem still remains unanswered. This study was planned to see the effect of recentrifugation on high sensitivity troponin assay in plasma samples of patients presenting to the Armed Forces Institute of Cardiology, Rawalpindi with symptoms of acute coronary syndrome. MATERIAL AND METHODS It was a cross sectional study carried out in the department of Pathology, Armed Forces through the chemiluminescence technique on ADVIA CENTAUR XP immunoassay analyzer using Trop I Ultra (SIEMENS ADVIA CENTAUR). Performance of the assay was monitored using two levels of quality control material. Analytical CV of the assay was <10%. Centrifuges were calibrated by biomedical engineers and verification of calibration was done by laboratory technologists. Samples which had higher troponin levels exceeding the positive cutoff of >0.06 ng/ml were separated and stored at room temperature in plastic tubes and were recentrifuged (2000 g, 10 min) followed by reanalysis of troponin levels. Data Analysis Troponin I and age were represented as median. Two-tailed Wilcoxon analysis was applied to determine the difference in high Figure-1: Passing Bablock regression. Dashed line indicates identity line; bold line, regression line. Intercept: ng/ml (95% confidence interval [CI], ng/ml), slope: (95% confidence interval [CI], ). Institute of Cardiology, Rawalpindi, from Sep to Nov Seventy five samples of patients that reported to emergency reception of hospital with symptoms of acute coronary syndrome were analyzed. Blood was collected in K/EDTA evacuated tubes. Specimens revealing obvious hemolysis, lipemia, and icterus were excluded. Specimens stored in refrigerator were also excluded from the study considering stability of the specimen also affects results of the assay. High sensitivity troponin I was measured S199 sensitivity troponin I specimens before and after recentrifugation. Bland Altman plot was constructed to see the difference betweeen the two samples. Passing- Bablock regression was done to quantify the difference. A p-value <0.05 was considered statistically significant. RESULTS A total of 75 patients serum samples were collected on consecutive days. Normality of data was checked by Shapiro Wilk test that showed

203 Levels of High Sensitivity Troponin-I Pak Armed Forces Med J 2018; 68 (Suppl-1): S p-value <0.01, showing that the data was non- Gaussian. Median age of the patients was 59 years with IQR of 17 years. Median value of high sensitivity troponin I before and after recentrifugation was ng/ml and ng/ml, respectively, whereas 2.5 th to 97.5 th percentile interval was ng/ml to ng/ml (95% CI, ) and ng/ml to 48.7 ng/ml (95% CI, ), respectively. To see whether the difference between the two samples were statistically significant, two tailed Wilcoxon analysis was carried out that showed a p-value<0.01, showing that the samples after recentrifugation had a significantly lower value of high sensitivity troponin I. In order to see the effects of recentrifugation on results near recentrifugation that was previously observed by researchers while dealing with high troponin levels 8. Various pre-analytical, analytical and post-analytical factors have been reported to affect the results of cardiac troponins I, but we focused only on recentrifugation. Effect of recentrifugation on the conventional troponin levels has previously showed a negative bias of 0.01 ng/ml in a previous study 3, but it did not include high sensitivity troponin I. Limit of detection of this assay was ng/ml and the limit of quantification was 2.05 ng/ml. Data was checked for any outliers to further ensure the reliability of the results since the effect of outliers on troponin assay has been reported earlier 9. Importance of quality control has been Figure-2: Bland Altman plot showing a difference between the two samples, blue line shows the mean difference showing a mean value of 8.4 ng/ml with SD of ± 1.96 ng/ml. the cut off, we analyzed the data by using non parametric Passing- Bablock regression which showed a median reduction of ng/ml (95% CI, ng/ml) after recen-trifugation of troponin I concentration that was statistically significant (p-value<0.01) (fig-1). A Bland Altman plot for the data was constructed to see the difference between the two samples showing mean of 8.4 ng/ml with SD of ± 1.96 ng/ml (fig-2). DISCUSSION Cardiac troponins have been studied for possible interferences in various studies. This study was carried out to see the effect of S200 emphasized repeatedly for such assays, so it was assessed by using two levels of control materials 10. In this study, recentrifugation resulted in reduction in the levels of high sensitivity troponin I to ng/ml (95% CI, to ) which was statistically significant (p-value <0.01), this finding being consistent with the study mentioned previously 7. Reason for this negative bias however remains a question. Some researchers think it could either be due to degradation of cardiac troponin or its adherence to the walls of the tube 6. Whatever the reason may be, recentrifugation may result in

204 Levels of High Sensitivity Troponin-I Pak Armed Forces Med J 2018; 68 (Suppl-1): S misdiagnosis and subsequent wrong treatment of the patient. The process of unnecessary recentrifugation may also increase the turnaround time of the assay, thus resulting in delay in management of the patient. CONCLUSION Recentrifugation of specimens is followed by a significant reduction in high sensitivity troponin I levels which may result in misdiagnosis and treatment of the patients. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Herman DS, Kavsak PA, Greene DN. Variability and Error in Cardiac Troponin Testing: A CLPS Critical Review. Am J Clin Pathol 2017; 148(4): Jaffe AS, Apple FS, Morrow DA, Lindahl B, Katus HA. Being rational about (im) precision: A statement from the biochemistry subcommittee of the joint European Society of Cardiology/ American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the definition of myocardial infarction. Clin Chem 2010; 56: Dimeski G. Evidence on the cause of false positive troponin I results with the Beckman AccuTnI method. Clin Chem Lab Med 2011; 49(6): Grunbaum AM, Gilfix BM, Hoffman RS, Lavergne V, Morris M, Miller-Nesbitt A. Review of the effect of intravenous lipid emulsion on laboratory analyses. Clin Toxicol (Phila) 2016; 54: Kavsak PA, Caruso N, Beattie J, Clark L. Centrifugation - An important pre-analytical factor for the Abbott Architect highsensitivity cardiac troponin I assay. Clin Chim Acta 2014; 436: Pfäfflin A. Doubt on prevention of false-positive results of cardiac troponin I by recentrifugation. Clin Chem Lab Med 2009; 47(7): Canovi S, Campioli D, Marcheselli L. Specimen recentrifugation and elevated Troponin I levels. Lab Med 2015; 46(1): Er TK, Tsai LY, Jong YJ, Chen BH. Falsely elevated troponin I attributed to inadequate centrifugation using the Access immunoassay analyzer. Clin Chem Lab Med 2006; 44(7): Sawyer N, Blennerhassett J, Lambert R, Sheehan P, Vasikaran SD. Outliers affecting cardiac Troponin I measurement: comparison of a new high sensitivity assay with a contemporary assay on the Abbott ARCHITECT analyser. Ann Clin Biochem 2014; 51(Pt 4): Kavsak PA. Quality control material testing and the importance of "treating it like a patient's sample". Clin Biochem 2014; 47(3): S201

205 Open Access Coronary Grafts Short Communication Pak Armed Forces Med J 2018; 68 (Suppl-1): S202-S205 ANGIOGRAPHIC STUDY OF CORONARY GRAFTS Asif Nadeem Armed Forces Institute of Cardiology/National University of Medical Sciences (NUMS) Rawalpindi Pakistan ABSTRACT In last couple of decades, the number of graft study cases in cath labs has increased due to increasing number of post coronary artery bypass surgery cases presenting with angina or ischemia. Coronary angiography in the setting of coronary artery bypass grafting (CABG) is an important diagnostic tool for the evaluation of graft patency in such patients 1. Angiography in the setting of CABG is more complex and challenging than the conventional angiography, but with increasing experience, the procedure can be made easy, sleek and comfortable both for the patient and for the operator 2. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pre-Requisite Before the graft angiography is performed, it is very important to have the CABG report available. It will assist the operator to know the exact number and anatomical features of grafts. At least the types and number of vein grafts should be available before pursuing with an angiogram. It can substantially decrease radiation exposure, procedural time, contrast use and the risk to the patient 3. For example, the knowledge about lack of internal mammary artery (IMA) as a bypass graft conduit will eliminate the need for left or right subclavian artery catheterization. Similarly, information about the number of grafts will eliminate the search for unknown number of grafts. Vein grafts to the right coronary arteries have usually right-sided take off from the aorta while left coronary grafts usually have an anterior take off 2,3. Sequential vein grafts supplying two coronaries with one vein graft are not uncommon. Therefore, the knowledge about the presence of sequential vein grafts will aid the operator to avoid searching for additional non existing vein graft ostia 4. Indications The indications for performing graft angiography in patients with CABG surgery are similar to those without bypass surgery. Unstable Correspondence: Dr Asif Nadeem, Armed Forces Institute of Cardiology/NHID Rawalpindi Pakistan asifcardiologist@gmail.com or symptomatic patients who are candidates for coronary intervention, should undergo this procedure. Asymptomatic patients with a large area of ischemia documented on perfusion scans also benefit from angiography. Significant disease in native coronaries or in the grafts documented on CT angiogram is also an indication for graft study. CABG patients with new onset of left ventricular dysfunction, LBBB or congestive heart failure especially in the setting of diabetes mellitus are another group with potential benefit 4. Limitations Higher use of contrast and longer procedural time should be discussed with the patients and their family members. Other limitations of coronary angiography are similar to the patients undergoing native coronary angiography 5. Patients with risk of bleeding, infection, peripheral vascular disease, renal failure, anemia, coagulopathy, congestive heart failure and significant co-morbid conditions are at higher risk for complications. Informed consent is necessary before the patient undergoes graft angiography 6. Sequence Usually, it is the native coronary angiogram which is performed before the graft study but there are no specific guidelines regarding this sequence. In addition to give the detailed anatomical information, performing native S202

206 Coronary Grafts Pak Armed Forces Med J 2018; 68 (Suppl-1): S202-S205 coronary angiography first has the advantage of visualizing distal graft insertion site for competitive flow/flash filling that suggests patent graft 7. This is more helpful when the operator does not have accurate information about the numbers and types of vein grafts before performing angiography 8. Arterial Access Although majority of graft studies are performed by the femoral arterial site, but the radial arteries can be used for graft angiography. However, in the presence of left internal mammary artery (LIMA), left arm should be utilized in order to have easy access to the left IMA and vein grafts. For the presence of right IMA, right arm should be selected 9. As in conventional angiogram, the radial access site is associated with a risk of thrombotic complication. Therefore, intra-arterial injection of 5000 units of heparin is routinely given after the sheath insertion. In addition, the radial artery is prone to develop spasm. Intra-arterial injections of nitroglycerin and/or verapamil after sheath insertion can abate this. Radial artery is small which cannot accumulate large sheath size. Usually a 5 or 6 French sheath is used. Once the sheath is inserted and flushed with saline solution, a diagnostic catheter is advanced over inch J wire into the ascending aorta. After the removal of the wire, the catheter is connected to the manifold and double-flushed (aspirating blood followed by flushing with heparin saline) vigorously with the removal of all bubbles. Next, contrast is drawn into the injecting syringe and pressure is monitored during the entire procedure 10,11. An Over-View of Location of Grafts It is better to convince the surgeons to use tiny rings to help in marking the ostia of the vein grafts which can substantially aid the interventionist to localize the ostia during subsequent angiographic studies. The lack of markers increases the contrast use, procedure time and radiation particularly in patients without the knowledge of the types and number of vein grafts 12. As mentioned earlier, right coronary grafts usually have a right sided take off from the aorta. Therefore, using the standard left anterior oblique (LAO) view, which is used for right coronary artery catheterization, is the view of choice. The catheter tip should be oriented in the same direction as in engaging the right coronary artery with a slightly higher search. However, the left sided grafts usually have an anterior take off 10,12. Therefore, a right anterior oblique (RAO) view makes it easier to engage the left-sided vein graft ostia preventing fore shortening of the catheter tip. Using RAO, the catheter tip should be oriented to the right side of the screen. LAD vein graft ostia are usually closest grafts to the aortic valve if IMA is not used as graft conduit. This is followed by diagonal and then the circumflex grafts. Circumflex graft ostia usually have the highest take off from the aorta 13. There are occasional cases with different take offs making vein graft angiography difficult. In such a situation, the angiography catheter has to be probed across the aorta in different level in order to engage the ostium. A non-selective strong contrast injection or aortogram using a pigtail catheter may be necessary to delineate the unusual take off of missing vein grafts or documenting total occlusion of missing vein grafts. Totally occluded vein grafts usually have a residual knob in the aorta that can be seen during angiography 14. Appropriate views are selected to see the graft landing zone and the native coronary arteries distal to the insertion site of the grafts as that portion might be diseased. When the grafts ostia are engaged, the subsequent views depend upon the native vessel, i.e. the caudal views for LCX grafts and cranial views for the LAD grafts. Any additional views to complete the study and to define the anatomy should be taken 15. It is important to watch for any damping or ventricularization of the aortic pressure. These signify a high grade ostial lesion or catheter touching the vessel wall. It is important to avoid injecting into the vessel wall as it can cause major dissection. Injection into the vein graft with a high grade S203

207 Coronary Grafts Pak Armed Forces Med J 2018; 68 (Suppl-1): S202-S205 ostial lesion increases the risk of arrhythmias and sudden death 15. Catheters For Vein Grafts Regardless of the right or left coronary artery grafts, most of the vein grafts can successfully be engaged by a commonly used Judkin s right 4 (JR4) catheter. The JR4 is therefore the most commonly used catheter for graft study including the IMAs. However, many vein grafts have unusual take off requiring different catheters. Many right coronary vein grafts have steep inferior take off making the ostial engagement with JR4 difficult or impossible. In such a scenario, a multipurpose catheter which has a shallow angulation is the best choice. The second major challenge in engaging vein graft ostia, particularly vein grafts supplying the left coronary arteries, is the shape of the aorta 16. A large aorta can make it very difficult for the JR4 catheter to reach the ostial vein grafts. In such a situation, Amplatz right (AR) and left (AL) catheters can be very helpful to reach the vein graft ostia. Amplatz catheters have a larger primary curve and have been used successfully in unusual superior take off of left coronary arteries or vein grafts and in large aorta. Amplatz catheters are available in different sizes (from smaller to larger curve: AR 1, AR2, AL 0.75, AL1, AL2 and AL3) 17. Occasionally, a very superior take off of a vein graft requires specially designed bypass graft catheters. Amplatz catheters are also extremely helpful in engaging native right coronary ostium with a high anterior take off 17. Arterial Graft Angiography For left IMA angiography, the major challenge is the advancement of wire and catheter into the subclavian artery. Older age and peripheral vascular disease are the risk factors for tortuous anatomy. Subclavian stenosis is another cause of difficult subclavian catheterization 17,18. In most instances, a JR4 catheter can be positioned into the subclavian artery ostium by counter-clockwise rotation and withdraw of the catheter after positioning it in the ascending aorta. Once the catheter is engaged in the subclavian artery ostium, any manipulation of the catheter has to be performed over the J tipped wire with extreme caution in order to avoid injury to the subclavian artery and embolism in the territory of vertebral artery. The later can cause posterior circulation stroke 18. In case the IMA is not engaged, it is reasonable to inflate a blood pressure cuff in the left arm and perform a non-selective angiography of the left IMA. In the majority of cases, IMA opacification is satisfactory by manipulating the catheter 30-degree counter clock wise. However, for unsatisfactory opacification and when further detail of anatomical information of IMA is needed, a JR4 catheter needs to be exchanged to a left IMA catheter (LIMA seeker) using a long exchange J tip wire 10. Exchange wire can also be used earlier after subclavian engagement particularly when a JR4 catheter cannot be advanced easily. In the majority of cases using left IMA catheter, excellent engagement and angiography of the left IMA can be performed. Again, it is important to avoid extreme manipulations of any catheters in the subclavian artery to avoid any vascular injury and embolism 18. Contrast injection in the IMA can trigger severe pain in the arm. The patient needs to be warned and informed before injecting the contrast. If subclavian ostial engagement cannot be achieved with a JR4 catheter, a J-wire could be utilized and positioned into the subclavian artery followed by the left IMA or JR4 catheter advancement. There are rare instances when subclavian engagement cannot be achieved from femoral arterial route. In such a situation, using the left radial artery gives direct access into the left IMA ostia 17,19. The technique for engaging right IMA is similar to the left IMA. However, right IMA angiography and engagement can be more difficult in dilated aortic root and abnormal steep take off of the right innominate artery. Similar to the left IMA, the right arm can be used in difficult cases. Aortogram and left ventriculography are usually performed using a pigtail catheter and power injector for the assessment of the left ventricular function, aortic S204

208 Coronary Grafts Pak Armed Forces Med J 2018; 68 (Suppl-1): S202-S205 valve regurgitation or missing or occluded vein grafts with only a stub visible 20. Special Issues Related To Vein Graft Angiography Higher contrast use with increasing risk of contrast induced nephropathy. Increased radiation exposure to the patients and angiographers. Longer procedural time. Higher risk for thromboembolism and aortic injury during additional catheter manipulations in the aorta. Risk of injury to the subclavian artery and aorta during IMA angiography. Difficulty in engaging angulated vein grafts take off and subclavian artery in some patients. CONFLICT OF INTEREST This study has no conflict of interest to declare by any author. REFERENCES 1. Movahed MR, Stinis CT. A new proposed simplified classification of coronary artery bifurcation lesions and bifurcation interventional techniques. J Invasive Cardiol 2006; 18(5): Engler RL, Schmid-Schonbein GW, PavelecRS. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 1983; 11(1): Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 2001; 22(9): Movahed MR, Butman SM. The pathogenesis and treatment of no-reflow occurring during percutaneous coronary intervention. Cardiovasc Revasc Med 2008; 9(1): Fischell TA, Carter AJ, Foster MT, Hempsall K, DeVries J, Kim DH, et al. Reversal of "no reflow" during vein graft stenting using high velocity boluses of intracoronary adenosine. Cathet Cardiovasc Diagn 1998; 45(4): Fugit MD, Rubal BJ, Donovan DJ. Effects of intracoronary nicardipine, diltiazem and verapamil on coronary blood flow. J Invasive Cardiol 2000; 12(2): Kaplan BM, Benzuly KH, Kinn JW,, Bowers TR, Tilli FV, Grines CL, et al. Treatment of no-reflow in degenerated saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin. Cathet Cardiovasc Diagn 1996; 39(2): Michaels AD, Appleby M, Otten MH, Dauterman K, Ports TA, Chou TM, et al. Pretreatment with intragraft verapamil prior to percutaneous coronary intervention of saphenous vein graft lesions: results of the randomized, controlled vasodilator prevention on No-Reflow (VAPOR) Trial. J Invasive Cardiol 2002; 14(6): Piana RN, Paik GY, Moscucci M, Cohen DJ,Gibson M, Kugelmass AD, et al. Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. Circulation 1994; 89: delemos JA, Antman EM, Gibson CM, McCabe CH, Giugliano RP, Murphy SA, et al. Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 Trial. Circulation 2000; 101(3): Roffi M, Mukherjee D, Chew DP, Bhatt DL, Cho L, Robbins MA, et al. Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials. Circulation 2002; 106 (24): Stone GW, Rogers C, Hermiller J, Feldman R, Hall P, Haber R, et al. Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts. Circulation 2003; 108(5): Gick M, Jander N, Bestehorn HP, Kienzle RP, Ferenc M, Werner K, et al. Randomized evaluation of the effects of filter-based distal protection on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation. Circulation 2005; 112(10): Huang Z, Katoh O, Nakamura S, Negoro S, Kobayashi T, Tanigawa J. Evaluation of the Percu Surge Guardwire Plus Temporary Occlusion and Aspiration System during primary angioplasty in acute myocardial infarction. Catheter CardiovascInterv 2003; 60(4): Mauri L, Cox D, Hermiller J, Massaro J, Wahr J, Tay SW, et al. The PROXIMAL Trial: proximal protection during saphenous vein graft intervention using the Proxis Embolic Protection System: A randomized, prospective, multicenter clinical trial. J Am Coll Cardiol 2007; 50: Fischell TA, Subraya RG, Ashraf K, Perry B, Haller S. "Pharmacologic" distal protection using prophylactic, intragraft nicardipine to prevent no-reflow and non-q-wave myocardial infarction during elective saphenous vein graft intervention. J Invasive Cardiol 2007; 19(2): Lee MS, Shah AP, Aragon J, Jamali A, Dohad S, Kar S, et al. Drug-eluting stenting is superior to bare metal stenting in saphenous vein grafts. Catheter Cardiovasc Interv 2005; 66(4): Vermeersch P, Agostoni P, Verheye S, Heuvel YD, Convens C, Ven-den Brenden F, et al. Randomized double-blind comparison of sirolimus-eluting stent versus bare-metal stent implantation in diseased saphenous vein grafts: six-month angiographic, intravascular ultrasound, and clinical follow-up of the RRISC Trial. J Am Coll Cardiol 2006; 48(12): Vermeersch P, Agostoni P, Verheye S, Van den Heuvel P, Convens C, Van den Branden F, et al. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenous vein grafts: Results from the randomized DELAYED RRISC Trial. J Am CollCardiol 2007; 50(3): Bansal D, Muppidi R, Singla S, Sukhija R, Zarich S, Mehta JL, et al. Percutaneous intervention on the saphenous vein bypass grafts - long-term outcomes. Catheter Cardiovasc Interv 2008; 71(1): S205

209 Open Access Diphtheria Myocarditis Case Report Pak Armed Forces Med J 2018; 68 (Suppl-1): S206-S07 CASE REPORTS DIPHTHERIA MYOCARDITIS: CASE REPORT Muhammad Nadir Khan, Tahira Muqaddas Army Cardiac Center, Lahore Pakistan ABSTRACT Diphtheria is a communicable disease which is caused by Corynebacterium diphtheria. Global incidence of diphtheria has declined due to worldwide immunization programs, but still cases of diphtheria are reported across the world because of poor vaccine coverage, population growth and low socio economic status. We report here a case of diphtheria in a 13-years-old girl who presented to us with ventricular tachycardia. Keywords: Bull neck, Cardiac involvement, Chinese letter appearance, Corynebacterium diphtheria. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Diphtheria is still an important public health problem in developing countries 1. The incidence of diphtheria in the developed nations has declined because of effective immunization program. Factors like inadequate vaccine coverage, low socio-economic status, delayed reporting of such cases and non availability or delayed administration of diphtheria antitoxin lead to resurgence 2. The clinical features of diphtheria are fever, sore throat, pseudo membrane, muffled voice and bull neck. Antitoxin is the mainstay of the treatment. CASE REPORT A 13 years old girl was transferred from a hospital to our hospital in Oct 2016, with 3 days history of continuous high grade fever, severe sore throat rendering her unable to eat and drink. She also developed gradual neck swelling along with nausea, headache and malaise from second day of illness followed by hoarseness of voice. Later she developed palpitation and shortness of breath. ECG showed broad complex tachycardia. Then the clinical provisional diagnosis of diphtheria myocarditis was made and she was transferred to our hospital due to unavailability of diphtheria antitoxin. On arrival to our hospital, a detailed history revealed that she was not Correspondence: Dr Muhammad Nadir Khan, Associate Professor, Army Cardiac Center Lahore Pakistan yesnadirkhan@gmail.com vaccinated as per expanded program on immunization (EPI). On examination sick looking girl, oriented in time place and person was lying on bed without obvious respiratory distress. She had tachycardia, low grade fever and normal blood pressure. Both her height and body mass index for age were at 50th centile. She was irritable, had marked swelling of neck. Throat was examined in controlled settings which showed marked congestion and a grey white membrane covering tonsils and posterior pharyngeal wall. Cervical lymph nodes were markedly enlarged and tender leading to diffuse swelling of neck conventionally called BULL NECK. Rest of systemic examination was unremarkable. Throat swab containing portion of membrane and blood was sent for culture and sensitivity along with other investigations. Lab tests revealed elevated WBC count with predominant neutrophils. CRP was raised. CK, CK-MB, AST, LDH were markedly raised, RFT were mildly deranged. ECG showed ventricular tachycardia which was reverted to sinus rhythm with IV lignocaine 50mg after which ECG showed heart rate of 110/min, sickle shaped ST depression in anterior precordial leads and broad QRS complexes. Echocardiography was normal. CXR was normal. Chinese letter appearance was seen on gram staining of throat swab. While on Albert stain club shaped rods containing metachromatic granules were found. Throat swab culture and sensitivity report was awaited. S206

210 Diphtheria Myocarditis Pak Armed Forces Med J 2018; 68 (Suppl-1): S206-S07 Treatment with barrier nursing techniques along with strict bed rest was started. Diphtheria anti toxin 40,000 units were transfused over 1 hour after test dose. IM procaine penicillin G 600,000 units 12 hourly started. All contacts were given prophylactic Erythromycin. Patient s general look was improved after antitoxin administration and she started taking orally but unfortunately next day patient suddenly again went into pulseless ventricular tachycardia. Immediately biphasic DC shock with 200 joules was given after which she had complete heart block. Temporary pacemaker was passed but myocardium failed to capture. CPR done with full protocol for 45 minutes but patient didn t survive. DISCUSSION Diphtheria is an acute, communicable disease with overall fatality rate as high as 20-30% in toxic forms up to 70% in diphtheritic myocarditis. The ECG changes of myocarditis may be sickle-shaped sagging of the ST segment (specific for diphtheritic myocarditis), arrhythmias and other conduction abnormailities 3. If complete heart block develops, the prognosis is usually death 4. Insertion of a pacemaker in severely ill patients can be difficult and risky. Mainstay of treatment in diphtheria is administration of diphtheria anti toxin. Dose ranges from 20,000 to 120,000 units depending upon clinical state, site and size of membrane 5. Antibiotics like Penicillin or Erythromycin is given for 14 days. Availability of antitoxin must be ensured at all times. Timely intervention and treatment of patients and contacts can save life and prevent complications 6. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFFERNCES 1. Ornek E, Ureyen CM, Kurtul A, Oksüz F. Diphtheria myocarditis in Turkey after years. Anadolu Kardiyol Derg 2012; 12: Gupta S, Jayashree M. Diphtheria: Relic or Relevant. J Pediatr Crit Care 2017; 4(3): Alakes KK, Rammohan R, Suvendu SK. Cardiac involvement in diphtheria: Study from a tertiary referral infectious disease hospital. Ann Trop Med Public Health 2012; 5: Gundam BR, Sudarsi RK, Gundam A. Study of cardiac involvement in diphtheria. J Evid Based Med Healthc 2016; 3(61): Shahid M, Shahzad R, Sajid AS, Salman A. Eleven-year-old-girl with membranous sore throat. Pak Armed Forces Med J 2015; 65: Meera M, Rajarao M. Diphtheria in Andhra Pradesh - A clinicalepidemiological study. Int J Infect Dis 2014; 19: S207

211 Open Access Linezolid Resistance in Coagulase-Negative Staphylococcus Case Report Pak Armed Forces Med J 2018; 68 (Suppl-1): S208-S09 EMERGENCE OF LINEZOLID RESISTANCE IN COAGULASE-NEGATIVE STAPHYLOCOCCUS ISOLATED FROM A POST-SURGICAL CASE OF CORONARY ARTERY BYPASS AT A TERTIARY CARE CARDIAC SETUP IN PAKISTAN Raja Kamran Afzal, Sumbal Nida, Mohammad Zaheer Us Saeed, Hafsa Khalil Armed Forces Institute of Cardiology/ National University of Medical Sciences (NUMS), Rawalpindi Pakistan ABSTRACT Linezolid is first choice in the treatment of methicillin resistant Staphylococci. Resistance to this antibiotic is quite rare. We report the first case of linezolid resistant coagulase negative Staphylococcus from a tertiary care cardiac setup in Pakistan. The strain was isolated from pus swab of a 62 year old female from post-coronary bypass grafting sites. Keywords: Coagulase negative Staphylococcus, Linezolid resistance. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Linezolid is the first licensed antibiotic to be used for gram positive bacteria having adequate efficacy for the methicillin resistant Staphylococcal species 1. Oxazolidinones block the initiation complex formation, by binding to the 50S ribosomal subunit, resulting in a bacteriostatic action 2. Staphylococcus causes various infections of skin and soft tissues, of surgical sites, endocarditis and hospital acquired infections 3. The organism develops resistance by mutating and DNA transfer resulting in difficulties in treating infections that contribute to increased morbidity and mortality. The increasing use of broad spectrum antibiotics is resulting in emergence of resistance in coagulase negative staphylococci (CoNS) as well 4. Apart from linezolid resistance in Staphylococcus aureus, its resistance has been documented in various species of CoNS such as Staphylococcus cohnii, Staphylococcus kloosii, Staphylococcus hominis and Staphylococcus lugdunensis 5. A study that was conducted in Pakistan in the department of Microbiology, University of Health Sciences, Lahore to determine the in-vitro activity of linezolid against clinical isolates of methicillin resistant Staphylococci showed that linezolid Correspondence: Dr Raja Kamran Afzal, Dept of Pathology, Armed Forces Institute of Cardiology/NIHD Rawalpindi Pakistan rajakamranafzal@yahoo.co.uk was effective against all the strains of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase-negative Staphylococci (MRCoNS) in the range of mg/l and mg/l MICs, respectively 6. Here we report a post-surgical case from the largest tertiary care cardiac setup in Pakistan in which an MRCoNS Staphylococcus haemolyticus showed resistance to linezolid. This further emphasizes on the fact that if linezolid becomes ineffective we shall be left with very limited options for MRSA and MRCoNS. CASE REPORT A 62 years old hypertensive and diabetic female patient was admitted in Armed Forces Institute of Cardiology, Pakistan for coronary artery bypass grafting (CABG) surgery for triple vessel coronary artery disease (TVCAD). She underwent CABG on 10th July, 2017 and was put empirically on the antibiotics amikacin and cefazolin parenterally. After four days, her intravenous antibiotics were stopped and she was put on oral linezolid. About ten days later, graft sites showed bleeding and soakage, her right leg wound was stitched and debridement was done for the left leg wound. Patient was then put on injections linezolid and piperacillintazobactam. Serial pus swab samples yielded multi-drug resistant strains of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. S208

212 Linezolid Resistance in Coagulase-Negative Staphylococcus Pak Armed Forces Med J 2018; 68 (Suppl-1): S208-S09 Secondary suturing of her left leg wound was done. On 7 th July, culture yielded growth of CoNS that was characterized phenotypically as Staphylococcus haemolyticus, based on coagulase and DNAse tests and biochemical reactions. The species was confirmed to be Staphylococcus haemolyticus at Armed Forces Institute of Pathology, by VITEK-2 Walkaway automated culture system. The isolate showed susceptibility to teicoplanin, vancomycin and tigecycline mainly. The isolate was resistant to linezolid (MIC 8 g/ml) so it was stopped and the patient was started on a combination of clindamycin and rifampicin according to susceptibility report. The patient responded well to the above treatment and her surgical site healed. DISCUSSION Bacteria as we know seem to develop resistance against the antibiotics rapidly. Recent studies have shown increasing resistance in strains of MRSA and MRCoNS that contributes to morbidity and mortality in the hospital. Linezolid and glycopeptides are the main choice of treatment for such patients. However since cases have been reported around the world that have documented the emerging resistance to linezolid, physicians shall have limited options in future 8. In a country like Pakistan with limited resources this is an even bigger issue. The recent prevalence of multidrug resistant Staphylococcus species in Lahore, Quetta, and Rawalpindi was 83%, 86% and 75%, respectively 6,7. Studies around the world have shown variable results regarding resistance to linezolid such as the one conducted in Cleveland in which 10.4% MRSA strains were resistant to it. These included strains isolated from patients of cystic fibrosis who had history of prolonged antibiotic therapy 8. Although a study carried out in Karachi, Pakistan showed 100% susceptibility of MRSA isolates to linezolid 9. Cases have been reported in which strains developed linezolid resistance after taking a course of linezolid for MRSA treatment. Similar situation occurred in our patient in whom the culture of pus swab had revealed an MRSA strain that was susceptible to linezolid initially. However after about 10 days linezolid resistant strain of Staphylococcus haemolyticus was isolated from her wound pus swab. This strengthens the view point that prolonged admissions and antibiotic therapy leads to the development of multi-drug resistant strains of bacteria. The linezolid resistance has become a serious concern worldwide and is based on multiresistance gene cfr 10. This gene is located near plasmids in different strains of MRSA. The location of gene near the plasmids helps to spread the resistance against linezolid. We were not able to do sequence analysis of the isolate due to non-availability of the technique readily. However, this case should alert us to follow the infection control guidelines stringently. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Hashem AA, Abd El Fadeal NM, Shehata AS. In vitro activities of vancomycin and linezolid against biofilm-producing methicillinresistant staphylococci species isolated from catheter-related bloodstream infections from an Egyptian tertiary hospital. J Med Microbiol 2017; 66(6): Perez F, Salata RA, Bonomo RA. Current and novel antibiotics against resistant Gram-positive bacteria. Infect Drug Resist 2008; 1: Tarai B, Das P, Kumar D. Recurrent Challenges for Clinicians: Emergence of Methicillin-Resistant Staphylococcus aureus, Vancomycin Resistance, and CurrentTreatment Options. J Lab Physicians 2013; 5(2): Raad I, Alrahwan A, Rolston K. Staphylococcus epidermidis: emerging resistance and need for alternative agents. Clin Infect Dis 1998; 26: Peer MA, Nasir RA, Kakru DK, Fomda BA, Bashir G, Sheikh IA. Sepsis due to linezolid resistant Staphylococcus cohnii and Staphylococcus kloosii: First reports of linezolid resistance in coagulase-negative Staphylococci from India. Indian J Med Microbiol 2011; 29: Hannan A, Absar M, Usman M, Naeem T, Saleem S, Arshad M. In vitro activity of linezolid against clinical isolates of methacillin resistant Staphylocoocus. J Ayub Med Coll Abbottabad 2009; 21(1): Qureshi AH, Rafi S, Qureshi SM, Ali AM. The current susceptibility patterns of methicillin resistant Staphylococcus aureus to conventional anti staphylococcus antimicrobials at Rawalpindi. Pak J Med Sci 2004; 20: Endimiani A, Blackford M, Dasenbrook EC, Reed MD, Bajaksouszian S, Hujer AM, et al. Emergence of linezolid-resistant Staphylococcus aureus after prolonged treatment of cystic fibrosis patients in Cleveland, Ohio. Antimicrob Agents Chemother 2011; 55: Shariq A, Tanvir SB, Zaman A, Khan S, Anis A, Khan MA, et al. Susceptibility profile of methicillin-resistant Staphylococcus aureus to linezolid in clinical isolates. Int J Health Sci (Qassim) 2017; 11(1): Shen J, Wang Y, Schwarz S. Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. J Antimicrob Chemother 2013; 68: S209

213 Open Access Transradial Carotid Stenting With Bovine Arch Anatomy Case Report Pak Armed Forces Med J 2018; 68 (Suppl-1): S210-S11 TRANSRADIAL CAROTID STENTING IN A PATIENT WITH BOVINE ARCH ANATOMY Muhammad Nadir Khan, Tahira Muqaddas Army Cardiac Center, Lahore Pakistan ABSTRACT Carotid artery disease is a major cause of ischemic CVA. We report our experience in stenting of the left internal carotid artery (LICA) in patients with bovine arch, in which right brachiocephalic and left carotid share a common trunk from the aortic arch1. Keywords: Bovine arch, Carotid artery, Stenting. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Carotid artery stenting (CAS) is a widely used procedure to treat carotid artery stenosis, especially in patients at high risk for carotid challenges to the procedure. CASE REPORT A 85 years old lady with underlying HTN, DM and IHD came with sudden transient loss of Figure: 1-Bovine arch, 2-Stenosis of LCCA, 3-Distal protection device in LICA, 4-Post stenting result. endarterectomy (CEA) 2. Outcomes of the SAPPHIRE trial demonstrated the equivalence of CAS to CEA in patients considered at risk for complications. The bovine arch introduces new Correspondence: Dr Muhammad Nadir Khan, Associate Professor, Army Cardiac Center Lahore Pakistan yesnadirkhan@gmail.com left eye vision. She has history of TIA in form of Rt hemiplegia, which recovered after 12 hours about 4 weeks before admission. She had normal visual acuity at time of examination and rest of the physical examination was also unremarkable. Duplex USG of carotid arteries showed 70 to 80% left carotid bulb stenosis. Echo was normal. S210

214 Transradial Carotid Stenting With Bovine Arch Anatomy Pak Armed Forces Med J 2018; 68 (Suppl-1): S210-S11 CT scan of brain showed left MCA infarct. CT angiography neck confirmed the lesion in Left carotid bulb causing 70-80% stenosis but missed to show bovine arch anatomy. An 8F arterial sheath was inserted via the right femoral artery. The RCCA was directly engaged by the 6 F diagnostic catheter. Right carotid angiography was normal. Catheter or wire could be crossed into the left common carotid artery. JB 3 diagnostic catheter was used to define the anatomy of the left carotid which showed a bovine arch in figure. The LCA was originating from the Brachiocephalic artery. There was 70% stenosis before the bifurcation of the LCA. We tried to place a inch guide wire in the LCA but were not successful. Another inch Hydrophilic guidewire was placed in the LCA but it would prolapse into the Aorta once guide catheter was advanced. A inch PTCA guidewire was then advanced into the LCA and the guide catheter was advanced over it with the help of a inch guidewire but again the PTCA guidewire prolapsed into the Aorta. It was decided to approach the LCA from the right radial artery with a sheathless technique. A 6F radial sheath was passed in the right radial artrery. A inch PTCA guidewire was advanced through the right radial sheath into the Aorta. The 6F arterial sheath was removed and manual pressure was applied over the right radial artery for temporary haemostasis. A 2.5 x 15 mm Balloon was inflated ahead of the 8F guide catheter and the whole assembly was advanced over the PTCA guidewire until the guide catheter reached the ostium of the LCA. Then a inch wire was placed in a 5 French Heart Rail catheter and both were advanced in the 8F guide catheter till the wire and the child catheter reached LCA. The 8F guide catheter was then telescoped over the 5F catheter till it finally reached the LCA. A 7.5 mm Accunet distal protection device was deployed in the straight portion of the LICA distal to the lesion. IV 0.5 mg of atropine was given before stenting and before post dilatation. Direct stenting of the lesion was performed with a 7-10 x 40mm self-expandable Acculink stent. It was post dilated with a 5.0 x 15 mm NC at 12 atm balloon with good end result. The distal protection device was removed. Post procedure view showed no residual stenosis. Pt developed mild transient weakness of right leg on 2nd day which improved within 24 hours. DISCUSSION The Bovine arch occurs in 13% of population. Transfemoral approach is still the most common route for carotid angiography 3 and stenting LICA stenosis with Bovine arch anatomy can be approached by right arm approach 4 and it is still possible to proceed with carotid stenting using our novel sheathless guide advancement technique which is reproducib 5. This method of advancing guiding catheter is useful and safer than others for carotid artery stenting. CONFLICT OF INTEREST This study has no conflict of interest to be declare by any author. REFERENCES 1. Barbiero G, Cognolato D, Casarin A. Carotid artery stenting in difficult aortic arch anatomy with and without a new dedicated guiding catheter: preliminary experience. Eu Radiol 2013; 23: Piero M, Stefano G, Paolo M, Daniela T, Franco F, Alessandro L, et al. Carotid Artery Stenting in Patients With Left ICA Stenosis and Bovine Aortic Arch: A Single-Center Experience in 60 Consecutive Patients Treated Via the Right Radial or Brachial Approach. JEVT 2014; 21(1): Giorgio V, Giuseppe BZ, Guido B. Choose the Appropriate Access Route in Bovine Arch and You Will Turn a Complex Left Carotid Artery Stenting Procedure Into a Simple One. JEVT 2014; 21(1): Giorgio V, Giuseppe BZ, Filippo M, Francesco L, Leonardo B, et al. A Tailored Approach to Overcoming Challenges of a Bovine Aortic Arch During Left Internal Carotid Artery Stenting. JEVT 2012; 19(3): Wei-Chieh L, Hsiu-Yu F, Huang-Chung C, Shu-Kai H, Chih- Yuan F, Chien-Jen C, et al. Comparison of a Sheathless Transradial Access With Looping Technique and Transbrachial Access for Carotid Artery Stenting. JEVT 2016; 23(3): S211

215 Open Access Dual LAD Coronary Artery Case Report Pak Armed Forces Med J 2018; 68 (Suppl-1): S212-S14 DUAL LAD CORONARY ARTERY - A RARE CONGENITAL ANOMALY Hamza Iqbal, Imtiaz Ahmed Chaudhry, Muhammad Imran Asghar Army Cardiac Centre Lahore Pakistan ABSTRACT Coronary anomalies are one of the most common cardiovascular causes of sudden death in young patients 3, although the dual LAD remains a benign one. Dual LAD involves two distinct segments of LAD artery - Short and Long - that occupies the anterior interventricular septum. Until now, ten different variants of dual LAD system have been reported in different studies. Keyword: Left Anterior Descending, Computed tomography angiography, Non ST elevation myocardial infarction. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Dual Left Anterior Descending (LAD) coronary artery is a rare congenital anomaly. The reported incidence of dual LAD is approximately % in various coronary angiographic studies 1,2. Coronary anomalies are one of the most common cardiovascular causes of sudden death in young patients 3, although the dual LAD remains a benign one. Dual LAD involves two distinct segments of LAD artery - Short and Long - that occupies the anterior interventricular septum. Until now, ten different variants of dual LAD system have been reported in different studies. We are reporting type-1 dual LAD system. In this, the main LAD originates from the left main coronary artery which then bifurcates into short and long LAD. Short LAD runs in the anterior interventricular groove, giving rise to septal perforator and ends in the proximal anterior interventricular groove. The long LAD also runs in the anterior interventricular groove, descends on the left ventricular side of it, giving rise to LV diagonals, and then reenters the distal anterior interventricular groove down till apex. CASE REPORT Fifty five years old, male, hypertensive patient presented in the emergency department with typical chest pain. Electrocardiograph showed t-wave inversion in anterior chest leads. Correspondence: Dr Imtiaz Ahmed Chaudhry, Army Cardiac Centre, Lahore Pakistan imtiazchaudhry@gmail.com Trop-T was positive. He was diagnosed as having Non ST elevation myocardial infarction. Transthoracic echocardiography showed fair left ventricular systolic function. No wall motion abnormality was noticed. He underwent coronary angiography that revealed dual LAD system (fig-1 & 2) with critical lesion in LAD and left circumflex coronary artery. Patient was planned for CABG surgery. Conventional CABG Figure-1: Dual LAD 1. was done; LIMA was anastomosed to long LAD, saphenous vein graft to short LAD and obtuse marginal artery. Patient made an uneventful recovery and was discharged on 6th postoperative day. DISCUSSION Malformation during the formation of cardiac sinusoids, coronary budding on aortopulmonary trunk and connection between the two systems may lead to development of coronary artery anomalies 4. Coronary artery anomalies, predominantly in the male population, are uncommon findings during S212

216 Dual LAD Coronary Artery Pak Armed Forces Med J 2018; 68 (Suppl-1): S212-S14 coronary angiography with incidence rate of 0.64 to 1.3% 1,2. Often it causes no signs and symptoms, but can lead to sudden cardiac death. According to the Sudden Death Committee of the American Heart Association, coronary anomalies are responsible for 19% of death in athletes 5. Coronary CT angiography remains the primary imaging modality for evaluation of coronary artery anomalies in recent years. The course of LAD is almost constant amongst all other major coronary arteries 6. It courses in the anterior interventricular groove down towards the apex and gives off septal perforators to the interventricular septum and diagonal branches to the anterior wall of the left ventricle. Dual LAD was first described and classified by Spindola- Franco et al in Four subtypes of dual LAD system were reported. In type 1-3, both short and long LAD originates from the left main coronary artery. Short LAD travels along the proximal part of the anterior interventricular groove but stops well short of the apex (short LAD), long LAD artery joins the anterior interventricular groove distally and reaches the apex after originating elsewhere (long LAD) as shown in fig-3. In type 4 dual LAD, short LAD is formed by the LAD proper, whereas the long LAD originated from the right coronary artery that later enters into the anterior interventricular groove. Type 3 dual LAD system was the least common that was reported by Spindola-Franco et al, with only one of twenty three cases described 7. In the dual LAD system, short LAD give rise to septal perforators and the diagonals originates from the LAD proper or long LAD. In our case, the left main coronary artery originates from the left coronary sinus which divides into left anterior descending artery and left circumflex artery. LAD proper then bifurcates into short and long LAD. Short LAD gave septal perforator branches and terminated higher up in the anterior interventricular groove, whiles the long LAD gives diagonal branches and enters late in the anterior interventricular groove. The long LAD was epicardial and towards the left ventricular side. These fndings were consistent with type 1 of dual LAD system that was described by Spindola-Franco s classification. One of the positive attribute suggested of dual LAD system is that in case of significant atherosclerotic disease the binary distribution may limit the extent of ischemic insult to the myocardium 8. It is extremely important for a surgeon to know the exact coronary anatomy especially when considering anomalous origin and course Figure-2: Dual LAD 2. Figure-3: Dual LAD 3. of anomalous LAD and the variants of dual LAD system before proceeding with any intervention. Lack of this knowledge may lead to incomplete revascularization of the anterolateral wall or the interventricular septum. The presence of short LAD can be mistaken for total mid-lad occlusion. In case if both the LADs are critically diseased, graft to both vessels is important to revascularize anterolateral wall, interventricular septum and apex. S213