Myocardial Damage in Successful Single Vessel Coronary Angioplasty as Assessed by Creatinine Kinase and its Myocardium Band Isoenzyme Levels

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1 ORIGINAL ARTICLE Myocardial Damage in Successful Single Vessel Coronary Angioplasty as Assessed by Creatinine Kinase and its Myocardium Band Isoenzyme Levels Shahid Abbas, Farhan Tayyab, Naseer Ahmed Samor, Muhammad Shabir and Azhar Mahmood Kayani ABSTRACT Objective: To determine the frequency of myocardial damage in elective, successful, single vessel percutaneous coronary angioplasty by assessing myocardial band (MB), creatinine kinase levels and to find out the association of common modifiable risk factors with myocardial damage in patients undergoing single vessel coronary angioplasty. Study Design: Descriptive. Place and Duration of Study: Armed Forces Institute of Cardiology / National Institute of Heart Disease, Rawalpindi, from September 2006 to September Patients and Methods: Fifty patients undergoing elective and successful single vessel percutaneous coronary angioplasty were evaluated with creatinine kinase and creatinine kinase MB levels before and after 8 hours and 1 st day following coronary angioplasty. Studied variables included the length of stent deployed, maximum deployment pressure and total balloon inflation time, apart from hypertension, cholesterol level, smoking and diabetes mellitus. Results: Out of 50 patients, 9 had raised creatinine kinase at 8 hours (18%) and 10 had raised creatinine kinase (20%) on 1 st day following coronary angioplasty, 7 (14%) patients and 8 (16%) patients had raised creatinine kinase MB levels at 8 hours and 1st day following coronary angioplasty respectively. The rise of either was equal to or more than 3 times the normal limits. Modifiable risk factors, significantly associated with myocardial damage, were diabetes mellitus (p=0.006) and LDL levels (p=0.009) in patients undergoing single vessel coronary angioplasty. Conclusion: Successful elective, uncomplicated, single vessel coronary angioplasty resulted in some myocardial damage evident by mild rise in cardiac enzymes but rise of creatinine kinase MB above 3 times of normal, which signifies percutaneous coronary angioplasty-related myocardial infarction, was not seen. There was a significant association between diabetes mellitus, LDL levels and myocardial damage in patients undergoing coronary angioplasty but no significant association was found between hypertension, smoking and myocardial damage. Key words: Creatinine kinase MB. Stents. Angioplasty. INTRODUCTION Percutaneous coronary angioplasty is one of the most widely practiced invasive procedures for myocardial revascularization. Drug-eluting stents have further reduced angina, re-stenosis and long-term morbidity. In spite of these advances, raised levels of cardiac enzymes have been reported in 5-30% of successful precautious coronary interventions suggesting myocardial damage and cell death. 1-3 Most patients, though asymptomatic with no changes in cardiac functions, have raised levels of cardiac markers, which are directly proportional to the extent of myocardial damage and are associated with increased long-term mortality and morbidity. 3-5 Rise of enzyme creatinine Department of Adult Cardiology, Armed Forces Institute of Cardiology/National Institute of Health Diseases, Rawalpindi. Correspondence: Maj. Dr. Shahid Abbas, Resident Cardiologist, VIP Ward, Armed Forces Institute of Cardiology/ National Institute of Health Diseases, Rawalpindi. shahabbas0@gmail.com Received October 30, 2007; accepted February 7, kinase (CK) and enzyme creatinine kinase MB (Myocardium Band an isoenzyme) by more than 5 times the normal values following percutaneous coronary angioplasty is associated with worse prognosis. 6-9 Cardiac markers level rise after the percutaneous coronary angioplasty reaching peak on day 1. Troponin-T or I levels rise after percutaneous coronary angioplasty ranges from 13-44% depending on the number of stents used Troponins T and I are more sensitive than CK-MB for detection of minor myocardial damage after percutaneous coronary angioplasty Increased cardiac troponins postprocedurally were seen in one-third of a stable patient population undergoing elective percutaneous coronary angioplasty and were independently and significantly predictive of an increased risk of adverse events at 18 months, mostly in the form of repeat percutaneous coronary angioplasty. 16 Follow-up for all cause mortality following first year after stent deployment revealed that unsuccessful procedure was the key event, which decided the postprocedural mortality. 17 It has been established beyond doubt that any increase in enzyme creatinine kinase MB after 142 Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (3):

2 Myocardial damage assessment by CK-MB assessment percutaneous coronary angioplasty is associated with statistically and clinically significant increase in the subsequent risk of death. 18 In addition to that, it is more economical in the local setup to follow creatinine kinase MB levels than the troponin-t or I levels. The current definition of myocardial infarction given by Joint ESC/ACCF/AHA/WHF Task Force for the re-definition of myocardial infarction has designated elevation of cardiac biomarkers greater than 3 times of 99 th percentile upper reference limit as defining percutaneous coronary angioplasty-related myocardial infarction. 19 No data exists on the postcoronary angioplasty rise of creatinine kinase and creatinine kinase MB fraction in our setup. The purpose of this study is to measure creatinine kinase and creatinine kinase MB fraction, after successful stent deployment and find out the relationship of myocardial damage with percutaneous coronary angioplasty. Furthermore, the association of common modifiable risk factors (hypertension, diabetes mellitus, low density lipoproteins level and smoking) with myocardial damage was evaluated in patients undergoing single vessel coronary angioplasty. This information will be the platform to carry out further studies to make the process of stent deployment as myocardial friendly as possible. PATIENTS AND METHODS In the period from September 2006 to September 2007, 50 patients were evaluated, while undergoing elective and successful percutaneous coronary angioplasty carried out at Armed Forces Institute of Cardiology/ National Institute of Heart Disease, Rawalpindi. It was a descriptive study and non-probability convenient sampling technique was utilized for collection of relevant blood samples. Inclusion criteria were presence of typical stable effort angina, positive stress test (ECG, stress echocardiogram or nuclear scan) and indication for angioplasty. Exclusion criteria were acute myocardial infarction (< 3 months), unstable angina, any rise of cardiac enzymes at presentation, and left ventricle ejection fraction of < 30%. Patients having a significant side branch artery (> 2.5 cm) at the target lesion, co-morbidity state like renal failure with creatinine of > 3 mg, refractory diabetes mellitus, hypertension or chronic obstructive airway disease were excluded. Patients who developed instant thrombosis during the procedure evident by clinical presentation and ECG changes were confirmed by re-angiography and excluded from the study. Angiographic success was defined as final angiographic residual stenosis of < 20% by visual estimation. Standard drug regimen was given to all patients before the procedure. All patients underwent coronary angioplasty from right femoral approach. Multiple views were taken to localize the target lesion. Patients with target lesion of more than 60% on quantitative angiography were selected and percutaneous coronary angioplasty with stenting was carried out. Postpercutaneous coronary angioplasty stenosis of < 20% in the target vessel was accepted. The length of the stent deployed, maximum deployment pressure along with relevant details regarding predilatation and postdilatation were recorded. Creatinine kinase and creatinine kinase MB were measured before, after 8 hours and 24 hours of percutaneous coronary angioplasty on centrifuged serum by immuno-inhibitory assay for quantitative invitro determination using HITACHI 911 clinical chemistry analyzer. Fasting lipid profile was carried out before the coronary angioplasty to evaluate Low Density Lipoprotein (LDL) levels by calculated parameter method using HITACHI 911/ SELECTRA 2 equipment. The ECG was recorded before, just after and 24 hours after the percutaneous coronary angioplasty and evaluated by an experienced cardiologist who was unaware of the test results. A detailed performa was filled from each patient covering the necessary variables. Details of percutaneous coronary angioplasty and its result were recorded for every case. Data was expressed as means + standard deviation for continuous variables and as frequencies for categorical variables using SPSS. The association of certain risk factors (hypertension, diabetes mellitus, LDL levels and smoking) and raised creatinine kinase levels was calculated along with statistical significance using Pearson chi-square tests. Informed written consent was taken from each patient and the study details were explained to the patient in the language that he understood. The study was approved by ethical committee of Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi. RESULTS All patients were over 20 years of age and target lesions had a stenosis of more than 60% by visual quantitative angiography. All percutaneous coronary angioplasties were elective and successful. Some of the variables are shown in Table I. All patients had normal renal functions as evaluated by serum creatinine measurement, the day before percutaneous coronary angioplasty and had normal values of serum creatinine/creatinine kinase MB before percutaneous coronary angioplasty. Table I: Selected demographic variables of the study population (n=50). Age (years) and range 52.3 (35-74) Gender (M/F) 45/5 Previous MI n (%) 24 (48%) CABG n (%) 1 (2%) Treated hypertension n (%) 11 (22%) Diabetes mellitus n (%) 15 (30%) Smoking n (%) 13 (26%) Prior PTCA n (%) 05 (10%) PTCA = Primary coronary angioplasty. Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (3):

3 Shahid Abbas, Farhan Tayyab, Naseer Ahmed Samor, Muhammad Shabir and Azhar Mahmood Kayani There were no in-hospital major complication (death or need for urgent re-vascularization) in the study. As is obvious in Table II, out of 50 patients, 9 had raised creatinine kinase at 8 hours (18 %) and 10 had raised creatinine kinase (20%) at 1st day following coronary angioplasty. Whereas, 7 (14%) patients and 8 (16%) patients had raised creatinine kinase MB levels at 8 hours and 1 st day following coronary angioplasty respectively. Considering the target lesion, 2 (4%) patients of type-a target lesion had raised creatinine kinase MB levels as compared to 1 (2%) patients of type-b lesion and 3 (6%) patients of type-c target lesions, 8 hours following percutaneous coronary angioplasty. Similarly, 3 (6%) patients of type-a target lesion had raised creatinine kinase MB levels as compared to 3 (6%) patients of type-b lesion and 2 (4%) patients of type-c target lesions on first day following percutaneous coronary angioplasty. Raised creatinine kinase MB was seen in 15 patients with diabetes mellitus (30%), 11 patients with hypertension (22%) and 13 patients were smokers (26%). No patient showed rise of either enzyme by more than 5 times above the normal limits. There was a significant association between diabetes mellitus and raised creatinine kinase MB levels (p=0.006) in patients undergoing coronary angioplasty. Similarly, there was significant association between raised LDL (low density lipoprotein) levels and raised creatinine kinase MB levels (p=0.009) in patients association was found between hypertension (p=0.57), smoking (p=0.34) and raised creatinine kinase levels (Table II). In patients with raised creatinine kinase MB levels following percutaneous coronary angioplasty, the average length of stent deployed was 23 mm (ranging from mm) in comparison with 25 mm (ranging from mm) in patients with normal creatinine kinase MB levels following percutaneous coronary angioplasty (Table III). The average balloon inflation time in patients with raised creatinine kinase MB following percutaneous coronary angioplasty was 19.3 seconds (ranging from seconds) whereas, in the patients with normal creatinine kinase MB levels, following percutaneous coronary angioplasty, it was 17 Table II: Cardiac enzyme characteristics and association with risk factors. At 8 hrs of PCI At 24 hrs of PCI n (%) n (%) No of cases with raised CK 9 (18%) 10 (20%) No of cases with raised CK- MB 7 (14%) 8 (16%) Risk Factors No of pts with raised CK-MB p-values* at 24 hrs following PCI n (%) Smoking 13 (26%) 0.34 Hypertension 11 (22%) Diabetes mellitus 15 (30%) Raised LDL levels 16 (32%) *p value < 0.05 is statistically significant ; PCI=Percutaneous coronary intervention; CK=Creatinine kinase; CK-MB=Creatinine kinase MB fraction. Table III: Comparison of creatinine kinase MB levels at 24 hours with procedure variables. CK- MB Average Average balloon Pre-dilation Post- Maximum levels stent length inflation time n (%) dilation deployment (range) seconds (range) n (%) pressure bars (range) Patients with raised levels n=8 23 (12-31) 19 (14-20) 3 (37) 5 (50) 22 (9-22) Patients with normal levels n=42 25 (12-56) 17 (14-20) 25 (59) 21 (50) 18 (12-18) CK-MB Creatinine kinase MB fraction at 24 hours. seconds (ranging from seconds). In patients with raised creatinine kinase MB levels following percutaneous coronary angioplasty, 3 (37%) patients and 4 (50%) patients had pre-dilatation and postdilatation respectively. In patients with normal creatinine kinase MB levels following percutaneous coronary angioplasty, 25 (60%) patients and 21 (50%) patients had pre-dilatation and postdilatation respectively. The maximum balloon inflation pressure in the raised creatinine kinase MB levels following percutaneous coronary angioplasty was 22 bars (ranging from 9-22 bars) in comparison with 18 bars (12-18 bars) in patients with normal creatinine kinase MB levels following percutaneous coronary angioplasty. Intra-aortic balloon was placed in one patient and 22 (44%) patients were administered Gp IIb IIIa inhibitors during coronary angioplasty. Out of the total, 3 (6%) patients had transient-t inversions in anterior leads, which reverted to normal on 1 st day following coronary angioplasty but no rise of creatinine kinase or creatinine kinase MB was seen in those patients. DISCUSSION Creatinine kinase MB is a purely cytosol enzyme mainly in myocardium. It may start to rise in few hours after an ischemic event but minor myocardial injury like unstable angina can be associated with release of creatinine kinase MB. It has a half life of hours and returns to normal value in hours after myocardial infarction. 20 In this study, 20% and 14% patients had raised creatinine kinase levels after 8 hours and at 1st day following single vessel coronary angioplasty respectively. Similarly, 12% and 16% patients had raised creatinine kinase MB after 8 hours and 1st day following single vessel coronary angioplasty respectively. None of the patient had rise of creatinine kinase MB by more than 3 times of normal. During successful single vessel coronary angioplasty, there was some myocardial damage evident by mild increase of cardiac enzymes but since rise of creatinine kinase MB fraction was no greater than 3 times the normal range, which could signify worse prognosis. This may have been observed because patients with a significant side branch artery (> 2.5 cm) at the target lesion site were excluded. 144 Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (3):

4 Myocardial damage assessment by CK-MB assessment Similarly, complicated coronary interventions (intracoronary dissections, stent stenosis and perforations) were also not included in the study. There was a significant association between diabetes mellitus, LDL levels and myocardial damage in patients association was found between hypertension, smoking and myocardial damage following single vessel coronary angioplasty. It emerges that deployed stent length or pre-dilatation has no correlation with raised creatinine kinase MB levels following coronary angioplasty but maximum stent deployment pressure and average balloon inflation time is correlated with raised creatinine kinase levels. However, this correlation observed was not statistically significant. Karim 12 et al. selected 25 patients undergoing single vessel percutaneous transluminal coronary angioplasty involving one vessel dilatation. They reported elevated creatinine kinase MB levels in 16% and 28% just after and at 1st day following transluminal coronary angioplasty respectively. They further claimed higher diagnostic sensitivity of troponin-t than creatinine kinase but it is difficult to decide whether their results represented reversible or irreversible ischemia. In a similar study, Ravkilde 11 et al. reported raised creatinine kinase MB in 6 of 23 (26%) patients following coronary angioplasty while evaluating every 6 hours for 48 hours and then after on 4th and 8th day. As expected strategies which reduce the peri-procedural myocardial damage by anti-thrombotic, anti-inflammatory measures and prevention of embolization decrease the periprocedural myonecrosis. 21 Addressing the same issue Cutlip 22 et al. debated that the low to moderate level creatinine kinase MB elevation does not predict the mortality but the peri-procedural complications decide the future outcome. It seems that during single vessel coronary angioplasty, the myocardial damage is usually small but clinically significant. 11,15 A meta analysis of seven studies with creatinine kinase MB measurements and subsequent mortality was carried out, which showed an increase in creatinine kinase MB after coronary angioplasty, which was associated with small but statistically and clinically significant increase in mortality following the procedure. 18 ECG is comparatively insensitive in detecting minor irreversible myocardial injury. Likewise, only 3 of the present patients had transient non-specific ST changes. The transient ECG changes can not be fully explained but myocardial stunning can be a possibility. It can be safely commented that in majority of cases only a small release of myocardial enzymes can be detected without ECG changes or cardiac function impairment. This study was a single-center non-randomized small selective patient study having a limited statistical power to detect a significant difference in creatinine kinase MB levels in patients undergoing coronary angioplasty. Furthermore, only single vessel coronary angioplasty has been studied that also in the absence of a major off shoot branch at the lesion. Still, this study can provide a framework and a platform for a bigger larger prospective study on patient undergoing variety of stent deployment in bonanza of circumstances. Larger patient population with multi-vessel stenting can unveil the true significance of myocardial enzymes and their prognostic implications. CONCLUSION We concluded that successful elective, uncomplicated, single vessel coronary angioplasty results in some myocardial damage evident by mild rise in cardiac enzymes but rise of creatinine kinase MB above the 3 times of normal, which signifies percutaneous coronary angioplasty related myocardial infarction is not seen. There was a significant association between diabetes mellitus, LDL levels and myocardial damage in patients association was found between hypertension, smoking and myocardial damage following single vessel coronary angioplasty. REFERENCES 1. Califf RM, Abdelmeguid AE, Kuntz RE, Popma JJ, Davidson CJ, Cohen EA, et al. Myonecrosis after revascularization procedures. J Am Coll Cardiol 1998; 31: Klein LW, Kramer BL, Howard E, Lesch M. Incidence and clinical significance of transient creatinine kinase elevations and the diagnosis of non-q wave myocardial infarction associated with coronary angioplasty. 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