Introduction. Al Kindy Col Med J 2013; Vol. 9 No. 1 P: 36. Al Kindy Col Med J 2013; Vol. 9 No. 1 P:36

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1 among beta-thalassemic major patients in ibn al-baladi thalassemia center-baghdad Dr. SuhadJassim Mohammed M.B.Ch.B, F.I.C.M.S(Com.Med.) Dr.FarisH.Al-LamiM.B.Ch.B,M.Sc,Ph.DDr.MousaQasim Hussein M.B.Ch.B, M.D, F.I.C.M.S (Int.Med.) Background :Thalassemia is an autosomal disease of the haemoglobin. Two types of thalassemia are recognized: thalassemia major and thalassemia intermedia. The most serious cardiac complication in thalassemia major is due to multiple blood transfusions rather than the disease itself, which is due to iron overload. Cardiomyopathy is the most common cardiac defect that occurs with iron overload. Pricarditis, congestive heart failure and arrhythmias are due to hemosidrosis and chronic aneamia. Aim of the study: to demonstrate the prevalence and types of electrocardiographic changes among thalassemic patients with aged over ten years old. Methods :The study is a cross sectional study conducted in Thalassemic center in Ibn Al-Baladi Hospital/Resafa Directorate of Health/ Baghdad during the period of December/ 1 st /2010-May/ 30 th/ Data collection was carried out using a questionnaire included basic demographic data clinical and epidemiological variables, and filled through direct interview with the patients or their relatives. ECG record for every patient, and then Introduction B eta thalassemia is a genetic disorder with mutations in the globin gene that reduce or abolish globin protein production(1). The thalassemic syndromes range from subclinical to life-threatening, depending on the number and severity of the genetic defects (2)). The disease causes anemia of variable severity which becomes manifested in early childhood. Most patients have the severe form of the disease referred to as thalassemia major, characterized by lifelong blood transfusion dependance. A smaller proportion of patients have a milder form of the disease known as thalassemia intermediate, in which there is only moderate anemia, with minimal or no transfusion required (3). The most serious cardiac abnormalities in B- thalassemia major, often eventually fatal, are due to the treatment of disease with multiple blood transfusions (which are required to Abstract evaluated for any abnormalities by consultant cardiologist. Results:The total number of Thalassemic patients in the study was 180 cases; overall prevalence of electrocardiographic changes was (61.7%). (38.3%) were in the age group years. Seventy five percentages have thalassemia major. About (73%) were on irregular treatment with desferal. Most electrocardiographic changes are with tachycardia (52.25%) and (29.7%) have left ventricular hypertrophy. Conclusion Electrocardiographic changes were higher in the age group years (65.2%) were males, and (69.4%)females. Electrocardiographic changes affect about two thirds of thalassemia patients, and the most common types were the tachycardia, and left ventricular hypertrophy. Key words: Electrocardiography, Betathalassemia major Al Kindy Col Med J 2013; Vol. 9 No. 1 P:36 maintain life) rather than the disease itself. These blood transfusions, plus increased gastrointestinal absorption, result in an iron overload state which leads to myocardial iron deposition, causing a restrictive cardiomyopathy, cardiac enlargement, ventricular dysfunction, and congestive heart failure. Arrhythmias, (atrial and ventricular tachycardia and bradyarrythmias, particularly involving atrioventricular block) may result from this cardiomyopathy or from hemosidrosis-related damage to the conduction system. Pericarditis is also commonly seen (2). Pulmonary hypertensions and right ventricle failure have been reported (4). Iron metabolism and its derangements, may have profound effects on the cardiovascular system.. Cardiac dysfunction is a primary cause of death in people with iron overload(5). Cardiac cells are particularly sensitive to oxidant-mediated injury because they must perform a number of complex functions, which include contraction and transmission Al Kindy Col Med J 2013; Vol. 9 No. 1 P: 36

2 of electrical impulses, with iron loading, cardiac cells in the culture begin to fail, including loss of their characteristic pattern of beating. Desferrioxamine, a powerful iron chelatingagent that binds iron in the culture and prevents generation of reactive oxygen species by the Fenton reaction, can restore normal cellular activity (6). Aim of the study To demonstrate the prevalence and types of electrocardiographic changes among patients with thalassemia aged over ten. Methods Study Design: A cross sectional study. Setting: The study was conducted in thalassemic unit in Ibn Al-Baladi Hospital/ Resafa Directorate of Health/ Baghdad. Data collection Time: Data collection was carried out for four hours a day, three days a week over the period of December/ 1 st /2010-May/ 30 th/ Study Group: All male and female thalassemicmajor patients aged ten years or over who attended the thalassemic unit in Ibn Al-Baladi Hospital during the allocated time for data collection and who accept to participate were induced in the study. Data collection method: A structured questionnaire developed and filled by the researcher through direct interview with participated thalassimic patients, their attending relatives and the treating physicians. The questionnaire includes questions to gather information on history of the diseases, family history of the thalassemia, other inherited diseases, whether the patients had other co-morbid illnesses or surgical operations. The questionnaire also included information on the type of thalassemia of the patient (classified as major or intrmedia). The clinical manifestations were assessed (pallor, dyspnea, chest pain, hepatomegaly, spllenomegaly or spleenoctomy). The history of desferal therapy was classified as regular or irregulardepending on the patient's subjective response. ECG record was done for every case which was evaluated for any abnormalities by consultant cardiologist. Electrocardiographic criteria of LVH: 1. Voltage R- wave in V5orV6 27 mm. S in V1+ R in V5 orv6 over 35mm. 2. STsegment depression and T wave inversion inv QRS interval may be prolonging over 0.1 second in V5-6. Sinus tachycardia is a regular sinus rhythm with a rate in excess of 100 beats / minuet. First degree heart block P-R interval greater than 0.21 second(7). Statistical analysis: Statistical Package for Social Sciences (SPSS) version (16) was used for data entry and data analysis. The data were grouped and tabulated. Frequency data were tested using chi square test of independence. P value less than 0.05 considered significant. Results The total number of thalassemic patients in the study was 180 cases. Regarding the age distribution, we found that the major proportion is in the age group years (38.3%), and then it declined in other age groups. Those above 30 years represented only (6.7%). Regarding gender, the male to female ratio is (1.12:1). [Table 1]. Table (1): Distribution of the study group according to age and gender: Demographic variable N (180) % Age Sex > Male Female Al Kindy Col Med J 2013; Vol. 9 No. 1 P:37

3 The majority of the cases had thalassemia major (75.0%), the remaining had thalassemia intermedia (25.0%). Regarding desferal therapy, 48 cases only were on regular treatment (27.0%). About (77%) of the cases had pallor, (21.5%) had dyspnea. About (60%) had speenomegally, and (60.8%) had hepatomegally [Table 2]. Table (2): Distribution of the study group by characteristics of the disease Characteristic of disease N(180) % Major Type of thalassemia Intermedia History of desferal therapy Symptoms and signs Regular Irregular Pallor Dyspnea Chest pain Spleenpmegaly 109* 60.2 Hepatomegaly *Patients with spleenectomy were excluded Table (3) demonstrated the distribution of the study group by co-morbid diseases. Only 26 (14.4%) have certain co-morbid illnesses, includingtwelve (46.2%) had DM, 8 had heart failure (30.8%) and 3 had sickle cell anemia (11.5%) and 3 had HT (11.5%). [Table 4] Table (3) Distributions of study group by co-morbid diseases Disease N (26) % DM HT HF Sickle cell anemia Table (4) shows the distribution of the study group by presence of ECG change. The overall prevalence of ECG changeswas evident in 111 patients (61.7%). Table (4): Distribution of the study group by presence of ECG changes ECG change N (180) % Present Absent Regarding the type of ECG changes, we found that 58 cases had tachycardia (52.25%), 33 had LVH (29.7%)and 25 had T-wave changes (22.5%). Only one case had first degree Heart block(0.9%) [Table 5]. Table (5): Distribution of the study group by type of ECG changes ECG change N (111) % Tachycardia LVH T-wave changes Heart block(1 st degree) Table (6) shows the distribution of the study group by ECG changes with sociodemographic variable. More than half of the males have positive ECG changes (54.3%), Al Kindy Col Med J 2013; Vol. 9 No. 1 P:38

4 while the percentage was higher in female patients (69.2%). There is a statically significant association between gender and ECG changes (P =0.043) [table 9]. The highest proportion of cases with ECG changes was among those aged years (65.2%), and those aged years (64.7%).While it was (50%) among the other two groups. No statically significant association was found between age and ECG changes(p= 0.690) [table 6]. Table (6): Distribution of the study group by ECG changes with age and gender ECG change Total present Absent Demographic variable N % N % N % (111) (69) sex male female Age > Chisquare P value Table (7) shows the distribution of study group by presence of ECG changes and certain characteristics of disease. More than (64%) of those with thalassamia major had ECG changes compared to (53.3%) of those with thalassemia intermedia. No statistical significant association was found between types of the thalassemia and ECG changes (P=0.184) [table 10]. About (65%) of those with irregular desferal therapy had ECG changes compared to (54.2%) of those with regular desferal therapy. No statistical significant association was found between type of the thalassemia and ECG changes (P=0.212)[table 7]. Regarding the association between the signs and symptoms of thalassemia with presence of ECG changes, no statistical significant association was found. Similarly no statistical significant association was found between presence of ECG changes with presence of splenomegaly (P =.0165) or hepatomegaly (P= 0.077) [Table 7]. Table (7): Distribution of study group by ECG changes with characteristics of disease Characteristic of disease ECG changes total present Absent N N N % % % (111) (69) (180) Type of Major Thalasemia Intermedia Desferal Regular therapy Irregular Sign symptom and Chisquare P value Pallor Dyspnia Chest pain Spleenomega ly Hepatomegal y Discussion In this study, the age of our sample is over 10 years, because cardiac complications appear at this age. More than (66.6%) of Al Kindy Col Med J 2013; Vol. 9 No. 1 P:40

5 patients are less than 20 years and only (6.7%) over 30 years. This may reflect the poor survival of the patients till fourth decade of life. Engle1964, described increase in the heart size after 10 years of age with first degree heart block in one third of the patients (8). In this study,(52%) are males; many authors show similar male preponderance (2, 9). In this study, (75%)of the patients were of thalassemia major type, and most of the patients who were transfusiondependant are from this type. The extremely low level of regular desferal therapy may be explained by the fact that this therapy is not always available in the hospitals in a good amount to be given freely. Another finding was noted during the work in the unit, that the subcutaneous infusion pumps are available only to a limited number of patients, who used toreceive larger dose of desferal. Some studies revealed that proper use of desferalcan effectively decrease cardiac complications(10,11). The current study shows a relatively high proportion of patients with signs and symptoms of cardiac complications particularly dyspnea (21%). Among the nonspleenoctomized individuals, splenomegaly was quite common, and profound liver enlargement was also common among the whole study group. This is consistent with the findings of Anthanassios 1995(4). In this study, (61.3%) of thalassemic patients have abnormal ECG findings,(52.25%)were tachycardia,(29.7%)were LVH,(22.5%)were T-wave changes and 0.9% is first degree of heart block, however, Walter 1978(12) and Reza1972(13)demonstrated that the most common abnormalities in their patients were supraventricular arrhythmias. Engel 1964(31) showed that some of those patients developed acute pericaditis commonly stated at the age of 10 years for which no cause could be found. Non of our patients gave such clinical history but heart failure is found in eight of our patients (30.8%).Anna Ramazzotti et al 2008showed the ECG changes were read in about (45%)of the cases, and the most common finding in thalassemia major patients were T-wave inversion (27%), RBBB (12%) and flat T- wave( 7%)(14). Atuq M. et al, 2006 showed the presence of prolongedqtc interval (33%) patients,lvh in(47%) patients, and ventricular ectopic in (4%)patients one of whom arecoupled.25 (33%) patients had repolarization abnormalities with ST depression and flat T wave (15). It is stated that maintenance of the hemoglobin above 10 g/dl is good leading to normal life activity and make complication less (13,14 and 15). Hemoglobin level although low in many patients but was of no significance combined with ECG findings, proves that the amount of blood transfusion has the major inflict on cardiac function and the attempt to eliminate anemia may prevent further cardiac complication and this coincides with the finding of Keremasten1985 and his group who questioned the role of iron overload in the development of congestive heart failure and arrhythmias(16). In the current study, we found ECG abnormalities more in females than in males. Anna Ramazzatti et al 2008 found ECG change in (72%) female patients and (32%) in male patients (14). Pepe A. et al, 2009, found a significant correlation between the presence of myocardial fibrosis or necrosis and ECG changes.the most common findings in the patients were T-wave inversion, flat T wave and RBBB (17). The ECG could be a good marker to predict myocardial complication, ECG owing to its low cost as a guide for performing examination particularly in countries where there is high prevalence of patients with thalassemia and availability of cardiovascular magnetic resonance is poor (14, 17). Conclusion Around two third of thalassemic patients had some sort of ECG changes. Tachycardia and LVHare the most prevalent.it may be difficult to determine whether myocardial dysfunction is due to chronic anemia or to myocardial haemosiderosis,or combination of bothsince the majority of the cases were not on regular desferal therapy. Recommendations Al Kindy Col Med J 2013; Vol. 9 No. 1 P:41

6 1. Ensure availability of Desferal (chelating therapy) in the hospitals and enhance proper dose to the patients with subcutaneous pump. 2. Electrocardiogram and echocardiography should be available in thalassemic units/hospitals. 3. ECG monitoring approximately every 2 years until age 12 years, and then yearly or as clinical indication. 4. Health education of patients families to ensure their cooperation in long life treatment. References 1-Paritha Arumugam, punammalik.genetic Therapy For Beta- Thalassemia: from the bench to Bedside.Hematology2010: ; Doi /asheducation TopalEJ,Traill TA, Fortuin NJ. Hypertentive hypertrophic cardiomyopathy in the elderlyengl J Med 1985; 312: Gaasch WH, Quiones MA, WaisserE,etal.Diastolic compliance of the left ventricle in men.amjcardiol 1975; 36: Athanassios A., Georgios S., Vassilios S., et al.pulmonary Hypertension and Right Heart Failure in Patients with B-Thalassemia Intermedia. Chest1995; 107; Andrews NC: Disorder of iron metabolism. N Engl J Med, 1999; 341: Link G, Konijn AM, Hershko C; Cardio protective effect of alpha-tocopherol, ascorbate, deferoxamin, and deferiprone: Mitochondrial function in cultured, iron-loaded heart cell. J Lab Clin Med 1999; 133: Mervin J. Goldman, MD, Principles of clinical Electrocardiography, 11 1th edition Middle East Edition.Hypertrophypattern.Lang medical publications1982; chapter 8; Engl MA, ErlandsonM,Smith CA: Late cardiac complication of chronic severe refractory anemia with hemochromatosis. Circulation 1964; 30: Gilman JG,HuismanTH,etal:Dutch betathalassemia :a 10 Kilobase DNA deletion associated with significant gamma-chain production. Br J Hematology 1984; 56; Lawrence W. Nancy O, Darlene S, Steven C: Prevention of cardiac disease by subcutaneous desferroxamine in patients with thalassemia major. N Engle J Med 1985; 312/25; Levin a, R., Klein A.A: the cardiac manifestation of thalassemia major, natural history, non-invasive cardiac diagnosis studies and result of cardiac catheterization. Cardiovascular clinic 1998; 11(2): Walter L. Henry, Arthur W. Nienhuis: Echocardiographic abnormalities in patients with transfusion dependant anemia and secondary myocardial iron deposition Am J Med 1978; 64: Reza Gharib, Sharman Ayazi: Electrocardiographic finding in Iranian children with severe chronic anemia. Clinic Pediatric 1972; 11: Anna Ramzzooti, Aiessia, Pepe, VencenzaPasitano, Barbara Scattini, Maria F. Santerelli, Luigi Landini, Daneil. March: Standarized T2* map of normal human heart to correct iron overload and fibrosis in thalassemia intermedia versus thalassemia major patients and electrocardiogram change in thalassemia major patients. Hemoglobin, 2008; 32 (1-2): AtiqM,BanaM,Ahmed U S, Bano S, Yousuf M, FadooZ,Khurshid M. Cardiac disease in betathalassemia major: is it reversible? Singapore Med.J.2006; 47(8): Keremastin D.T., Toutouzas P.K., VyssoulisGP:Global and segmental ventricular function in B-thalassemia cardiology 1985;72(3): Pep A., Positano V., CapraM.et al: Myocardiovascular magnetic resonance in thalassemia major. Heart 2009; 95: Al Kindy Col Med J 2013; Vol. 9 No. 1 P:41 * Specialist doctor(com.med),directorate of medical operations and specialized services Ministry of Health-Iraq **Ass.professor-department of community Medicinen,Baghdad College Of Medicine University of Baghdad ***Ass. Professor-department of Internal Medicine,Al-Kindy College of Medicine University of Baghdad Al Kindy Col Med J 2013; Vol. 9 No. 1 P:42