EFFECTS OF VITAMIN D SUPPLEMENTATION ON THE ELECTROCARDIOGRAPH RECORDS OF PATIENTS WITH BETA THALASSEMIA MAJOR: AN OPEN-LABEL RANDOMIZED CLINICAL TRIAL
Raz M. HamaSalih a and Marwan S.M. Al-Nimer b
a Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region/ Iraq.
b College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region/ Iraq.
Submitted: 2/9/2019; Accepted: 18/2/2020; Published: 21/3/2020
DOI Link: https://doi.org/10.17656/jsmc.10246
Cardiac disease is believed to be the leading cause of death in thalassemia major. Iron cardiomyopathy is the primary cause of death in thalassemia major patients. Monitoring cardiac function with electrocardiography is essential in thalassemia major patients, however, diastolic and systolic dysfunction are later signs of iron overload.
This study aimed to investigate the pleiotropic effect of vitamin D supplementation on the electrocardiograph records and cardiac risk variables in patients with beta thalassemia major.
Patients and Methods
Forty-six patients of beta thalassemia major were recruited in an open label, randomized clinical trial, from the Thalassemia Center of the General hospital in the Sulaimani city, Kurdistan Region. Oral dose of vitamin D of 100,000 IU ampoule was administered to the patients every two weeks for eight weeks as add on therapy. Electrocardiography (ECG), serum vitamin D levels, serum ferritin, body mass index (BMI), waist circumference and blood pressure were determined before (at baseline) and after eight weeks of vitamin D treatment.
Vitamin D3 supplements significantly prolonged PR period, QTcB interval, JTc interval and T-Pe duration in the electrocardiograph records. Additionally, a significant increase in body mass index and blood pressure were observed after supplementation with vitamin D. Furthermore, serum vitamin D was significantly increased and serum ferritin was significantly reduced after 8 weeks of supplementation with vitamin D.
Vitamin D supplement of 100,000 IU every two weeks causes risk when prescribed to patients with beta thalassemia major, since it impairs cardiac conduction.
Thalassemia, Vitamin D3, Electrocardiography.
1. Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010;12:61–76.
2. Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D, Keren A. Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail. 2010; 3: 451–8.
3. Lekawanvijit S, Chattipakorn N. Iron overload thalassemic cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol. 2009; 25: 213–8.
4. Koonrungsesomboon N, Chattipakorn SC, Fucharoen S, Chattipakorn N. Early detection of cardiac involvement in thalassemia: From bench to bedside perspective. World j cardiol. 2013;5(8), 270–279.
5. Qureshi N, Avasarala K, Foote D, Vichinsky EP. Utility of Holter electrocardiogram in iron-overloaded hemoglobinopathies. Ann N Y Acad Sci. 2005; 1054:476–480.
6. Gupta A, Lawrence AT, Krishnan K, Kavinsky CJ, Trohman RG. Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J. 2007;153:891–899.
7. Haugaa KH, Martijn Bos J, Borkenhagen EJ, Tarrel RF, Morlan BW, Caraballo PJ, Ackerman MJ. Impact of left ventricular hypertrophy on QT prolongation and associated mortality. Heart Rhythm. 2014;11(11):1957-65.
8. Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C, Escande D, Franz M, Malik M, Moss A, Shah R. The potential for QT prorogation and proarrhythmia by non-antiarrhythmic drugs: Clinical and regulatory implications. Report on a policy conference of European society of cardiology. Eur Heart J. 2000;21(15):1216-31.
9. van Melle JP, de Jonge P, Honig A, Schene AH, Kuyper AM, Crijns HJ, Schins A, Tulner D, van den Berg MP, Ormel J. Effects of antidepressant treatment following myocardial infarction. Br J Psychiatry. 2007; 190: 460–66.
10. Kilicaslan Fethi, Tokatli Alptug, Ozdag Fatih, Uzun Mehmet, Uz Omer, Isilak Zafer, Yiginer Omer, Yalcin Murat, Guney Mehmet Senol, Cebeci Bekir Sitki. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea. Pacing Clin Electrophysiol. 2012;35 (8):966–72.
11. Rund D, Rachmilewitz E. β-Thalassemia. N Engl J Med. 2005; 353: 1135–1146.
12. Santos PP, Rafacho BP, Gonçalves Ade F, Jaldin RG, Nascimento TB, Silva MA, et al. Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties. PLoS One. 2014;12;9(6):e98895.
13. Santos PP, Assalin HB, Rafacho BP, Minicucci MF, Azevedo PS. Influence of different vitamin D doses on structure, function, energy metabolism and inflammatory mediators in the heart of Wistar rats. Eur Heart J. 2011; 32: 719–719.
14. Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, Shahbazi S, Khooshehchin G, Bandarian F, Larijani B. Effect of vitamin D on insulin resistance and anthropometric parameters in Type 2 diabetes; a randomized double-blind clinical trial. Daru. 2012;28;20(1):10.
15. Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin. Nutr. 2013;32:970–975.
16. Chai W, Cooney RV, Franke AA, Bostick RM. Effects of calcium and vitamin D supplementation on blood pressure and serum lipids and carotenoids: a randomized, double-blind, placebo-controlled, clinical trial. Ann Epidemiol. 2013;23:564–570.
17. Ulger Z, Aydinok Y, Levent E, Gurses D, Ozyurek AR. Evaluation of QT dispersion in β-thalassemia major patients. Am J Hematol. 2006; 81:901–6.
18. Russo V, Rago A, Politano L, Papa AA, Di Meo F, Russo MG, Golino P, Calabrò R, Nigro G. Increased dispersion of ventricular repolarization in Emery Dreifuss muscular dystrophy patients. Med Sci Monit. 2012;18(11):CR643-7.
19. Russo V, Rago A, Pannone B, Papa AA, Di Meo F, Mayer MC, et al. Dispersion of repolarization and beta-thalassemia major: the prognostic role of QT and JT dispersion for identifying the high-risk patients for sudden death. Eur J Haematol. 2011; 86:324.
20. Crow RS, Hannan PJ, Folsom AR. Prognostic significance of corrected QT and corrected JT interval for incident coronary heart disease in a general population sample stratified by presence or absence of wide QRS complex: the ARIC Study with 13 years of follow-up. Circulation. 2003;108(16): 1985–89.
21. Cheng M, Lu X, Huang J, Zhang S, Gu D. Electrocardiographic PR prolongation and atrial fibrillation risk: a meta-analysis of prospective cohort studies. J Cardiovasc Electrophysiol. 2015; 26(1):36–41.
22. Zhao Z, Yuan Z, Ji Y, Wu Y, Qi Y. Left ventricular hypertrophy amplifies the QT, and Tp-e intervals and the Tp-e/QT ratio of left chest ECG. J Biomed Res. 2010; 24:69–72.
© The Authors, published by University of Sulaimani, College of Medicine
This work is licensed under a Creative Commons Attribution 4.0 International License.