Myocardial repolarization is affected in patients with diabetic retinopathy

Abstract

Background/Aim: Diabetes Mellitus (DM), considered the equivalent of coronary artery disease, is one cause of ventricular repolarization (VR) dispersion. Retinopathy is one of the vascular consequences of diabetes. The association between myocardial repolarization dispersion and diabetic retinopathy is not fully elucidated. We aimed to evaluate ventricular repolarization using Tp-e interval and corrected (c) Tp-e/QT ratio in DM patients with and without retinopathy. Methods: A total of 124 diabetic subjects were included in this retrospective cohort study. All medical data were obtained from the electronic database of our university hospital. The subjects were divided into the no diabetic retinopathy (NDR) group (n=45), and the diabetic retinopathy (DR) group (n=79), which were compared in terms of demographic features, clinic and laboratory findings, and electrocardiographic findings such as QT, QTc, Tp-e, Tp-e/QT, Tp-e/QTc. Results: The groups were similar in terms of demographic features (P>0.05). Both Tp-e interval and Tp-e/QTc were significantly prolonged in the DR group compared to the NDR group. There were significant correlations between Tp-e, Tp-e/QTc, DM duration, and age. In multivariate logistic regression analysis, Tp-e (OR=6.01, %95 CI=4.17-7.52, P=0.012), Tp-e/QTc (OR=1.215, 95% CI=0.874-1.612, P=0.029), and DM duration (OR=1.422, 95% CI= 1.146–1.712, P<0.001) were independent predictors of DR. Conclusion: We showed that DM patients with retinopathy may also have an increased risk for sudden cardiac death due to ventricular arrhythmogenesis.

Keywords

• Ventricular repolarization
• Diabetic retinopathy
• Sudden cardiac death
• Tp-e interval
• Tp-e/QTc interval

Kaynakça

1. 1. Rana JS, Dunning A, Achenbach S, Al-Mallah M, Budoff MJ, Cademartiri F, et al. Differences in prevalence, extent, severity, and prognosis of coronary artery disease among patients with and without diabetes undergoing coronary computed tomography angiography: results from 10,110 individuals from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes): an InteRnational Multicenter Registry. Diabetes care. 2012;35:1787-94.
2. 2. Rosenson RS, Fioretto P, Dodson PM. Does microvascular disease predict macrovascular events in type 2 diabetes? Atherosclerosis. 2011;218:13-8.
3. 3. Jouven X, Lemaitre RN, Rea TD, Sotoodehnia N, Empana JP, Siscovick DS. Diabetes, glucose level, and risk of sudden cardiac death. Eur Heart J. 2005;26:2142–7.
4. 4. Yamada M, Hiratsuka Y, Roberts CB, Pezzullo ML, Yates K, Takano S, et al. Prevalence of visual impairment in the adult Japanese population by cause and severity and future projections. Ophthalmic Epidemiol. 2010;17:50-7.
5. 5. El-Asrar AMA. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol. 2012;19:70-4.
6. 6. Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J. QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation. 1991;84:1516-23.
7. 7. Goldberg RJ, Bengston J, Chen Z, Anderson KM, Locati E, Levy D. Duration of the QT interval and total and cardiovascular mortality in healthy persons (the Framingham Heart Study Experience). Am J Cardiol. 1991;67:55-8.
8. 8. Okin PM, Devereux RB, Howard BV, Fabsitz RR, Lee ET, Welty TK. Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians: the Strong Heart Study. Circulation. 2000;101:61-6.

9. 9. Taggart P, Sutton PM, Opthof T, Coronel R, Trimlett R, Pugsley W, et al. Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia. Cardiovasc Res. 2001;50:454-62.
10. 10. Opthof T, Coronel R, Janse MJ. Is there a significant transmural gradient in repolarization time in the intact heart? Repolarization gradients in the intact heart. Circ Arrhythm Electrophysiol .2009;2:89–96.
11. 11. Panikkath R, Reinier K, Uy-Evanado A, Teodorescu C, Hattenhauer J, Mariani R, et al. Prolonged Tpeak-to-tend interval on the resting ECG is associated with increased risk of sudden cardiac death. Circ Arrhythm Electrophysiol. 2011;4:441-7.
12. 12. Antzelevitch C, Sicouri S, Di Diego JM, Yan GX, Kowey P, Zhang L, et al. Does Tpeak‐Tend provide an index of transmural dispersion of repolarization? Heart Rhythm. 2007;4:1114-6.
13. 13. Hevia JC, Antzelevitch C, Bárzaga FT, Sánchez MD, Balea FD, Molina RZ, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol. 2006;47:1828-34.
14. 14. Wilkinson C, Ferris III FL, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110: 1677-82. 15. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart. 1920;7:353-70.
15. 16. Suys BE, Katier N, Rooman RP, Matthys D, De Beeck LO, Du Caju MVL, et al. Female children and adolescents with type 1 diabetes have more pronounced early echocardiographic signs of diabetic cardiomyopathy. Diabetes Care. 2004;27:1947-53.
16. 17. Mandala S, Di TC. ECG Parameters for Malignant Ventricular Arrhythmias: A Comprehensive Review. J Med Biol Eng. 2017;37:441-53.
17. 18. Kato T, Yamashita T, Sekiguchi A, Sagara K, Takamura M, Takata S, et al. What are arrhythmogenic substrates in diabetic rat atria? J Cardiovasc Electrophysiol. 2006;17:890-4.
18. 19. Subbalakshmi NK, Adhikari PM, Sathyanarayana Rao KN, Jeganathan PS. Influencing factors of QTc among the clinical characteristics in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2010;88:265-72.
19. 20. Ninkovic VM, Ninkovic SM, Miloradovic V, Stanojevic D, Babic M, Giga V, et al. Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes. Acta Diabetol. 2016;53:737-44.
20. 21. Kobayashi S, Nagao M, Asai A, Fukuda I, Oikawa S, Sugihara H. Severity and multiplicity of microvascular complications are associated with QT interval prolongation in patients with type 2 diabetes. J Diabetes Investig. 2018;9:946-51.
21. 22. Kunihiro EE, Keigo NN, Chikato OO, Tetsuhiro KK, Michiko AA, Masahiro NN, et al. Increased QTc dispersion and relationship between QTc dispersion and retinopathy in Japanese Type 2 diabetic Patients. J Jpn Diabetic Soc. 2002;45:21-6.
22. 23. Okin PM, Devereux RB, Lee ET, Galloway JM, Howard BV. Electrocardiographic repolarization complexity and abnormality predict all-cause and cardiovascular mortality in diabetes: the strong heart study. Diabetes. 2004;53:434-40.
23. 24. Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41:567-74.
24. 25. Shimizu M, Ino H, Okeie K, Yamaguchi M, Nagata M, Hayashi K, et al. T-peak to T-end interval may be a better predictor of high-risk patients with hypertrophic cardiomyopathy associated with a cardiac troponin I mutation than QT dispersion. Clin Cardiol. 2002;25:335-9.
25. 26. Yeung CY, Lam KSL, Li SW, Lam KF, Tse HF, Siu CW. Sudden cardiac death after myocardial infarction in type 2 diabetic patients with no residual myocardial ischemia. Diabetes Care. 2012;35:2564-9.
26. 27. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012;366:1227-39.
27. 28. Balkau B, Jouven X, Ducimetière P, Eschwege E. Diabetes as a risk factor for sudden death. Lancet. 1999;354:1968-9.
28. 29. Jouven X, Desnos M, Guerot C, Ducimetière P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation. 1999;99:1978-83.
29. 30. Suhonen O, Reunanen A, Knekt P, Aromaa A. Risk factors for sudden and non-sudden coronary death. Acta Med Scand. 1988;223:19-25.
30. 31. Wannamethee G, Shaper AG, Macfarlane PW, Walker M. Risk factors for sudden cardiac death in middle-aged British men. Circulation. 1995;91:1749-56.
31. 32. Clemente D, Pereira T, Ribeiro S. Ventricular repolarization in diabetic patients: characterization and clinical implications. Arq Bras Cardiol. 2012;99:1015-22.
32. 33. Takebayashi K, Aso Y, Sugita R, Takemura Y, Inukai T. Clinical usefulness of corrected QT intervals in diabetic autonomic neuropathy in patients with type 2 diabetes. Diabetes & Metabolism. 2002;28:127-32.
33. 34. Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC, et al. The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group. Diabetologia. 1999;42:68-75.