The Impact of 3:1 Ketogenic Diet on Cardiac Repolarization Changes in Children with Refractory Seizures: A Prospective Follow-Up Study

Abstract

Background The association between ketogenic diet (KD) and prolonged QT interval, life-threatening ventricular arrhythmias, and sudden death is controversial.

Aim We aimed to prospectively evaluate the effect of KD on electrocardiography (ECG) measures in children with refractory epilepsy.

Method A total of 70 children with drug-resistant epilepsy who received a KD for at least 12 months were included in the study. The standard 12-lead electrocardiography was performed in all patients before the beginning and in the 12th month of KD. Heart rate, P-wave duration and dispersion, corrected QT interval and QT dispersion, and Tp-e interval were measured.

Results All ECG-derived parameters, but P-wave dispersion increased after 12 months of KD compared with the baseline values. However, these changes were not statistically significant.

Conclusion A 12-month long 3:1 KD treatment exerts no deleterious effect on cardiac repolarization measures.

Keywords

ketogenic diet - children - electrocardiography - cardiac repolarization - T peak–T end interval

• References

• 1 Seo JH, Lee YM, Lee JS, Kang HC, Kim HD. Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios—comparison of 3:1 with 4:1 diet. Epilepsia 2007; 48 (4) 801-805
• 2 Nizamuddin J, Turner Z, Rubenstein JE, Pyzik PL, Kossoff EH. Management and risk factors for dyslipidemia with the ketogenic diet. J Child Neurol 2008; 23 (7) 758-761
• 3 Kang HC, Chung DE, Kim DW, Kim HD. Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004; 45 (9) 1116-1123
• 4 Bank IM, Shemie SD, Rosenblatt B, Bernard C, Mackie AS. Sudden cardiac death in association with the ketogenic diet. Pediatr Neurol 2008; 39 (6) 429-431
• 5 Best TH, Franz DN, Gilbert DL, Nelson DP, Epstein MR. Cardiac complications in pediatric patients on the ketogenic diet. Neurology 2000; 54 (12) 2328-2330
• 6 Sharma S, Gulati S. The ketogenic diet and the QT interval. J Clin Neurosci 2012; 19 (1) 181-182
• 7 Christensen PK, Gall MA, Major-Pedersen A , et al. QTc interval length and QT dispersion as predictors of mortality in patients with non-insulin-dependent diabetes. Scand J Clin Lab Invest 2000; 60 (4) 323-332
• 8 Remigio de Aguiar MI, Saraiva LC, Santos CL. QT Dispersion predicting acute rheumatic carditis. Cardiol Young 2010; 20 (5) 473-476
• 9 Doksöz Ö, Güzel O, Yılmaz Ü, Işgüder R, Çeleğen K, Meşe T. Dispersion durations of P-wave and QT interval in children treated with a ketogenic diet. Pediatr Neurol 2014; 50 (4) 343-346
• 10 Rossing P, Breum L, Major-Pedersen A , et al. Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus. Diabet Med 2001; 18 (3) 199-205
• 11 Ulger Z, Aydinok Y, Levent E, Gurses D, Ozyurek AR. Evaluation of QT dispersion in beta thalassaemia major patients. Am J Hematol 2006; 81 (12) 901-906
• 12 de Bruyne MC, Hoes AW, Kors JA, Hofman A, van Bemmel JH, Grobbee DE. QTc dispersion predicts cardiac mortality in the elderly: the Rotterdam Study. Circulation 1998; 97 (5) 467-472
• 13 Bieganowska K, Sawicka-Parobczyk M, Bieganowski M, Piskorski J. Tpeak -tend interval in 12-lead electrocardiogram of healthy children and adolescents tpeak -tend interval in childhood. Ann Noninvasive Electrocardiol 2013; 18 (4) 344-351
• 14 Kors JA, Ritsema van Eck HJ, van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol 2008; 41 (6) 575-580
• 15 Antzelevitch C, Sicouri S, Di Diego JM , et al. Does Tpeak-Tend provide an index of transmural dispersion of repolarization?. Heart Rhythm 2007; 4 (8) 1114-1116, author reply 1116–1119
• 16 Yayla Ç, Bilgin M, Akboğa MK , et al. Evaluation of Tp-E interval and Tp-E/QT ratio in patients with aortic stenosis. Ann Noninvasive Electrocardiol 2015; (e-pub ahead of print). doi: 10.1111/anec.12298
• 17 Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 2010; 92 (5) 1189-1196
• 18 Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med 2009; 169 (7) 659-669
• 19 Bazett HC. An analysis of time relations of the electrocardiogram. Heart 1920; 7: 353-370
• 20 Shimizu M, Ino H, Okeie 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 (7) 335-339
• 21 Surges R, Adjei P, Kallis C , et al. Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study. Epilepsia 2010; 51 (2) 233-242
• 22 Surges R, Taggart P, Sander JW, Walker MC. Too long or too short? New insights into abnormal cardiac repolarization in people with chronic epilepsy and its potential role in sudden unexpected death. Epilepsia 2010; 51 (5) 738-744
• 23 Nashef L, Walker F, Allen P, Sander JW, Shorvon SD, Fish DR. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry 1996; 60 (3) 297-300
• 24 Haarmark C, Hansen PR, Vedel-Larsen E , et al. The prognostic value of the Tpeak-Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Electrocardiol 2009; 42 (6) 555-560
• 25 Garaizar C. Sudden unexpected and unexplained death in epilepsy[in Spanish]. Rev Neurol 2000; 31 (5) 436-441
• 26 Elzouki AY, Harfi HA, Nazer HM, Stapleton FB, Oh W, Whitley RJ. Sudden cardiac death and preparticipation sports screening. In: Corrado D, Migliore F, Zorzi A, Basso C, Thiene G, eds. Textbook of Clinical Pediatrics. 2nd ed. New York, NY: Springer; 2012: 2399-2411
• 27 Sperling MR. Sudden unexplained death in epilepsy. Epilepsy Curr 2001; 1 (1) 21-23
• 28 Natelson BH, Suarez RV, Terrence CF, Turizo R. Patients with epilepsy who die suddenly have cardiac disease. Arch Neurol 1998; 55 (6) 857-860
• 29 Opeskin K, Thomas A, Berkovic SF. Does cardiac conduction pathology contribute to sudden unexpected death in epilepsy?. Epilepsy Res 2000; 40 (1) 17-24
• 30 Tomson T, Walczak T, Sillanpaa M, Sander JW. Sudden unexpected death in epilepsy: a review of incidence and risk factors. Epilepsia 2005; 46 (Suppl. 11) 54-61
• 31 Delogu AB, Spinelli A, Battaglia D , et al. Electrical and autonomic cardiac function in patients with Dravet syndrome. Epilepsia 2011; 52 (Suppl. 02) 55-58