Role of genetic and electrolyte abnormalities in prolonged QTc interval and sudden cardiac death in end-stage renal disease patients

Abstract

BackgroundPatients with end-stage renal disease have very high mortality. In individuals on hemodialysis, cardiovascular deaths account for ~50% of all deaths in this population, mostly due to arrhythmia. To determine the causes of these arrhythmic deaths is essential in order to adopt preventive strategies. The main objective of this study was to investigate whether, the presence of QTc interval alterations, from electrolyte abnormalities or presence of rare genetic variants, could have a relationship with sudden arrhythmogenic deaths in end-stage renal disease patients.MethodsWe recorded the pre- and post-dialysis QTc interval in 111 patients undergoing hemodialysis. In 47 of them, we analyzed 24 SCD-related genes including the most prevalent genes associated with long QT syndrome using a custom resequencing panel.ResultsWe found a positive although not significant association between the presence of long QTc and mortality in a subset of end-stage renal disease patients. In addition, in five patients with long QTc only after dialysis (21.7%) we detected rare potentially pathogenic genetic variants. Three out of these five carriers subsequently died suddenly.ConclusionsGenetic background may be determinant in the risk of sudden cardiac death in these patients. We recommend evaluating the QTc interval before and after hemodialysis, and performing a genetic analysis of individuals with long QTc after hemodialysis.

European Resuscitation Council Guidelines 2021: Epidemiology of cardiac arrest in Europe

“…214À216 and genomic factors (Brugada syndrome, LQTS, arrhythmogenic right ventricular cardiomyopathy (ARVC), catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, etc. 205À207,217À227 ) and their combinations 228 determine the individual risk of sudden cardiac arrest. Moreover, genetic susceptibility to long-term alcohol effects, drug-and drug-drug interactions induced sudden cardiac arrest i.e.…”

Enhanced Klotho availability protects against cardiac dysfunction induced by uraemic cardiomyopathy by regulating Ca2+ handling

“…The increased cardiovascular morbidity and mortality linked to renal dysfunction are due, at least in part, to the high prevalence of heart failure and arrhythmias in patients with CKD, mainly those undergoing dialysis (Charytan et al, 2016; Verde et al, 2016; Wanner, Amann, & Shoji, 2016). Indeed, cardiovascular deaths account for ~50% of all deaths in CKD, especially in patients on dialysis, which is chiefly due to fatal arrhythmias (Coll et al, 2018). Alterations in intracellular Ca 2+ cycling, such as changes in Ca 2+ release from the sarcoplasmic reticulum (SR) mediated by ryanodine receptor (RyR) channels in cardiomyocytes, are well‐documented mechanisms involved in cardiac dysfunction and arrhythmias (Bers, 2014; Nattel, Maguy, Le Bouter, & Yeh, 2007).…”

The ketogenic diet and the QT interval

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