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

PLoS One. 2018 Jul 18;13(7):e0200756. doi: 10.1371/journal.pone.0200756. eCollection 2018.

Abstract

Background: Patients 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.

Methods: We 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.

Results: We 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.

Conclusions: Genetic 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology*
  • Computational Biology
  • Death, Sudden, Cardiac / pathology*
  • Electrocardiography
  • Electrolytes / metabolism*
  • Female
  • Humans
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / physiopathology*
  • Long QT Syndrome / physiopathology*
  • Male
  • Middle Aged

Substances

  • Electrolytes

Grants and funding

This work was supported by Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, Fondo de Desarrollo Regional Europeo (Red de Investigación Cardiovascular RD12/0042/0013-0061); Fondo de Investigación Sanitaria (FIS PI12/00232); Agencia de Gestió d’Ajuts Universitaris i de Recerca (2009 SGR 1195). The author Ramon Brugada receives salary in compensation for his work as a consultant for Ferrer-InCode, a biotechnological services company. The specific roles of this author is articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.