Genetic arrhythmias complicating patients with dilated cardiomyopathy

Zongzhe Li, Peng Chen, Chenze Li, Lun Tan, Jinchao Xu, Hong Wang, Yang Sun, Yan Wang, Chunxia Zhao, Mark S. Link, Arthur A.M. Wilde, Dao Wu Wang, Dao Wen Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sudden cardiac death due to malignant arrhythmias is a common cause of death in dilated cardiomyopathy (DCM). Whether genetic variants increase the risk of arrhythmias in DCM is unknown. Objective: The purpose of this study was to investigate the genetic causes of arrhythmias in DCM patients. Methods: Whole-exome sequencing and high-depth targeted next-generation sequencing (142-gene panel) were used. Eight specific DCM pedigrees with arrhythmias and 2 separate cohorts of 1232 consecutive unrelated sporadic DCM patients from 3 medical centers (550 in the discovery cohort, 682 in the replication cohort) were analyzed; 470 (250 in the discovery cohort, 220 in the replication cohort) suffered from arrhythmias (DCM-A group) and 762 (300 in the discovery cohort, 462 in the replication cohort) did not (DCM-NA group). All identified causative variants were Sanger sequenced to eliminate false-positive results and then screened in 700 unrelated matched arrhythmia- and DCM-free healthy controls. Results: We identified long QT syndrome (LQTS)-causative variants that independently cosegregated in 2 unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes (ion channelopathies) were identified in 4.9% (23/470) of sporadic DCM-A patients (4.0% in the discovery cohort, 5.9% in the replication cohort) but only 0.1% (1/762) of sporadic DCM-NA patients (P = 2.16 × 10–9). These arrhythmia-related pathogenic variants included long QT syndrome, atrial fibrillation, sick sinus syndrome, cardiac conduction disease, and Brugada syndrome. Conclusion: Some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants. For DCM patients with explicit arrhythmias, arrhythmia-causative genetic screening may help to explain the etiology and decision-making.

Original languageEnglish (US)
Pages (from-to)305-312
Number of pages8
JournalHeart Rhythm
Volume17
Issue number2
DOIs
StatePublished - Feb 2020

Keywords

  • Arrhythmia
  • Dilated cardiomyopathy
  • Genetic diagnosis
  • Next-generation sequencing
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Genetic arrhythmias complicating patients with dilated cardiomyopathy'. Together they form a unique fingerprint.

Cite this