Implications of Genetic Testing in Dilated Cardiomyopathy

Job A. J. Verdonschot, Mark R. Hazebroek, Ingrid P. C. Krapels, Michiel T. H. M. Henkens, Anne Raafs, Ping Wang, Jort J. Merken, Godelieve R. F. Claes, Els K. Vanhoutte, Arthur van den Wijngaard, Stephane R. B. Heymans, Han G. Brunner*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background:

Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM, but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population and determined the role of electrical phenotypes in association with outcome.

Methods:

This study included 689 patients with DCM from the Maastricht Cardiomyopathy Registry, undergoing genetic evaluation using a 48 cardiomyopathy-associated gene-panel, echocardiography, endomyocardial biopsies, and Holter monitoring. Upon detection of a pathogenic variant in a patient with DCM, familial segregation was performed. Outcome was defined as cardiovascular death, heart transplantation, heart failure hospitalization, and/or occurrence of life-threatening arrhythmias.

Results:

A (likely) pathogenic gene variant was found in 19% of patients, varying from 36% in familial to 13% in nonfamilial DCM. Family segregation analysis showed familial disease in 46% of patients with DCM who were initially deemed nonfamilial by history. Overall, 18% of patients with a nongenetic risk factor had a pathogenic gene variant. Almost all pathogenic gene variants occurred in just 12 genes previously shown to have robust disease association with DCM. Genetic DCM was independently associated with electrical phenotypes such as atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block and inversely correlated with the presence of a left bundle branch block (P

Conclusions:

One in 5 patients with an established nongenetic risk factor or a nonfamilial disease still carries a pathogenic gene variant. Genetic DCM is characterized by a profile of electrical phenotypes (atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block), which carries increased risk for adverse outcomes. Based on these findings, we envisage a broader role for genetic testing in DCM.

Original languageEnglish
Article number003031
Pages (from-to)476-487
Number of pages12
JournalCirculation: Genomic and Precision Medicine
Volume13
Issue number5
DOIs
Publication statusPublished - Oct 2020

Keywords

  • arrhythmia
  • cardiomyopathy
  • dilated
  • heart failure
  • phenotype
  • prevalence
  • STATEMENT
  • DIAGNOSIS
  • GENOTYPE

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