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Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left

Juha H Vähätalo1, Lauri T A Holmström1, Katri Pylkäs2

  • 1Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.

Frontiers in Cardiovascular Medicine
|January 28, 2022
PubMed

Insights

Genetic variants linked to cardiomyopathies are common in sudden cardiac death (SCD) victims with coronary artery disease (CAD) and hypertrophy. These variants may increase the risk of fatal arrhythmias in ischemic heart disease.

Area of Science:

  • Cardiovascular Genetics
  • Pathology
  • Molecular Cardiology

Background:

  • Coronary artery disease (CAD) related sudden cardiac death (SCD) often occurs without clear explanations in younger individuals.
  • Cardiac hypertrophy and myocardial fibrosis are frequently observed in SCD victims, particularly those with CAD.
  • The underlying genetic factors contributing to hypertrophy in SCD patients with single-vessel CAD remain incompletely understood.

Purpose of the Study:

  • To investigate the genetic basis of cardiac hypertrophy, with or without fibrosis, in victims of SCD linked to single-vessel CAD.
  • To identify rare genetic variants in genes related to myocardial structure and ion channel function.

Main Methods:

  • Targeted next-generation sequencing of 174 genes was performed on autopsy samples from 95 SCD victims with single-vessel CAD.
  • The study population was derived from the Fingesture study, encompassing autopsy-verified SCDs in Northern Finland (1998-2017).
  • Genetic variants were analyzed for their association with cardiomyopathies and ion channel function.

Main Results:

  • Rare genetic variants were detected in 45.3% of the study subjects.
  • Five variants (8.4%) were classified as pathogenic or likely pathogenic.
  • Variants were found in genes associated with various cardiomyopathies (arrhythmogenic right ventricular, dilated, hypertrophic, left ventricular non-compaction) and RYR2, linked to cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias.

Conclusions:

  • Rare variants associated with cardiomyopathies are prevalent in CAD-related SCD victims with myocardial hypertrophy, even without clear anatomic evidence of inherited cardiomyopathies.
  • These genetic variants may play a significant role in modulating the risk of fatal arrhythmias and SCD in the context of ischemic heart disease.
  • The findings highlight the importance of genetic screening in understanding SCD mechanisms in patients with CAD and hypertrophy.

Keywords:
coronary artery diseasegeneticsleft ventricular hypertrophymedicolegal autopsysudden cardiac death

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