University of Oulu

Vähätalo JH, Holmström LTA, Pylkäs K, Skarp S, Porvari K, Pakanen L, Kaikkonen KS, Perkiömäki JS, Kerkelä R, Huikuri HV, Myerburg RJ and Junttila MJ (2022) Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left Ventricular Hypertrophy With or Without Fibrosis. Front. Cardiovasc. Med. 8:755062. doi: 10.3389/fcvm.2021.755062

Genetic variants associated with sudden cardiac death in victims with single vessel coronary artery disease and left ventricular hypertrophy with or without fibrosis

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Author: Vähätalo, Juha H.1; Holmström, Lauri T. A.1; Pylkäs, Katri2;
Organizations: 1Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
2Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland
3Research Unit of Biomedicine and Biocenter Oulu, University of Oulu, Oulu, Finland
4Department of Forensic Medicine, Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland
5Forensic Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland
6Division of Cardiology, Miller School of Medicine, University of Miami, Miami, FL, United States
7Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
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Language: English
Published: Frontiers Media, 2022
Publish Date: 2022-06-15


Objective: Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD.

Methods: The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 (n = 5,869). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean age 63.6 ± 10.3 years; 88.4% males) with single-vessel CAD in the absence of previously diagnosed CAD and cardiac hypertrophy with or without myocardial fibrosis at autopsy.

Results: A total of 42 rare variants were detected in 43 subjects (45.3% of the study subjects). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 37 variants of uncertain significance in 39 subjects (40.6%). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular, dilated, hypertrophic and left ventricular non-compaction cardiomyopathies. Also, variants were detected in ryanodine receptor 2 (RYR2), a gene associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias.

Conclusions: Rare variants associated with cardiomyopathies, in the absence of anatomic evidence of the specific inherited cardiomyopathies, were common findings among CAD-related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and SCD in ischemic disease.

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Series: Frontiers in cardiovascular medicine
ISSN: 2297-055X
ISSN-E: 2297-055X
ISSN-L: 2297-055X
Volume: 8
Article number: 755062
DOI: 10.3389/fcvm.2021.755062
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by Aarne Koskelo Foundation, Finnish Foundation for Cardiovascular Research, The Finnish Medical Foundation, Instrumentarium Science Foundation, The Maud Kuistila Memorial Foundation, Ida Montin Foundation, The University of Oulu Scholarship Foundation, Paavo Nurmi Foundation, and Maire Taponen Foundation.
Copyright information: Copyright © 2022 Vähätalo, Holmström, Pylkäs, Skarp, Porvari, Pakanen, Kaikkonen, Perkiömäki, Kerkelä, Huikuri, Myerburg and Junttila. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.