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03.03.2017 | Original Research Article

Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis

verfasst von: Oscar Campuzano, Olallo Sanchez-Molero, Anna Fernandez, Irene Mademont-Soler, Monica Coll, Alexandra Perez-Serra, Jesus Mates, Bernat del Olmo, Ferran Pico, Laia Nogue-Navarro, Georgia Sarquella-Brugada, Anna Iglesias, Sergi Cesar, Esther Carro, Juan Carlos Borondo, Josep Brugada, Josep Castellà, Jordi Medallo, Ramon Brugada

Erschienen in: Sports Medicine | Ausgabe 10/2017

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Abstract

Background

Sudden cardiac death is a natural and unexpected death that occurs within 1 h of the first symptom. Most sudden cardiac deaths occur during exercise, mostly as a result of myocardial infarction. After autopsy, some cases, especially in the young, are diagnosed as cardiomyopathies or remain without a conclusive cause of death. In both situations, genetic alterations may explain the arrhythmia.

Objective

Our aim was to identify a genetic predisposition to sudden cardiac death in a cohort of post-mortem cases of individuals who died during exercise, with a structurally normal heart, and were classified as arrhythmogenic death.

Methods

We analyzed a cohort of 52 post-mortem samples from individuals <50 years old who had a negative autopsy. Next-generation sequencing technology was used to screen genes associated with sudden cardiac death.

Results

Our cohort showed a male prevalence (12:1). Half of the deaths occurred in individuals 41–50 years of age. Running was the most common exercise activity during the fatal event, accounting for 46.15% of cases. Genetic analysis identified 83 rare variants in 37 samples (71.15% of all samples). Of all rare variants, 36.14% were classified as deleterious, being present in 53.84% of all cases.

Conclusions

A comprehensive analysis of sudden cardiac death-related genes in individuals who died suddenly while exercising enabled the identification of potentially causative variants. However, many genetic variants remain of indeterminate significance, thus further work is needed before clinical translation. Nonetheless, comprehensive genetic analysis of individuals who died during exercise enables the detection of potentially causative variants and helps to identify at-risk relatives.

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Titel: Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis
verfasst von: Oscar Campuzano
Olallo Sanchez-Molero
Anna Fernandez
Irene Mademont-Soler
Monica Coll
Alexandra Perez-Serra
Jesus Mates
Bernat del Olmo
Ferran Pico
Laia Nogue-Navarro
Georgia Sarquella-Brugada
Anna Iglesias
Sergi Cesar
Esther Carro
Juan Carlos Borondo
Josep Brugada
Josep Castellà
Jordi Medallo
Ramon Brugada
Publikationsdatum: 03.03.2017
Verlag: Springer International Publishing
Erschienen in: Sports Medicine / Ausgabe 10/2017
Print ISSN: 0112-1642
Elektronische ISSN: 1179-2035
DOI: https://doi.org/10.1007/s40279-017-0705-3

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Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis