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

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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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Acknowledgements

The authors thank the personnel of the Institut de Medicina Legal i Ciències Forenses de Catalunya (IMLCFC) for their help in the collection of samples for the study.

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    Authors and Affiliations

    1. Cardiovascular Genetics Center, Institut d’Investigació Biomèdica Girona (IDIBGI), University of Girona, C/Dr Castany s/n, Parc Hospitalari Martí i Julià (M-2), Salt, 17190, Girona, Spain

      Oscar Campuzano, Olallo Sanchez-Molero, Anna Fernandez, Irene Mademont-Soler, Monica Coll, Alexandra Perez-Serra, Jesus Mates, Bernat del Olmo, Ferran Pico, Anna Iglesias & Ramon Brugada

    2. Medical Science Department, School of Medicine, University of Girona, Girona, Spain

      Oscar Campuzano, Laia Nogue-Navarro & Ramon Brugada

    3. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

      Oscar Campuzano, Irene Mademont-Soler, Alexandra Perez-Serra, Anna Iglesias & Ramon Brugada

    4. Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

      Georgia Sarquella-Brugada, Sergi Cesar, Esther Carro & Josep Brugada

    5. Histopathology Unit, Instituto Nacional Toxicología y Ciencias Forenses (INTCF), Barcelona, Spain

      Juan Carlos Borondo

    6. Forensic Pathology Service, Institut de Medicina Legal i Ciències Forenses de Catalunya (IMLCFC), Barcelona, Spain

      Josep Castellà & Jordi Medallo

    7. Cardiology Service, Hospital Josep Trueta, Girona, Spain

      Ramon Brugada

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    1. Oscar Campuzano
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    2. Olallo Sanchez-Molero
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    Correspondence to Ramon Brugada.

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    Conflict of interest

    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, and Ramon Brugada declare they have no conflicts of interest directly relevant to the content of this study.

    Funding

    This work was supported by Obra Social ‘La Caixa’, Fondo Investigacion Sanitaria (FIS PI14/01773) from the Instituto de Salud Carlos III (ISCIII), and Fundació Academia de Ciències Mèdiques i de la Salut de Catalunya i de Balears (ACMCB-2013). The CIBERCV is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness.

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    Oscar Campuzano and Olallo Sanchez-Molero authors contributed equally.

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    Campuzano, O., Sanchez-Molero, O., Fernandez, A. et al. Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis. Sports Med 47, 2101–2115 (2017). https://doi.org/10.1007/s40279-017-0705-3

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