Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis
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ORIGINAL RESEARCH ARTICLE
Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis Oscar Campuzano1,2,3 • Olallo Sanchez-Molero1 • Anna Fernandez1 • Irene Mademont-Soler1,3 • Monica Coll1 • Alexandra Perez-Serra1,3 • Jesus Mates1 • Bernat del Olmo1 • Ferran Pico1 • Laia Nogue-Navarro2 • Georgia Sarquella-Brugada4 • Anna Iglesias1,3 • Sergi Cesar4 • Esther Carro4 Juan Carlos Borondo5 • Josep Brugada4 • Josep Castella`6 • Jordi Medallo6 • Ramon Brugada1,2,3,7
•
Ó Springer International Publishing Switzerland 2017
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 Oscar Campuzano and Olallo Sanchez-Molero authors contributed equally.
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.
& Ramon Brugada [email protected] 1
Cardiovascular Genetics Center, Institut d’Investigacio´ Biome`dica Girona (IDIBGI), University of Girona, C/Dr Castany s/n, Parc Hospitalari Martı´ i Julia` (M-2), Salt, 17190 Girona, Spain
2
Medical Science Department, School of Medicine, University of Girona, Girona, Spain
3
Centro de Investigacio´n Biome´dica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
4
Arrhythmias Unit, Hospital Sant Joan de De´u, University of Barcelona, Barcelona, Spain
5
Histopathology Unit, Instituto Nacional Toxicologı´a y Ciencias Forenses (INTCF), Barcelona, Spain
6
Forensic Pathology Service, Institut de Medicina Legal i Cie`ncies Forenses de C
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