Lower than expected desmosomal gene mutation prevalence in endurance athletes with complex ventricular arrhythmias of right ventricular origin.
OBJECTIVE
To determine the prevalence of desmosomal gene mutations in athletes with complex arrhythmias (VA) of right ventricular (RV) origin and structural RV abnormalities to evaluate whether there is sufficient genetic overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC) to consider them the same or different entities.


METHODS
Observational cohort


METHODS
Tertiary hospital referrals


METHODS
Forty-seven consecutive athletes (age 42 (11) years) with complex VA of RV morphology (excluding idiopathic right ventricular outflow tract ventricular tachycardia), who performed 14 (9) h/week of moderate to intense sport practise for 19 (9) years.


METHODS
Clinical evaluation (detailed sports history, multi-modality imaging, electrophysiological study) and sequencing of five candidate desmosomal genes.


RESULTS
A clinical diagnosis of definite or suspected ARVC by task force criteria (TFC) was met in 24 (51%) and 17 (36%), respectively. ARVC classification was not related to the rate of major arrhythmic events (p=0.28). Pathogenic mutations (four novel) were identified in six athletes (12.8%), which is below published rates for familial ARVC (27-52%). Moreover, only two athletes had a suggestive family history. Severe RV dysfunction was more frequent in mutation carriers (33% vs 2%, p=0.04), but otherwise TFC features were similar to those without mutations. No mutations were found in the 20 athletes performing more than average weekly exercise, yet all met the criteria for definite or suspected ARVC.


CONCLUSIONS
In this athletic cohort, we found lower than expected rates of desmosomal gene mutations, particularly among those performing the most exercise. This adds further weight to the hypothesis that an ARVC-like phenotype may be acquired through intense exercise without an identifiable genetic predisposition.
La Gerche
A
A
Department of Cardiovascular Medicine, University Hospital, University of Leuven, Belgium.
Robberecht
C
C
Kuiperi
C
C
Nuyens
D
D
Willems
R
R
de Ravel
T
T
Matthijs
G
G
Heidbüchel
H
H
D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D003896:Desmosomes / Q000235:genetics*; D004562:Electrocardiography / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D010807:Physical Endurance / Q000502:physiology; D013177:Sports / Q000502:physiology*; D055815:Young Adult