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Cited by 221Cardiovascular Effects of ExerciseCardiomyopathy and Myosin StudiesCardiac electrophysiology and arrhythmias

Exercise has a Disproportionate Role in the Pathogenesis of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy in Patients Without Desmosomal Mutations

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Sawant, Abhishek C., Bhonsale, Aditya, te Riele, Anneline S. J. M., Tichnell, Crystal, Murray, Brittney, Russell, Stuart D., Tandri, Harikrishna, Tedford, Ryan J. +3 more·2014·Journal of the American Heart Association
DOI 10.1161/jaha.114.001471PMC PMC4338738
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Abstract

Background: Exercise is associated with age‐related penetrance and arrhythmic risk in carriers of arrhythmogenic right ventricular dysplasia/cardiomyopathy ( ARVD /C)‐associated desmosomal mutations; however, its role in patients without desmosomal mutations (gene‐elusive) is uncertain. This study investigates whether exercise is (1) associated with onset of gene‐elusive ARVD /C and (2) has a differential impact in desmosomal and gene‐elusive patients. Methods and Results: Eighty‐two ARVD /C patients (39 desmosomal, all probands) were interviewed about regular physical activity from age 10. Participation in endurance athletics, duration (hours/year), and intensity ( MET ‐Hours/year) of exercise prior to clinical presentation were compared between patients with desmosomal and gene‐elusive ARVD /C. All gene‐elusive patients were endurance athletes. Gene‐elusive patients were more likely to be endurance athletes ( P <0.001) and had done significantly more intense ( MET ‐Hrs/year) exercise prior to presentation ( P <0.001), particularly among cases presenting < age 25 ( P =0.027). Family history was less prevalent among gene‐elusive patients (9% versus 40% desmosomal, P <0.001), suggesting a greater environmental influence. Gene‐elusive patients without family history did considerably more intense exercise than other ARVD /C patients ( P =0.004). Gene‐elusive patients who had done the most intense (top quartile MET ‐Hrs/year) exercise prior to presentation had a younger age of presentation ( P =0.025), greater likelihood of meeting ARVD /C structural Task Force Criteria (100% versus 43%, P =0.02), and shorter survival free from a ventricular arrhythmia in follow‐up ( P =0.002). Conclusions: Gene‐elusive, non‐familial ARVD /C is associated with very high intensity exercise suggesting exercise has a disproportionate role in the pathogenesis of these cases. As exercise negatively modifies cardiac structure and promotes arrhythmias, exercise restriction is warranted.

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  • Environmental modifiers such as endurance exercise, psychological stress, diet, alcohol, and metabolic dysregulation influence ACM disease penetrance and progression, in part through modulation of inflammatory processes.

    “environmental modifiers such as endurance exercise [24,25,26,27,28,29,30], psychological stress [31,32,33], diet [34,35], alcohol [36], and metabolic dysregulation [37,38,39] have been shown to influence disease penetrance and progression, in part, through modulation of inflammatory processes.”

    From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [27]

    The Discussion (Main Findings; Study Findings) reports that intense endurance exercise is associated with earlier presentation, worse structural disease, and a more aggressive arrhythmic course in gene-elusive ARVD/C. The citation is attached to endurance exercise, not the other listed modifiers. Our copy does not establish that exercise acts through modulation of inflammatory processes. (LLM, conf=0.85)

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  • Physical exercise, specifically endurance and high-intensity, significantly correlates with disease progression and arrhythmias in PKP2 mutation carriers, as well as in DSP carriers and gene-elusive ACM subjects, suggesting a gene-environment interaction.

    “Clinical data indicates that physical exercise, specifically endurance and high-intensity, significantly correlates with disease progression and arrhythmias in PKP2 mutation carriers [24], as well as in DSP carriers and gene-elusive ACM subjects [25,27], suggesting a gene–environment interaction.”

    From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [27]

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Authors
Sawant, A. C., Bhonsale, A., te Riele, A. S. J. M., Tichnell, C., Murray, B., Russell, S. D., Tandri, H., Tedford, R. J., Judge, D. P., Calkins, H., & James, C. A.
Affiliations
  • Johns Hopkins University (US)
  • Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2014-12-17
Volume
3
Issue
6
Pages
e001471-e001471
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.114.001471
PMC
PMC4338738
OpenAlex
W2125542173
Cited by
221
References
3
Citations by year
2026: 15 · 2025: 17 · 2024: 14 · 2023: 18 · 2022: 22 · 2021: 23 · 2020: 21 · 2019: 17 · 2018: 14 · 2017: 24 · 2016: 16 · 2015: 20
FWCI
13.74
Type
journal article
Language
en
Open access
Locations
  • Journal of the American Heart Association (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
arrhythmogenic right ventricular cardiomyopathy, physical activity, endurance athletes, desmosomal mutations, pathogenesis, exercise intensity, age of onset, family history (medicine), ventricular arrhythmias, physical activity limitation, cardiac structure
MeSH terms
Adolescent, Adult, Aged, Desmosomes, Female, Humans, Interviews as Topic, Male, Middle Aged, Mutation, Pedigree, Phenotype, Registries, Retrospective Studies, Risk Factors, Exercise, Exercise Tolerance, Age of Onset, Disease-Free Survival, Arrhythmogenic Right Ventricular Dysplasia, Genetic Predisposition to Disease, Young Adult, Gene-Environment Interaction

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