Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers
Abstract
Background Endurance exercise is associated with adverse outcomes in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Exercise recommendations for family members remain undetermined. Objective The purposes of this study were to determine if (1) endurance exercise (Bethesda class C) and exercise intensity (metabolic equivalent hours per year [MET-Hr/year]) increase the likelihood of fulfilling 2010 Task Force Criteria and ventricular arrhythmias/implantable cardioverter-defibrillator shock (ventricular tachycardia/ventricular fibrillation [VT/VF]), and (2) exercise restriction to the American Heart Association (AHA)-recommended minimum for healthy adults is associated with favorable outcomes of at-risk family members. Methods Twenty-eight family members of 10 probands inheriting a PKP2 mutation were interviewed about exercise from age 10. Exercise threshold to maintain overall health was based on the 2007 AHA guidelines of a minimum 390 to 650 MET-Hr/year. Results After adjustment for age, sex, and family membership, both participation in endurance athletics (odds ratio [OR] 7.4, P = .03) and higher-intensity exercise (OR = 4.2, P = .004) were associated with diagnosis (n = 13). Endurance athletes were also significantly more likely to develop VT/VF (n = 6, P = .02). Family members who restricted exercise at or below the upper bound of the AHA goal (≤650 MET-Hr/year) were significantly less likely to be diagnosed (OR = 0.07, P = .002) and had no VT/VF. At diagnosis and first VT/VF, family members had accumulated 2.8-fold (P = .002) and 3.5-fold (P = .03), respectively, greater MET-Hr exercise than the AHA-recommended minimum. Those who developed VT/VF had performed particularly high-intensity exercise in adolescence compared to unaffected family members (age 10-14: P = .04; age 14-19: P = .02). Conclusion The results of this study suggest restricting unaffected desmosomal mutation carriers from endurance and high-intensity athletics but potentially not from AHA-recommended minimum levels of exercise for healthy adults.
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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 [24]
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 [24]
Cites
Does sports activity enhance the risk of sudden death in adolescents and young adults?
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Al-Khatib, S. M., Stevenson, W. G., Ackerman, M. J., Bryant, W. J., Callans, D. J., Curtis, A. B., Deal, B. J., Dickfeld, T., Field, M. E., Fonarow, G. C., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000548 · Cited by 412 · see citing works
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Self-citationNielsen, J. C., Lin, Y.-J., de Oliveira Figueiredo, M. J., Sepehri Shamloo, A., Alfie, A., Boveda, S., Dagres, N., Di Toro, D., Eckhardt, L. L., Ellenbogen, K., et al. (2020) · EP Europace · doi:10.1093/europace/euaa065 · Cited by 98 · see citing works
A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease
Ariyaratne, G. H. D. N., Villatore, A., Peretto, G., & Chelko, S. P. (2026) · Cells · doi:10.3390/cells15100868 · Cited by 2 · see citing works
- Authors
- Sawant, A. C., te Riele, A. S. J. M., Tichnell, C., Murray, B., Bhonsale, A., Tandri, H., Judge, D. P., Calkins, H., & James, C. A.
- Affiliations
- Johns Hopkins University (US)
- ORCID
- Venue
- Heart Rhythm
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 13
- Issue
- 1
- Pages
- 199-207
- ISSN
- 1547-5271 (ISSN-L)
- OpenAlex
- W1943646498
- Cited by
- 106
- References
- 2
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 7 · 2023: 9 · 2022: 13 · 2021: 4 · 2020: 10 · 2019: 12 · 2018: 8 · 2017: 15 · 2016: 4 · 2015: 1
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Heart Rhythm (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- American Heart Association
- Medtronic
- St. Jude Medical
- 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, PKP2 mutation, endurance exercise, high-intensity exercise, physical activity limitation, metabolic equivalent hours, ventricular tachycardia, ventricular fibrillation, implantable cardioverter-defibrillator shocks, family members, exercise safety
- MeSH terms
- Adult, American Heart Association, Desmosomes, Physical Exertion, Family, Female, Heterozygote, Humans, Male, Middle Aged, Physical Endurance, Preventive Health Services, United States, Exercise, Likelihood Functions, Tachycardia, Ventricular, Risk Assessment, Arrhythmogenic Right Ventricular Dysplasia, Plakophilins
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