Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating MYBPC3 Founder Variant Carriers
Year: 2024
Type: article
Study design: Observational Study
Abstract: Background MYBPC3 founder variants cause hypertrophic cardiomyopathy (HCM) leading to heart failure (HF) and malignant ventricular arrhythmias (MVA). Exercise is typically regarded a risk factor for disease expression, although evidence is conflicting. Stratifying by type of exercise may discriminate low-from high-risk activities in these patients. Objective(s) Evaluate effects of exercise, stratified by high-static and high-dynamic component, on risk of major cardiomyopathy-related events (MCE) and cardiomyopathy penetrance among MYBPC3 founder variant carriers. Methods We interviewed 188 carriers (57% male, 43.4±14.8 years) on exercise participation since age ten. Exercise was quantified as metabolic equivalent task (MET)-hours/week before presentation. MCE was defined as a composite of MVA (sustained ventricular tachycardia/fibrillation), HF (HF hospitalizations or transplantation), and septal reduction therapy. Static and dynamic exercise were defined per Bethesda classification. Associations of exercise with MCE and cardiomyopathy penetrance were adjusted for sex and assessed using Cox regression. Results Overall, 40 (21%) subjects experienced MCE and 139 (74%) were diagnosed with cardiomyopathy. No association was found for overall physical activity and high-static activity with MCE (p=0.900 overall; p=0.274 high-static) or cardiomyopathy penetrance (p=0.787 overall; p=0.774 high-static). In contrast, high-dynamic activity was associated with MVA (dichotomized at 75 th percentile: adjusted hazard ratio 2.70, 95% confidence interval 1.01-7.24, p=0.049). Conclusions Overall exercise participation does not generally increase the risk of adverse events among MYBPC3 founder variant carriers. Nonetheless, an increased risk of MVA was observed among those engaged in the highest quartile of high-dynamic-sports, suggesting that high-level high-intensity exercise activities should be entertained with caution.
Authors: Fahima Hassanzada, Mark Jansen, Freyja H.M. van Lint, Laurens P. Bosman, Amand F. Schmidt, Dennis Dooijes, Danny van de Sande, Bristi Miah, Saskia N. van der Crabben, Arthur A.M. Wilde, Ronald H. Lekanne Deprez, Rudolf A. de Boer, Imke Christiaans, Jan D.H. Jongbloed, Harald T. Jorstad, Folkert W. Asselbergs, J. Peter van Tintelen, Annette F. Baas, Anneline S.J.M. te Riele
Institutions: Utrecht University, University Medical Center Utrecht, ERN GUARD-Heart, Radboud University Nijmegen, Radboud University Medical Center, Amsterdam University Medical Centers, University of Amsterdam, Netherlands Heart Institute, Amsterdam Cardiovascular Sciences, University Medical Center Groningen, University of Groningen, Erasmus MC, Erasmus University Rotterdam, Amsterdam Movement Sciences, Health Data Research UK, University College London
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1119746730, Predicting patient relevant outcomes in people with diabetes through integration of electronic healthcare records, genomics and machine learning, Accelerator Award, Evaluating combination therapeutics for CVD prevention using Mendelian randomisation and phenome-wide scans, G5605945002, G7447173239
OpenAlex ID: W4405506433