TY - JOUR
T1 - Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating
MYBPC3 Founder Variant Carriers.
AU - Hassanzada, Fahima
AU - Jansen, Mark
AU - van Lint, Freyja H M
AU - Bosman, Laurens P
AU - Schmidt, Amand F
AU - Dooijes, Dennis
AU - van de Sande, Danny
AU - Miah, Bristi
AU - van der Crabben, Saskia N
AU - Wilde, Arthur A M
AU - Lekanne Deprez, Ronald H
AU - de Boer, Rudolf A
AU - Christiaans, Imke
AU - Jongbloed, Jan D H
AU - Jorstad, Harald T
AU - Asselbergs, Folkert W
AU - van Tintelen, J Peter
AU - Baas, Annette F
AU - Te Riele, Anneline S J M
N1 - Publisher Copyright:
© 2024 American Heart Association, Inc.
PY - 2024/12
Y1 - 2024/12
N2 - BACKGROUND:
MYBPC3 founder variants cause hypertrophic cardiomyopathy leading to heart failure and malignant ventricular arrhythmias. Exercise is typically regarded as 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. Here, we evaluate the effects of exercise, stratified by high-static and high-dynamic components, on the risk of major cardiomyopathy-related events (MCEs) and cardiomyopathy penetrance among
MYBPC3 founder variant carriers.
METHODS: We interviewed 188 carriers (57.4% male; aged 43.0±15.0 years) on exercise participation since the age of 10 years. The exercise was quantified as the metabolic equivalent of task-h/wk before the presentation. MCE was defined as a composite of malignant ventricular arrhythmia (sustained ventricular tachycardia/fibrillation), heart failure (heart failure hospitalizations or transplantation), and septal reduction therapy. Static and dynamic exercises were defined per the Bethesda classification. Associations of exercise with MCE and cardiomyopathy penetrance were adjusted for sex and assessed using Cox regression.RESULTS: Overall, 43 (22.9%) subjects experienced MCE and 139 (73.9%) were diagnosed with cardiomyopathy. No association was found between overall physical activity and high-static activity with MCE (
P=0.587 overall;
P=0.322 high static) or cardiomyopathy penetrance (
P=0.317 overall;
P=0.623 high static). In contrast, high-dynamic activity was associated with malignant ventricular arrhythmia (dichotomized at the 75th percentile: adjusted hazard ratio, 3.26 [95% CI, 1.26-8.44];
P=0.015).
CONCLUSIONS: Overall exercise participation does not generally increase the risk of adverse events among
MYBPC3 founder variant carriers. Nonetheless, an increased risk of malignant ventricular arrhythmia 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.
AB - BACKGROUND:
MYBPC3 founder variants cause hypertrophic cardiomyopathy leading to heart failure and malignant ventricular arrhythmias. Exercise is typically regarded as 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. Here, we evaluate the effects of exercise, stratified by high-static and high-dynamic components, on the risk of major cardiomyopathy-related events (MCEs) and cardiomyopathy penetrance among
MYBPC3 founder variant carriers.
METHODS: We interviewed 188 carriers (57.4% male; aged 43.0±15.0 years) on exercise participation since the age of 10 years. The exercise was quantified as the metabolic equivalent of task-h/wk before the presentation. MCE was defined as a composite of malignant ventricular arrhythmia (sustained ventricular tachycardia/fibrillation), heart failure (heart failure hospitalizations or transplantation), and septal reduction therapy. Static and dynamic exercises were defined per the Bethesda classification. Associations of exercise with MCE and cardiomyopathy penetrance were adjusted for sex and assessed using Cox regression.RESULTS: Overall, 43 (22.9%) subjects experienced MCE and 139 (73.9%) were diagnosed with cardiomyopathy. No association was found between overall physical activity and high-static activity with MCE (
P=0.587 overall;
P=0.322 high static) or cardiomyopathy penetrance (
P=0.317 overall;
P=0.623 high static). In contrast, high-dynamic activity was associated with malignant ventricular arrhythmia (dichotomized at the 75th percentile: adjusted hazard ratio, 3.26 [95% CI, 1.26-8.44];
P=0.015).
CONCLUSIONS: Overall exercise participation does not generally increase the risk of adverse events among
MYBPC3 founder variant carriers. Nonetheless, an increased risk of malignant ventricular arrhythmia 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.
KW - Adult
KW - Cardiomyopathy, Hypertrophic/genetics
KW - Carrier Proteins/genetics
KW - Exercise
KW - Female
KW - Heterozygote
KW - Humans
KW - Male
KW - Middle Aged
KW - Recreation
KW - Risk Factors
U2 - 10.1161/CIRCGEN.124.004561
DO - 10.1161/CIRCGEN.124.004561
M3 - Article
C2 - 39689185
SN - 2574-8300
VL - 17
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
IS - 6
M1 - e004561
ER -