Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating MYBPC3 Founder Variant...

Area of Science:

• Cardiology
• Genetics
• Exercise Physiology

Background:

• MYBPC3 founder variants are a significant cause of hypertrophic cardiomyopathy (HCM), leading to heart failure and arrhythmias.
• The role of exercise in HCM expression among MYBPC3 variant carriers is debated, with conflicting evidence.
• Differentiating exercise types (static vs. dynamic) may clarify risks associated with physical activity.

Purpose of the Study:

• To evaluate the impact of exercise, stratified by static and dynamic components, on major adverse cardiovascular events (MACE) and cardiomyopathy penetrance in MYBPC3 founder variant carriers.
• To investigate whether different exercise intensities and types influence the risk of disease progression and adverse outcomes.

Main Methods:

• 188 MYBPC3 variant carriers were interviewed about their exercise history since age 10.
• Exercise was quantified using metabolic equivalents (METs) per week; static and dynamic components were classified per Bethesda guidelines.
• Major adverse cardiovascular events (MACE) included malignant ventricular arrhythmias, heart failure events, and septal reduction therapy; Cox regression adjusted for sex was used.

Main Results:

• No significant association was found between overall physical activity or high-static exercise and MACE or cardiomyopathy penetrance.
• High-dynamic exercise, particularly in the highest quartile, was significantly associated with an increased risk of malignant ventricular arrhythmia (aHR, 3.26; P=0.015).

Conclusions:

• General exercise participation does not appear to elevate the risk of adverse events in MYBPC3 variant carriers.
• High-intensity, high-dynamic exercise is associated with an increased risk of malignant ventricular arrhythmias, suggesting a need for caution with such activities.