Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients With Lamin A/C Genotype.

Area of Science:

• Cardiology
• Genetics
• Exercise Physiology

Background:

• Lamin A/C cardiomyopathy is a severe, inherited heart condition with high penetrance.
• While competitive sports are linked to adverse events, the impact of recreational exercise remains unclear.
• Understanding exercise effects is crucial for managing this genetic disorder.

Purpose of the Study:

• To investigate the association between cumulative lifetime exercise and disease severity in lamin A/C genotype-positive patients.
• To determine if exercise habits influence cardiac function and clinical outcomes in this population.

Main Methods:

• Sixty-nine patients with lamin A/C genotype completed exercise questionnaires from age 7 to diagnosis.
• Cumulative lifetime exercise (hours >3 metabolic equivalents) was calculated, categorizing patients as active or sedate.
• Cardiac function was assessed via echocardiography, ECG, Holter monitoring, and NT-proBNP levels.

Main Results:

• Active patients exhibited lower left ventricular ejection fraction (43% vs. 51%, P=0.006) and higher NT-proBNP (P=0.03).
• Each tertile increase in lifetime exercise correlated with a 4% decrease in left ventricular ejection fraction (P=0.03).
• Clinically significant left ventricular ejection fraction (<45%) occurred at a younger age in active patients (P=0.007).

Conclusions:

• Increased exercise exposure in lamin A/C patients is associated with worse systolic function and earlier disease manifestation.
• These findings suggest that physical activity may accelerate disease progression in lamin A/C cardiomyopathy.
• Results may inform revised exercise guidelines for individuals with lamin A/C genotype.