Hypertrophic cardiomyopathy: genetics and clinical perspectives

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, characterized by myocardial hypertrophy and potential for sudden cardiac death.
• Mutations in sarcomere protein genes are primary drivers, leading to altered cardiomyocyte function, calcium handling, and metabolism.
• Disease expression is heterogeneous due to genetic, epigenetic, and environmental factors, complicating prognosis and management.

Purpose of the Study:

• To review current knowledge on the molecular genetics and pathogenesis of HCM.
• To provide an overview of evidence-based clinical management guidelines for HCM patients.
• To focus on clinical staging based on disease mechanisms for timely preventative interventions.

Main Methods:

• Review of current literature on HCM genetics, pathogenesis, and clinical management.
• Analysis of molecular diagnostic and clinical cascade screening approaches.
• Evaluation of sudden death risk stratification strategies and preventative therapies.

Main Results:

• Sarcomere gene mutations disrupt cardiomyocyte function and can activate signaling pathways affecting other cells.
• Clinical presentation and disease course are highly variable, ranging from asymptomatic to severe heart failure or sudden death.
• Advances in genetic diagnosis and imaging have improved risk stratification and reduced mortality.

Conclusions:

• Effective HCM management requires early identification of at-risk individuals through genetic screening and rigorous risk stratification.
• Preventative therapies are essential to avoid disease progression and irreversible myocardial remodeling.
• While causal therapies are lacking, a comprehensive understanding of pathogenesis guides current management and future therapeutic development.