Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise...

Area of Science:

• Cardiology
• Genetics
• Exercise Physiology

Background:

• Hypertrophic cardiomyopathy (HCM) risk stratification requires integrating genetic data with clinical and functional variables.
• The predictive value of genetic testing versus cardiopulmonary exercise test (CPET) data in HCM remains incompletely understood.

Purpose of the Study:

• To investigate the role of genetic variants and CPET-derived functional variables in predicting adverse outcomes in HCM patients.
• To compare the predictive power of genotype-phenotype correlations with clinical and CPET data for heart failure (HF) and sudden cardiac death (SCD).

Main Methods:

• Retrospective analysis of 371 HCM patients, including genetic screening of key sarcomeric genes (MYBPC3, MYH7, TNNI3, TNNT2).
• Correlation of genetic findings (likely pathogenic/pathogenic variants, variants of uncertain significance) with clinical data and CPET results.
• Longitudinal follow-up for a median of 5.4 years to assess development of HF and SCD or SCD-equivalents.

Main Results:

• Patients with likely pathogenic/pathogenic (LP/P) variants showed a more aggressive HCM phenotype.
• Left atrial diameter (LAd) and circulatory power (CP%) were independent predictors of HF (C-index = 0.839).
• LAd and CP% also predicted SCD end-point (C-index = 0.738), highlighting their prognostic significance.

Conclusions:

• Clinical variables, especially CPET-derived metrics like LAd and CP%, are pivotal for accurate HCM risk stratification.
• Genetic testing alone is less effective than integrated clinical and functional assessments for predicting adverse events in HCM.
• CPET data provides essential prognostic information for managing HCM patients.