Differences in Disease Trajectory, Comorbidities, and Mortality in Sarcomeric and Nonsarcomeric Hypertrophic Cardiomyopathy - PubMed
3 days ago
- #genetics
- #cardiovascular outcomes
- #hypertrophic cardiomyopathy
- Sarcomere gene variants are a key cause of hypertrophic cardiomyopathy (HCM) and are associated with worse prognosis.
- The study compared sarcomeric HCM (with pathogenic/likely pathogenic sarcomere variants) and nonsarcomeric HCM (genetically elusive) in 6,120 patients.
- Sarcomeric HCM patients were diagnosed younger (median 38.1 vs. 54.3 years) and had less obesity, hypertension, and left ventricular (LV) obstruction.
- After age standardization, sarcomeric HCM had higher incidences of atrial fibrillation, LV systolic dysfunction, and ventricular arrhythmias compared to nonsarcomeric HCM.
- All-cause mortality was similar between groups, but sarcomeric HCM patients died younger, losing an estimated 3.5 life-years between ages 44 and 85.
- Sarcomeric HCM was associated with higher HCM-related mortality (HR 1.61).
- Atrial fibrillation was identified as the strongest disease-modifier, increasing risks of LV systolic dysfunction, ventricular arrhythmias, and mortality in both groups.
- Genotype-interaction analyses showed a larger impact of atrial fibrillation and LV systolic dysfunction on adverse outcomes in sarcomeric HCM.
- Sarcomeric HCM may benefit from more vigilant surveillance for arrhythmias and systolic dysfunction, with a lower threshold for advanced therapies.
- Comorbidities like hypertension and obesity may be modifiable risk factors for nonsarcomeric HCM patients.