Key result
Pathogenic or likely pathogenic sarcomere mutations were associated with a more than 2-fold greater risk of adverse clinical outcomes compared to patients without mutations (HR 2.20).
Why the study?
The precise mechanisms linking known pathogenic gene mutations and the variable clinical prognosis in hypertrophic cardiomyopathy remain elusive.
Does the presence of sarcomere mutations predict adverse clinical outcomes and lifetime disease burden in patients with hypertrophic cardiomyopathy?
Cohort (n=4,591)
Yes
Does the presence of sarcomere mutations predict adverse clinical outcomes and lifetime disease burden in patients with hypertrophic cardiomyopathy?
Hazard Ratio: 2.2 (95% CI 1.89–2.54)
p-value: p=<0.001
Younger age at diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes and lifetime disease burden in hypertrophic cardiomyopathy.
May support sarcomere testing for HCM risk stratification; leaves open impact on therapy decisions pending prospective validation.
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy. It is one of the chief causes of sudden cardiac death in younger people and athletes. Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins. HCM has a relatively wide phenotypic heterogeneity, varying from asymptomatic to sudden cardiac death, because of the many different mutations and pathogenic genes underlying it. Many studies have explored the clinical symptoms and prognosis of HCM, emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM. To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease. Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients. As sequencing technology advances, the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer. HCM is a widespread inherited disease with a highly variable clinical phenotype. The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.
No takes yet. Share an insight, caveat, or question.
Hong et al. (2025) conducted a cohort in Hypertrophic cardiomyopathy (n=4,591). Pathogenic or likely pathogenic sarcomere mutations vs. No sarcomere mutations was evaluated on Overall composite outcome (ventricular arrhythmic or heart failure composite, all-cause mortality, atrial fibrillation, stroke, or death) (HR 2.20, 95% CI 1.89-2.54, p=<0.001). Pathogenic or likely pathogenic sarcomere mutations were associated with a more than 2-fold greater risk of adverse clinical outcomes compared to patients without mutations (HR 2.20).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: