Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy
View Full Paper
Ask AI
Bookmark
Share
Why the study?
Low penetrance sarcomere variants at intermediate frequencies and effect sizes have not been systematically investigated in hypertrophic cardiomyopathy.
Does the presence of low penetrance sarcomere variants increase disease severity and adverse clinical outcomes in patients with hypertrophic cardiomyopathy?
Population
6045 patients with HCM in the SHaRe registry
Comparison
Low penetrance sarcomere variants alone or with pathogenic variants vs other genetic profiles
Design
Registry-based genetic and observational cohort study with functional and population-based validation
Authors
Discussion
Loading...
Member takes
Implication
LowSVs may contribute to HCM risk in registry data; leaves open their inclusion in clinical genetic panels.
Structured PICO
Does the presence of low penetrance sarcomere variants increase disease severity and adverse clinical outcomes in patients with hypertrophic cardiomyopathy?
P
Population
6,045 patients with hypertrophic cardiomyopathy (HCM) who underwent genetic testing in the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), median age of diagnosis 46.6 years, 61.6% male.
I
Intervention
Presence of low penetrance sarcomere variants (LowSVs), either isolated or in combination with pathogenic sarcomere variants.
C
Comparator
Patients with isolated pathogenic sarcomere variants (HCMPath) or negative genetic testing for sarcomere variants (HCMSarcNeg).
O
Outcome
Composite of death, transplant, cardiac arrest, ventricular arrhythmia, or New York Heart Association class III/IV heart failure.composite
Low penetrance sarcomere variants are relatively common and cause mild HCM in isolation, but markedly increase disease severity when combined with pathogenic variants, supporting an additive genetic risk model.
Cite This Study
Meisner et al. (2024) studied this question.
Topics
View Full Paper
Ask AI
Bookmark
Share