Key result
Thin-filament HCM mutations are linked to ~460% greater risk of advanced HF versus thick-filament mutations.
Why the study?
Recent studies revealed distinct disease mechanisms linked to rare thin-filament mutations in HCM, highlighting the need for further investigation into this subgroup.
Does the presence of thin-filament mutations compared to thick-filament mutations affect disease progression and phenotype in adults with sarcomere-positive hypertrophic cardiomyopathy?
Cohort (n=82)
Does the presence of thin-filament mutations compared to thick-filament mutations affect disease progression and phenotype in adults with sarcomere-positive hypertrophic cardiomyopathy?
In adults with sarcomere-positive HCM, thin-filament mutations are associated with a thinner phenotype and more rapid progression to advanced heart failure compared to thick-filament mutations.
Answers are grounded in this paper and cite their sources.
May warrant closer HF surveillance in thin-filament HCM; leaves open whether genotype should guide therapy.
Background/Objectives: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. The most frequently mutated genes encode proteins of the thick filament of the sarcomere, while mutations in thin-filament genes are rare findings in HCM cohorts. Recent studies have revealed distinct mechanisms of disease development linked to thin-filament mutations, highlighting the need for further investigation into this rare subgroup. Methods: A total of 82 adult patients with sarcomere-positive HCM were enrolled. Baseline characteristics and nearly five years of follow-up data from 15 patients with thin-filament mutations were analyzed and compared with those from 67 patients with thick-filament mutations and findings from other studies. Results: Compared to thick-filament HCM patients, individuals with thin-filament mutations exhibited significantly lower maximum left ventricular wall thickness, as measured by both echocardiography (p = 0.024) and cardiac magnetic resonance (p = 0.006), showed more rapid progression to advanced heart failure (HR = 5.6, p = 0.018), and less often underwent septal reduction therapy (p = 0.025). None of the thin-filament HCM patients experienced malignant arrhythmic events. Conclusions: In adults, thin-filament HCM is associated with a ‘thinner’ phenotype and a more rapid progression to advanced heart failure compared to thick-filament HCM. Data on a higher risk of malignant arrhythmias in thin-filament HCM remain controversial between studies and rather depend on the age of onset and genotype in each particular family.
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Чумакова et al. (2025) conducted a cohort in Hypertrophic cardiomyopathy (n=82). Thin-filament mutations vs. Thick-filament mutations was evaluated on Progression to advanced heart failure (HR 5.6, p=0.018). Thin-filament mutations in adult hypertrophic cardiomyopathy were associated with a more rapid progression to advanced heart failure compared to thick-filament mutations (HR 5.6, p=0.018).
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