Clinical Features and Prospective Outcomes of Thin Filament Hypertrophic Cardiomyopathy: Intrinsic Data and Comparative Insights from Other Cohorts

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 were less often underwent septal reduction therapy (p = 0.025). None of 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 partic-ular family.