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Published on: August 8, 2022
Clinical Features and Prospective Outcomes of Thin-Filament Hypertrophic Cardiomyopathy: Intrinsic Data and
Olga S Chumakova1,2, Tatiana N Baklanova1, Dmitry A Zateyshchikov1,2
1Moscow Healthcare Department, City Clinical Hospital 17, 119620 Moscow, Russia.
Insights
Thin-filament hypertrophic cardiomyopathy (HCM) presents a thinner heart muscle phenotype and faster progression to heart failure compared to thick-filament HCM. Arrhythmia risk is not definitively higher in thin-filament HCM.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart disease, typically linked to sarcomere thick filament mutations.
- Thin-filament gene mutations are rare causes of HCM, yet recent research suggests unique disease mechanisms.
- Further investigation into thin-filament HCM is crucial for understanding disease heterogeneity.
Purpose of the Study:
- To investigate the clinical characteristics and progression of hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations.
- To compare the phenotype and outcomes of thin-filament HCM with those of thick-filament HCM.
Main Methods:
- Analysis of baseline and follow-up data from 15 adult patients with thin-filament HCM.
- Comparison with 67 adult patients with thick-filament HCM.
- Utilized echocardiography and cardiac magnetic resonance imaging for assessing left ventricular wall thickness.
Main Results:
- Thin-filament HCM patients showed significantly lower maximum left ventricular wall thickness compared to thick-filament HCM patients (echocardiography p=0.024, cardiac MRI p=0.006).
- Individuals with thin-filament mutations had a more rapid progression to advanced heart failure (HR=5.6, p=0.018) and less frequently underwent septal reduction therapy (p=0.025).
- No malignant arrhythmic events were observed in the thin-filament HCM cohort.
Conclusions:
- Adults with thin-filament HCM exhibit a distinct 'thinner' phenotype and a more aggressive disease course leading to advanced heart failure.
- The association of thin-filament HCM with malignant arrhythmias remains controversial and may depend on specific genetic factors and age of onset.
Abstract:
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.
