Thin Filament Cardiomyopathy: Natural History, Clinical Features, And Outcomes

Abstract

Introduction Hypertrophic cardiomyopathy due to thin filament mutations (HCM-Thin) has classically been characterized as more malignant with a higher burden of lethal arrhythmias and higher risk for sudden cardiac death compared to HCM from thick filament mutations (HCM-Thick). However, due to paucity of data and conflicting reports from small retrospective studies, the treatment of patients with HCM from thin and thick filament mutations have largely been the same. Objectives This systemic review includes all published case reports and series on HCM-Thin to understand the natural history and clinical outcomes in those with this condition. Methods A PubMed query regarding HCM-TF cases published until April 22, 2020 yielded twenty manuscripts that met inclusion criteria. Patients were included if a pathogenic mutation was identified or if the patient had clinical manifestations of hypertrophic cardiomyopathy and a first degree relative with positive genetic testing. Demographic, clinical characteristics, imaging data and outcomes were collected. Results A total of 211 HCM-Thin patients were identified with the most common mutations being TNNT2 (50.0%), TNNI3 (23.7%), and TPM1 (22.2%). The most common symptom reported was dyspnea (62.4%) with 22.4% classified as NYHA III and IV. Left ventricular outflow obstruction was present in 9.6% patients with the median left ventricular maximal thickness of 16.5 mm. Cardiac conduction abnormalities were frequent (56.9%) with the most common being ST-T abnormalities; Notably 26% were found to have atrial fibrillation and 18.3% had ventricular arrhythmias. The composite outcome of death, heart transplant, or ventricular assist device occurred in 18.5% of the cohort. Sudden cardiac death (55.6%) was the most common cause of mortality, but only 15.9% of patients received an ICD. Conclusion In this systematic analysis, HCM-Thin patients had a high risk of all-cause mortality or heart transplant, arrhythmia and advanced heart failure despite low rates of obstruction and hypertrophy. HCM-Thin may be a unique endotype that deserves distinct therapeutic approaches. Hypertrophic cardiomyopathy due to thin filament mutations (HCM-Thin) has classically been characterized as more malignant with a higher burden of lethal arrhythmias and higher risk for sudden cardiac death compared to HCM from thick filament mutations (HCM-Thick). However, due to paucity of data and conflicting reports from small retrospective studies, the treatment of patients with HCM from thin and thick filament mutations have largely been the same. This systemic review includes all published case reports and series on HCM-Thin to understand the natural history and clinical outcomes in those with this condition. A PubMed query regarding HCM-TF cases published until April 22, 2020 yielded twenty manuscripts that met inclusion criteria. Patients were included if a pathogenic mutation was identified or if the patient had clinical manifestations of hypertrophic cardiomyopathy and a first degree relative with positive genetic testing. Demographic, clinical characteristics, imaging data and outcomes were collected. A total of 211 HCM-Thin patients were identified with the most common mutations being TNNT2 (50.0%), TNNI3 (23.7%), and TPM1 (22.2%). The most common symptom reported was dyspnea (62.4%) with 22.4% classified as NYHA III and IV. Left ventricular outflow obstruction was present in 9.6% patients with the median left ventricular maximal thickness of 16.5 mm. Cardiac conduction abnormalities were frequent (56.9%) with the most common being ST-T abnormalities; Notably 26% were found to have atrial fibrillation and 18.3% had ventricular arrhythmias. The composite outcome of death, heart transplant, or ventricular assist device occurred in 18.5% of the cohort. Sudden cardiac death (55.6%) was the most common cause of mortality, but only 15.9% of patients received an ICD. In this systematic analysis, HCM-Thin patients had a high risk of all-cause mortality or heart transplant, arrhythmia and advanced heart failure despite low rates of obstruction and hypertrophy. HCM-Thin may be a unique endotype that deserves distinct therapeutic approaches.