Echocardiographic Strain Abnormalities Precede Left Ventricular Hypertrophy Development in Hypertrophic Cardiomyopathy Mutation Carriers

• Published in: International journal of molecular sciences Vol. 25; no. 15; p. 8128
• Main Authors: Canciello, Grazia, Lombardi, Raffaella, Borrelli, Felice, Ordine, Leopoldo, Chen, Suet-Nee, Santoro, Ciro, Frisso, Giulia, di Napoli, Salvatore, Polizzi, Roberto, Cristiano, Stefano, Esposito, Giovanni, Losi, Maria-Angela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2024
• Subjects: Adolescent; Adult; Cardiac Myosins - genetics; Cardiomyopathy; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Hypertrophic - diagnostic imaging; Cardiomyopathy, Hypertrophic - genetics; Carrier Proteins - genetics; Development and progression; Doppler effect; Echocardiography - methods; Ejection fraction; Ethylenediaminetetraacetic acid; Female; Genes; Genetic aspects; Genetic disorders; Genotype & phenotype; Heart enlargement; Heterozygote; Humans; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - genetics; Male; Medicine, Preventive; Middle Aged; Mutation; Myosin Heavy Chains - genetics; Phenotype; Population; Preventive health services; Proteins; Troponin T - genetics; Young Adult; global longitudinal strain; screening; subclinical detection; genetics; left ventricular hypertrophy; hypertrophic cardiomyopathy; diastolic strain rate; strain echocardiography
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158128

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen−) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen−. Sixteen Gen+/Phen− (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH−) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (−19.8 ± 0.4 vs. −22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen− subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.