Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy

• Published in: Journal of cardiovascular magnetic resonance Vol. 23; no. 1; p. 18
• Main Authors: Chung, Hyemoon, Kim, Yoonjung, Park, Chul-Hwan, Kim, Jong-Youn, Min, Pil-Ki, Yoon, Young Won, Kim, Tae Hoon, Lee, Byoung Kwon, Hong, Bum-Kee, Rim, Se-Joong, Kwon, Hyuck Moon, Lee, Kyung-A, Choi, Eui-Young
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04-03-2021; BioMed Central; Elsevier
• Subjects: Adult; Aged; Cardiomyopathy; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Hypertrophic - diagnostic imaging; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - pathology; Care and treatment; Case-Control Studies; Contrast agents; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; Doppler effect; Echocardiography, Doppler; Female; Fibrosis; Gadolinium; Gene mutations; Genes; Genetic analysis; Genetic aspects; Genetic Predisposition to Disease; Genomes; Genomics; Humans; Hypertrophic cardiomyopathy; Magnetic resonance; Magnetic Resonance Imaging, Cine; Male; Medical imaging; Middle Aged; Mitochondria; Mitochondria - genetics; Mitochondrial DNA; Mutation; Myocardial fibrosis; Myocardium - pathology; Phenotype; Prognosis; Sarcomere gene mutation; Sarcomeres - genetics; Segments; Software; Hypertrophic cardiomyopathy; Sarcomere gene mutation; Mitochondria; Myocardial fibrosis
• ISSN: 1097-6647; 1532-429X
• DOI: 10.1186/s12968-021-00718-3

Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM.
In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations.
Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group.
SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis.