Microstructural and Microvascular Phenotype of Sarcomere Mutation Carriers and Overt Hypertrophic Cardiomyopathy

• DOI: 10.1161/circulationaha.123.063835
• Publication Date: 2023-07-18T23:01:11Z
• Authors: George Joy; Christopher I. Kelly; Matthew Webber; Iain Pierce; Irvin Teh; Louise McGrath; Paula Velazquez; Rebecca K. Hughes; Huafrin Kotwal; Arka Das; Fiona Chan; Athanasios Bakalakos; Massimiliano Lore...; Konstantinos Savv...; Saidi A. Mohiddin; Peter W. Macfarlane; Michele Orini; Charlotte Manisty; Peter Kellman; Rhodri H. Davies; Pier D. Lambiase; Christopher Nguyen; Jurgen E. Schneider; Maite Tome; Gabriella Captur; Erica Dall’Armellina; James C. Moon; Luis R. Lopes
• Keywords: Sarcomeres; hypertrophic; Cardiomyopathy, Hypertrophic; diffusion tensor imaging; Fibrosis; perfusion; sarcomeres; 3. Good health; Diffusion Tensor Imaging; Phenotype; Original Research Articles; Mutation; magnetic resonance imaging; Humans; Hypertrophy, Left Ventricular; Genetic Predisposition to Disease; cardiomyopathy; Biomarkers

In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, recent evidence suggests that these may occur early. As novel therapy provides promise for modification, detection of phenotype development is an emerging priority. To evaluate their utility as early disease-specific biomarkers, we measured myocardial microstructure MVD 3 HCM groups-overt, either genotype-positive (G+LVH+) or genotype-negative (G-LVH+), subclinical (G+LVH-) HCM-exploring relationships with electrical changes genetic substrate. This was a multicenter collaboration to study 206 subjects: 101 patients overt (51 G+LVH+ 50 G-LVH+), 77 G+LVH-, 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring blood flow, reserve, defects), diffusion tensor measuring fractional anisotropy (lower values expected more disarray), mean diffusivity (reflecting packing/interstitial expansion), second eigenvector angle sheetlet orientation). Compared volunteers, had altered anisotropy, higher diffusivity, angle; all P<0.001) stress flow reserve; both P<0.001). Patients G-LVH+ were similar those but elevated (P<0.001 after adjustment left ventricular hypertrophy fibrosis). disease, defects found G+ not G- (100% [51/51] versus 82% [41/50]; P=0.001). G+LVH- compared volunteers similarly microstructure, although lesser extent (all parameters; P<0.001), (reduced [P=0.015] 28% 0 [P=0.002]). Disarray independently associated pathological electrocardiographic abnormalities fibrosis (overt: anisotropy: odds ratio abnormal 3.3, P=0.01; flow: ratio, 2.8, P=0.015; subclinical: 4.0, P=0.001; reserve 2.2, P=0.049). Microstructural alteration are different patients. Both also the absence sarcomeric mutation carriers, whom abnormalities. Measurable function early-phenotype biomarkers era disease-modifying therapy.