Abstract
BACKGROUND: Hypertrophic cardiomyopathy (HCM) diagnosis often occurs after myocardium thickening develops, delaying intervention. Cardiac diffusion tensor imaging (cDTI) detects microstructural myocardial remodeling, offering potential for improved risk stratification, especially in patients with preserved ejection fraction. OBJECTIVES: The objective of the study was to determine whether cDTI-derived fractional anisotropy (FA), mean diffusivity, and helix angle (HA) identify myocardial disarray and structural remodeling in HCM in patients and in mouse models. METHODS: Cardiovascular magnetic resonance imaging at 3T with cDTI (FA, mean diffusivity, and HA) and cine imaging was performed in 10 HCM patients with prior late gadolinium enhanced imaging and 10 healthy volunteers. In parallel, 6 myosin binding protein C3-knock-in and 6 wild-type mice (7-8 weeks) underwent cine-cardiovascular magnetic resonance imaging (9.4 T), ex vivo cDTI, scanning electron microscopy, and histology for microstructural, collagen area fraction and fibrosis analysis. RESULTS: HCM patients exhibited reduced FA vs controls (0.29 ± 0.03 vs 0.34 ± 0.02; P = 0.002), correlating with strain impairment (R(2) = 0.67; P = 0.003) and reaching the lowest value in patients with late gadolinium enhancement (P = 0.02). In knock-in mice, the reduction in FA mirrored the human findings. However, additional alterations were observed, including elevated HA transmurality, significant systolic dysfunction, and a strong correlation between FA and interstitial fibrosis. CONCLUSIONS: FA may reflect critical aspects of myocardial remodeling in HCM, including fibrosis, and mechanical dysfunction, as demonstrated in both preclinical and clinical settings. Its ability to detect abnormalities even in patients with preserved ejection fraction supports its potential as a translational marker for risk stratification and guiding therapeutic intervention.