Translational Insights Into Myocardial Deformation and Fibrosis in Hypertrophic Cardiomyopathy Using Diffusion Tensor...

Area of Science:

• Cardiovascular Imaging
• Biomedical Engineering
• Medical Diagnostics

Background:

• Hypertrophic cardiomyopathy (HCM) diagnosis is often delayed until significant myocardial thickening occurs.
• Cardiac diffusion tensor imaging (cDTI) can detect microstructural myocardial remodeling, aiding early risk stratification, particularly in patients with preserved ejection fraction.

Purpose of the Study:

• To evaluate if cDTI-derived fractional anisotropy (FA), mean diffusivity, and helix angle (HA) can identify myocardial disarray and structural remodeling in HCM.
• To assess the utility of these cDTI parameters in both human patients and preclinical mouse models of HCM.

Main Methods:

• Cardiovascular magnetic resonance imaging with cDTI and cine imaging was performed on 10 HCM patients and 10 healthy volunteers.
• A parallel study involved cine-MRI, ex vivo cDTI, scanning electron microscopy, and histology on myosin binding protein C3-knock-in and wild-type mice.

Main Results:

• HCM patients showed significantly reduced FA compared to controls, correlating with impaired strain.
• FA values were lowest in HCM patients with late gadolinium enhancement.
• Knock-in mice exhibited similar FA reductions, along with elevated HA transmurality, systolic dysfunction, and a correlation between FA and interstitial fibrosis.

Conclusions:

• Fractional anisotropy (FA) may serve as a crucial marker for myocardial remodeling in HCM, reflecting fibrosis and mechanical dysfunction.
• The ability of FA to detect abnormalities in patients with preserved ejection fraction highlights its potential as a translational marker for risk stratification and guiding therapy.