Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients

Area of Science:

• Cardiovascular Physiology
• Biomedical Engineering
• Computational Biology

Background:

• Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular (LV) hypertrophy, myofiber disarray, and reduced global longitudinal strain (GLS).
• The distinct impacts of these pathological features on LV function in obstructive versus non-obstructive HCM phenotypes remain unclear.

Purpose of the Study:

• To investigate the effects of myofiber disarray on LV mechanics in obstructive and non-obstructive HCM using patient-specific computational models.
• To compare LV function between HCM phenotypes and a control subject.

Main Methods:

• Developed patient-specific LV computational models using cardiac MRI data from two female HCM patients and one control.
• Incorporated active stress formulation and structural tensors to model LV mechanics and myofiber disarray.
• Calibrated models using clinical measurements including LV pressure/volume, peak GLS, and blood pressure within a closed-loop circulatory system.

Main Results:

• Without considering myofiber disarray, peak myofiber tension was lowest in obstructive HCM, followed by non-obstructive HCM, and then the control subject.
• Increasing myofiber disarray necessitated higher peak tension in HCM models to match clinical data.
• Obstructive HCM patients exhibited depressed peak tension even at maximal observed myofiber disarray levels.

Conclusions:

• Patient-specific computational modeling provides insights into the complex mechanics of HCM.
• Myofiber disarray plays a crucial role in modulating LV tension in HCM, but obstructive HCM may have unique mechanical characteristics.
• This modeling approach can be extended for future studies with larger HCM patient cohorts.