Does EDPVR Represent Myocardial Tissue Stiffness? Toward a Better Definition

Accurate assessment of myocardial tissue stiffness is pivotal for the diagnosis and prognosis of heart diseases. Left ventricular diastolic stiffness (β) obtained from the end-diastolic pressure-volume relationship (EDPVR) has conventionally been utilized as a representative metric of myocardial stiffness. The EDPVR can be employed to estimate the intrinsic stiffness of myocardial tissues through image-based in-silico inverse optimization. However, whether β, as an organ-level metric, accurately represents the tissue-level myocardial tissue stiffness in healthy and diseased myocardium remains elusive. We developed a modeling-based approach utilizing a two-parameter material model for the myocardium (denoted by a_f and b_f) in image-based in-silico biventricular heart models to generate EDPVRs for different material parameters. Our results indicated a variable relationship between β and the material parameters depending on the range of the parameters. Interestingly, β showed a very low sensitivity to a_f, once averaged across several LV geometries, and even a negative correlation with a_f for small values of a_f. These findings call for a critical assessment of the reliability and confoundedness of EDPVR-derived metrics to represent tissue-level myocardial stiffness. Our results also underscore the necessity to explore image-based in-silico frameworks, promising to provide a high-fidelity and potentially non-invasive assessment of myocardial stiffness.