Biomechanics of diastolic dysfunction: a one-dimensional computational modeling approach

Diastolic dysfunction (DD) is a major component of heart failure with preserved ejection fraction (HFpEF). Accordingly. a profound understanding of the underlying biomechanical mechanisms involved in DD is needed to elucidate all aspects of HFpEF. In this study, we have developed a computational model of DD by leveraging the power of an advanced one-dimensional arterial network coupled to a four-chambered zero-dimensional cardiac model. The two main pathologies investigated were linked to the active relaxation of the myocardium and the passive stiffness of the left ventricular wall. These pathologies were quantified through two parameters for the biphasic delay of active relaxation, which simulate the early and late-phase relaxation delay, and one parameter for passive stiffness, which simulates the increased nonlinear stiffness of the ventricular wall. A parameter sensitivity analysis was conducted on each of the three parameters to investigate their effect in isolation. The three parameters were then concurrently adjusted to produce the three main phenotypes of DD. It was found that the impaired relaxation phenotype can be replicated by mainly manipulating the active relaxation, the pseudo-normal phenotype was replicated by manipulating both the active relaxation and passive stiffness, and, finally, the restricted phenotype was replicated by mainly changing the passive stiffness. This article presents a simple model producing a holistic and comprehensive replication of the main DD phenotypes and presents novel biomechanical insights on how key parameters defining the relaxation and stiffness properties of the myocardium affect the development and manifestation of DD.