Causes of Altered Ventricular Mechanics in Hypertrophic Cardiomyopathy—an In-Silico Study

Abstract

Background: Hypertrophic cardiomyopathy is a common heart disease causing alteration in the mechanical behaviour of the left ventricle (LV). Decreased myocardial velocities, reduced strain and strain rates have been reported clinically. These alterations result from underlying pathological mechanisms in the tissue: increased wall thickness, altered active and passive force development and/or fiber disarray, which are cumbersome to measure clinically. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the LV and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements. Results: We conducted an in-silico sensitivity study on physiological and pathological mechanisms potentially underlying the clinical hypertrophic cardiomyopathy phenotype. Deformation and mechanical behaviour of whole heart models was evaluated globally and regionally. Hypertrophy of the LV affected the course of strain, strain rate and wall thickening—the root mean squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10 %. A reduction of active force development by 40 % led to less overall deformation: maximal radial strain reduced from 26 % to 21 %. A five-fold increase in tissue stiffness caused a more homogeneous distribution of the strain values among the 17 AHA segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the left atria. Conclusions: This study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay hypertrophic cardiomybopathy. This knowledge can complement imaging-derived information to obtain a more accurate diagnosis of hypertrophic cardiomyopathy.