Abstract 16506: Regional Heterogeneity of Ventricular Contractility Enhances Efficacy of Cardiac Resynchronization
Cardiac resynchronization therapy (CRT) improves systolic function of the failing heart, increasing ejection fraction and stroke work of the left ventricle (LV). However, the mechanisms by which this improvement takes place are not fully understood. Research has shown that in the failing heart the maximal circumferential shortening was significantly greater in the lateral wall than in other LV locations. We hypothesize that regional heterogeneity in ventricular contractility is an important mechanism underlying CRT efficacy. We employed a novel MRI-based 3D electromechanical model of the failing canine ventricles to simulate contraction under left bundle branch block (LBBB). Systolic improvements induced by epicardial LV pacing at the midbase of the lateral wall were compared between model ventricles with spatially homogeneous and heterogeneous mechanical properties of cardiac tissue. Heterogeneity in ventricular contractility was introduced by increasing myofilament Ca sensitivity (ΔpCa50=0.31 at sarcomere length=2.1 um) in the lateral LV wall. Systolic improvement following LV pacing was quantified as acute changes in stroke work. CRT increased stroke work by 4% and 18% in the homogeneous and heterogeneous models, respectively. Examination of the mechanisms revealed that in the heterogeneous model, LV pacing resulted in pre-stretch of myofibers (indicated by arrows in the Figure) at ventricular regions with lower myofilament Ca sensitivity. Pre-stretch prolonged the onset of myofiber relaxation at these regions, synchronizing relaxation throughout the ventricles. This finding indicates that regional heterogeneity in ventricular contractility is a possible mechanism underlying acute systolic improvement induced by CRT in the failing ventricles.
- © 2011 by American Heart Association, Inc.