Effect of Continuous-Flow Mechanical Support on Microvasculature Remodeling in the Failing Heart

Abstract

Purpose Left ventricle (LV) unloading using a left ventricular assist device (LVAD) has been shown to enhance reverse LV remodeling in end-stage cardiomyopathy. Despite the increasing need for its usage, the direct effect of continuous-flow LVAD with decreased pulsatility on microvasculature is unknown. We examined that continuous-flow support may affect microvasculature and remodeling of the failing heart. Methods and Materials The study included 24 patients with chronic heart failure who underwent LVAD implantation. Pulsatile-flow LVAD was used in 11 patients (P group), whereas continuous-flow LVAD was used in 13 patients (C group). Serial echocardiograms were compared between the 2 groups. Transmural LV tissues were sampled during both the implantation of the LVAD and removal of the implant for histopathological assessment including immunolabeling for CD31, α-smooth muscle actin (SMA), and Proliferating cell nuclear antigen (PCNA). Results Echocardiography showed that the LV systolic dimension and LV ejection fraction improved to a significantly greater extent in the P group than in the C group. Histological analysis showed significantly increased microvasculature density and decreased cardiomyocyte size during LVAD support in the P and C groups, without significant difference between the P and the C groups. Further, thickness of the SMA-positive layer of myocardial arterioles significantly increased during LVAD support in the C group (9±0.4 μm to 14±0.6 μm, P=0.0002), but did not change in the P group (10±1.7 μm to 12±0.7 μm, P=0.28). The number of PCNA positive cells per vessel was significantly increased in Group C, but not increased in group P, suggesting that hypertrophy of smooth muscle cell layer might be caused by proliferation of smooth muscle cells. Conclusions Use of the continuous-flow LVAD induced proliferation of smooth muscle cells of myocardial arterioles and it may limit the degree of functional reverse LV remodeling.