Macrovascular and microvascular function after implantation of left ventricular assist devices in end-stage heart failure: Role of microparticles

Abstract

The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction. Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-), CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay. FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx. Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.