Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices

Abstract

Background: Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients.

Methods: We enrolled 20 patients undergoing implantation of the HeartMate II LVAD (Thoratec Corp, Pleasanton, CA) and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at the 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry.

Results: During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm in 1, non-ST-elevation myocardial infarction in 2, arterial thrombosis in 2, gastrointestinal bleeding in 2, and stroke in 3. Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11% ± 1.26% vs 0.69% ± 0.46%, p = 0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39% ± 1.22% at discharge and then leveled to 1.97% ± 1.25% at the 3-month follow-up. Importantly, levels of PS+ microparticles were significantly higher in patients who developed an adverse event than in patients with no events (3.82% ± 1.17% vs 1.57% ± 0.59%, p < 0.001), even though the 2 patient groups did not markedly differ in other clinical and hematologic parameters.

Conclusions: Our results suggest that an elevation of PS+ microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events.

Keywords: cell-derived microparticles; phosphatidylserine; ventricular assist device.

Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Box plot showing the percentage of phosphatidylserine-positive (PS+) microparticles in healthy controls and in patients at baseline, discharge (approximately 1 month after LVAD implantation), and 3-month follow-up. A paired t test was used to compare values between patients and healthy subjects. Vertical axis measurements represent the mean percentage of PS+ microparticles in cell-free plasma.

Figure 2

Box plot showing the percentage of phosphatidylserine-positive (PS+) microparticles in healthy controls (Healthy), in patients before LVAD implantation (Baseline), in patients after LVAD implantation when an adverse event occurred [Events (+)], and in patients who had no adverse events after LVAD implantation (No events). Vertical axis measurements are given as the mean percentage of PS+ microparticles in cell-free plasma. A two-tailed t test was used to compare values between groups.