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 and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at 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 (n=1), non–ST-elevation myocardial infarction (n=2), arterial thrombosis (n=2), gastrointestinal bleeding (n=2), and stroke (n=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 3-month follow-up. Importantly, patients who developed an adverse event had significantly higher levels of PS+ microparticles than did 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.

Platelet-Derived Microparticles Generated by Neonatal Extracorporeal Membrane Oxygenation Systems

“…This is concerning because a recent study on left ventricular assist devices documents that increased phosphatidylserine + MPs are associated with adverse clinical outcomes. 34 Therefore, this study confirms a new biological consequence that may promote thrombosis in biomedical devices. Future studies will use human blood, improved microparticle enumeration methods, correlation to clinically relevant thrombosis assays, and clinical studies on neonatal patients supported with extracorporeal blood pumps.…”

Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms

“…Again this could relate in part to disease modification. Nevertheless, a study of patients with continuous-flow left ventricular assist devices, which directly expose blood cells to high shear stress, also found increased levels of PS (phosphatidylserine)-exposing MVs associated with the activity of the device [53].…”

“…This is suggested by studies which have looked at release following prolonged therapies that study MV levels after several weeks or even months from the initial baseline assessment [52,53] and show significant sustained changes in circulating MV levels. However, such studies are limited by the potential modifying effect of therapies on the underlying triggers for MV release.…”

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

“…17 Although microparticles circulate in blood from healthy individuals, their numbers are increased in blood samples from patients several cardiovascular diseases and conditions that predispose to cardiovascular disease, [13][14][15] and they are associated with adverse outcomes in patients with ischemic chronic heart failure 18 and in patients after LVAD implantation. 19 The literature suggests that the number of circulating microparticles may be a marker of endothelial activation or damage and platelet activation. 13,15 In addition, it was appreciated that microparticles harbor numerous membrane and cytoplasmic proteins from the cells from which they originate [20][21][22] and may play a role as a disseminated storage pool of bioactive effectors in intercellular communication mediating effects in cardiovascular physiology and pathophysiology.…”