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Project

Mechanical cardiac unloading with micro-axial flow pumps: post-implantation effects on remodelling and bleeding/thrombosis

The use of micro-axial flow pumps to support the left (and recently also the right) ventricle in cardiogenic shock patients has increased dramatically over the last decade. Although the device was primarily developed to support patients briefly during high-risk percutaneous coronary interventions (PCI), the benefit on longer-term support in cardiogenic shock patients became quickly apparent. Therefore, many questions in the medium-term follow-up (several days to 2 weeks) of these pump-supported patients remain unresolved. The major advantage of micro-axial pump support (especially after the onset of a large myocardial infarction), lies in the fact that these pumps can partly take over the failing native pumping function of the heart to supply critical organs with blood. This 'unloading' strategy of the failing heart appears to result in a better recovery of the heart muscle with smaller infarct size compared to unsupported patients after major myocardial infarction. Most severe and frequent complications during micro-axial flow pump-support patients occur related to the complex balance between thrombosis and bleeding and in the development of pump-motor induced hemolysis. This project aims to investigate crucial questions in the post-implantation course of these micro-axial flow pumps in order to provide clear-cut answers to some basic questions that may improve the daily management and outcome of these critically-ill patients in the cardiac intensive care unit. Through a large-animal model (sheep, calf) and an in-house designed ex-vivo Impella flow model, we will study: (a) Can infarct size by device support primarily be reduced in the first hours to days, or is there lasting benefit when the myocardium remains supported/unloaded for a longer time-frame after infarction? b) Today, therapeutic doses of heparin are advised as standard of care, although this is not supported by any scientific research. This brings up the question what the effect of low (intermediate) versus high (therapeutic) doses of heparin with respect to bleeding and pump thrombosis might be? (c) Recent research shows that the position and angle at which the pump is placed in the left ventricle is critical to induce or prevent device-induced hemolysis. This brings up the question what the effect of aberrant pump position in the ventricle with respect to hemolysis might be: can we draw any conclusions here about the optimal position of the device during echocardiographic monitoring? d) Micro-axial flow pumps do not have a continuous but a pulsatile flow. Do we find reorganization of the endothelium in the gastrointestinal tract due to loss of pulsatility in the systemic circulation (as seen in more aggressive forms of mechanical support - VA-ECMO); or is this effect much more limited during micro-axial flow pump support? This analysis is important given the fact that reorganization of the endothelium results into the acquired von willebrand syndrome and in turn greatly increases the incidence of gastrointestinal bleeding.  (e) Retrospective studies on a large VA-ECMO population by our own group have shown that the bleeding incidence in patients on VA-ECMO (plus heparin) post-infarction is not higher as compared to VA-ECMO patients (plus heparin) and dual antiplatelet therapy. This raises the question whether micro-axial flow pumps induce platelet degranulation. In other words, does the high shear stress of the pump cause platelet dysfunction and, consequently, is there a place for associating antiplatelet medication in these patients post-infarction as is standard of care today?

Date:16 Sep 2021 →  Today
Keywords:micro-axial flow pumps, unloading, Bleeding complications
Disciplines:Cardiology
Project type:PhD project