A Novel Hybrid Membrane VAD as First Step Toward Hemocompatible Blood Propulsion

Aldo Ferrari,Evgenij Potapov,Laura Bernardi,Bente Thamsen,Dimos Poulikakos,Costanza Giampietro,Mirko Meboldt,Giovanni Pellegrini,Björn J Bachmann ,Marianne Schmid Daners,Christoph Starck,Christian Loosli,Peter Zilla,Paolo Ermanni,Georgios Stefopoulos,Raoul Hopf,Gerald Kress,Volkmar Falk,Vita Marina,Mathias Rebholz,Tanja Schmidt,Simon H Sündermann ,Sarah Kitz,Deon Bezuidenhhout,Edoardo Mazza

doi:10.1007/s10439-020-02590-1

Abstract

Heart failure is a raising cause of mortality. Heart transplantation and ventricular assist device (VAD) support represent the only available lifelines for end stage disease. In the context of donor organ shortage, the future role of VAD as destination therapy is emerging. Yet, major drawbacks are connected to the long-term implantation of current devices. Poor VAD hemocompatibility exposes the patient to life-threatening events, including haemorrhagic syndromes and thrombosis. Here, we introduce a new concept of artificial support, the Hybrid Membrane VAD, as a first-of-its-kind pump prototype enabling physiological blood propulsion through the cyclic actuation of a hyperelastic membrane, enabling the protection from the thrombogenic interaction between blood and the implant materials. The centre of the luminal membrane surface displays a rationally-developed surface topography interfering with flow to support a living endothelium. The precast cell layer survives to a range of dynamically changing pump actuating conditions i.e., actuation frequency from 1 to 4 Hz, stroke volume from 12 to 30 mL, and support duration up to 313 min, which are tested both in vitro and in vivo, ensuring the full retention of tissue integrity and connectivity under challenging conditions. In summary, the presented results constitute a proof of principle for the Hybrid Membrane VAD concept and represent the basis for its future development towards clinical validation.

Highlights

Continuous flow left ventricular assist devices (VADs) represent a routine treatment option for patients in end stage heart failure
Patients with continuous flow pumps show a pathologic decrease of von Willebrand Factor originating from an imbalance between the increased degradation induced by high wall shear stress (WSS) and the decreased endothelial release due to the absence of pulsatility.[5,7,8,31,32,40]
The effect is obtained through a mitigation of the apparent WSS at the apical side of endothelial cells (ECs) nested in the hexagonal wells, as previously demonstrated by in vitro tests under a range of supraphysiological actuating conditions.[4]

Summary

Introduction

Continuous flow left ventricular assist devices (VADs) represent a routine treatment option for patients in end stage heart failure. In the first 2 years after implantation, the current generation of continuous flow VADs achieves survival comparable to heart transplantation.[21,33] Survival and functional status are markedly improved when compared to medical therapy alone.[38]. Patients supported with the CARMAT total artificial heart, a pulsatile device partially covered with bovine pericardium at its luminal surface, showed reduced thromboembolic complications without the need for anticoagulation, highlighting the importance of a hemocompatible interface.[17] The generation of surface textures at the luminal interface of HeartMate XVE supported the formation of a protective biological layer upon patient implantation[12] and reduced the risk of thromboembolic events without the need of anticoagulation therapy.[35]. The overall large pump size, its nonphysiological actuation and the uncontrolled generation of a biological layer represent limitations to be addressed

Methods

Results

Conclusion