Editors' ChoiceHeart Failure

Building a better way to mend a broken heart

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Science Translational Medicine  23 Sep 2020:
Vol. 12, Issue 562, eabe6020
DOI: 10.1126/scitranslmed.abe6020

Abstract

A novel hybrid pulsatile ventricular assist device uses an endothelialized pump surface to achieve biocompatibility.

About 6 million patients suffer from heart failure in the United States, which contributes to more than 13% of annual deaths. Advancements in interventional therapies and circulatory support enable survival from what was previously devastating myocardial injury and contribute to a rising prevalence of heart failure. Heart transplantation is the definitive treatment for patients with debilitating disease; however, demand far outstrips donor organ availability and drives an urgent need for new therapies.

Ventricular assist devices (VADs), surgically implanted mechanical pumps capable of maintaining systemic perfusion, are increasingly considered as long-term support options for patients with heart failure. Previously used primarily as a bridge to transplantation, VADs are now considered a viable alternative to transplantation, with survival rates similar to those for patients receiving a transplanted heart, but are not without complications. Blood contact with the nonbiological pump surface is a constant risk for thrombosis and requires lifelong anticoagulation. Additionally, high-wall shear stress generated by these devices degrades von Willebrand factor, while non-pulsatile flow promotes the formation of arteriovenous malformations. These factors lead to the ever-present simultaneous risk of both life-threatening clotting and hemorrhage for patients with VADs.

Ferrari et al. detail an innovative biocompatible pump that may provide a solution to these challenges and open the door for greatly improved long-term support of patients with heart failure. They designed a pulsatile volume displacement pump in which a molded elliptic layer of hyperelastic silicone was used as the pumping chamber surface. They further modified the surface through the creation of hexagonal wells into which they seeded endothelial cells to create a biocompatible cellular monolayer. Using computational fluid dynamics, Ferrari and colleagues quantified flow conditions within the pump to determine the physiological operating range of the device to ensure cell monolayer integrity. The team evaluated the device in a mechanical circulatory loop setup to assess the pump’s durability and endothelial cell viability over more than 25 million pumping cycles conducted over 10 weeks. The device demonstrated no evidence of structural impairment over this test period, and endothelial cells were maintained in monolayer throughout the pump activity. The device was then validated in a short-term ovine model to test biocompatibility and pump function.

Although the novel pump design represents an exciting advance in durable mechanical support, multiple hurdles must still be cleared prior to clinical use. Only the actuating silicone membrane was endothelialized in the study whereas the remainder of the tubing and chamber remained exposed to blood, constituting potential sites of thrombosis. Additionally, silicone membrane deformation during pump actuation is at risk for wear, and long-term durability must be further assessed. Although daunting, Ferrari and colleagues may yet clear these hurdles and demonstrate the potential of their solution for mending a broken heart.

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