Large Animal Models for Left Ventricular Assist Device Research and Development

In vivo preclinical testing of left ventricular assist devices (LVADs) warrants a large animal model that faithfully simulates human etiology. Although LVAD recipients are in end-stage heart failure (HF), healthy, young animals have served as the experimental platform for most LVAD research and development (R&D) to demonstrate device safety, reliability, and biocompatibility. The rapidly growing HF epidemic, donor heart shortage, and clinical acceptance of LVAD for bridge-to-transplant therapy (BTT) has led to the expanded role of LVAD for destination therapy and bridge-to-recovery therapy. New paradigms for the clinical care of these emerging patient populations are needed. Clinically relevant, robust, and reproducible large animal models of HF are required to demonstrate efficacy, investigate physiologic responses, elucidate genetic, molecular, and cellular mechanism(s), and develop LVAD control strategies. The animal model must be comparable in size, anatomical structure, and phenotype; the technique used to initiate HF must reflect the clinical portrait, should be technically and financially feasible, result in predictable, stable, and irreversible HF, and demonstrate bidirectionality of the remodeling cascade. In this review, large animal species commonly used in cardiac research, techniques used to create chronic HF, and the combined applicability to preclinical LVAD R&D studies are presented.