Preclinical large animal models of heart failure (HF) play a critical and expanding role in translating basic science findings to the development and clinical approval of novel therapeutics and devices. The complex combination of cardiovascular events and risk factors leading to HF has proved challenging for the development of new treatments for these patients. This state-of-the-art review presents historical and recent studies in porcine, ovine, and canine models of HF and outlines existing methodologies and physiological phenotypes. The translational importance of large animal studies to clinical success is also highlighted with an overview of recent devices approved by the Food and Drug Administration, together with preclinical HF animal studies used to aid both development and safety and/or efficacy testing. Increasing the use of large animal models of HF holds significant potential for identifying the novel mechanisms underlying the clinical condition and to improving physiological and economical translation of animal research to successfully treat human HF.
Keywords: AF, atrial fibrillation; ECM, extracellular matrix; EDP, end-diastolic pressure; EF, ejection fraction; FDA, Food and Drug Administration; HF, heart failure; HFpEF; HFpEF, heart failure with preserved ejection fraction; HFrEF; HFrEF, heart failure with reduced ejection fraction; I/R, ischemia/reperfusion; IABP, intra-aortic balloon pump; LAD, left anterior descending; LCx, left circumflex; LV, left ventricular; MI, myocardial infarction; PCI, percutaneous coronary intervention; RV, right ventricular; heart failure; large animal model; preclinical.
© 2020 The Authors.