Abstract 17429: A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Sustained Severe Hypertension

Abstract

Background: Currently, the lack of well-established large animal models of heart failure with preserved ejection fraction (HFpEF) is one of the major hurdles for developing effective therapies for HFpEF. Here, we describe a large animal model of HFpEF induced by sustained hypertension (HT) that mimics human diseases. Methods: We induced sustained severe hypertension in 9 adult pigs using a combination of intravenous Angiotensin-II (Ang-II, 0.015mg/hr) delivery with an osmotic infusion pump and subcutaneous implantation of deoxycorticosterone acetate (DOCA) pellets (100mg/kg) for 10 weeks. All animals underwent invasive blood pressure (BP) telemetry monitoring and serial invasive pressure-volume (PV) loop assessment as well as echocardiographic examination at baseline, 10 weeks and 18 weeks. Results: Mean systolic and diastolic BP at baseline was 88/61 mmHg which increased immediately after Ang-II infusion plus DOCA (Week 0,158/105 mmHg) and progressively elevated up to Week 10 (171/126mmHg) that persisted out to Week 18 (183/137mmHg) despite termination of Ang-II infusion. Serial echocardiograms showed the development of left ventricular hypertrophy with significant increase in left ventricular mass with preserved left ventricular ejection fraction (Figure, upper panel). PV loop showed progressive elevation of pulmonary artery capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and end-diastolic pressure volume relationship (EDPVR) without change in end-systolic pressure volume relationship, suggestive of left ventricular diastolic dysfunction (Figure, lower panel). Conclusions: We successfully established a clinically relevant large animal model of HFpEF induced by sustained HT, which can be used for future investigation of new treatments for HFpEF.