Animal models of heart failure with preserved ejection fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50 % of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models.

Keywords: Animal models, Rodents; Diastolic dysfunction; Heart failure with preserved ejection fraction.

Fig. 1

Schematic representation of HFpEF pathophysiology. Comorbidities are associated with systemic changes and myocardial molecular dysfunction translating into structural changes that contribute to HFpEF pathophysiology. IL-6 interleukin-6, TNF-α tumour necrosis factor alpha, NO nitric oxide, ROS reactive oxygen species, MMPs matrix metalloproteinases, TGF-β transforming growth factor beta.

Fig. 2

Representative pressure-volume (P-V) loops and echocardiography tracings from Wistar-Kyoto (normotensive control group of obese ZSF1 rats), lean ZSF1 (hypertensive lean control group of obese ZSF1 rats, ZSF1 Ln) and obese ZSF1 (ZSF1 Ob). A late diastolic transmitral filling velocities, A’ late diastolic tissue Doppler mitral annulus velocity, E early filling transmitral Doppler velocity, E’ early diastolic tissue Doppler mitral annulus velocity, S’ peak systolic tissue Doppler mitral annular velocity