Animal models of heart failure with preserved ejection fraction

G Conceição,A P Lourenço,D J Duncker,I Heinonen,I Falcão-Pires

doi:10.1007/s12471-016-0815-9

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.

Highlights

Heart failure is amongst the leading causes of death and disability worldwide and can be defined as the end result of any abnormality in cardiac structure and function that leads to impaired ventricular filling or ejection [1].Heart failure can be divided into two distinct entities, i.e. heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)
We present an overview of the currently available animal models that are employed in the study of HFpEF, including rodent and large animal models, and discuss the strengths and weaknesses of these models
The animal models highlighted in this review were successfully established in rodents (Table 1), while others were developed in large animals (Table 2)

Summary

Introduction

Heart failure is amongst the leading causes of death and disability worldwide and can be defined as the end result of any abnormality in cardiac structure and function that leads to impaired ventricular filling or ejection [1]. Neth Heart J (2016) 24:275–286 ated with increased interstitial fibrosis with LV concentric remodelling/hypertrophy and atrial enlargement (Fig. 1; [2]) These patients are generally older and mainly female and exhibit a large number of comorbidities, including diabetes mellitus (DM), hypertension, obesity and renal dysfunction [1]. The limited availability of animal models of HFpEF has potentially represented a major limitation in conducting mechanistic studies and unravelling HFpEF pathophysiology [4]. This is due to the absence of clear criteria and cut-off values for the diagnosis of HFpEF in animals and due to the fact that these experimental models are more challenging, expensive and time consuming when compared to HFrEF. The animal models highlighted in this review were successfully established in rodents (Table 1), while others were developed in large animals (Table 2)

21 Obese Zucker rat G R

41 MC Renal wrap ND

Findings

Discussion

Conclusion