Murine Models of Heart Failure with Preserved Ejection Fraction: a "Fishing Expedition"

Abstract

Heart failure with preserved ejection fraction (HFpEF) is characterized by signs and symptoms of HF in the presence of a normal left ventricular (LV) ejection fraction (EF). Despite accounting for up to 50% of all clinical presentations of HF, the mechanisms implicated in HFpEF are poorly understood, thus precluding effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype also contributes to this disease and likely to the absence of evidence-based therapies. Limited access to human samples and imperfect animal models that completely recapitulate the human HFpEF phenotype have impeded our understanding of the mechanistic underpinnings that exist in this disease. Aging and comorbidities such as atrial fibrillation, hypertension, diabetes and obesity, pulmonary hypertension and renal dysfunction are highly associated with HFpEF. Yet, the relationship and contribution between them remains ill-defined. This review discusses some of the distinctive clinical features of HFpEF in association with these comorbidities and highlights the advantages and disadvantage of commonly used murine models, used to study the HFpEF phenotype.

Keywords: HFpEF; comorbidities; murine model.

Graphical abstract

Figure 1

Flowchart Identifying Major Features to Fulfill When Modeling HFpEF in Preclinical Studies

Central Illustration

HFpEF (A) Modeling heart failure with preserved ejection fraction (HFpEF) in the lab with major comorbidities and conditions highly associated with human HFpEF. (B) However, murine models touted as HFpEF models are often lost in translation when applied to the clinical situation.