Searching for an experimental rodent model of heart failure with preserved ejection fraction: Re-visited

Heart failure with preserved ejection fraction (HFpEF) currently accounts for over 50% of all heart failure cases. It displays a large number of comorbidities, and the pathophysiological mechanisms underlying the disease remain uncertain and treatment options are limited. The heterogeneity and complexity of the disease, and its specific comorbidities, can limit the number of animal models that could ideally mimic it. The current study describes and compares the efficacy of the most popular approaches from a quantitative point of view. A review and meta-analysis of more than 500 experimental protocols was performed with special attention to these models created to induce heart failure by the most common comorbidities associated with human HFpEF, e.g., hypertension, diabetes, obesity and aging. The analysis included a wide spectrum of outcomes (alterations in body weight, lung and left ventricle weights, laboratory, hemodynamic, echocardiographic, and histopathological data as well as animal mortality) and possible covariates that could determine the utility of the particular model, such as animal age, species, experimental period and genetic modification. A wide range of systemic hypertension as well as diabetes (obesity) - related animal models are used for pre-clinical studies on heart failure, but some of them fail to replicate HFpEF. Future studies should include an evaluation of other features besides diastolic dysfunction that confirm that this is an HFpEF model, or the potential to progress to heart failure with reduced ejection fraction (HFrEF).