Defining HFpEF in rodents: a systematic review

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) has become the most diagnosed HF subtype representing a major public health burden with poor clinical outcome. Available treatment options for HFpEF are limited; hence, more in-depth basic/translational research is needed to identify novel therapeutic targets. Preclinical investigations frequently rely on mice and rat models of HFpEF, yet their phenotypic accuracy is often not sufficiently verified. Here, we explore the extent to which rodent models labelled as 'HFpEF' reflect clinical diagnostic guidelines. We hypothesized that many basic/translational research articles use the term 'HFpEF' for rodent models, though the extent to which they demonstrate HFpEF signs and symptoms according to clinical definitions may be limited. METHODS AND RESULTS: Using the PubMed database, we identified N = 475 studies using animal models of HFpEF that were published between 2008 and 2023. After exclusion of non-original research articles, articles using animal species other than mice or rats, and articles which did not claim the label 'HFpEF', N = 407 studies remained and were evaluated, featuring a total of N = 317 experimental groups labelled as 'HFpEF'. Based on predefined diagnostic clusters derived from the HF guidelines of the European Society of Cardiology, we found that 57% of these experimental groups (N = 179) presented with the recommended level of evidence to support the use of the label 'HFpEF'. More recent publication dates and higher journal impact factors were positively associated with HFpEF probability. CONCLUSION: Despite many original articles labelling mouse and rat models as 'HFpEF', approximately two out of five studies fail to provide sufficient evidence to back this claim. Hence, caution is advised when interpreting mechanistic or interventional findings from studies involving rodent HFpEF models, and phenotypic documentation should be thoroughly assessed by readers and reviewers prior to drawing conclusions on the pathophysiology or treatment of HFpEF.