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Defining HFpEF in rodents: a systematic review
Yamen Adrah1,2, Niklas Hegemann1,2,3, David Faidel1,2,3
1Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Augustenburger Platz 1, Berlin 13353, Germany.
Cardiovascular Research
|September 25, 2025
Summary
Many studies use rodent models for heart failure with preserved ejection fraction (HFpEF), but over 40% lack sufficient evidence to support the HFpEF label. Careful review of phenotypic documentation in HFpEF research is crucial.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Preclinical Models
Background:
- Heart failure with preserved ejection fraction (HFpEF) is a prevalent subtype of heart failure with limited treatment options.
- Preclinical research heavily relies on rodent models to study HFpEF, necessitating validation of their clinical accuracy.
- Existing HFpEF rodent models may not consistently reflect established clinical diagnostic guidelines.
Purpose of the Study:
- To assess the extent to which rodent models labeled as "HFpEF" align with current clinical diagnostic guidelines.
- To evaluate the phenotypic accuracy of commonly used preclinical models in HFpEF research.
- To identify potential discrepancies between claimed HFpEF phenotypes in animal studies and clinical definitions.
Main Methods:
- A systematic literature search was conducted on the PubMed database for studies published between 2008 and 2023.
- Identified 475 studies using animal models of HFpEF; N=407 original research articles using mice or rats labeled "HFpEF" were analyzed.
- Evaluated 317 experimental groups against predefined diagnostic clusters derived from European Society of Cardiology HF guidelines.
Main Results:
- Only 57% (N=179) of experimental groups labeled as "HFpEF" met the recommended evidence criteria based on clinical guidelines.
- A significant proportion of studies (approximately 43%) failed to provide adequate evidence for the "HFpEF" designation in rodent models.
- Higher journal impact factors and more recent publication dates correlated positively with the probability of a study meeting HFpEF criteria.
Conclusions:
- A substantial number of preclinical studies mislabel or inadequately document HFpEF phenotypes in rodent models.
- Readers and reviewers should exercise caution and rigorously assess phenotypic documentation in HFpEF rodent studies.
- Improved standardization and validation of HFpEF animal models are needed to ensure reliable translation to clinical applications.
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