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Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction
Patrick M Pilz1,2, Jennifer E Ward3, Wei-Ting Chang4,5
1Stanford Cardiovascular Institute, Stanford University School of Medicine, CA (P.M.P., E.B., R.L.).
Insights
This review evaluates animal models for heart failure with reduced ejection fraction (HFrEF). Understanding their strengths and limitations is crucial for advancing translational research and developing effective human therapies.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Animal Models
Background:
- Heart failure (HF) is a complex condition involving cardiac remodeling and impaired function, rising globally due to aging populations.
- HF encompasses conditions like systolic and diastolic dysfunction, exacerbated by comorbidities such as hypertension, diabetes, and obesity.
- Heart failure with reduced ejection fraction (HFrEF) is characterized by compromised cardiac output, with left ventricular ejection fraction typically below 40%.
Purpose of the Study:
- To review and analyze the strengths, limitations, and outcomes of current small and large animal models of HFrEF.
- To guide the selection of appropriate animal models for basic and translational research into HFrEF.
- To highlight the importance of accurately recapitulating HFrEF symptoms and pathology in preclinical models.
Main Methods:
- Systematic review of existing literature on small and large animal models of HFrEF.
- Analysis of reported outcomes, including physiological, pathological, and functional parameters.
- Evaluation of how well each model replicates human HFrEF symptoms and underlying mechanisms.
Main Results:
- No single animal model fully replicates the complexity of human HFrEF.
- Various models offer insights into specific aspects of HFrEF, such as cardiac remodeling, fibrosis, and reduced ejection fraction.
- Strengths and weaknesses vary significantly across different species and induction methods.
Conclusions:
- Careful selection of animal models based on research questions is essential for advancing HFrEF understanding.
- Continued development and refinement of HFrEF animal models are needed to improve translational success.
- Evaluating model limitations is critical for interpreting research findings and guiding future therapeutic strategies.
Abstract:
Heart failure (HF) describes a heterogenous complex spectrum of pathological conditions that results in structural and functional remodeling leading to subsequent impairment of cardiac function, including either systolic dysfunction, diastolic dysfunction, or both. Several factors chronically lead to HF, including cardiac volume and pressure overload that may result from hypertension, valvular lesions, acute, or chronic ischemic injuries. Major forms of HF include hypertrophic, dilated, and restrictive cardiomyopathy. The severity of cardiomyopathy can be impacted by other comorbidities such as diabetes or obesity and external stress factors. Age is another major contributor, and the number of patients with HF is rising worldwide in part due to an increase in the aged population. HF can occur with reduced ejection fraction (HF with reduced ejection fraction), that is, the overall cardiac function is compromised, and typically the left ventricular ejection fraction is lower than 40%. In some cases of HF, the ejection fraction is preserved (HF with preserved ejection fraction). Animal models play a critical role in facilitating the understanding of molecular mechanisms of how hearts fail. This review aims to summarize and describe the strengths, limitations, and outcomes of both small and large animal models of HF with reduced ejection fraction that are currently used in basic and translational research. The driving defect is a failure of the heart to adequately supply the tissues with blood due to impaired filling or pumping. An accurate model of HF with reduced ejection fraction would encompass the symptoms (fatigue, dyspnea, exercise intolerance, and edema) along with the pathology (collagen fibrosis, ventricular hypertrophy) and ultimately exhibit a decrease in cardiac output. Although countless experimental studies have been published, no model completely recapitulates the full human disease. Therefore, it is critical to evaluate the strength and weakness of each animal model to allow better selection of what animal models to use to address the scientific question proposed.
