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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.<\/jats:p>","DOI":"10.1161\/circresaha.122.320246","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T18:00:26Z","timestamp":1654797626000},"page":"1888-1905","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":94,"title":["Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction"],"prefix":"10.1161","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-8736","authenticated-orcid":true,"given":"Patrick M.","family":"Pilz","sequence":"first","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, CA (P.M.P., E.B., R.L.)."},{"name":"Ludwig Boltzmann Institute at the Center for Biomedical Research, Medical University of Vienna, Austria (P.M.P., A.K., B.K.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-8736","authenticated-orcid":true,"given":"Jennifer E.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, MA (J.E.W., S.F., R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-2144","authenticated-orcid":true,"given":"Wei-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Taiwan (W.-T.C.)."},{"name":"Department of Cardiology, Chi-Mei Medical Center, Taiwan (W.-T.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-2144","authenticated-orcid":true,"given":"Attila","family":"Kiss","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute at the Center for Biomedical Research, Medical University of Vienna, Austria (P.M.P., A.K., B.K.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-9474","authenticated-orcid":true,"given":"Edward","family":"Bateh","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, CA (P.M.P., E.B., R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-8736","authenticated-orcid":true,"given":"Alokkumar","family":"Jha","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, CA (P.M.P., E.B., R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-8736","authenticated-orcid":true,"given":"Sudeshna","family":"Fisch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, MA (J.E.W., S.F., R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-8736","authenticated-orcid":true,"given":"Bruno K.","family":"Podesser","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute at the Center for Biomedical Research, Medical University of Vienna, Austria (P.M.P., A.K., B.K.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-9020","authenticated-orcid":true,"given":"Ronglih","family":"Liao","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute, Stanford University School of Medicine, CA (P.M.P., E.B., R.L.)."},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, MA (J.E.W., S.F., R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2017.08.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz835"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.117.031622"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.04.011"},{"key":"e_1_3_3_8_2","unstructured":"Speaking of research. 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