{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:23:38Z","timestamp":1790835818057,"version":"4.1.0"},"reference-count":128,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1601,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001030","name":"National Heart Foundation","doi-asserted-by":"publisher","award":["JFOS NHF104853"],"award-info":[{"award-number":["JFOS NHF104853"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009287","name":"NSW Health","doi-asserted-by":"publisher","award":["JFOS DOH1006"],"award-info":[{"award-number":["JFOS DOH1006"]}],"id":[{"id":"10.13039\/501100009287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009287","name":"NSW Health","doi-asserted-by":"publisher","award":["JFOS DOH1003"],"award-info":[{"award-number":["JFOS DOH1003"]}],"id":[{"id":"10.13039\/501100009287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007811","name":"Sydney Medical School Foundation [JFOS]","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["JFOS NHF104853"],"award-info":[{"award-number":["JFOS NHF104853"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009287","name":"NSW Health","doi-asserted-by":"publisher","award":["JFOS DOH1006"],"award-info":[{"award-number":["JFOS DOH1006"]}],"id":[{"id":"10.13039\/501100009287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009287","name":"NSW Health","doi-asserted-by":"publisher","award":["JFOS DOH1003"],"award-info":[{"award-number":["JFOS DOH1003"]}],"id":[{"id":"10.13039\/501100009287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007811","name":"Sydney Medical School Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is an urgent need for models that faithfully replicate heart failure with preserved ejection fraction (HFpEF), now recognized as the most common form of heart failure in the world. In vitro approaches have several shortcomings, most notably the immature nature of stem cell-derived human cardiomyocytes [induced pluripotent stem cells (iPSC)] and the relatively short lifespan of primary cardiomyocytes. Three-dimensional \u2018organoids\u2019 incorporating mature iPSCs with other cell types such as endothelial cells and fibroblasts are a significant advance, but lack the complexity of true myocardium. Animal models can replicate many features of human HFpEF, and rodent models are the most common, and recent attempts to incorporate haemodynamic, metabolic, and ageing contributions are encouraging. Differences relating to species, physiology, heart rate, and heart size are major limitations for rodent models. Porcine models mitigate many of these shortcomings and approximate human physiology more closely, but cost and time considerations limit their potential for widespread use. Ex vivo analysis of failing hearts from animal models offer intriguing possibilities regarding cardiac substrate utilisation, but are ultimately subject to the same constrains as the animal models from which the hearts are obtained. Ex vivo approaches using human myocardial biopsies can uncover new insights into pathobiology leveraging myocardial energetics, substrate turnover, molecular changes, and systolic\/diastolic function. In collaboration with a skilled cardiothoracic surgeon, left ventricular endomyocardial biopsies can be obtained at the time of valvular surgery in HFpEF patients. Critically, these tissues maintain their disease phenotype, preserving inter-relationship of myocardial cells and extracellular matrix. This review highlights a novel approach, where ultra-thin myocardial tissue slices from human HFpEF hearts can be used to assess changes in myocardial structure and function. We discuss current approaches to modelling HFpEF, describe in detail the novel tissue slice model, expand on exciting opportunities this model provides, and outline ways to improve this model further.<\/jats:p>","DOI":"10.1002\/ehf2.13504","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T02:55:56Z","timestamp":1627959356000},"page":"3643-3655","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Optimizing the Discovery and Assessment of Therapeutic Targets in Heart Failure with Preserved Ejection Fraction"],"prefix":"10.1093","volume":"8","author":[{"given":"Gabrielle","family":"Fusco-Allison","sequence":"first","affiliation":[{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Heart Research Institute , Newtown, Sydney, New South Wales ,","place":["Australia"]},{"name":"Central Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmond K.","family":"Li","sequence":"additional","affiliation":[{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Heart Research Institute , Newtown, Sydney, New South Wales ,","place":["Australia"]},{"name":"Central Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Hunter","sequence":"additional","affiliation":[{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Central Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Jackson","sequence":"additional","affiliation":[{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Central Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Discipline of Surgery, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Bannon","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Discipline of Surgery, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Lal","sequence":"additional","affiliation":[{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8016-5128","authenticated-orcid":false,"given":"John F.","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Charles Perkins Centre, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Heart Research Institute , Newtown, Sydney, New South Wales 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