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Research Priorities for Heart Failure With Preserved Ejection Fraction: National Heart, Lung, and Blood Institute Working Group Summary
Open accessAbstract
Heart failure with preserved ejection fraction (HFpEF), a major public health problem that is rising in prevalence, is associated with high morbidity and mortality and is considered to be the greatest unmet need in cardiovascular medicine today because of a general lack of effective treatments. To address this challenging syndrome, the National Heart, Lung, and Blood Institute convened a working group made up of experts in HFpEF and novel research methodologies to discuss research gaps and to prioritize research directions over the next decade. Here, we summarize the discussion of the working group, followed by key recommendations for future research priorities. There was uniform recognition that HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach in both humans and animal models to improve understanding of mechanisms and treatment of HFpEF. It was recognized that advances in the understanding of basic mechanisms and the roles of inflammation, macrovascular and microvascular dysfunction, fibrosis, and tissue remodeling are needed and ideally would be obtained from (1) improved animal models, including large animal models, which incorporate the effects of aging and associated comorbid conditions; (2) repositories of deeply phenotyped physiological data and human tissue, made accessible to researchers to enhance collaboration and research advances; and (3) novel research methods that take advantage of computational advances and multiscale modeling for the analysis of complex, high-density data across multiple domains. The working group emphasized the need for interactions among basic, translational, clinical, and epidemiological scientists and across organ systems and cell types, leveraging different areas or research focus, and between research centers. A network of collaborative centers to accelerate basic, translational, and clinical research of pathobiological mechanisms and treatment strategies in HFpEF was discussed as an example of a strategy to advance research progress. This resource would facilitate comprehensive, deep phenotyping of a multicenter HFpEF patient cohort with standardized protocols and a robust biorepository. The research priorities outlined in this document are meant to stimulate scientific advances in HFpEF by providing a road map for future collaborative investigations among a diverse group of scientists across multiple domains.
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“Obesity and diabetes create a pro-inflammatory state and promote endothelial and coronary microvascular dysfunction. 1,7,8”
From Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials (2024) · cites this paper as [1]
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“Obesity is a major risk factor for heart failure (HF) with preserved ejection fraction (HFpEF). 1,2”
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Bakhshi, H., Michelhaugh, S. A., Bruce, S. A., Seliger, S. L., Qian, X., Ambale‐Venkatesh, B., Varadarajan, V., Bagchi, P., Lima, J. A. C., & deFilippi, C. R. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104490 · Cited by 35
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Endothelial-Mesenchymal Transition in Heart Failure With a Preserved Ejection Fraction
Valero‐Muñoz, M., Oh, A., Faudoa, E., Bretón‐Romero, R., El-Adili, F., Bujor, A. M., & Sam, F. (2021) · Circulation Heart Failure · doi:10.1161/circheartfailure.121.008372 · Cited by 31
Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction
Omote, K., & Borlaug, B. A. (2021) · Circulation Journal · doi:10.1253/circj.cj-21-0795 · Cited by 32
Impaired Right Atrial Reserve Function in Heart Failure with Preserved Ejection Fraction
Kagami, K., Harada, T., Yoshida, K., Amanai, S., Kato, T., Wada, N., Adachi, T. K., & Obokata, M. (2022) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2022.03.006 · Cited by 30
Harada, T., Yamaguchi, M., Omote, K., Iwano, H., Mizuguchi, Y., Amanai, S., Yoshida, K., Kato, T., Kurosawa, K., Nagai, T., et al. (2022) · Circulation Cardiovascular Imaging · doi:10.1161/circimaging.121.013495 · Cited by 30
Shi, Y., Dong, G., Liu, J., Xiong, S., Liu, C., Yang, C., Wang, Q., & Qiao, W. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.854501 · Cited by 30
Desai, N. R., Olewińska, E., Famulska, A., Rémuzat, C., François, C., & Folkerts, K. (2024) · Heart Failure Reviews · doi:10.1007/s10741-024-10385-y · Cited by 36
Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?
Dhyani, N., Tian, C., Gao, L., Rudebush, T., & Zucker, I. H. (2024) · Physiology · doi:10.1152/physiol.00015.2024 · Cited by 30
Cardiovascular, Kidney, Liver, and Metabolic Interactions in Heart Failure: Breaking Down Silos
Lee, C. J. M., Kosyakovsky, L. B., Khan, M. S., Wu, F., Chen, G., Hill, J. A., Ho, J. E., Foo, R., & Zannad, F. M. (2025) · Circulation Research · doi:10.1161/circresaha.125.325602 · Cited by 33
Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond
Morfino, P., Aimo, A., Castiglione, V., Vergaro, G., Emdin, M., & Clerico, A. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9080256 · Cited by 31
Non-invasive assessment of HFpEF in mouse models: current gaps and future directions
Villalba‐Orero, M., García‐Pavía, P., & Lara‐Pezzi, E. (2022) · BMC Medicine · doi:10.1186/s12916-022-02546-3 · Cited by 29
Abélanet, A., Camoin, M., Rubin, S., Bougaran, P., Delobel, V., Pernot, M., Forfar, I., Guilbeau‐Frugier, C., Galès, C., Bats, M., et al. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.317319 · Cited by 31
Shahmoradi, L., Rezaei, N., Rezayi, S., Zolfaghari, M., & Manafi, B. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02728-0 · Cited by 28
Functional Roles of Furin in Cardio-Cerebrovascular Diseases
Wichaiyo, S., Koonyosying, P., & Morales, N. P. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00325 · Cited by 26
Wang, N., Rueter, P., Ng, M., Chandramohan, S., Hibbert, T., O’Sullivan, J., Kaye, D. M., & Lal, S. (2024) · European Journal of Heart Failure · doi:10.1002/ejhf.3271 · Cited by 27
Epelde, F. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14144820 · Cited by 32
Rieger, A. C., Bagno, L., Salerno, A. G., Florea, V., Rodriguez, J. E., Rosado, M., Turner, D., Dulce, R. A., Takeuchi, L. M., Kanashiro‐Takeuchi, R. M., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2019835118 · Cited by 27
Gaziano, L., Cho, K., Djoussé, L., Schubert, P. L., Galloway, A., Ho, Y.-L. A., Kurgansky, K. E., GAGNON, D. R., Russo, J. P., Angelantonio, E. D., et al. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13429 · Cited by 26
Jheng, J.-R., Bai, Y., Noda, K., Huot, J. R., Cook, T. G., Fisher, A. J., Chen, Y.-Y., Goncharov, D. A., Goncharova, E. A., Simon, M. A. M., et al. (2024) · Circulation · doi:10.1161/circulationaha.124.068624 · Cited by 26
Lifestyle interventions in cardiometabolic HFpEF: dietary and exercise modalities
Vacca, A., Wang, R., Nambiar, N., Capone, F., Farrelly, C., Mostafa, A., Sechi, L. A., & Schiattarella, G. G. (2024) · Heart Failure Reviews · doi:10.1007/s10741-024-10439-1 · Cited by 32
Dulce, R. A., Kanashiro‐Takeuchi, R. M., Takeuchi, L. M., Salerno, A. G., Wanschel, A. C. B. A., Kulandavelu, S., Balkan, W., Zuttion, M. S. S. R., Cai, R., Schally, A. V., et al. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac098 · Cited by 27
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Zhou, H., Peng, W., Li, F., Wang, Y., Wang, B., Ding, Y., Lin, Q., Zhao, Y., Pan, G., & Wang, X. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.875327 · Cited by 31
Hiraiwa, H., Yura, Y., Okumura, T., & Murohara, T. (2024) · Heart Failure Reviews · doi:10.1007/s10741-024-10418-6 · Cited by 23
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Circulating Non-Coding RNAs as Indicators of Fibrosis and Heart Failure Severity
Boichenko, V., Noakes, V. M., Reilly-O’Donnell, B., Luciani, G. B., Emanueli, C., Martelli, F., & Gorelik, J. (2025) · Cells · doi:10.3390/cells14070553 · Cited by 23
Metadata
- Authors
- Shah, S. J., Borlaug, B. A., Kitzman, D. W., McCulloch, A. D., Blaxall, B. C., Agarwal, R., Chirinos, J. A., Collins, S., Deo, R. C., Gladwin, M. T., Granzier, H., Hummel, S. L., Kass, D. A., Redfield, M. M., Sam, F., Wang, T. J., Desvigne-Nickens, P., & Adhikari, B. B.
- Affiliations
- Northwestern University (US)
- Mayo Clinic (US)
- Wake Forest University Health Sciences (US)
- University of California San Diego (US)
- Christ Hospital (US)
- Indiana University Indianapolis (US)
- University of Pennsylvania (US)
- Vanderbilt University (US)
- Brigham and Women's Hospital (US)
- University of Pittsburgh (US)
- University of Arizona (US)
- University of Michigan (US)
- Johns Hopkins University (US)
- Boston University (US)
- National Institutes of Health (US)
- ORCID
- Venue
- Circulation
- Published
- 2020-03-24
- Volume
- 141
- Issue
- 12
- Pages
- 1001-1026
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC7101072
- OpenAlex
- W3012616651
- Cited by
- 436
- References
- 114
- Citations by year
- 2026: 53 · 2025: 74 · 2024: 74 · 2023: 67 · 2022: 99 · 2021: 49 · 2020: 19
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG018915, R01AG045551, R01AG058969, P30AG021332, U24AG059624)
- National Heart, Lung, and Blood Institute (R01HL128526, R61HL146390, R01HL118524, U01HL125175, R01HL127028, R01HL144657, R01HL104106, R01HL126638, U10HL110262, R01HL149423, DP2HL123228, R35HL135827, P01HL103455, R01HL117153, R01HL140731, P01HL094307, R01HL132551, U01HL125205, R01HL133695, R01HL121510, R01HL107577, R56HL136730, R01HL134321, R01HL125886, R01HL098032, T32HL110849)
- National Cancer Institute (K12CA090625)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK103056, P50DK096418)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- heart failure with preserved ejection fraction, research priorities, research gaps, animal models, inflammation, microvascular dysfunction, macrovascular dysfunction, fibrosis, tissue remodeling, biorepository, multiscale modeling, translational research
- MeSH terms
- Heart Failure, Humans, Research, Stroke Volume, United States, National Heart, Lung, and Blood Institute (U.S.)
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