Rationale and Design of the HeartShare/AMP-HF Deep Phenotyping Study to Improve Understanding of Heart Failure With Preserved Ejection Fraction

Barry A Borlaug¹, Julio A Chirinos², Gregory D Lewis³, Margaret M Redfield⁴, Alain G Bertoni⁵, Martin Cadeiras⁶, Nipavan Chiamvimonvat⁷, Akshay S Desai⁸, Michael M Givertz⁸, David A Kass⁹, Sadiya S Khan¹⁰, Dalane W Kitzman⁵, Javier E López⁶, Laura J Rasmussen-Torvik¹⁰, Kavita Sharma⁹, Scott D Solomon⁸, Bret Goodpaster¹¹, Lauren Sparks¹¹, Jeffrey Olgin¹², Rima Arnaout¹², Uma Mylavarapu¹⁰, Laura Alagna¹⁰, Yuan Luo¹⁰, Renee Wong¹³, Patrice Desvigne-Nickens¹³, Emily Tinsley¹³, Tania N Kamphaus¹⁴, Jennifer L Taylor¹⁴, Melissa A Jones¹⁴, Mariell Jessup¹⁵, Steffen Schaper¹⁶, William A Chutnow¹⁷, Svati H Shah¹⁸, Javed Butler¹⁹, Vandana Sachdev¹³, Sanjiv J Shah¹⁰

Affiliations

¹ Mayo Clinic, Rochester, Minnesota, USA. Electronic address: Borlaug.Barry@mayo.edu.
² University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
³ Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Mayo Clinic, Rochester, Minnesota, USA.
⁵ Wake Forest University School of Medicine, Winston Salem, North Carolina, USA.
⁶ University of California Davis, Sacramento, California, USA.
⁷ University of California Davis, Sacramento, California, USA; University of Arizona College of Medicine, Phoenix, Arizona, USA.
⁸ Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹¹ AdventHealth Research Institute, Orlando, Florida, USA.
¹² University of California-San Francisco, San Francisco, California, USA.
¹³ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
¹⁴ Foundation for the National Institutes of Health, North Bethesda, Maryland, USA.
¹⁵ American Heart Association, Dallas, Texas, USA.
¹⁶ Bayer Pharmaceuticals, Leverkusen, Germany.
¹⁷ Novartis Biomedical Research, Cambridge, Massachusetts, USA.
¹⁸ Duke Clinical Research Institute, Chapel Hill, North Carolina, USA.
¹⁹ Baylor Scott and White Research Institute, Dallas, Texas, USA; University of Mississippi, Jackson, Mississippi, USA.

PMID: 41338833
PMCID: PMC12694977 (available on 2026-12-01)
DOI: 10.1016/j.jchf.2025.102714

Review

Rationale and Design of the HeartShare/AMP-HF Deep Phenotyping Study to Improve Understanding of Heart Failure With Preserved Ejection Fraction

Barry A Borlaug et al. JACC Heart Fail. 2025 Dec.

. 2025 Dec;13(12):102714.

doi: 10.1016/j.jchf.2025.102714.

Authors

Affiliations

¹ Mayo Clinic, Rochester, Minnesota, USA. Electronic address: Borlaug.Barry@mayo.edu.
² University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
³ Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Mayo Clinic, Rochester, Minnesota, USA.
⁵ Wake Forest University School of Medicine, Winston Salem, North Carolina, USA.
⁶ University of California Davis, Sacramento, California, USA.
⁷ University of California Davis, Sacramento, California, USA; University of Arizona College of Medicine, Phoenix, Arizona, USA.
⁸ Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹¹ AdventHealth Research Institute, Orlando, Florida, USA.
¹² University of California-San Francisco, San Francisco, California, USA.
¹³ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
¹⁴ Foundation for the National Institutes of Health, North Bethesda, Maryland, USA.
¹⁵ American Heart Association, Dallas, Texas, USA.
¹⁶ Bayer Pharmaceuticals, Leverkusen, Germany.
¹⁷ Novartis Biomedical Research, Cambridge, Massachusetts, USA.
¹⁸ Duke Clinical Research Institute, Chapel Hill, North Carolina, USA.
¹⁹ Baylor Scott and White Research Institute, Dallas, Texas, USA; University of Mississippi, Jackson, Mississippi, USA.

PMID: 41338833
PMCID: PMC12694977 (available on 2026-12-01)
DOI: 10.1016/j.jchf.2025.102714

Abstract

Heart failure with preserved ejection fraction (HFpEF) has risen to become the most common form of heart failure (HF) worldwide. The pathophysiology of HFpEF is complex and intimately tied to cardiac-metabolic-kidney abnormalities, spanning cardiac, vascular, and noncardiovascular organ systems. Large-scale prospective phenotyping studies that comprehensively examine these abnormalities in the same patient are not available, an evidence gap recognized by a NHLBI (National Heart, Lung, and Blood Institute)-assembled working group of experts as a major bottleneck impeding new therapeutic innovations. Here, we present the rationale and design for the HeartShare/AMP-HF (Accelerating Medicines Partnership-Heart Failure) program, supported through the NHLBI, the FNIH (Foundation for the National Institutes of Health), the U.S. FDA (Food and Drug Administration), and multiple industry and nonprofit partners.

Keywords: AMP (Accelerating Medicines Partnership); HeartShare; heart failure; heart failure with preserved ejection fraction; phenotyping.

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Conflict of interest statement

Funding Support and Author Disclosures The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the U.S. Department of Health and Human Services. This work was supported by the AMP-HF (Accelerating Medicines Partnership Heart Failure) Network. Managed through the Foundation for the National Institutes of Health, AMP is a public-private partnership (American Heart Association, American Society of Echocardiography, Anumana, Bayer AG, Cytokinetics Inc, Ionis Pharmaceuticals, Inc, National Heart, Lung, and Blood Institute, Novartis Pharmaceuticals, and Ultromics) created to deconstruct the syndrome of HFpEF and classify potential disease subtypes. Funding was provided through grants from the National Institutes of Health U54 HL160273 (Northwestern University Data Translation Center); U01 HL160279 (Northwestern University); U01 HL160277 (University of Pennsylvania); U01 HL160274 (University of California at Davis); U01 HL160226 (Mayo Clinic); U01 HL160272 (Wake Forest); U01 HL160278 (Massachusetts General Hospital); and AMP HF RFP 2023-1345-001 (Johns Hopkins University). Dr Borlaug is supported by R01 HL128526, R01 HL162828, and U01 HL160226 from the National Heart, Lung, and Blood Institute; W81XWH2210245 from the U.S. Department of Defense; and the Schoen Foundation; has received research support from the National Institutes of Health and the United States Department of Defense; has received research grant funding from AstraZeneca, Axon, Corvia, Novo Nordisk, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; and is named inventor (U.S. Patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat HF. Dr Chirinos has consulted for Bayer, Fukuda-Denshi, Bristol Myers Squibb, Biohaven Pharmaceuticals, Johnson and Johnson, Edwards Life Sciences, Merck, NGM Biopharmaceuticals, S2N Health, Health Advances, Emory University, University of Delaware, and East Carolina University; has received University of Pennsylvania research grants from the National Institutes of Health, Fukuda-Denshi, Bristol Myers Squibb, Microsoft, Amgen, and Abbott; is named as inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of HFpEF and for the use of biomarkers in HF; has received payments for editorial roles from the American Heart Association, the American College of Cardiology, Elsevier and Wiley; has received payments for academic roles from the University of Texas, Boston University, Rochester Regional Health, Virginia Commonwealth University, and the Korean Vascular Society; and has received research device loans from Atcor Medical, Fukuda-Denshi, Unex, Uscom, NDD Medical Technologies, Microsoft, and MicroVision Medical. Dr Kitzman is supported by National Institutes of Health grants U01AG076928, R01AG078153, R01AG045551, P30AG021332, U24AG059624, and U01HL160272; and the Kermit Glenn Phillips II Chair in Cardiovascular Medicine; has received institutional grants for research studies and personal honoraria for consulting for Bayer, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, Novo Nordisk, AstraZeneca, Novartis, Bayer, and Pfizer; and has stock ownership in Gilead Sciences. Dr Butler has served as a consultant for Abbott, Adaptyx, American Regent, Amgen, AskBio, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardior, CSL Vifor, CVRx, Cytokinetics, Daxor, Diastol, Edwards, Element Sciences, Faraday, Idorsia, Impulse Dynamics, Imbria, Innolife, Intellia, Inventiva, Levator, Lexicon, Eli Lilly, Mankind, Medtronic, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Reprieve, Roche, Rycarma, Saillent, Salamandra, Salubris, SC Pharma, SQ Innovation, Secretome, Sequanna, Transmural, TekkunLev, Tenex, Tricog, Ultromics, Vera, and Zoll. Dr Shah was supported by research grants from the National Institutes of Health (U54 HL160273, R01 HL140731, R01 HL149423, X01 HL169712), American Heart Association 24SFRNPCN1291224), AstraZeneca, Boston Scientific, Corvia, Pfizer, and Tempus; and has received consulting fees from 35Pharma, Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, BaroPace, Bayer, Boehringer Ingelheim, Boston Scientific, BridgeBio, Bristol Myers Squibb, Corvia, Cyclerion, Cytokinetics, Diastol Therapeutics, Edwards Lifesciences, Eidos, eMyosound, Ensho, Fauna Bio, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, OrbiMed, Pfizer, Prothena, ReCor, Regeneron, Rivus, SalubriusBio, Sardocor, Shifamed, Tectonic, Tenax, Tenaya, Ulink Labs, and Ultromics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

References

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1. Redfield MM & Borlaug BA Heart Failure With Preserved Ejection Fraction: A Review. JAMA. 329, 827–838 (2023). - PubMed
1. Shah SJ, et al. Research Priorities for Heart Failure With Preserved Ejection Fraction: National Heart, Lung, and Blood Institute Working Group Summary. Circulation. 141, 1001–1026 (2020). - PMC - PubMed
1. Anker SD, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. (2021). - PubMed
1. Solomon SD, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. (2022). - PubMed

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Rationale and Design of the HeartShare/AMP-HF Deep Phenotyping Study to Improve Understanding of Heart Failure With Preserved Ejection Fraction

Affiliations

Rationale and Design of the HeartShare/AMP-HF Deep Phenotyping Study to Improve Understanding of Heart Failure With Preserved Ejection Fraction

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous