{
  "abstract": "Heart failure with preserved ejection fraction (HFpEF) accounts for over half of heart failure cases but remains poorly defined due to its clinical heterogeneity. In the prospective PACIFIC-Preserved cohort (NCT04189029, n = 155), we applied multimodal deep phenotyping, including high-throughput proteomics, and unsupervised machine learning to identify biologically distinct HFpEF subgroups. Multiview clustering revealed two major HFpEF phenogroups: PEF1, characterized by inflammatory signaling, TNF receptor activation, cardio-skeletal injury, and greater renal dysfunction; and PEF2, marked by endothelial stress and milder perturbations. Conventional diagnostics alone could not reliably distinguish these subgroups, but a multimodal classifier integrating clinical, imaging, and proteomic variables achieved high predictive accuracy (F1-score 0.87). External validation in the MEDIA-DHF cohort (n = 456) confirmed that PEF1 was independently associated with adverse outcomes (adjusted HR 2.27, 95% CI 1.04-4.94). These findings establish a classifier-driven, biologically informed stratification of HFpEF, providing a framework for precision medicine in heart failure.",
  "abstract_shown": true,
  "affiliations": [
    "Université Paris Cité, INSERM, PARCC, Paris, France. jean-sebastien.hulot@aphp.fr.",
    "CIC1418 and DMU CARTE, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France. jean-sebastien.hulot@aphp.fr.",
    "Fealinx, 42 route du Pont de Chêne, Francheville, France.",
    "CHRU de Nancy, Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Nancy, France.",
    "INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Nancy, France.",
    "Sanofi R&D, Gentilly, France.",
    "Université Paris Cité, INSERM, PARCC, Paris, France.",
    "Pharmacology and DMU CARTE, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.",
    "CASIS - CArdiac Simulation & Imaging Software, Quetigny, France.",
    "Cardiology, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, ICAN 1166, Paris, France.",
    "Cardiology, AP-HP, Hôpital Henri Mondor, Créteil, France.",
    "Clinical research unit, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.",
    "Firalis, Huningue, France.",
    "UMR 1144, Université Paris Cité, Department of Geriatrics, AP-HP, Hôpital Broca, Paris, France.",
    "Cardiology, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.",
    "Cardiology, AP-HP, Hôpital Bichat, Paris, France.",
    "Cardiac Imaging Radiology, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.",
    "Physics for Medicine Paris, INSERM U1273, ESPCI Paris, PSL University, CNRS FRE 2031, Paris, France.",
    "Servier R&D, Suresnes, France.",
    "Université Paris Cité, AP-HP, Hôpital Lariboisière, Paris, France."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jean-Sébastien Hulot",
      "orcid": "0000-0001-5463-6117"
    },
    {
      "affs": [
        2
      ],
      "name": "Pierre-Yves Hervé",
      "orcid": "0000-0002-5525-1750"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Nicolas Girerd",
      "orcid": "0000-0002-3278-2057"
    },
    {
      "affs": [
        5
      ],
      "name": "Frédérique Chézalviel-Guilbert",
      "orcid": "0000-0001-9731-4951"
    },
    {
      "affs": [
        5
      ],
      "name": "Philip Janiak"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Pierre Boutouyrie"
    },
    {
      "affs": [
        8
      ],
      "name": "Jean-Joseph Christophe"
    },
    {
      "affs": [
        9
      ],
      "name": "Ariel Cohen"
    },
    {
      "affs": [
        10
      ],
      "name": "Thibaud Damy"
    },
    {
      "affs": [
        11
      ],
      "name": "Liliane Berkani"
    },
    {
      "affs": [
        3
      ],
      "name": "Kevin Duarte"
    },
    {
      "affs": [
        5
      ],
      "name": "Caroline Fraslon"
    },
    {
      "affs": [
        12
      ],
      "name": "Hüseyin Firat"
    },
    {
      "affs": [
        13
      ],
      "name": "Olivier Hanon"
    },
    {
      "affs": [
        14
      ],
      "name": "Richard Isnard"
    },
    {
      "affs": [
        15
      ],
      "name": "Guillaume Jondeau",
      "orcid": "0000-0002-0101-2076"
    },
    {
      "affs": [
        6,
        16
      ],
      "name": "Elie Mousseaux",
      "orcid": "0000-0002-8076-1445"
    },
    {
      "affs": [
        17
      ],
      "name": "Mathieu Pernot",
      "orcid": "0000-0001-6713-4642"
    },
    {
      "affs": [
        6
      ],
      "name": "Andrea Ruiz-Velasco",
      "orcid": "0000-0003-0660-5855"
    },
    {
      "affs": [
        18
      ],
      "name": "Alfonso Sartorius",
      "orcid": "0009-0001-8498-2704"
    },
    {
      "affs": [
        18
      ],
      "name": "Benoit Tyl",
      "orcid": "0000-0001-5297-8412"
    },
    {
      "affs": [
        6,
        16
      ],
      "name": "Gilles Soulat"
    },
    {
      "affs": [
        2
      ],
      "name": "Philippe Boutinaud",
      "orcid": "0000-0003-3662-1119"
    },
    {
      "affs": [
        19
      ],
      "name": "Damien Logeart"
    },
    {
      "name": "PACIFIC consortium"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eqk2x13q8qkcs.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77642-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13669343",
  "id": "eqk2x13q8qkcs",
  "issns": [
    "2041-1723",
    "2041-1723"
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  "landing_url": "https://hal.univ-lorraine.fr/hal-05801681v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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  "pdf_url": "https://hal.univ-lorraine.fr/hal-05801681/document",
  "pmcid": "PMC13669343",
  "pmid": "42875459",
  "published": "2026-09-15",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/eqk2x13q8qkcs.ris",
  "sources": [
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Heart Failure Treatment and Management",
      "subfield": "cardiovascular"
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  ],
  "title": "Multimodal data-driven clustering analysis of heart failure patients identifies two distinct patterns of heart failure with preserved ejection fraction: Results from the PACIFIC-PRESERVED study",
  "title_text": "Multimodal data-driven clustering analysis of heart failure patients identifies two distinct patterns of heart failure with preserved ejection fraction: Results from the PACIFIC-PRESERVED study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/eqk2x13q8qkcs",
  "venue": "Nature Communications",
  "versions": []
}