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Publications

Journal Article Epublish

PubMed: 42875459 DOI: 10.1038/s41467-026-77642-6

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.

Nat Commun 17(1)

Authors: Jean-Sébastien Hulot, Pierre-Yves Hervé, Nicolas Girerd, Frédérique Chézalviel-Guilbert, Philip Janiak, Pierre Boutouyrie, Jean-Joseph Christophe, Ariel Cohen, Thibaud Damy, Liliane Berkani, Kevin Duarte, Caroline Fraslon, Hüseyin Firat, Olivier Hanon, Richard Isnard, Guillaume Jondeau, Elie Mousseaux, Mathieu Pernot, Andrea Ruiz-Velasco, Alfonso Sartorius, Benoit Tyl, Gilles Soulat, Philippe Boutinaud, Damien Logeart

Affiliations

  • Université Paris Cité, INSERM, PARCC, Paris, France.
  • CIC1418 and DMU CARTE, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.
  • 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.

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.

MeSH

Biological Science Disciplines, Heart Failure, Heart, Heart Failure, Diastolic, Cluster Analysis