{
  "abstract": "Background: Heart failure in younger women is understudied and may reflect heterogeneous pathways and risk not adequately captured by conventional classifications. We aimed to identify clinically distinct phenotypes of early-onset heart failure in women, assess their prognostic significance, and evaluate their transportability in an independent national cohort. Methods: We identified women aged 18-55 years with heart failure using electronic health record data from a large multi-hospital system. A variational deep embedding model incorporating 283 clinical features was used for unsupervised phenotyping. Associations with subsequent inpatient hospitalization, emergency department utilization, and mortality were evaluated using age-stratified Cox models. Phenotype transportability was assessed by both applying the institutionally trained model and by independent de novo clustering as a replication analysis in the All of Us cohort. Results: Among 1,407 young women with heart failure (median age, 45 years), four phenotypes were identified: hypertensive pregnancy (n=494), cardiorenal (n=276), autoimmune (n=394), and cardiometabolic-ischemic (n=243), with a bootstrap adjusted Rand index of 0.65 and silhouette score of 0.45. Compared with the hypertensive pregnancy phenotype, risks of inpatient hospitalization were highest for the cardiorenal (HR 2.86 [95% CI, 2.35?3.49]) and autoimmune (HR 2.25 [95% CI, 1.87?2.70]) phenotypes; mortality risks were similarly elevated (HR 4.65 [95% CI, 3.17?6.82] and HR 4.38 [95% CI, 3.03?6.31], respectively) in these two groups. In All of Us participants (n=682), transferred phenotypes retained their principal clinical characteristics and continued to stratify hospitalization risk. Independent clustering most strongly reproduced the cardiorenal phenotype (Jaccard index, 0.744). Conclusions: Early-onset heart failure in women comprises distinct cardio-obstetric, cardiorenal, autoimmune, and cardiometabolic-ischemic phenotypes with divergent clinical outcomes. These findings support a life-course approach to heart failure classification in women that complements conventional frameworks and incorporates pregnancy history and female-predominant systemic conditions.",
  "abstract_shown": true,
  "affiliations": [
    "Johns Hopkins University School of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "J. Khorsandi"
    },
    {
      "name": "Y. Yu"
    },
    {
      "name": "D. Tinnium"
    },
    {
      "name": "S. Ganesh"
    },
    {
      "name": "R. Alahapphan"
    },
    {
      "name": "P. Oyinloye"
    },
    {
      "name": "K. Mueller"
    },
    {
      "name": "S. Ardekani"
    },
    {
      "name": "C. O. Taylor"
    },
    {
      "name": "J. L. Greenstein"
    },
    {
      "name": "C. E. Ndumele"
    },
    {
      "name": "E. D. Michos"
    },
    {
      "name": "C. N. Bairey Merz"
    },
    {
      "name": "R. B. Barrett"
    },
    {
      "affs": [
        0
      ],
      "name": "A. S. Minhas"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8vcd1hych1kz2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.26367323",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367323v1.full",
  "id": "8vcd1hych1kz2",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367323v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "cardiovascular medicine"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367323v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8vcd1hych1kz2.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:06Z",
      "native_id": "10.64898/2026.11.04.26367323",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367323v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:cardiovascular medicine",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Uncovering Distinct Phenotypes of Early Onset Heart Failure in Women",
  "title_text": "Uncovering Distinct Phenotypes of Early Onset Heart Failure in Women",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:53Z",
  "url": "https://research.draconitic.com/paper/8vcd1hych1kz2",
  "venue": "medRxiv",
  "versions": []
}