{
  "abstract": "Efforts to validate the comorbidity-driven interleukin-6-mediated systemic inflammation framework have been unable to support the postulated sequence of pathophysiological events. The treatment of comorbidities (other than obesity) has not alleviated systemic inflammatory biomarkers or ameliorated the course of HFpEF. Additionally, drugs that exert systemic anti-inflammatory effects by interfering with the effects of classical cytokines have not improved exercise tolerance or reduced the risk of worsening heart failure events. Only one-third of patients with HFpEF show coronary microvascular dysfunction that is endothelium-dependent, and drugs that act to reverse the consequences of coronary microvascular endothelial dysfunction by augmenting NO-cGMP signaling (nitrates, nitrites, soluble guanylate cyclase stimulators or phosphodiesterase 5 inhibitors) do not exert favorable effects on symptoms, exercise capacity or health status in HFpEF. The recently announced findings from the HERMES and ATHENA trials with interleukin-6 antagonism with ziltivekimab reinforce the premise that systemic inflammation produced by classical cytokines may not have pathogenic significance in HFpEF.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Milton Packer"
    },
    {
      "name": "Javed Butler"
    },
    {
      "name": "Faiez Zannad"
    },
    {
      "name": "Muthiah Vaduganathan"
    },
    {
      "name": "Barry A Borlaug"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/awp7zzs8d3s9k.bib",
  "cited_by": 0,
  "doi": "10.1016/j.cardfail.2026.09.029",
  "fulltext_url": null,
  "id": "awp7zzs8d3s9k",
  "issns": [
    "1071-9164"
  ],
  "landing_url": "https://hal.univ-lorraine.fr/hal-05789194v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2705|Heart Failure Treatment and Management"
    ]
  ],
  "openalex": "W7220401710",
  "pdf_url": "https://hal.univ-lorraine.fr/hal-05789194/document",
  "pmcid": null,
  "pmid": "42833572",
  "published": "2026-10-09",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/awp7zzs8d3s9k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:52Z",
      "native_id": "hal-05789194",
      "source": "hal",
      "url": "https://hal.univ-lorraine.fr/hal-05789194v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Heart Failure Treatment and Management",
      "subfield": "cardiovascular"
    }
  ],
  "title": "The Comorbidity-Driven Interleukin-6-Mediated Systemic Inflammation Hypothesis of Heart Failure With Preserved Ejection Fraction: A Decade of Testing Ends in Disappointment",
  "title_text": "The Comorbidity-Driven Interleukin-6-Mediated Systemic Inflammation Hypothesis of Heart Failure With Preserved Ejection Fraction: A Decade of Testing Ends in Disappointment",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:52Z",
  "url": "https://research.draconitic.com/paper/awp7zzs8d3s9k",
  "venue": "Journal of Cardiac Failure",
  "versions": []
}