Evidence mapPaperPMID 41711727Full record

ArticleESC heart failure2026

Arterio-venous gradient of active interleukin-18 is associated with diastolic dysfunction: a cross-sectional study.

Hirofumi Makino, Yu Yasuda, Yusuke Morita, Hiroshi Kawahara, Yuzo Kagawa, Akihiro Endo, Hiroki Kamino, Kazuaki Tanabe, Takeshi Urano, Keizo Kanasaki

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Article in ESC heart failure, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Hirofumi MakinoInternal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
Yu YasudaInternal Medicine 4, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Yusuke MoritaInternal Medicine 4, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Hiroshi KawaharaInternal Medicine 4, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Yuzo KagawaInternal Medicine 4, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Akihiro EndoInternal Medicine 4, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Hiroki KaminoCenter for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases, Shimane University, Izumo 693-8501, Japan.
Kazuaki TanabeInternal Medicine 4, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.ORCID 0000-0002-8910-8389
Takeshi UranoCenter for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases, Shimane University, Izumo 693-8501, Japan.
Keizo KanasakiInternal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.ORCID 0000-0002-9563-502X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDiastolic dysfunction is a key determinant of symptoms and prognosis in heart failure (HF). Interleukin (IL)-18 and IL-6 are key inflammatory cytokines in HF; however, their local activation within the cardiopulmonary circulation and relevance to diastolic dysfunction remain unclear. This exploratory study investigated associations between arterio-venous (A/V) cytokine gradients and diastolic dysfunction.

methodsEighty-seven patients undergoing diagnostic cardiac catheterization were enrolled. Paired arterial samples from the left ventricle (LV) or ascending aorta and peripheral venous samples were obtained simultaneously or within 24 h of the procedure. Active IL-18 (aIL-18) and IL-6 concentrations were measured, and associations with echocardiographic and clinical parameters were evaluated. Active interleukin-18-induced fibrotic responses were evaluated in human cardiac fibroblasts.

resultsThe cohort exhibited impaired myocardial relaxation (septal e': 5.3 ± 2.0 cm/s) and preserved ejection fraction (57.4 ±11.8%). The aIL-18 A/V ratio correlated with average E/e' (r = 0.31, P < .01), tricuspid regurgitation pressure gradient (r = 0.29, P = .015), and Heart Failure Association-Pre-test assessment, Echocardiography & natriuretic peptide, Functional testing, Final aetiology (HFA-PEFF) score (r = 0.23, P = .034). Correlations between the aIL-18 A/V ratio and E/e' were more pronounced in non-diabetic patients and in those with elevated LV filling pressure (average E/e' ≥ 15). Interleukin-6 correlated with albuminuria and pulmonary function; however, no synergistic interaction with aIL-18 was observed. In vitro, aIL-18 stimulated fibroblast proliferation and collagen synthesis.

conclusionThe aIL-18 A/V ratio correlated with markers of diastolic dysfunction, particularly in patients with increased filling pressure. These exploratory findings indicate an association between local IL-18 gradients and diastolic dysfunction, warranting further investigation.

Indexed as

Heart FailureHeart Failure, DiastolicHeart VentriclesInterleukin-18Stroke VolumeVentricular Dysfunction, LeftVentricular Function, LeftAgedBiomarkersCardiac CatheterizationCells, CulturedCross-Sectional StudiesDiastoleEchocardiographyFemaleHumansBiomarkersIL18 protein, humanInterleukin-18Interleukin-6Cardiac fibrosisDiastolic dysfunctionHeart failureInflammatory cytokinesInterleukin-18

Identifiers

PMID41711727
PMCPMC13168766

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.