{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:13:54Z","timestamp":1792541634835,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diastolic 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eighty-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\u2005h 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort exhibited impaired myocardial relaxation (septal e\u2032: 5.3 \u00b1 2.0\u2005cm\/s) and preserved ejection fraction (57.4 \u00b111.8%). The aIL-18 A\/V ratio correlated with average E\/e\u2032 (r = 0.31, P &amp;lt; .01), tricuspid regurgitation pressure gradient (r = 0.29, P = .015), and Heart Failure Association-Pre-test assessment, Echocardiography &amp; 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\u2032 were more pronounced in non-diabetic patients and in those with elevated LV filling pressure (average E\/e\u2032 \u2265 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eschf\/xvaf041","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:25:34Z","timestamp":1767702334000},"source":"Crossref","is-referenced-by-count":1,"title":["Arterio-venous gradient of active interleukin-18 is associated with diastolic dysfunction: a cross-sectional study"],"prefix":"10.1093","volume":"13","author":[{"given":"Hirofumi","family":"Makino","sequence":"first","affiliation":[{"name":"Internal Medicine 1, Shimane University Faculty of Medicine , 89-1 Enya-cho, Izumo, Shimane 693-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Internal Medicine 4, Shimane University Faculty of Medicine , Izumo 693-8501 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