{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:43:01Z","timestamp":1791272581434,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1998,11,24]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>\u2014The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>\u2014Thirty-six men (mean age\u00b1SD, 55\u00b18 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4\u00b14.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean arterial pressure (difference from baseline over 12 hours [95% CIs], \u221213.9% [\u221216.0% to \u221211.7%]), pulmonary artery mean (\u221212.9% [\u221217.4% to \u22128.3%]) and capillary wedge (\u221214.5% [\u221220.5% to \u22128.5%]) pressures, and right atrial pressure (\u221220.2% [\u221229.4% to \u221211.0%]). Cardiac output increased (15.1% [10.7% to 19.7%]), but heart rate was unchanged. Both systemic (\u221224.2% [\u221228.1% to \u221220.3%]) and pulmonary (\u221219.9% [\u221228.4% to \u221211.4%]) vascular resistance were reduced. After 2 weeks, cardiac output had further increased (by 15.2% [10.8% to 19.6%]) and systemic (\u22129.3% [\u221212.3% to \u22126.4%]) and pulmonary (\u22129.7% [\u221216.3% to \u22123.1%]) vascular resistances further decreased compared with day 1. Heart rate remained unchanged. Plasma ET-1 levels increased after bosentan, but baseline levels of the other hormones were unchanged.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014Additional short-term oral endothelin-receptor antagonist therapy improved systemic and pulmonary hemodynamics in heart failure patients who were symptomatic with standard triple-drug therapy. Further investigations are warranted to characterize the effects of long-term endothelin-receptor antagonist therapy on symptoms, morbidity, and mortality in such patients.<\/jats:p>","DOI":"10.1161\/01.cir.98.21.2262","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"2262-2268","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":223,"title":["Short-Term Oral Endothelin-Receptor Antagonist Therapy in Conventionally Treated Patients With Symptomatic Severe Chronic Heart Failure"],"prefix":"10.1161","volume":"98","author":[{"given":"Gabor","family":"Su\u0308tsch","sequence":"first","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kiowski","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wei","family":"Yan","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hunziker","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Christen","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Strobel","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hun","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rickenbacher","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osmund","family":"Bertel","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiology, Departments of Medicine, University Hospital Zu\u0308rich (G.S., W.K., X.Y., Y.K.), Triemli Hospital Zu\u0308rich (P.H., S.C, O.B.), and University Hospital Basel (W.S., P.R.), Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.4.8149524"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91504-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00520-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80783-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0022-3565(25)22357-6","volume":"270","year":"1994","unstructured":"Clozel M, Breu V, Gray GA, Kalina B, L\u00f6ffler BM, Burri K, Cassal JM, Hirth G, M\u00fcller M, Neidhart W, Ramuz H. 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