{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T03:31:07Z","timestamp":1782012667828,"version":"3.54.5"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Research Agency","award":["2019\/ABM\/01\/00017"],"award-info":[{"award-number":["2019\/ABM\/01\/00017"]}]}],"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>Intermittent administration of levosimendan has recently been introduced for long-term use in patients with advanced heart failure (HF). However, the impact of this therapy on survival remains inconclusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Levosimendan in ambulatory HF patients was a multicentre, randomized, double-blind, placebo-controlled, Phase IV clinical trial of intermittent levosimendan administration in patients with ambulatory stable advanced HF [left ventricular ejection fraction \u226435%, New York Heart Association Classes III and IV]. The primary clinical endpoint of the study was composed of death from any cause or unplanned hospitalization for HF, whichever occurred first in a 12-month follow-up period. Infusion started at a dose of 0.05\u2005\u03bcg\/kg\/min and lasted \u223c24 h (up to a maximum dose of 12.5\u2005mg) every 4 weeks. The study was conducted in nine centres around Poland. The study was prematurely terminated due to excess of deaths in the active treatment group. Finally, 64 (out of 350 planned) patients were recruited to the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty-four patients with advanced HF [age\u201464.2 \u00b1 13.1 years, 57 (89%) men] were enrolled into the study. At baseline visit 34 (53%) patients were randomly assigned to the levosimendan group (study group) and 30 (47%) to the placebo group. Study drug administration resulted in a significant decrease in N-terminal pro-B-type natriuretic peptide concentrations [5084\u2005pg\/ml (306\u201323.203) vs 2027 pg\/ml (872\u20132174), P = .02) and left ventricular ejection fraction improvement (20.9 \u00b1 5.9% vs 29.27 \u00b1 5.23%, P = .015) in the study group. These patients also had clinical endpoint numerically more often than patients in the placebo group [22 (64.71%) vs 14 (46.67%); P = .14], including significantly higher deaths [7 (100%) vs 0, P = .02].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a selected group of stable ambulatory advanced HF (left ventricular ejection fraction \u226435%, New York Heart Association Classes III and IV) patients, repetitive levosimendan 24 h infusion might be an additional therapeutic option but observed deaths may raise its safety issue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eschf\/xvag021","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T12:27:59Z","timestamp":1768307279000},"source":"Crossref","is-referenced-by-count":1,"title":["The possible impact of levosimendan infusions on clinical course of heart failure: the results of the LEIA-HF study"],"prefix":"10.1093","volume":"13","author":[{"given":"Ewelina","family":"Kazimierczyk","sequence":"first","affiliation":[{"name":"Department of Cardiology and Internal Medicine with Cardiac Intensive Care Unit, Medical University of Bialystok , Bialystok ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4517-1498","authenticated-orcid":false,"given":"Remigiusz","family":"Kazimierczyk","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Internal Medicine with Cardiac Intensive Care Unit, Medical University of Bialystok , Bialystok ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Imiela","sequence":"additional","affiliation":[{"name":"Department of Internal Disease and Cardiology, Center for Management of Venous Thromboembolic Disease, Medical University of Warsaw , Warsaw 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,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Mickiewicz","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Internal Medicine with Cardiac Intensive Care Unit, Medical University of Bialystok , Bialystok ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciszek","family":"Kukli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Intensive Cardiac Care, Medical University of Bialystok , Bialystok ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Fernandez-Moreno","sequence":"additional","affiliation":[{"name":"Department of Intensive Cardiac Care, Medical University of Bialystok , Bialystok ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Gierlotka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of 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