{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:13:46Z","timestamp":1789557226502,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":364,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020390","name":"Windtree Therapeutics, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020390","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020390","name":"Windtree Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre-CS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>The SEISMiC study is a multinational, multicentre, randomized, double-blind, placebo-controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre-CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70\u2013100 mmHg for at least 2 h] and clinically confirmed congestion, NT-proBNP \u22651400 pg\/mL, and LVEF\u226440%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6 h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60 h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study\u2019s primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24 h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study results will contribute to our understanding of the role of istaroxime in pre-CS patients and potentially provide insight into the drug\u2019s haemodynamic effects and safety in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15102","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:39:12Z","timestamp":1728347952000},"page":"189-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Safety and Efficacy of up to 60 h of iv Istaroxime in Pre-Cardiogenic Shock Patients: Design of the SEISMiC Trial"],"prefix":"10.1093","volume":"12","author":[{"given":"Jan","family":"Biegus","sequence":"first","affiliation":[{"name":"Institute of Heart Diseases, Wroclaw Medical University , Wroc\u0142aw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Mebazaa","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care and Burn Unit, Saint-Louis and Lariboisi\u00e8re Hospitals, FHU PROMICE, DMU Parabol, APHP Nord , Paris ,","place":["France"]},{"name":"Cardiovascular Markers in Stress Conditions (MASCOT), Universit\u00e9 Paris Cit\u00e9, Inserm UMR-S 942 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Cardiology Unit, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pagnesi","sequence":"additional","affiliation":[{"name":"Cardiology Unit, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ovidiu","family":"Chioncel","sequence":"additional","affiliation":[{"name":"Emergency Institute for Cardiovascular Diseases \u2019Prof. C.C. 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