{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:04:59Z","timestamp":1789621499849,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014764","name":"China International Medical Foundation","doi-asserted-by":"publisher","award":["2022-N-01-02"],"award-info":[{"award-number":["2022-N-01-02"]}],"id":[{"id":"10.13039\/501100014764","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Post-cardiac arrest myocardial dysfunction (PAMD) is a major contributor to early death (within 72\u2005hours) following return of spontaneous circulation (ROSC). Levosimendan, a calcium-sensitizing inotrope with vasodilatory and mitochondrial-protective properties, offers a potential therapeutic strategy by increasing cardiac output, improving organ perfusion, and attenuating mitochondrial ischemia-reperfusion injury. While experimental evidence suggests multi-organ benefits in cardiac arrest (CA), robust clinical data are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This exploratory, partially blinded, randomized, placebo-controlled trial will enroll 60 comatose CA patients with PAMD across three centers in China. Within 180 minutes after ROSC, eligible participants will be randomized (1:1) to receive either intravenous levosimendan (0.05\u20130.2\u2009\u03bcg\/kg\/min for 24 hours) or volume-matched saline placebo; the assigned infusion will begin within 6 hours after ROSC. The primary outcome is 30-day all-cause mortality, interpreted within an exploratory signal-generating framework. Secondary outcomes explore 30-day neurological recovery assessed by the Cerebral Performance Category (CPC) and Modified Rankin Scale (mRS), along with cardiac function and hemodynamic stability during the first week post-resuscitation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This exploratory trial is designed to align early levosimendan infusion (within 6\u2005hours post-ROSC) with its pharmacokinetics to cover the anticipated nadir of myocardial dysfunction. By targeting a homogeneous cohort with witnessed arrest, rapid ROSC (&amp;lt;60\u2005min), and LVEF &amp;lt;40%, the trial focuses on patients with potentially reversible injury who may benefit most. The findings will provide preliminary evidence on efficacy and safety to inform a definitive Phase III trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT05956431<\/jats:ext-link>\n                      , ClinicalTrials.gov NCT05956431. Registered on 21 July 2023.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1850394","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:48:36Z","timestamp":1789620516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early use of levosimendan to improve survival and neurological outcomes after cardiac arrest with myocardial dysfunction: a protocol for a randomized controlled trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhen","family":"De","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nengyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Research Center, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100962","DOI":"10.1016\/j.resplu.2025.100962","article-title":"Epidemiology and outcomes of out-of-hospital cardiac arrest in Zhejiang, China based on electronic medical record surveillance","volume":"23","author":"Chen","year":"2025","journal-title":"Resusc Plus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart Disease and Stroke Statistics-2023 Update: a report from the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1161\/CIRCULATIONAHA.108.190652","article-title":"Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. 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