{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:10:33Z","timestamp":1759396233119,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output\/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion\/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 \u03bcg\/kg\/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 \u00b1 17.5 years and severe LV dysfunction (LVEF 30.6 \u00b1 9.8%). Median treatment duration was 131 days (IQR 60\u2013241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement.<\/jats:p>","DOI":"10.3390\/jpm15100473","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T08:20:28Z","timestamp":1759393228000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotype-Guided Outpatient Levosimendan as a Bridge-to-Transplant in Low-Output Advanced Heart Failure: A Single-Center Cohort"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6342-1146","authenticated-orcid":false,"given":"Ricardo","family":"Carvalheiro","sequence":"first","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Raquel","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Rita","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Ferreira","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ant\u00f3nio Valentim","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita Ilh\u00e3o","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago","family":"Pereira da Silva","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valdemar","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui Cruz","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Unidade Local de S\u00e3o Jos\u00e9\/Hospital de Santa Marta, R. de Santa Marta 50, 1169-024 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. 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Rep."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/10\/473\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T08:31:52Z","timestamp":1759393912000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/10\/473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":17,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jpm15100473"],"URL":"https:\/\/doi.org\/10.3390\/jpm15100473","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]}}}