{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:27:30Z","timestamp":1786537650184,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Traditionally, risk stratification in heart failure with reduced ejection fraction (HFrEF) patients has been a static process. This study aims to identify clinical predictors and causes of mortality at different stages of the disease, distinguishing between early mortality (\u22641 year) and late mortality (&gt;1 year), as well as cardiovascular and non-cardiovascular causes. Methods: This is an observational, longitudinal study of a cohort of 1510 patients with HFrEF followed up in a specialist heart failure unit between 2011 and 2023. Patients were categorized into three groups: alive (n = 1093), early mortality (n = 55) and late mortality (n = 362). Multivariate Cox regression models were used to identify mortality independent predictors in each period. Results: During the first year, cardiovascular and non-cardiovascular mortality showed a relatively balanced distribution, with a slight predominance of non-cardiovascular causes (52.8%). Progression of heart failure remained the leading individual cause of early death (38.2%). Independent predictors of early cardiovascular death included ischemic etiology (HR 2.78; 95% CI: 1.20\u20136.40; p = 0.01), NYHA functional class (HR 4.38; 95% CI: 2.18\u20138.81; p &lt; 0.001) and renal function (HR 0.60; 95% CI: 0.44\u20130.84; p = 0.002). In contrast, late mortality (&gt;1 year) was predominantly due to non-cardiovascular causes (59.7%), notably cancer (24.3%) and infections (7.5%). Late all-cause mortality was independently associated with age (HR 1.35; 95% CI: 1.17\u20131.56; p &lt; 0.001), hypertension (HR 1.38; 95% CI: 1.06\u20131.81; p = 0.015) and ischemic etiology (HR 1.45; 95% CI: 1.16\u20131.80; p &lt; 0.001). In the follow-up, the improvement of left ventricular ejection fraction (LVEF) emerged as a protective factor against long-term all-cause mortality (HR 0.77; 95% CI: 0.63\u20130.94; p = 0.01) and, even more markedly, against late cardiovascular mortality (HR 0.47; 95% CI: 0.33\u20130.66; p &lt; 0.001), whereas baseline LVEF at diagnosis lacked significant predictive value in either model. Conclusions: Mortality in HFrEF is a dynamic process. Early survival is determined by hemodynamic stability, renal function and functional severity, whilst late survival is predominantly driven by non-cardiovascular comorbidities, biological aging, and ventricular remodeling trajectory. The improvement of LVEF during follow-up is a more reliable prognostic marker than the baseline measurement, suggesting that clinical management should shift from early pharmacological optimization towards a multidisciplinary approach focused on long-term non-cardiovascular risk.<\/jats:p>","DOI":"10.3390\/jcm15166223","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:30:32Z","timestamp":1786465832000},"page":"6223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal Trends and Predictors of Mortality in Heart Failure with Reduced Ejection Fraction: The Role of Renal Function and Left Ventricular Improvement"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6724-4187","authenticated-orcid":false,"given":"Andrea","family":"Lopez-Lopez","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"},{"name":"Doctorate Program, Department of Anatomy, Animal Production and Veterinary Clinical Sciences, Universidad de Santiago de Compostela, 27001 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Rivas V\u00e1zquez","sequence":"additional","affiliation":[{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Regueiro-Abel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4743-0787","authenticated-orcid":false,"given":"Carmen Cristina","family":"\u00c1lvarez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charigan","family":"Abou Johk-Casas","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Elices-Teja","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"R\u00edos V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-171X","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Santamarina-Pernas","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universidad de Santiago de Compostela, 27001 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-9778","authenticated-orcid":false,"given":"Carlos","family":"Gonz\u00e1lez-Juanatey","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain"},{"name":"CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain"},{"name":"Nursing School, Universidad de Santiago de Compostela, Campus Lugo, 27001 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106457","DOI":"10.1016\/j.ejim.2025.106457","article-title":"Non cardiovascular comorbidities in Heart Failure. 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