{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:04:23Z","timestamp":1791644663750,"version":"4.3.4"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Cardiac resynchronization therapy (CRT) is a cornerstone treatment for heart failure with reduced ejection fraction (HFrEF), yet many patients remain symptomatic despite long-term electrical optimization. Although sacubitril\/valsartan (ARNI) is central to guideline-directed medical therapy (GDMT), data on its late initiation in patients with chronic CRT are scarce. This study evaluated the impact of delayed ARNI initiation on clinical status, functional capacity, and cardiac remodelling in a real-world CRT population. Methods: We performed a single-centre, retrospective observational study including 76 HFrEF patients with chronic CRT who started ARNI between 2022 and late 2024. Patients underwent standardized assessment at baseline (T0) and after 12 \u00b1 3 months (T1), including clinical evaluation, 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), symptom-limited bicycle exercise testing, and comprehensive echocardiography. The primary endpoint was change in quality of life (QoL). Secondary endpoints included exercise capacity, echocardiographic reverse remodelling, NYHA class, loop diuretic dose, and device-detected arrhythmias. Dose\u2013response and multidimensional response patterns were explored. Results: KCCQ-12 increased from 52.96 \u00b1 16.33 to 75.55 \u00b1 18.12 (\u0394 +22.59 \u00b1 13.22, p &lt; 0.001), with 89.5% achieving a clinically meaningful improvement. Exercise duration and peak workload improved significantly. LVEF increased from 35.08 \u00b1 6.96% to 43.18 \u00b1 8.42% (\u0394 +8.11%, p &lt; 0.001), with reductions in left ventricular and atrial volumes. Loop diuretic dose decreased (median \u221210 mg\/day furosemide equivalent, p &lt; 0.001), and 26.3% discontinued diuretics. A lower prevalence of device-detected arrhythmias was observed at follow-up, from 34.2% to 6.6% (p &lt; 0.001). Higher ARNI doses were associated with greater likelihood of clinical, functional, and structural response. Longer CRT duration reduced the probability of structural remodelling but not symptomatic or functional benefit. Conclusions: In patients with long-standing CRT, delayed ARNI initiation was associated with improvements in QoL, exercise capacity, cardiac remodelling, congestion status, and electrical stability. These findings suggest that CRT is not a therapeutic ceiling and that late ARNI initiation remains a valuable component of comprehensive GDMT.<\/jats:p>","DOI":"10.3390\/jcm15041617","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:47:02Z","timestamp":1771508822000},"page":"1617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of Late ARNI Initiation on Quality of Life and Functional Capacity in CRT-Treated HFrEF Patients: A Single-Centre Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6510-5921","authenticated-orcid":false,"given":"Oana","family":"Patru","sequence":"first","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0859-2498","authenticated-orcid":false,"given":"Silvia","family":"Luca","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7378-7787","authenticated-orcid":false,"given":"Dragos","family":"Cozma","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Vacarescu","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-5605","authenticated-orcid":false,"given":"Simina","family":"Crisan","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Bena","sequence":"additional","affiliation":[{"name":"Discipline of Endocrinology, Second Department of Internal Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Center for Molecular Research in Nephrology and Vascular Disease, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Virtosu","sequence":"additional","affiliation":[{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3377-1465","authenticated-orcid":false,"given":"Adrian Sebastian","family":"Zus","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin Tudor","family":"Luca","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-0211","authenticated-orcid":false,"given":"Simona Ruxanda","family":"Dragan","sequence":"additional","affiliation":[{"name":"Cardiology Department, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"},{"name":"Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1001\/jama.2020.10262","article-title":"Heart Failure with Reduced Ejection Fraction: A Review","volume":"324","author":"Murphy","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0140-6736(25)01851-3","article-title":"Heart Failure with Reduced Ejection 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Rev."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:55:17Z","timestamp":1771509317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15041617"],"URL":"https:\/\/doi.org\/10.3390\/jcm15041617","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}