{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:57:42Z","timestamp":1790485062072,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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: Reverse remodeling after cardiac resynchronization therapy with defibrillator backup (CRT-D) is heterogeneous and may reflect both pre-implant substrate and post-implant electrical response, with implications for subsequent outcomes. Objectives: This study evaluated a graded echocardiographic response framework after CRT-D as an integrative phenotype linking pre-implant substrate, peri-implant electrical features, and post-landmark clinical outcomes. Methods: The analytic cohort included 334 CRT-D recipients with complete four-group classification based on relative left ventricular end-systolic volume reduction at the first eligible post-implant echocardiogram. Baseline correlates of the 4-class response phenotype were assessed using ordinal logistic regression, supported by permutation-importance analysis. A stacked peri-implant model added \u0394QRS, RV1SI pattern on ECG, left ventricular lead position, and lead depth. Time-to-event analyses used a landmark design anchored at the first post-CRT echocardiogram. Results: In the pre-implantation ordinal model, female sex (p = 0.005), higher baseline left ventricular ejection fraction (p = 0.032), left bundle branch block (p = 0.038), and dilated cardiomyopathy (p = 0.048) were associated with a more favorable response class. In the stacked peri-implant model, \u0394QRS was the strongest correlate of higher response class (OR: 1.41; 95% CI: 1.15\u20131.73; p = 0.0008). Mortality differed across response classes (log-rank p &lt; 0.001); compared with super-responders, negative responders had higher adjusted mortality (HR: 4.41; 95% CI: 1.82\u201310.70). At 60 months, heart failure hospitalization ranged from 23.3% to 2.9% and first appropriate ICD shock from 29.3% to 9.0% from negative responders to super-responders. Conclusions: After CRT-D, reverse-remodeling phenotype identified clinically distinct post-landmark risk profiles. Less favorable remodeling was associated with worse mortality, heart failure hospitalization, and appropriate ICD shock.<\/jats:p>","DOI":"10.3390\/jcm15197443","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:29:53Z","timestamp":1790267393000},"page":"7443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre-Implant Substrate, Peri-Implant Electrical Features, and Outcomes Across Four Echocardiographic Phenotypes After CRT-D"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5789-0256","authenticated-orcid":false,"given":"Vasileios","family":"Cheilas","sequence":"first","affiliation":[{"name":"School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2733-2729","authenticated-orcid":false,"given":"Anna","family":"Kostopoulou","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgos","family":"Filandrianos","sequence":"additional","affiliation":[{"name":"Artificial Intelligence and Learning Systems Laboratory, National Technical University of Athens, 15780 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel M.","family":"Kanoupakis","sequence":"additional","affiliation":[{"name":"University Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Poulos","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Koutalas","sequence":"additional","affiliation":[{"name":"University Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-4050","authenticated-orcid":false,"given":"Athanasios","family":"Saplaouras","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Mililis","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michalis","family":"Efremidis","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4793-0224","authenticated-orcid":false,"given":"Giorgos","family":"Tsironis","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-3430","authenticated-orcid":false,"given":"Maria","family":"Marketou","sequence":"additional","affiliation":[{"name":"University Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos P.","family":"Letsas","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Kochiadakis","sequence":"additional","affiliation":[{"name":"University Hospital of Heraklion, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","unstructured":"K\u00f8ber, L., Adamo, M., Ruwald, A.-C., Tomasoni, D., Anderson, L.J., Andersson, C., Brugts, J.J., Chioncel, O., Donal, E., and Ferdinandy, P. 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