{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:26:44Z","timestamp":1786613204253,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced melanoma, but the comparative cardiac safety of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)-containing regimens versus programmed cell death protein 1 (PD-1)-only regimens in real-world populations remains poorly characterized. We compared cardiac outcomes between melanoma patients exposed to CTLA-4 blockade (ipilimumab) and those treated with anti-PD-1 therapy alone (nivolumab or pembrolizumab) using a large multicenter electronic health record database. Methods: This retrospective cohort study used de-identified data from the TriNetX Research Network (111 US healthcare organizations). Adults with melanoma (ICD-10-CM C43) who received ipilimumab (CTLA-4 exposed) were compared with those who received nivolumab or pembrolizumab without ipilimumab (anti\u2013PD-1 only); both groups were therefore treated with immune checkpoint inhibitors, isolating the effect of CTLA-4 exposure. Propensity score matching (1:1) balanced demographics, cardiovascular comorbidities, and baseline antiarrhythmic use. The primary outcome was a cardiac conduction disorder composite; outcomes were assessed at 1 and 3 years. Results: Of 7313 CTLA-4-exposed and 11,481 anti-PD-1-only patients, 6841 matched pairs were analyzed (all standardized mean differences &lt;0.03). CTLA-4 exposure was associated with a significantly higher incidence of cardiac conduction disorders that was already present at 1 year (3.8% vs. 2.1%; RR 1.82; 95% CI 1.48\u20132.24; p &lt; 0.001) and persisted at 3 years (5.1% vs. 3.7%; RR 1.36; 95% CI 1.16\u20131.60; p &lt; 0.001). Atrioventricular block was higher at both 1 year (RR 2.10; 95% CI 1.59\u20132.78) and 3 years (RR 1.49; 95% CI 1.20\u20131.85), and complete heart block was markedly increased at 3 years (0.5% vs. 0.2%; RR 3.28; 95% CI 1.67\u20136.43; p &lt; 0.001). Heart failure was modestly higher with CTLA-4 exposure at both timepoints (1-year RR 1.35; 3-year RR 1.17). Conclusions: Among melanoma patients treated with immune checkpoint inhibitors, CTLA-4-containing therapy is associated with a higher burden of cardiac conduction disorders, including a roughly three-fold excess of complete heart block, that is evident within the first year and sustained thereafter. Because the CTLA-4-exposed cohort comprised both ipilimumab monotherapy and nivolumab plus ipilimumab and the subgroup analyses localized the excess risk to the combination regimen, this association reflects CTLA-4-containing (predominantly combination) therapy rather than ipilimumab monotherapy in isolation. These findings support electrocardiographic surveillance beginning during, not only after, treatment for patients receiving CTLA-4-containing immunotherapy.<\/jats:p>","DOI":"10.3390\/cancers18162608","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"2608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac Conduction Disorders in Melanoma Patients Treated with CTLA-4-Containing Versus PD-1-Only Immune Checkpoint Inhibitor Therapy: A Propensity Score-Matched Real-World Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Ali","family":"Awad","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Detroit Medical Center, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Khodeir","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qusai","family":"AlQudah","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Detroit Medical Center, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8872-7412","authenticated-orcid":false,"given":"Mariam","family":"Chalhoub","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Chadi","family":"Alraies","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Detroit Medical Center, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1200\/JCO.2009.23.4799","article-title":"Final Version of 2009 AJCC Melanoma Staging and Classification","volume":"27","author":"Balch","year":"2009","journal-title":"J. Clin. 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