{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:39:59Z","timestamp":1789468799108,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013953","name":"Maccabi Institute for Health Services Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013953","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>One of the limiting toxicities of BTKi is the development of atrial fibrillation (AF), with an incidence of 3%\u201316%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to identify patients with chronic lymphocytic leukemia (CLL) starting both first\u2010 and second\u2010generation BTKis who are at high risk of developing AF using a machine learning approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The CLL cohort is based on data obtained from electronic medical records from Maccabi, the second\u2010largest healthcare organization in Israel. The optimal scoring model was determined using the Risk\u2010calibrated Supersparse Linear Integer Model (RiskSLIM) algorithm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 3964 patients with a CLL diagnosis were available in the database. Of these, 208 patients started BTKi during the study period (125 on ibrutinib and 83 on acalabrutinib), and 16 patients developed AF during follow\u2010up. In addition to well\u2010established factors such as age, sex, and hypertension, the algorithm detected other factors associated with a high risk for AF: type of BTKi used, low eGFR, elevated absolute monocytes (&gt;\u20091100\/\u03bcL), elevated CRP, elevated CK, and elevated B2MG (&gt;\u20092.5\u2009mg\/L). Based on the total AF\u2010free survival (AFS), we identified three main risk groups: low (0\u20136), intermediate (7\u201311) and high (\u2265\u200912). The median AF\u2010free survival (AFS) was 28 and 56\u2009months for the high\u2010risk and intermediate\u2010risk groups, respectively, and was not reached for the low\u2010risk group. The difference between the groups was statistically significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0013).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our novel score has a high concordance index for predicting the development of AF in patients with CLL treated with first\u2010 and second\u2010generation BTKis. It combines age, sex, medical history, and laboratory tests associated with inflammatory status and disease burden and can be applied in clinical settings worldwide.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.14400","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:33:42Z","timestamp":1741761222000},"page":"1011-1019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>CLLAF SCORE<\/scp>\n                    \u2014A New Risk Score for Predicting Atrial Fibrillation in Treatment\u2010Naive\n                    <scp>CLL<\/scp>\n                    Patients Initiating First\u2010 and Second\u2010Generation\n                    <scp>BTK<\/scp>\n                    Inhibitor Therapy"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8612","authenticated-orcid":false,"given":"Tamar","family":"Tadmor","sequence":"first","affiliation":[{"name":"Hematology Unit, Faculty of Medicine Bnai Zion Medical Center, and the Ruth and Bruce Rappaport, Technion  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Melamed","sequence":"additional","affiliation":[{"name":"Kahn Sagol Maccabi Research &amp; Innovation Center, Maccabi Healthcare Services  Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilel","family":"Alapi","sequence":"additional","affiliation":[{"name":"Kahn Sagol Maccabi Research &amp; Innovation Center, Maccabi Healthcare Services  Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Rokach","sequence":"additional","affiliation":[{"name":"Department of Software and Information Systems Engineering Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.687458"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1533129"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2016.1257795"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.3301.3301"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010020\u201004094\u20103"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3126"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2023.2299737"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.117.007849"},{"issue":"150","key":"e_1_2_11_10_1","first-page":"1","article-title":"Learning Optimized Risk Scores","volume":"20","author":"Ustun B.","year":"2019","journal-title":"Journal of Machine Learning Research"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780100508"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010018\u20100626\u20100"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4274\/tjh.galenos.2024.2024.0045"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.14698"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euv422"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200373"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH15\u201006\u20100477"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0240540"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.12.036"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000492873"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20190888"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30029-8"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.932813"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2023.07.023"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.114.001303"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001193"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2017.1394554"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(23)00220-0"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/echo.14946"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.14400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T06:51:52Z","timestamp":1746514312000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.14400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/ejh.14400"],"URL":"https:\/\/doi.org\/10.1111\/ejh.14400","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]},"assertion":[{"value":"2025-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}