{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:31:14Z","timestamp":1787725874874,"version":"build-2784847793"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ibrutinib is effective for B-cell malignancies but is associated with cardiovascular adverse events, including atrial fibrillation (AF) and hypertension. Longitudinal data on left atrial (LA) remodeling during treatment are limited. We characterized serial changes in LA size and function during chronic ibrutinib therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective observational cohort, 40 patients starting ibrutinib underwent clinical assessment, 24\u201372-hour Holter monitoring, and echocardiography with LA strain at baseline and 3, 6, 12, and long-term (nominal 36-month) follow-up. Primary analyses used observed paired data, random-intercept mixed models, standardized response means (SRMs), and Benjamini-Hochberg adjustment across 24 primary contrasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median age was 65 years and 53% were female. Paired mean LAVI changes were +1.52\u2005mL\/m\u00b2 at 3 months (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938), +1.68 at 6 months (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936), +2.62 at 12 months (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200933), and +2.15 at long-term follow-up (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931; all q\u2009\u2264\u20090.020). LA reservoir strain worsened from 6 months onward (all q\u2009\u2264\u20090.031), while LA contractile strain, LA lateral-wall TDI, and LV GLS worsened at every follow-up (all q\u2009\u2264\u20090.009). Results were materially unchanged after adjustment for time-varying hypertension and in complete-case sensitivity analyses. Incident AF occurred in 5\/40 patients (12.5%; 95% CI 5.5%\u201326.1%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>During chronic ibrutinib therapy, longitudinal imaging showed modest LA enlargement and consistent deterioration in several LA deformation indices. These treatment-associated observations require confirmation in controlled cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, identifier NCT03751410.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1914493","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:54Z","timestamp":1787724174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal changes in left atrial function during chronic ibrutinib therapy: a prospective observational study"],"prefix":"10.3389","volume":"13","author":[{"given":"Matea","family":"Kolacevic Zeljkovic","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Sisters of Mercy University Hospital Centre","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Basic-Kinda","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Zagreb University Hospital Centre","place":["Zagreb, Croatia"]},{"name":"Medical School, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dubravka","family":"\u010car\u017eavec","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sisters of Mercy University Hospital Centre","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijo","family":"Vodanovic","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Zagreb University Hospital Centre","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Mandac Smoljanovic","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Merkur University Hospital","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozren","family":"Jaksic","sequence":"additional","affiliation":[{"name":"Division of Haematology, Department of Internal Medicine, Dubrava University Hospital","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matea","family":"Novak","sequence":"additional","affiliation":[{"name":"Zagreb School of Economics and Management","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slobodanka","family":"Ostojic-Kolonic","sequence":"additional","affiliation":[{"name":"Medical School, University of Zagreb","place":["Zagreb, Croatia"]},{"name":"Division of Hematology, Department of Internal Medicine, Merkur University Hospital","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino","family":"Dujmovic","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Zagreb University Hospital Centre","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlatko","family":"Pejsa","sequence":"additional","affiliation":[{"name":"Medical School, University of Zagreb","place":["Zagreb, Croatia"]},{"name":"Division of Haematology, Department of Internal Medicine, Dubrava University Hospital","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Aurer","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Zagreb University Hospital Centre","place":["Zagreb, Croatia"]},{"name":"Medical School, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Bulj","sequence":"additional","affiliation":[{"name":"Medical School, University of Zagreb","place":["Zagreb, Croatia"]},{"name":"Department of Cardiology, Sisters of Mercy University Hospital Centre","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s40265-017-0695-3","article-title":"Ibrutinib: a review in chronic lymphocytic leukaemia","volume":"77","author":"Deeks","year":"2017","journal-title":"Drugs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1056\/NEJMoa1400376","article-title":"RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia","volume":"371","author":"Byrd","year":"2014","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1080\/13543784.2018.1404027","article-title":"Bruton's tyrosine kinase inhibitors: first and second generation agents for patients with chronic lymphocytic leukemia (CLL)","volume":"27","author":"Thompson","year":"2018","journal-title":"Expert Opin Investig Drugs"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1007\/s00277-017-2973-2","article-title":"Ibrutinib in CLL: a focus on adverse events, resistance, and novel approaches beyond ibrutinib","volume":"96","author":"Kaur","year":"2017","journal-title":"Ann Hematol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.clml.2018.06.016","article-title":"Safety analysis of four randomized controlled studies of ibrutinib in patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma or mantle cell lymphoma","volume":"18","author":"O'Brien","year":"2018","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B6","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1182\/blood-2015-03-635326","article-title":"Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results","volume":"126","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e2701","DOI":"10.7759\/cureus.2701","article-title":"Management of atrial fibrillation in patients on ibrutinib: a Cleveland clinic experience","volume":"10","author":"Khalid","year":"2018","journal-title":"Cureus"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1016\/j.jacep.2018.06.004","article-title":"Ibrutinib-associated atrial fibrillation","volume":"4","author":"Ganatra","year":"2018","journal-title":"JACC Clin Electrophysiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"792310","DOI":"10.3389\/fcvm.2021.792310","article-title":"Arrhythmia patterns in patients on ibrutinib","volume":"8","author":"Fazal","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1624761","DOI":"10.3389\/fonc.2025.1624761","article-title":"Real-world cardiovascular risks of ibrutinib in chronic lymphocytic leukemia: a retrospective study","volume":"15","author":"Ivanovic","year":"2025","journal-title":"Front Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e70004","DOI":"10.1002\/cai2.70004","article-title":"Inhibition of putative ibrutinib targets promotes atrial fibrillation, conduction blocks, and proarrhythmic electrocardiogram indices: a Mendelian randomization analysis","volume":"4","author":"Xu","year":"2025","journal-title":"Cancer Innov"},{"key":"B12","doi-asserted-by":"publisher","first-page":"176675","DOI":"10.1016\/j.ejphar.2024.176675","article-title":"Ibrutinib, a Bruton's tyrosine kinase inhibitor, regulates ventricular electromechanical activities and enhances arrhythmogenesis","volume":"977","author":"Liu","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.2147\/DDDT.S377697","article-title":"Ibrutinib-associated cardiotoxicity: from the pharmaceutical to the clinical","volume":"16","author":"Dong","year":"2022","journal-title":"Drug Des Devel Ther"},{"key":"B14","doi-asserted-by":"publisher","first-page":"201","DOI":"10.31083\/j.fbl2905201","article-title":"Ibrutinib contributes to atrial arrhythmia through the autophagic degradation of connexins by inhibiting the PI3K-AKT-mTOR signaling pathway","volume":"29","author":"Qin","year":"2024","journal-title":"Front Biosci (Landmark Ed)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"416","DOI":"10.5603\/AHP.a2022.2056","article-title":"Studies on platelet function during the first year of ibrutinib treatment in patients with chronic lymphocytic leukemia","volume":"53","author":"Soko\u0142owska","year":"2022","journal-title":"Acta Haematol Pol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.jaccao.2020.11.016","article-title":"How to manage atrial fibrillation secondary to ibrutinib","volume":"3","author":"Essa","year":"2021","journal-title":"JACC CardioOncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1007\/s10741-025-10569-0","article-title":"Echocardiographic monitoring in cancer therapy: clinical guidance for cardiologists and oncologists","volume":"30","author":"Sperlongano","year":"2025","journal-title":"Heart Fail Rev"},{"key":"B18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/echo.14946","article-title":"Utilizing left atrial strain to identify patients at risk for atrial fibrillation on ibrutinib","volume":"38","author":"Singh","year":"2021","journal-title":"Echocardiography"},{"key":"B19","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1093\/ehjci\/jey042","article-title":"Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI\/ASE\/industry task force to standardize deformation imaging","volume":"19","author":"Badano","year":"2018","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"B20","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ijcard.2016.06.197","article-title":"Left atrial strain: a useful index in atrial fibrillation","volume":"220","author":"Cameli","year":"2016","journal-title":"Int J Cardiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"100642","DOI":"10.1016\/j.ijcha.2020.100642","article-title":"Atrial appendages' Mechanics assessed by 3D transoesophageal echocardiography as predictors of atrial fibrillation recurrence after pulmonary vein isolation","volume":"31","author":"Zeljkovi\u0107","year":"2020","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1016\/j.jacc.2007.01.078","article-title":"Tissue Doppler imaging a new prognosticator for cardiovascular diseases","volume":"49","author":"Yu","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.3324\/haematol.2017.171041","article-title":"Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials","volume":"102","author":"Brown","year":"2017","journal-title":"Haematologica"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia","volume":"373","author":"Burger","year":"2015","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.amjcard.2019.05.029","article-title":"Rates and risk of atrial arrhythmias in patients treated with ibrutinib compared with cytotoxic chemotherapy","volume":"124","author":"Fradley","year":"2019","journal-title":"Am J Cardiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e001049","DOI":"10.1136\/openhrt-2019-001049","article-title":"High incidence of atrial fibrillation in patients treated with ibrutinib","volume":"6","author":"Baptiste","year":"2019","journal-title":"Open Heart"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5516","DOI":"10.1182\/bloodadvances.2022007938","article-title":"International consensus statement on the management of cardiovascular risk of Bruton's tyrosine kinase inhibitors in CLL","volume":"6","author":"Awan","year":"2022","journal-title":"Blood Adv"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1161\/CIRCULATIONAHA.120.049210","article-title":"Ibrutinib-mediated atrial fibrillation attributable to inhibition of C-terminal src kinase","volume":"142","author":"Xiao","year":"2020","journal-title":"Circulation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13045-018-0626-0","article-title":"Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study","volume":"11","author":"Reda","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1038\/s41375-024-02334-3","article-title":"Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation","volume":"38","author":"Gambril","year":"2024","journal-title":"Leukemia"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1513913","DOI":"10.3389\/fphar.2024.1513913","article-title":"Epidemiology, clinical characteristics and potential mechanism of ibrutinib-induced ventricular arrhythmias","volume":"15","author":"Pan","year":"2024","journal-title":"Front Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1038\/s41375-024-02413-5","article-title":"Is ibrutinib-related atrial fibrillation dose dependent? Insights from an individual case level analysis of the world health organization pharmacovigilance database","volume":"38","author":"Alexandre","year":"2024","journal-title":"Leukemia"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1357006","DOI":"10.3389\/fcvm.2024.1357006","article-title":"Left ventricular to left arial volume ratio in the assessment of filling pressure in patients with dyspnoea and preserved ejection fraction","volume":"11","author":"Palka","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1295537","DOI":"10.3389\/fcvm.2023.1295537","article-title":"Left heart remodelling in hypertensive patients: a comprehensive echocardiography and computed tomography study","volume":"10","author":"Lange","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1182\/blood.2019000840","article-title":"Hypertension and incident cardiovascular events following ibrutinib initiation","volume":"134","author":"Dickerson","year":"2019","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia","volume":"388","author":"Brown","year":"2023","journal-title":"N Engl J Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial","volume":"39","author":"Byrd","year":"2021","journal-title":"J Clin Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3324\/haematol.2024.285754","article-title":"Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I\/II BRUIN trial","volume":"110","author":"Shah","year":"2025","journal-title":"Haematologica"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1914493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:56Z","timestamp":1787724176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1914493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":38,"alternative-id":["10.3389\/fcvm.2026.1914493"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1914493","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"article-number":"1914493"}}