Cardiovascular Magnetic Resonance Imaging in Patients With Ibrutinib-Associated Cardiotoxicity.

Autor:	Buck B; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Chum AP; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Patel M; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Carter R; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Center for the Advancement of Team Science, Analytics, and Systems Thinking (CATALYST), Ohio State University College of Medicine, Columbus., Nawaz H; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Division of Cardiology, Northwestern Feinberg School of Medicine, Chicago, Illinois., Yildiz V; Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus., Ruz P; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Wiczer T; Department of Pharmacy, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus., Rogers KA; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus., Awan FT; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus.; Division of Hematology/Oncology, University of Texas-Southwestern Medical Center, Dallas., Bhat S; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus., Guha A; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Harrington Heart and Vascular Institute, Case Western Reserve University, Cleveland, Ohio., Kittai AS; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus., Simonetti OP; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Department of Biomedical Engineering, The Ohio State University, Columbus., Raman SV; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Division of Cardiology, Indiana University School of Medicine, Indianapolis., Wallace G; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Sanchez R; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Bonsu JM; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Gambril J; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Haddad D; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Mann J; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora., Wei L; Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus., Kola-Kehinde O; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus., Byrd JC; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus., Woyach JA; Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus., Addison D; Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus.; Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2023 Apr 01; Vol. 9 (4), pp. 552-555.
DOI:	10.1001/jamaoncol.2022.6869
Abstrakt:	Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, Setting, and Participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main Outcomes and Measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and Relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.
Databáze:	MEDLINE
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