Department of Internal Medicine, Ohio State University Medical Center, Columbus, OH, USA.
Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA.
Leukemia. 2024 Oct;38(10):2141-2149. doi: 10.1038/s41375-024-02334-3. Epub 2024 Aug 17.
Bruton's tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009-2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi's were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi's, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi's. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden (P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.
布鲁顿酪氨酸激酶抑制剂 (BTKi) 对 B 细胞恶性肿瘤具有显著疗效，但与包括心房颤动 (AF) 在内的心脏毒性相关。BTKi 相关 AF 的负担、严重程度和影响尚不清楚。利用 2009 年至 2020 年间接受 BTKi 治疗的连续 B 细胞恶性肿瘤患者的大型队列，我们确定了接受延长动态心电图监测的患者。主要结局是 BTKi 治疗后 AF 的负担。次要结局包括室性心律失常负担和其他心律失常。比较了新一代 BTKi 的观察到的新发 AF 发生率和负担与伊布替尼。多变量回归定义了节律测量与主要不良心脏事件 (MACE) 和死亡率之间的关联。98 例接受 BTKi 治疗的患者 [38.8%为新一代 BTKi，14.3%为既往 AF]，监测时间为 28224 小时。BTKi 治疗的中位时间为 34 个月。在平均 12 天的监测期间，72.4%的患者出现心律失常 (16.3%为新发 AF，31.6%为其他 SVT，14.3%为室性心动过速)。14.3%有高 AF 负担。伊布替尼和新一代 BTKi 的 AF 负担相似。没有单一的抗心律失常治疗可以预防 BTKi 相关的 AF。然而，抗心律失常治疗的起始与心律失常负担的降低相关 (P = 0.009)。在一个考虑到传统心血管危险因素的多变量模型中，既往 AF 与 BTKi 后 AF 负担增加相关。在随访中，高 AF 负担与 MACE (HR 3.12，P = 0.005) 和死亡率 (HR 2.97，P = 0.007) 相关。在接受 BTKi 治疗的患者中，高 AF 负担预示着未来发生 MACE 和死亡的风险。
