BTK抑制剂启动后房颤负荷与临床结局的关系
Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation
DOI 原文链接
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影响因子:13.4
分区:医学1区 Top / 血液学1区 肿瘤学2区
发表日期:2024 Oct
作者:
John Alan Gambril, Sanam M Ghazi, Stephen Sansoterra, Mussammat Ferdousi, Onaopepo Kola-Kehinde, Patrick Ruz, Adam S Kittai, Kerry Rogers, Michael Grever, Seema Bhat, Tracy Wiczer, John C Byrd, Jennifer Woyach, Daniel Addison
DOI:
10.1038/s41375-024-02334-3
摘要
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，但与心脏毒性相关，包括房颤（AF）。目前尚不清楚BTKi相关房颤的负荷、严重程度及其临床意义。利用2009-2020年连续接受BTKi治疗的B细胞恶性肿瘤患者大规模队列，我们筛选出进行了长时间心律监测的患者。主要观察指标为BTKi治疗后房颤负荷。次要指标包括心室性心律失常负荷及其他心律失常。将新一代BTKi的房颤发生率和负荷与伊布替尼进行比较。多变量回归分析了心律指标与主要不良心脏事件（MACE）及死亡率的关系。共纳入98例BTKi治疗患者（其中38.8%使用新一代BTKi，14.3%有既往房颤），监测时间共计22,224小时。中位用药时间为34个月。在平均监测12天期间，72.4%的患者出现心律失常（16.3%新发房颤，31.6%其他室上性心动过速，14.3%室性心动过速）。14.3%的患者房颤负荷较高。伊布替尼与新一代BTKi的房颤负荷相似。没有单一的抗心律失常药能预防BTKi相关的房颤，但抗心律失常药物的使用与心律失常负荷的降低相关（P=0.009）。在考虑传统心血管风险因素的多变量模型中，既往房颤与BTKi后房颤负荷增加相关。在随访中，房颤高负荷与MACE（HR 3.12，P=0.005）及死亡率（HR 2.97，P=0.007）相关。对于BTKi治疗的患者，高房颤负荷预示未来发生MACE和死亡的风险。
Abstract
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.