硼替佐米治疗多发性骨髓瘤患者期间相关心脏毒性分析

An analysis of bortezomib-related cardiotoxicity in treating the patients with multiple myeloma

目的 观察硼替佐米治疗多发性骨髓瘤(MM)期间的心脏毒性,分析硼替佐米相关心脏不良事件(CAEs)的危险因素。方法 接受包含硼替佐米方案初治MM患者180例分为CAEs和非CAEs两组。CAEs组25例,治疗期间发生CAEs,包括心力衰竭、急性冠脉综合征或症状性心律失常(需要治疗的心房颤动或心房扑动)。非CAEs组155例,治疗期间未发生CAEs。分析两组患者治疗前和治疗2个疗程及4个疗程脑利钠肽前体(NT-proBNP)、心肌肌钙蛋白I(cTnI)、高敏CRP(hsCRP)、中性粒细胞/淋巴细胞比值(NLR)、超声心动图左心室射血分数、HR以及P-R间期等的变化。采用单因素logistic回归分析硼替佐米致CAEs的影响因素。绘制ROC曲线。结果 与治疗前比较,治疗后NT-proBNP、cTnI、hsCRP和NLR均升高(P<0.01)。180例MM患者中,发生CAEs 25例,发生率为13.9%。主要见于第1个疗程,占64.0%(16/25)。CAEs组患者有心脏病和高血压病史的比例和治疗前NT-proBNP、cTnI、hsCRP、NLR、HR和P-R间期均高于非CAEs组,Hb低于非CAEs组(P<0.05)。ROC曲线分析结果显示,hsCRP预示CAEs的灵敏度为80%,特异度为96%,NLR预测CAEs的灵敏度为96%,特异度为65%。单因素logistic回归分析结果显示,心脏病史、高血压病史、治疗前Hb、hsCRP、NLR、HR、PR间期是硼替佐米致CAEs的影响因素。结论 采用硼替佐米方案初治MM患者疗效明显,但可伴有CAEs的发生;其危险因素主要为既往有心脏病、高血压病史和高水平hsCRP、NLR和HR及低水平Hb。

Objective To observe the bortezomib-related cardiotoxicity in the treatment of the patients with multiple myeloma(MM) and analyze the factors affecting bortezomib-induced cardiac adverse events(CAEs).Methods A total of 180 patients with MM were divided into two groups of CAEs(with CAEs, 25 cases) and non-CAEs(without CAEs, 155 cases).The CAEs included heart failure, acute coronary syndrome and symptomatic arrhythmias(atrial fibrillation or atrial flutter requiring treatment).The changes of relevant indicators before and after two courses and four courses of bortezomib-based chemotherapy were analyzed, which included N-terminal probrain natriuretic peptide(NT-proBNP),cardiac troponin I(cTnI),high-sensitivity CRP(hsCRP),neutrophil/lymphocyte ratio(NLR),left ventricular ejection fraction, HR and P-R interval.The factors affecting bortezomib-induced CAEs were analyzed with univariate logistic regression analysis.The ROC curve was drawn.Results Compared to before, the NT-proBNP,cTnI,hsCRP and NLR were increased after bortezomib treatment(P<0.01).The CAEs occurred in 25 cases of 180 cases with a CAEs incidence rate of 13.9%,which were seen mostly in the first course of treatment(64.0%).The percentage of the patients with heart disease and hypertension history and lower Hb, and the higher levels of NT-proBNP,cTnl, hsCRP,NLR,HR and P-R interval before treatment in group CAEs than those in group non-CAEs(P<0.05).The results of ROC curve analysis showed that in the prediction of CAEs occurrence the sensitivity was 80% and the specificity was 96% for hsCRP,and 96% and 65% for NLR,respectively.Univariate logistic regression analysis showed that cardiac history, history of hypertension, Hb, hsCRP,NLR,HR and P-R interval before treatment were the influencing factors for bortezomib-induced CAEs.Conclusion The initial treatment of MM patients with bortezomib regimen is obviously effective, but can be accompanied by the development of CAEs.The risk factors for the occurrence of CAEs are with heart disease and hypertension history, increased levels of hsCRP,NLR,HR and low level Hb value.