超声心动图应变分析对免疫检查点抑制剂相关心肌炎患者危险分层及预后评估的临床价值

Value of speckle tracking echocardiography in patients with immune checkpoint inhibitor-related myocarditis

目的探讨危重症与普通/轻症免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)相关心肌炎患者的超声心动图心肌应变特征。研究对象前瞻性入选中国医学科学院北京协和医院2020年5月至2022年9月的24例应用ICIs后出现心肌炎的住院患者,采集并分析患者基线超声心动图,末次随访时间为2022年12月。干预措施根据后续病情严重程度进行ICIs相关心肌炎分级,患者被归为2组:危重症组13例(Ⅳ级),普通/轻症组11例(Ⅰ~Ⅲ级)。比较2组患者超声心动图心肌应变特征。观测指标及测量方法采用EchoPAC软件分析2组患者左心室整体径向应变(global radial strain,GRS)、左心室心肌整体纵向应变(global longitudinal strain,GLS)、心内膜整体纵向应变(global longitudinal strain of endocardial layers,endoGLS)、心外膜整体纵向应变(global longitudinal strain of epicardial layers,epiGLS)、左心室整体环向应变(global circumferential strain,GCS)、心内膜整体环向应变(global circumferential strain of endocardial layers,endoGCS)、心外膜整体环向应变(global circumferential strain of epicardial layers,epiGCS)、左心室18节段纵向应变、左心房纵向峰值应变(peak left atrial longitudinal strain,PALS)、左心房收缩期应变(left atrial systolic strain,s-CT)和左心房管道期应变(left atrial strain during conduit phase,s-CD),并进行生存分析。结果在左心室应变方面,与Ⅰ~Ⅲ级患者相比,Ⅳ级患者整体GLS的绝对值(|GLS|)(10.6%vs.13.5%)、整体GRS(12.3%vs.22.5%),以及左心室epiGLS绝对值(epi|GLS|)(9.3%vs.12.0%)差异均有统计学意义;下侧壁基底段应变绝对值(basPost|GLS|)(11.4%vs.17.3%)、前间隔基底段应变绝对值(basAntSept|GLS|)(9.8%vs.13.5%)、下壁基底段应变绝对值(basInf|GLS|)(13.3%vs.18.6%)、下壁中间段应变绝对值(midInf|GLS|)(13.0%vs.18.2%)及前壁基底段应变绝对值(basAnt|GLS|)(8.1%vs.13.3%)差异均有统计学意义。左心房应变方面,Ⅳ级心肌炎患者的左心房纵向峰值应变(peak left atrial longitudinal strain,PALS)(13.9%vs.23.4%)及s-CT的绝对值(|s-CT|)显著低于Ⅰ~Ⅲ级组(7.7%vs.13.3%)。ROC曲线提示左心室|GLS|<12.9%、epi|GLS|<11.0%、basAntSept|GLS|<13.9%、basInf|GLS|<14.5%、midInf|GLS|<14.8%、s-CT<11.0%时,对出现Ⅳ级ICIs心肌炎的诊断价值较高。生存分析方面,epi|GLS|<11.0%及basInf|GLS|<14.5%的患者生存期较短(P均<0.05)。结论相比于Ⅰ~Ⅲ级心肌炎患者,Ⅳ级ICIs相关心肌炎患者左心室整体长轴及径向应变,左心室基底部应变及左心房应变下降明显,可用于评估ICIs相关心肌炎的严重程度;左心室外膜长轴应变和下壁基底部长轴应变更有助于预测患者短中期生存。

Objective To investigate the myocardial strain characteristics of echocardiography between patients with critical/severe and moderate/mild myocarditis related with immune checkpoint inhibitors(ICIs).Subjects This prospective study enrolled 24 patients with ICIs-related myocarditis at Peking Union Medical College Hospital from May 2020 to September 2022.The patients were followed up until December 2022.Interventions Patients with ICIs-related myocarditis were divided into gradeⅠtoⅣaccording to the disease severity.Echocardiographic strains were compared between 11 patients with gradeⅠ-Ⅲmyocarditis and 13 patients with gradeⅣmyocarditis.The myocardial strain parameters were compared between two groups.Main Outcomes and Measurements The EchoPAC software was utilized to analyze various strain parameters,including,global radial strain(GRS),left ventricular global longitudinal strain(GLS),endocardium and epicardial global longitudinal strain(endoGLS,epiGLS),global circumferential strain(GCS),endocardium and epicardial global circumferential strain(endoGCS,epiGCS),left ventricular 18-segment GLS,peak left atrial longitudinal strain(PALS),left atrial systolic strain(s-CT),and left atrial strain during conduit phase(s-CD).Results The absolute values of GLS(|GLS|)(10.6%vs.13.5%),GRS(12.3%vs.22.5%),epi|GLS|(9.3%vs.12.0%),basPost|GLS|(11.4%vs.17.3%),basAntSept|GLS|(9.8%vs.13.5%),basInf|GLS|(13.3%vs.18.6%),midInf|GLS|(13.0%vs.18.2%),and basAnt|GLS|(8.1%vs.13.3%)were significantly impaired in the gradeⅣgroup compared to the gradeⅠ-Ⅲgroup.Similarly,the absolute values of PALS(13.9%vs.23.4%)and s-CT were significantly lower in the gradeⅠ-Ⅲgroup compared to the gradeⅣgroup(7.7%vs.13.3%).To better predict the presence of gradeⅣICIs-related myocarditis,the ROC curve analysis suggested the following cut-off values:|GLS|<12.9%,epi|GLS|<11.0%,basAntSept|GLS|<13.9%,basInf|GLS|<14.5%,midInf|GLS|<14.8%and s-CT<11.0%.Survival analysis revealed that patients with epi|GLS|<11.0%and basInf|GLS|<14.5%had short survival period(all P<0.05).Conclusions Patients with critical/severe ICIs-related myocarditis have significantly decreased GLS,GRS,bas|GLS|and left atrial strain when compared with moderate/mild myocarditis.Moreover,epi|GLS|and basInf|GLS|may serve as potential indicators for predicting short-term survival.Speckle tracking echocardiography proves to be a valuable tool in assessing the severity of ICIs-related myocarditis and predicting the prognosis.