IMPORTANCE Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited. OBJECTIVE To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard. DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study. EXPOSURES Sequential therapy with anthracyclines and trastuzumab. MAIN OUTCOMES AND MEASURES Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models. RESULTS Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD. CONCLUSIONS AND RELEVANCE Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02306538.

中文翻译：

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联合超声心动图诊断早期乳腺癌女性癌症治疗相关心功能不全的方法。

重要性 癌症治疗相关的心功能不全 (CTRCD) 的诊断仍然是一个挑战。心血管磁共振 (CMR) 可准确测量左心室射血分数 (LVEF)，但重复扫描的访问受限。目的 以 CMR 作为参考标准，使用超声心动图 LVEF 和应变及生物标志物开发 CTRCD 诊断模型。设计、地点和参与者 在这项前瞻性队列研究中，患者于 2013 年 11 月至 2019 年 1 月从多伦多大学附属医院招募，所有心脏成像均在一个三级医疗中心进行。包括患有人类表皮生长因子受体 2 (HER2) 阳性早期乳腺癌的女性。主要排除标准是 CMR 的禁忌症。共招募了 160 名患者，其中 136 人完成了研究。接触 蒽环类药物和曲妥珠单抗的序贯治疗。主要结果和测量 患者在曲妥珠单抗治疗期间和之后每 3 个月接受一次超声心动图、高敏肌钙蛋白 I (hsTnI)、B 型利钠肽 (BNP) 和 CMR 检查蒽环类药物前和蒽环类药物后。超声心动图测量包括二维 (2-D) LVEF、3-D LVEF、峰值收缩整体纵向应变 (GLS) 和整体圆周应变 (GCS)。LVEF CTRCD 使用心脏审查和评估委员会标准、GLS 或 GCS CTRCD 定义为大于 15% 的相对变化，异常 hsTnI 和 BNP 分别定义为大于 26 pg/mL 和 ≥ 35 pg/mL，在任何后续点。使用条件推理树模型检查超声心动图测量和生物标志物的组合以诊断 CMR CTRCD。结果 在 136 名女性（平均 [SD] 年龄，51.1 [9.2] 岁）中，CMR 识别的 CTRCD 发生在 37 名 (27%) 中，并且在具有可分析图像的女性中，131 名中的 30 名 (23%) 通过 2-D LVEF , 124 例中的 27 例 (22%) 通过 3-D LVEF，126 例中的 53 例 (42%) 通过 GLS，123 例中的 61 例 (50%) 通过 GCS，136 例中的 32 例 (24%) 通过 BNP，以及 136 例中的 14 例 (10 %) 通过 hsTnI。单独来看，对于 CMR CTRCD，3-D LVEF 比 2-D LVEF 具有更高的敏感性和特异性，而 GLS 比 2-D 或 3-D LVEF 具有更高的敏感性。回归树分析确定了一种使用 3-D LVEF、GLS 和 GCS 的顺序算法，用于 CTRCD 的最佳诊断（接受者操作特征曲线下的面积，89.3%）。当所有 3 项测试的结果均为阴性时，CTRCD 的概率为 1.0%。当模型中的 3-D LVEF 被 2-D LVEF 替换时，该算法仍然表现良好；然而，它的主要价值是排除 CTRCD。生物标志物并未提高诊断 CTRCD 的能力。结这些措施单独。试验注册 ClinicalTrials.gov 标识符：NCT02306538。这些数据表明，将超声心动图 3-D LVEF 与 2-D GLS 和 2-D GCS 相结合的序贯方法可以在常规 CTRCD 监测期间提供 CTRCD 的及时诊断，其准确性高于单独使用这些措施。试验注册 ClinicalTrials.gov 标识符：NCT02306538。这些数据表明，将超声心动图 3-D LVEF 与 2-D GLS 和 2-D GCS 相结合的序贯方法可以在常规 CTRCD 监测期间提供 CTRCD 的及时诊断，其准确性高于单独使用这些措施。试验注册 ClinicalTrials.gov 标识符：NCT02306538。