A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy–Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer

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