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

Abstract

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 PARTICIPANTSIn 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 Ն 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 RELEVANCEUsing 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.

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

“…GLS is recommended in all patients with cancer having echocardiography, if available. 75,80,81,89,90,92,93,102,103 I C…”

The year in cardiovascular medicine 2022: the top 10 papers in cardiovascular imaging

“…A recent study in 136 women with human epidermal growth factor 2 (HER2)-positive breast cancer identified a sequential algorithm to diagnose cancer therapy related cardiac dysfunction (CTRCD) [using cardiac magnetic resonance (CMR) as reference] by combining echocardiographic 3D left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and global circumferential strain (GCS). 3 This approach showed to provide a timely diagnosis of CTRCD during routine surveillance with greater accuracy than using the three measures individually or biomarkers and a probability of CTRCD of only 1.0% when results for all three tests were negative.…”

Multimodality imaging for cardiotoxicity: state of the art and future perspectives

“…Good acoustic windows are crucial for accurate measurements, and this may be challenging especially in postmastectomy patients, in patients with breast reconstructions, and in patients postradiotherapy. 19…”

“…Good acoustic windows are crucial for accurate measurements, and this may be challenging especially in postmastectomy patients, in patients with breast reconstructions, and in patients postradiotherapy. 19 Surveillance for CTRCD requires serial imaging for detection of small changes in LVEF between scans. 2D echocardiography is known to have high test-retest variability (10%-11% on previous studies [20][21][22] ), and although improved by the use of transpulmonary contrast administration, more precise methods may be required to aid accurate clinical decision-making regarding the continuation or cessation of cancer treatment.…”