A sequential approach combining echocardiographic imaging techniques may be an effective diagnostic model for timely diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) during routine CTRCD monitoring in women with early-stage breast cancer. These findings were published in JAMA Cardiology.

Left ventricular ejection fraction (LVEF) can be accurately determined through the use of cardiovascular magnetic resonance (CMR) imaging, and the technique is considered the reference standard for this, explained the researchers. However, the feasibility of this technique for repeat measurements is limited.

Patients with HER2-positive breast cancer stages I to III scheduled to receive sequential anthracycline and trastuzumab, with and without adjuvant radiotherapy, were recruited from hospitals associated with the University of Toronto in Canada for this prospective cohort study (ClinicalTrials.gov Identifier: NCT02306538).

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The patients had baseline transthoracic echocardiograms obtained prior to anthracyclines, after anthracyclines but before trastuzumab, and every 3 months during trastuzumab therapy (at 3, 6, and 9 months), with the final measurement after trastuzumab (at 12 months). ECG monitoring included measurements of 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS).

Patients also underwent CMR imaging on the days ECGs were obtained, excluding the measurement at 9 months. Blood samples for biomarker analyses involving high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) were also taken on days of imaging. Using CMR imaging as the reference standard for CTRCD diagnosis, a goal of the study was to develop a diagnostic algorithm for CTRCD using results from ECG and biomarker analyses.

A total of 136 women, mean age 51.1 years, were included in the analyses. CTRCD was found through CMR imaging in 27% of the patients. Among evaluable patients for each assessment, CTRCD was found by ECG through 2-D LVEF measurement in 23%, through 3-D LVEF measurement in 22%, through GLS in 42%, and through GCS in 50%. Abnormal results in biomarker analyses were seen in 24% of patients based on BNP and in 10% of patients based on hsTnI.

In identifying CMR-defined CTRCD, ECG measurements through 3-D LVEF showed greater specificity and sensitivity than 2-D LVEF images did, and GLS showed better sensitivity than either 2-D LVEF, 3-D LVEF, or GCS did. Biomarkers had poor sensitivity at identifying CMR-defined CTRCD, even though they reportedly showed good specificity.

The researchers chose a diagnostic algorithm that included 3-D LVEF, GLS, and GCS measurements, and the area under the receiver operating characteristic curve for this model was 0.893 (95% CI, 0.829-0.945). They considered the model to also perform well with 2-D LVEF used in place of 3-D LVEF, but considered this substitution to be primarily effective at excluding CTRCD.

“In women with HER2-positive breast cancer receiving anthracyclines and trastuzumab treatment, combined sequential use of echocardiographic 3-D LVEF, 2-D GLS, and GCS may be a reliable way to diagnose CTRCD,” the researchers concluded.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Esmaeilzadeh M, Urzua Fresno CM, Somerset E, et al. A combined echocardiography approach for the diagnosis of cancer therapy-related cardiac dysfunction in women with early-stage breast cancer. JAMA Cardiol. Published online February 9, 2022. doi:10.1001/jamacardio.2021.5881