Features of trastuzumab-related cardiac dysfunction: deformation analysis outside left ventricular global longitudinal strain

Abstract

Background: Cancer therapy-related cardiac dysfunction due to trastuzumab has been well-known for many years, and echocardiographic surveillance is recommended every 3 months in patients undergoing trastuzumab treatment, irrespective of the baseline cardiotoxicity risk. However, the potential harm and cost of overscreening in low- and moderate-risk patients have become great concerns.

Objectives: This study aimed to identify the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the behaviours of left and right heart deformations during trastuzumab chemotherapy in low- and moderate-risk patients.

Methods: We prospectively enrolled 110 anthracycline-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive trastuzumab. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycle and 3 weeks after the final dose of trastuzumab. The baseline risk of CTRCD was graded according to the risk score proposed by the Heart Failure Association (HFA) Cardio-Oncology Working Group and the International Cardio-Oncology Society (ICOS). CTRCD and its severity were defined according to the current European Society of Cardiology (ESC) guidelines.

Results: Twelve (10.9%) patients had asymptomatic CTRCD. All CTRCD occurred sporadically during the first 9 months of the active trastuzumab regimen in both low- and moderate-risk patients. While CTRCD was graded as moderate severity in 41.7% of patients and heart failure therapy was initiated promptly, no irreversible cardiotoxicity or trastuzumab interruption was recorded at the end of follow-up. Among the left and right heart deformation indices, only LV-GLS decreased significantly in the CTRCD group during the trastuzumab regimen.

Conclusions: CTRCD is prevalent in patients with non-high-risk breast cancer undergoing trastuzumab chemotherapy. Low- and moderate-risk patients show distinct responses to trastuzumab. The LV-GLS is the only deformation index sensitive to early trastuzumab-related cardiac dysfunction.

Keywords: early cancer therapy-related cardiotoxicity; left atrial longitudinal strain; left ventricular ejection fraction; left ventricular global longitudinal strain; right ventricular longitudinal strain; trastuzumab.