Reliability of Left Ventricular Ejection Fraction from Three-Dimensional Echocardiography for Cardiotoxicity Onset Detection in Patients with Breast Cancer

Abstract

Background: Cardiotoxicity is a well-known adverse effect of various chemotherapeutic agents that can be monitored by echocardiography. A decrease in left ventricular ejection fraction (LVEF) triggers consideration for therapy modification or interruption. The aim of this study was to evaluate how variability in LVEF estimates computed using three-dimensional echocardiography could influence cardiotoxicity onset detection.

Methods: One hundred eighty one patients with breast cancer treated with anthracycline and trastuzumab were analyzed. LVEF was computed using two commercial software packages. In a subgroup of 40 patients, three-dimensional echocardiographic data were reanalyzed to assess intra- and interobserver variability by two expert investigators using both packages. Global longitudinal strain (GLS) imaging was evaluated in 64 patients.

Results: End-diastolic volume, end-systolic volume, and LVEF measurements obtained applying the two software packages were in good agreement, with small bias and acceptable limits of agreement. Intra- and interobserver variability was smaller using one of the two software packages. However, for both packages, variability indexes were in the range of affecting LVEF estimates at a level that could lead to an inaccurate assessment of cardiac adverse effects of cancer therapeutic drugs. On the basis of LVEF, 11 of 181 patients (6.1%) had cardiotoxicity at 3-month follow-up. The absolute value of GLS was smaller in 16 of 64 patients (25%) thought to have cardiotoxicity on the basis of GLS results, including six of seven patients who had cardiotoxicity considering LVEF in this subgroup.

Conclusions: Following clinical definition of cardiotoxicity onset, variability in LVEF computation by three-dimensional echocardiography could be a confounding factor for cardiotoxicity diagnosis, and different software packages should not be used interchangeably for LVEF monitoring. GLS confirms its predictive value for subsequent cardiotoxicity.

Keywords: 3D echocardiography; Breast cancer; Cardiotoxicity; Global longitudinal strain.