Prolonged electromechanical delay as an early predictor of trastuzumab-induced cardiotoxicity in patients undergoing treatment for breast cancer.

Background Hypothesis We aimed to investigate if left ventricular electromechanical delay (LVEMD) prolongation predicts trastuzumab-induced cardiotoxicity (TIC) in breast cancer patients. LVEMD prolongation on serial echocardiograms could be an indicator of subclinical TIC. Methods Results We included 237 breast cancer patients receiving trastuzumab chemotherapy, who underwent echocardiography at baseline and at 6 and 12 months after trastuzumab initiation. LVEMD was defined as the time from electrical activation to myocardial contraction. TIC was defined as left ventricular ejection fraction (LVEF) worsening to <55%, either as symptomatic decrease of >= 5% or asymptomatic decrease of >= 10%. During a mean follow-up of 547 days, TIC occurred in 27 patients (11.4%). Changes in the time intervals from QRS onset on electrocardiography to the beginning and peak of transaortic flow on pulsed-wave Doppler echocardiography (ie, Delta LVEMDi and Delta LVEMDp, respectively) were independent predictors of TIC. On receiver operating characteristic curve analysis, the optimal cutoff value for TIC prediction was 23 milliseconds for Delta LVEMDi (sensitivity, 0.85; specificity, 0.78; area under the curve [AUC], 0.882) and 21 milliseconds for Delta LVEMDp (sensitivity, 0.96; specificity, 0.68; AUC, 0.860). The C-index for TIC prediction increased significantly after adding Delta LVEMDi and Delta LVEMDp to conventional models that included clinical variables, baseline LVEF, and changes in global longitudinal peak systolic strain. Similarly, adding Delta LVEMDi or Delta LVEMDp to conventional models provided significant improvement in discrimination capability for TIC prediction (integrated discrimination improvement and continuous net reclassification improvement index). Conclusion Delta LVEMDi and Delta LVEMDp may serve as predictors of subclinical cardiac dysfunction in breast cancer patients receiving trastuzumab.