Deceleration capacity of heart rate predicts trastuzumab-related cardiotoxicity in patients with HER2-positive breast cancer: A prospective observational study.

Abstract

Trastuzumab is the standard choice for anti-human epidermal growth factor receptor 2 (HER2) therapy. Cardiotoxicity is one of the main adverse effects of trastuzumab. How to early predict trastuzumab-related cardiotoxicity remains a significant problem in clinical practice. The deceleration capacity of the heart rate (DC) has been shown to be a powerful predictor of adverse outcomes in various heart diseases. In the study, the role of DC in early predicting trastuzumab-related cardiotoxicity was investigated. A total of 150 patients were prospectively investigated the clinical value of the DC in predicting trastuzumab-related cardiotoxicity in patients with HER2-positive breast cancer treated with trastuzumab at Guangxi Medical University Cancer Hospital from June 2015 to June 2017. DC, mean heart rate and heart rate variability (HRV) indices, including the standard deviation of all normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD), were assessed before treatment, and the left ventricular ejection fraction (LVEF) was regularly monitored for 2years (before, during and after treatment) to evaluate cardiotoxicity. Among 150 eligible patients, 28 (18.7%) developed cardiotoxicity. Patients with cardiotoxicity were older (P<.05), higher anthracycline dose (P<.001) and had lower RMSSD (P<.05), SDNN, DC and baseline LVEF (P<.001), than patients without cardiotoxicity. Logistic regression analysis revealed lower DC, lower baseline LVEF and higher anthracycline dose were independent risk factors of trastuzumab-related cardiotoxicity. Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for DC than for the baseline LVEF in predicting cardiotoxicity (0.88 vs 0.77, P=.032). Additionally, DC had higher sensitivity (78.6% vs 67.9%) and specificity (83.6% vs 77.9%) in predicting cardiotoxicity than the baseline LVEF. Linear regression analysis showed among patients who developed cardiotoxicity, lower DC was associated with an earlier onset (P<.01). The present study found that DC was a stronger predictor of trastuzumab-related cardiotoxicity development than the baseline LVEF and HRV. Linear regression analysis showed among patients who developed cardiotoxicity, lower DC was associated with an earlier onset. DC should be a potential clinical indicator for the early prediction of trastuzumab-related cardiotoxicity.