Heart rate variability-based prediction of early cardiotoxicity in breast-cancer patients treated with anthracyclines and trastuzumab

Abstract Background Cardiotoxicity is a recognized complication in breast cancer (BC) patients undergoing chemotherapy with anthracyclines with or without trastuzumab. However, the prognostic value of heart rate variability (HRV) indexes for early cardiotoxicity development remains unknown. Purpose This study aimed to investigate cardiac autonomic responses to physiological stimuli in BC patients treated with anthracyclines with or without trastuzumab, and to evaluate the predictive value of transthoracic echocardiography (TTE) findings and HRV indexes for early cardiotoxicity. Methods A prospective cohort study involving 50 BC patients was conducted at a tertiary hospital with TTE assessments performed before and three months after chemotherapy. HRV indexes were obtained from continuous electrocardiograms in supine position with spontaneous breathing, active standing, and supine position with controlled breathing. The magnitude of change (Δ) between supine-standing and supine-controlled breathing was calculated. Variables were compared using t-test or ANOVA. Cardiotoxicity predictive value was assessed by ROC curve analysis. A p value of < 0.05 was considered significant. Results In our cohort, the mean age was 50 ± 8 years, and reported comorbidities included diabetes (n= 9), hypertension (n= 17), and dyslipidemia (n= 11). Twenty-three patients fulfilled echocardiographic and troponin cardiotoxicity criteria or both. TTE revealed reduced left atrial conduit strain in the cardiotoxicity group. Mean heart rate increased during all maneuvers at follow-up, with no differences in HRV indexes between patients with or without cardiotoxicity. However, a lower Δ in supine-controlled breathing of several HRV indexes predicted early cardiotoxicity identified by echocardiography (e.g. SDNN ≤ -8.44 ms: Sensitivity = 75%, Specificity = 69%). Conclusion BC patients treated with chemotherapy maintain cardiac autonomic responses to physiological stimuli after 3 months of chemotherapy. However, a lower Δ during active standing and controlled breathing before chemotherapy may predict early cardiotoxicity.Table 1.ROC curve analysisFigure 1.HRV-indexes