Abstract Introduction Doxorubicin-based chemotherapy remains a cornerstone of breast cancer management. Anthracyclines are a well-recognized cause of cancer therapeutics-related cardiac dysfunction (CTRCD). Whether anthracyclines alter cardiac autonomic nervous system responses has not been systematically studied. Purpose The main purpose of the PROTECTAA trial is to assess the role of dapagliflozin on the incidence of CTRCD. In this substudy, we aim to assess the effects of anthracyclines on heart rate variability (HRV) and cardiovascular autonomic test (CAT) results. Furthermore, the correlation of possible autonomic dysfunction with quality of life, echocardiographic parameters, troponin, and natriuretic peptide levels will be evaluated. Methods In the PROTECTAA trial, 188 breast cancer patients with stages I-III who are planned to receive doxorubicin treatment will be enrolled. All patients will undergo 24-hour Holter monitoring, and for the majority of them, CAT will be performed. Holter monitoring and CAT will be conducted at the screening visit, at 6 months, and at 12 months after chemotherapy. Results So far, 72 patients have been enrolled, and 15 of them have completed 6 months of follow-up. Among them, a significant increase in mean heart rate (79 bpm vs. 82.5 bpm, p0.05) and a decrease in mean SDNN (145.61 ms vs. 122.59 ms, p0.05), SDANN (138.09 ms vs. 119.1 ms, p0.05), RMSSD (25 ms vs. 18.97 ms, p0.05), and E/I (1.21 vs. 1.16, p0.05) were found. The values of SDNN and RMSSD positively correlated with self-reported health in the EQ-5D-5L questionnaire at follow-up (r-Pearson 0.49, p0.05 for SDNN; r-Pearson 0.49, p0.05 for RMSSD). Conclusions Anthracycline-based chemotherapy seems to alter cardiovascular autonomic system function. The decline in HRV correlates with worsening quality of life. Cardiac dysautonomia might be an early marker of cardiotoxicity from cancer therapeutics; however, further studies are necessary. The time course of autonomic dysfunction and its correlation with classical CTRCD components (clinical, echocardiographic, and laboratory) are planned to be assessed at the end of the trial.
Skonieczny et al. (Fri,) studied this question.