Repolarization effects of multiple-cycle chemotherapy and predictors of QTc prolongation: A prospective female cohort study on >2000 ECGs

Purpose: Oncological patients are at increasing risk of QT prolongation, a risk factor for ventricular arrhythmia. We assessed impact and risk factors for corrected QT (QTc) prolongation during multiple-cycle chemotherapy. Methods: We enrolled 100 outpatients initiating chemotherapy in a university center specializing in female cancer. Clinical, drug, laboratory, and 12-lead ECG data collection at baseline and at each chemotherapy cycle was performed. Results: Enrolled patients were followed for 992 chemotherapy cycles (median 7; interquartile range 6-13); 2438 ECGs were recorded (20; 18-31) 36.8 % pre-therapy, 36.8 % following chemotherapy, and 22.5 % 7-10 days after chemotherapy. Maximum QTc (Max-QTc) was recorded after 4 chemotherapy administrations in >50 % of the entire cohort and also within every subset of patients with prolonged QTc (57 % 471-480 ms; 54 % 481-500 ms; 66 % >500 ms). No cumulative effect on QTc was shown. QTc prolongation was comparable among the various protocols. Prophylactic/supportive drugs were not associated with additional QTc prolongation. Variables independently associated with QTc prolongation >470 ms were age (OR 1.056 95 % CI 1.006-1.108, p∈=∈0.028) and the baseline-first chemotherapy averaged QTc (BC-QTc) (OR 1.092 95 % CI 1.051-1.136), a novel parameter devised for this study. Only BC-QTc maintained significance for QTc >480 ms. BC-QTc >435 ms identified 100 % of patients with Max-QTc >500 ms, 96 % with Max-QTc 481-500 ms, and 66 % with Max-QTc 471-480 ms. Only 29 % of patients with Max-QTc 470 ms presented a BC-QTc >435 ms. Conclusions: Our results confirm the high prevalence of QTc prolongation after chemotherapy. Most of the patients reached Max-QTc after several cycles. BC-QTc may help in stratifying arrhythmic risk in real-world clinical practice.