title: Repolarization effects of multiple-cycle chemotherapy and predictors of QTc prolongation: a prospective female cohort study on >2000 ECGs.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti n. 9, 40138, Bologna, Italy, igor.diemberger@unibo.it.
authors.forename: Igor
authors.initials: I
authors.lastname: Diemberger
authors.forename: Giulia
authors.initials: G
authors.lastname: Massaro
authors.forename: Marta
authors.initials: M
authors.lastname: Cubelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Rubino
authors.forename: Sara
authors.initials: S
authors.lastname: Quercia
authors.forename: Cristian
authors.initials: C
authors.lastname: Martignani
authors.forename: Matteo
authors.initials: M
authors.lastname: Ziacchi
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bernardi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Cacciari
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boriani
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D010045:Outpatients; D015995:Prevalence; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents