Abstract
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.
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Acknowledgments
This work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 241679—the ARITMO project. The content is solely the responsibility of the authors and does not necessarily represent the official views of the other partners of the ARITMO project.
STROBE statement
The study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations.
Conflict of interest
The authors have declared no conflicts of interest.
Author contributions
Igor Diemberger had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis
Conception and design: Igor Diemberger, Giuseppe Boriani
Financial support: Giuseppe Boriani
Administrative support: Giuseppe Boriani, Claudio Zamagni
Creation of tools for collecting and storing data: Giulia Massaro
Collection and assembly of data: Giulia Massaro, Marta Cubelli, Daniela Rubino, Sara Quercia, Cristian Martignani, Matteo Ziacchi, Mauro Biffi, Alessandra Bernardi, and Nicoletta Cacciari.
Statistical analysis: Igor Diemberger
Data interpretation: Igor Diemberger, Giuseppe Boriani, and Claudio Zamagni
Manuscript draft: Igor Diemberger, Giulia Massaro
Manuscript revision: All authors
Final approval of manuscript: All authors
Role of Sponsor: The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 241679—the ARITMO project. The content is solely the responsibility of the authors and does not necessarily represent the official views of the other partners of the ARITMO project. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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Figure S1
Box plot of QTc values among the entire cohort during the first 6 cycles considering the type of ECG. Legend: Bas = basal ECG, Ch = chemotherapy ECG, Co = control ECG, Pre = pre-therapy ECG. Please note Pre-1 is more correctly reported as Bas. * = p < 0.001 with respect to the previous (pre-therapy) and subsequent ECG (control ECG). (GIF 68 kb)
Figure S2
Scatter plot distribution of maximum QTc over the cycles of chemotherapy (each including: pre-therapy, chemotherapy and control ECG; x-axis) for each patient in accordance with the type of ECG (ECG group). Maximum QTc: normal <450 ms, borderline 450–470 ms, slightly prolongation 471–480 ms, moderate prolongation 481–500 ms, severe prolongation >500 ms. For each category of QTc prolongation the number of included patients is reported. (GIF 37 kb)
Figure S3
Box plot of QTc values of chemotherapy ECGs in accordance with the chemotherapy protocol group (see Table 3). Legend: G = group. Kruskal-Wallis test p < 0.001 for the 6 groups. Bonferroni corrected Mann–Whitney U test p < 0.05 for all the following comparisons: G6 vs. G1-5; G4 vs. G1-3,G5. (GIF 32 kb)
Table S1
(DOC 23 kb)
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Diemberger, I., Massaro, G., Cubelli, M. et al. Repolarization effects of multiple-cycle chemotherapy and predictors of QTc prolongation: a prospective female cohort study on >2000 ECGs. Eur J Clin Pharmacol 71, 1001–1009 (2015). https://doi.org/10.1007/s00228-015-1874-3
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DOI: https://doi.org/10.1007/s00228-015-1874-3