QTc interval analysis in the ONCOECHO study population

Introduction

Anticancer therapies are associated with a potential negative impact on the QT interval on the ECG. The risk of arrhythmias from QT prolongation rises with polypharmacy, electrolyte abnormalities (including those due to treatment side effects), supportive therapies, and comorbid conditions.

Purpose

The aim of this study was to assess the prevalence of QTc prolongation in patients with newly diagnosed cancer initiating systemic treatment.

Methods

This post-hoc analysis of the ONCOECHO database included 291 out of 343 patients without significant baseline cardiovascular disease, enrolled before systemic therapy. Resting ECGs were recorded at baseline and after 3, 6, and 12 months. QTc was calculated using Fridericia (QTcF) and Bazett (QTcB) formulas. All continuous variables are presented as mean ± standard deviation or median (interquartile range), as appropriate for their distribution, while categorical variables are reported as frequencies. Normality was assessed with the Shapiro–Wilk test. Changes over time were analyzed using repeated-measures ANOVA or Friedman’s test, with correction for multiple comparisons. QTc prolongation (QTc >460, >480, >500 ms, or increase >60 ms) was compared using Fisher’s exact test.

Results

The study cohort consisted of 61.8% subjects with breast cancer, 26.5% with hematologic malignancies, 7.3% with colorectal cancer, 4.4% of patients with kidney cancer. Mean baseline QTc was 400.9 ± 29 ms. Only six patients had a QTcF > 460 ms and one > 500 ms. QTcF values differed significantly across time points (p=0.013), with a significant increase between baseline and month 6 (400.9 ± 29 ms vs. 409.6 ± 25 ms, p=0.0075). However, this change did not exceed 10 ms (6.7 ms). Notably, QTcF did not increase linearly in individual patients. Analysis using the Bazett formula also demonstrated differences across time points (p=0.048), with a borderline QTcB increase at month 6 compared with baseline (p=0.051), again not exceeding 10 ms (7.6 ms). Uncorrected QT interval analysis revealed significant differences (p=0.0023), with a significant increase at month 6 (p=0.0019), although the change remained below 10 ms (9.7ms). No clinically relevant ventricular arrhythmias occurred.

Importantly, the frequency of QTc > 460 ms was significantly higher when calculated using the Bazett formula compared with the Fridericia method across all time points. This discrepancy was also observed for QTc >480 ms at month 3 and not observed for QTc > 500 ms, which was rare and unrelated to arrhythmic events (Table 1).

Conclusions

This real-world analysis shows that cancer patients receiving cardiotoxic therapy are at risk of QT/QTc prolongation. Although these changes may reach statistical significance, they do not appear to be clinically meaningful. Use of guideline-recommended QTc formulas is essential to avoid overestimation of risk and unnecessary treatment modification.Cases of QTc prolongation  Differences in QT and QTc inteintervals