Cardiac arrhythmias during and after thoracic irradiation for malignancies

Abstract

Background: Cardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy.

Methods and results: A retrospective cohort study was conducted involving patients with CIEDs who received thoracic radiotherapy between January 2012 and December 2022. Two distinct analyses were performed involving (1) daily CIED follow-ups during radiotherapy and (2) long-term arrhythmic outcomes post-therapy. For long-term outcomes, Patients were matched in a 1:2 ratio with non-irradiated controls based on age, sex, cardiovascular risk factors, cardiac disease, and beta-blocker use. Statistical analyses included negative binomial regression and propensity score matching. A total of 186 patients underwent daily CIED monitoring during radiotherapy, with 79 receiving thoracic irradiation. Thoracic irradiation was negatively associated with atrial arrhythmia (OR 0.11 [0.02;0.70, 95% CI], adjusted p = 0.0498) and there was a tendency towards less ventricular events (OR 0.14 [0.02;1.41, 95% CI], adjusted p = 0.3572) during radiotherapy in a univariate regression analysis. This association was not significant in the multivariate (OR 0.44 [0.10;1.80, 95%-CI], p = 0.16) model including a history of atrial fibrillation, diabetes and beta-blocker use. Coronary artery disease was associated with an increase in atrial and ventricular arrhythmia. For the long-term analysis, 122 patients were followed up after thoracic (N = 33) and non-thoracic radiation (N = 89) and compared to 244 matched controls drawn from approximately 10.000 CIED-patients. There was no significant increase in arrhythmic events compared to controls over a median follow-up of 6.6 months. A previous history of ventricular or atrial arrhythmic events was the strongest predictor for events during the follow-up.

Conclusion: Thoracic radiotherapy can be safely administered in patients with CIEDs. However, patients with a history of arrhythmia are more prone to arrhythmic events during and after radiation. These findings highlight the need for personalized arrhythmia management strategies and further research to understand the mechanisms underlying the antiarrhythmic effects of thoracic radiation.

Keywords: Cardiac arrhythmia; Cardiac implantable electrical devices; Cardiovascular toxicity; Radiation-induced heart disease; Radiotherapy; Thoracic radiation.

Fig. 1

Flowchart of patient selection and categorization. A total of 10,026 patients were identified from the CIED-Registry. Two hundred fifty-six of these patients also had radiotherapy. One hundred twenty-two patients had a history of radiotherapy with a follow-up exam after radiotherapy. After propensity score matching (2:1), the cohort included 122 patients with a history of radiotherapy and 244 patients without. Thirty-three patients received thoracic irradiation and 89 patients had non-thoracic irradiation

Fig. 2

Atrial arrhythmic burden during radiotherapy. A Univariate negative binomial regression analysis assessing the impact of include smoking, hypertension, coronary artery disease, history of atrial fibrillation, high cholesterol levels, diabetes mellitus type 2, beta-blocker use, and thoracic radiation on arrhythmic burden. B Multivariate negative binomial regression analysis on history of atrial fibrillation, diabetes mellitus type 2, thoracic radiation, and beta-blocker use. Odds ratios (OR) and confidence intervals (CI) are displayed along with P-values and adjusted P-values (holm-bonferroni)

Fig. 3

Ventricular arrhythmic burden during radiotherapy. A Univariate negative binomial regression analyzing the impact of high cholesterol levels, coronary artery disease, beta-blocker use, previous ventricular event, diabetes mellitus type 2, smoking, hypertension, and thoracic radiation on ventricular arrhythmic burden. B Multivariate negative binomial regression analysis focusing on coronary artery disease, previous ventricular event, and thoracic radiation. Odds ratios (OR) and confidence intervals (CI) are displayed along with P-values and adjusted P-values

Fig. 4

Atrial arrhythmic burden during radiotherapy. A Univariate negative binomial regression analysis assessing the impact of history of atrial fibrillation, diabetes mellitus type 2, high cholesterol levels, arterial hypertension, beta-blocker use, non-thoracic radiation, coronary artery disease, smoking, and thoracic radiation. B Multivariate negative binomial regression analysis highlighting significant factors including history of atrial fibrillation, diabetes mellitus type 2, non-thoracic radiation, and thoracic radiation. Odds ratios (OR) and confidence intervals (CI) are displayed alongside P-values and adjusted P-values

Fig. 5

Ventricular arrhythmic burden after radiotherapy. A Univariate negative binomial regression analysis assessing the impact of previous ventricular event, non-thoracic radiation, beta-blocker use, hypertension, smoking, coronary artery disease, diabetes mellitus type 2, high cholesterol levels, and thoracic radiation. B Multivariate negative binomial regression analysis on ventricular arrhythmic burden including previous ventricular event, high cholesterol levels, smoking, and thoracic radiation. Odds ratios (OR) and confidence intervals (CI) are displayed alongside P-values and adjusted P-values