Escalation of Resting Heart Rate and Tachycardia as a Response to Thoracic Radiotherapy: Implications for Cardiovascular Outcomes after Radiotherapy.

Background

Cardiac toxicity is a well-recognized, but poorly understood complication of radiotherapy (RT). In non-oncological settings, there is an established relationship between resting heart rate and cardiovascular health.

Objectives

To study the incidence and pattern of resting heart rate (rHR) as an early sign of cardiotoxicity among patients with non-metastatic non-small cell lung cancer (NSCLC) treated with RT.

Methods

We retrospectively analyzed serial rHR measurements of consecutive patients with locally advanced NSCLC treated with definitive chemoradiation (CRT) over 6-7 weeks of daily radiation treatments followed by immunotherapy (durvalumab) between 2017-2022. Radiation dose to the heart and 17 cardiac substructures were extracted. Associations between heart rate elevation, tachycardia, cardiac substructure dose and outcomes were evaluated using generalized additive mixed models (GAMMs) and regression analysis.

Results

We identified 110 patients, 56.4% with pre-existing heart disease. Median follow-up was 33.6 months. Median age was 70.4 years. Median rHR increased significantly during RT, rising from 81.5 bpm to 93 bpm at end of RT (p < 0.0001), remaining elevated in 30.6% of patients 12 months post-RT. Tachycardia incidence rose from 11.2% at baseline to 36.5% at 1-month post-RT (p < 0.0001). After adjusting for comorbidities, higher mean sinoatrial node (SAN) dose was associated with higher rHR elevation, delayed HR recovery and persistent tachycardia (all p < 0.05). Higher rHR during and after RT (β = 0.23, p = 0.005, and β = 13.49, p = 0.049, respectively), as well as the incidence of tachycardia episodes during RT were associated with increased odds of developing an arrhythmia (OR, 2.97, 95% CI, 1.17-7.52, p = 0.022).

Conclusions

Elevated rHR and tachycardia are observed during and after RT for NSCLC and are associated with higher mean SAN dose. HR elevation was associated with increased risk of de novo arrhythmias, suggesting that heart rate may represent a non-invasive biomarker of subclinical cardiac injury. Prospective studies might be warranted to test the potential of routine HR monitoring and proactive dose reductions to the SAN to enable early detection and help mitigate the risk of post-treatment arrhythmia.