A Prospective Interventional Clinical Trial (MC1732): Characterization of Thoracic Chemoradiotherapy-Related Cardiac Changes Using an Implantable Cardiac Monitor (ICM)

Purpose/Objective(s)

Real-time cardiac side effects due to thoracic radiotherapy (RT) have never been previously characterized in patients (pts) with lung and esophageal cancers. We specifically designed and completed a prospective clinical trial to address this.

Materials/Methods

A planned cohort of 24 pts were accrued from Dec 2019 to Jan 2023. Two (8%) pts withdrew their consent prior to ICM insertion. All pts met eligibility criteria, which included ≥ 18 years; non-metastatic, de novo lung or esophageal cancer diagnosis; receiving standard-of-care curative RT or chemoRT with an anticipated heart dose V40 Gy ≥ 20 cc; and planned RT dose ≥ 40 Gy. Pts with any prior RT to the heart were excluded. The ICM provided continuous outpatient arrhythmia monitoring (24/7), and all cardiac rhythms were captured prior to RT, and 4 weeks, 3, 9, and 12 months after RT. The ICM was explanted at 12-month follow-up. The ICM automatically captured and alerted clinicians to the following cardiac events: bradycardia ≤ 40 bpm; asystole with pauses ≥ 3 seconds (s); high degree AV block ≤ 30 bpm lasting ≥ 8 seconds; symptomatic tachycardia ≥ 150 bpm for any duration; and atrial fibrillation. Clinical events such as heart failure were also recorded. The primary endpoint was pts’ 12-month cardiac event rate (both clinically and by ICM) after RT completion. Clopper-Pearson confidence intervals were used in the analysis.

Results

The final analysis included all 22 pts. Average age was 67 years; 13 pts were male. Eighteen pts finished 12-mo follow-up per protocol, 1 died during treatment, and 3 died during follow-up. At baseline, 4 (19%) reported arrhythmia, 2 (10%) had coronary artery disease, and 1 (5%) with prior myocardial infarction; 15 (68%) were past smokers. Seventeen (77%) received proton beam therapy, and 5 (23%) received photon therapy. The median RT dose was 50 Gy in 2 Gy/fraction. RT was interrupted in 2 (9%) pts, due to needing an ablation for atrial flutter and hospitalization. Cardiac changes as defined in the study were seen in 15 (68%) pts. ICMs detected events in 14 (64%) pts: 10 with atrial arrhythmias (fibrillation/flutter), 2 transient asystoles, 1 non-sustained ventricular tachycardia, and 1 paroxysmal 3rd degree AV block. These events led to 4 interventions including 2 atrial ablations, 1 pacemaker insertion, 1 aortic valve replacement (18% of pts, 95% CI = 5-40%).

Conclusion

With real-time cardiac monitoring, cardiac events were detected in 64% of pts within 12 months post-RT, leading to timely medical diagnoses and interventions, with potentially improved outcomes. This novel prospective data highlighted the possible benefits of close cardiac surveillance. Further prospective studies are warranted to study the broad impact of ICM-based cardiac evaluation in better characterizing the intricate effects of thoracic RT on the heart and the cardiac conduction system.