Autonomic Alterations After Pulmonary Vein Isolation or Antiarrhythmic Drug Therapy

BACKGROUND: The natural history of autonomic alterations following catheter ablation or antiarrhythmic drug therapy is poorly defined, largely owing to reliance on noninvasive intermittent rhythm monitoring and lack of comparative trials. OBJECTIVES: This study sought to evaluate the impact of catheter ablation or pharmacologic rhythm control on long-term autonomic parameters. METHODS: This study included 303 patients with paroxysmal treatment-naïve atrial fibrillation enrolled in the EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) trial who were randomized to initial rhythm control therapy with cryoballoon ablation (154 patients) or antiarrhythmic drug therapy (149 patients). All patients underwent insertion of an implantable cardiac monitor (ICM) at trial enrollment. The ICM continuously recorded physical activity, heart rate variability (HRV; measured as the standard deviation of the average normal-to-normal), daytime heart rate (DHR), and nighttime heart rate (NHR). Longitudinal outcomes were analyzed using inverse probability-weighted mixed-effects models. RESULTS: At baseline there were no significant differences in HRV, DHR, and NHR between randomized groups. Over a median follow-up of 1,143 days (Q1-Q3: 1,084-1,270 days), there were significant differences in DHR, NHR, and HRV between patients randomized to catheter ablation and those randomized to antiarrhythmic drug therapy. Patients randomized to ablation had reduced HRV and greater DHR and NHR. Ablation was associated with lower HRV and higher DHR and NHR early after treatment, with differences persisting through 24 months for NHR and HRV and through 36 months for DHR. These parameters did not differ from baseline in those randomized to antiarrhythmic drug therapy, but patients crossing over from antiarrhythmic drug therapy to ablation exhibited autonomic parameters consistent with the treatment received. Post-treatment NHR and HRV were significantly associated with arrhythmia recurrence. CONCLUSIONS: Cryoballoon-based pulmonary vein isolation results in significant sustained changes in the heart rate parameters related to autonomic function, compared with those randomized to antiarrhythmic drug therapy.