Ultrasound-Based Renal Sympathetic Denervation as Adjunctive Upstream Therapy During Atrial Fibrillation Ablation: The ULTRA-HFIB Pilot

Background: During atrial fibrillation (AF) ablation, adjunctive renal denervation (RDN), by virtue of its effect on the sympathetic/renin-angiotensin-aldosterone axis, has improved AF control. However, patients in these studies mostly had uncontrolled hypertension. Objectives: The aim of this study was to assess the effect of RDN using an ultrasound catheter to improve rhythm outcomes in patients with hypertension (including controlled hypertension) undergoing AF ablation. Methods: This investigator-initiated, sham-controlled, single-blind randomized controlled U.S. Food and Drug Administration trial included first-ever paroxysmal or persistent AF ablation patients with histories of hypertension receiving ≥1 antihypertensive medication. Post–AF ablation randomization was 1:1 to RDN using a circumferential ultrasound system or sham control; patients with ineligible renal arterial anatomy were screen failures. The primary endpoint was 12-month freedom from AF or atrial flutter (AFL) (≥30 seconds) off antiarrhythmic medications after 90-day blanking. Results: At 9 centers, 107 patients were randomized; excluding 7 screen failures, the 100-patient cohort (mean age 66 ± 9 years, 35% women, paroxysmal and persistent AF in 86% and 14%) underwent radiofrequency ablation (55%) or cryoablation (45%) for AF. The 1-year Kaplan-Meier estimates for freedom from AF or AFL were 49% for sham vs 67% for RDN (log-rank P = 0.17). In a Cox analysis adjusted for age, sex, and persistent AF, the HR for recurrent AF or AFL with RDN was 0.65 (95% CI: 0.32-1.31; P = 0.23). There were no RDN-related adverse events. Conclusions: In this AF ablation cohort, adjunctive RDN was safe and reduced AF and AFL recurrence by 35%, an effect not reaching statistical significance in this pilot trial. A fully powered randomized trial is warranted to define the impact of RDN among patients planned for AF ablation.