Renal Sympathetic Denervation as Adjunctive Upstream Therapy During Atrial Fibrillation Ablation: Pooled Analysis of the HFIB and Ultra-HFIB Studies
Clinical Summary
- Adjunctive renal denervation during atrial fibrillation (AF) ablation was associated with a 39% reduction in arrhythmia recurrence, though results did not reach statistical significance.
- Benefits were observed even among patients with controlled hypertension, suggesting effects beyond blood pressure modulation.
- Larger randomized trials are needed to confirm efficacy and define patient selection criteria before clinical adoption.
Introduction
Dr Vivek Y. Reddy presented findings from the HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation) series exploring the role of renal denervation as an adjunct to AF ablation in a Monday morning session at TCT 2025, held October 25 to 28 in San Francisco, California. While hypertension is a known predictor of AF recurrence, aggressive blood pressure control alone does not improve ablation outcomes. The evidence points toward targeting sympathetic nervous system overactivity and the renin-angiotensin-aldosterone system (RAAS) rather than blood pressure itself as a means to reduce AF recurrence.
Session Highlights
Dr Reddy reviewed the pathophysiologic link between hypertension and AF recurrence, emphasizing that excessive sympathetic activation and RAAS upregulation—rather than absolute blood pressure levels—appear to drive arrhythmogenesis.
The ERADICATE-AF trial, which randomized 300 patients with paroxysmal AF and uncontrolled hypertension to cryoballoon ablation with or without renal denervation, demonstrated a 43% reduction in AF recurrence with the addition of denervation. Building on this, the HFIB 1 and ULTRA HFIB pilot studies evaluated whether these benefits extend to patients with controlled hypertension.
Across the 2 pooled trials (N=130; mean age 65 years; 37% female; 82% paroxysmal AF), adjunctive renal denervation at the time of ablation yielded a hazard ratio (HR) of 0.61 for arrhythmia recurrence—an association that did not reach statistical significance; the findings remained consistent after adjusting for age, sex, and AF type (HR, 0.66).
Dr Reddy noted that the safety and efficacy profiles differed among devices: HFIB 1 used a traditional EP ablation catheter, while ULTRA HFIB used an unfocused ultrasound system for renal denervation, delivering 2 to 3 lesions per major vessel. Notably, the analysis excluded HFIB 2 because the device used in this study, the Vessix catheter (Boston Scientific), demonstrated limited denervation efficacy in other hypertension trials.
Expert Perspectives
According to Dr Reddy, adjunctive renal denervation could represent a new upstream therapy for AF recurrence prevention, particularly given that over half of ablation patients have hypertension—even when controlled. He cautioned, however, that the findings, while promising, derive from small pilot studies and must be validated in a fully powered randomized trial before application to clinical practice.
The session also explored mechanistic insights. Dr Reddy and colleagues proposed that renal denervation may mitigate sympathetic tone and RAAS activation, thereby reducing atrial remodeling and fibrosis. Discussion among panelists highlighted ongoing debates about defining ablation “success,” as even short AF recurrences can complicate long-term outcomes. Continuous rhythm monitoring via implantable loop recorders may help clarify clinically meaningful recurrence thresholds.
Panelists further debated causality—whether hypertension triggers AF or vice versa—acknowledging the interplay of neurohormonal and structural pathways. While hypertension amplifies AF risk, sympathetic modulation may benefit select patients even in the absence of overt hypertension.
Implications for Practice
Renal denervation during AF ablation shows potential to enhance rhythm-control outcomes by addressing upstream pathophysiology rather than hemodynamic targets alone. If validated in larger trials, it could offer a novel adjunctive strategy for patients with AF—particularly those with hypertension or heightened sympathetic activity—complementing procedural innovations such as pulsed-field ablation.
Conclusion
Pilot data suggest that adjunctive renal denervation may reduce AF recurrence after ablation, even in patients with controlled hypertension. Larger randomized controlled trials are warranted to confirm efficacy and inform guideline recommendations for incorporating this approach into AF management.
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