A Trial to Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation

Pulmonary vein isolation (PVI) is the cornerstone of ablation strategies for atrial fibrillation (AF) and is the only cardio-centric approach consistently shown to be effective for reducing arrhythmia recurrence and improving symptom status. Catheter ablation is superior to medical therapy and current antiarrhythmic drug options are limited, can have significant adverse effects, and are associated with a high arrhythmia recurrence rate, especially for persistent AF. Catheter ablation is now commonly prescribed for symptomatic AF patients who do not respond to medications and carries a class II indication. Thousands of patients undergo catheter ablation in the US each year. Nonetheless, even with technical advances, PVI has a recognized and significant rate of short- and long-term failure, and often requires multiple procedures to establish success.

The mechanisms of AF are diverse, but increased central sympathetic outflow and efferent cardiac sympathetic nerve stimulation can lead to enhanced automaticity and triggered activity, and thus contribute to the development and perpetuation of AF. Reduction in cardiac sympathetic input has been proposed as a logical adjunctive approach to PVI but its technical application via cardiac ablation (targeting autonomic ganglia) has had mixed results at best.

The therapeutic objective of lesser cardiac sympathetic stimulation can be potentially accomplished by renal artery denervation (RDN), a technique originally developed for the treatment of resistant hypertension. RDN's potential for antiarrhythmic effect may be mediated by reduced central nervous sympathetic output and is exemplified by a decrease in whole-body norepinephrine spillover and muscle-sympathetic nerve activity.

The recently completed large-scale, randomized, multicenter, single-blind clinical trial, ERADICATE-AF, demonstrated that RDN plus PVI resulted in a relative 43% reduction (absolute change, 15%; P < 0.001) in recurrent incident AF during one year of follow-up. The trial enrolled > 300 patients with paroxysmal AF referred for ablation, all with poorly controlled hypertension despite medication. There was no difference in complications between the 2 groups, and the procedure with RDN was only lengthened by about 24 minutes.

The trial results suggested that a strategy of reducing cardiac autonomic input is an effective antiarrhythmic approach, in line with many preclinical models. It also represents a paradigm of the potential for complementary noncardiac ablation that is effective and safe when coupled with PVI. Until now, this approach has only been tested in patients with resistant and/or poorly controlled hypertension.