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.
A randomized controlled pilot clinical trial has been proposed: "A Trial to Evaluate
Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial
Fibrillation" (ERADICATE-AF II), to test the hypothesis that RDN in addition to PVI
enhances long-term antiarrhythmic efficacy in comparison to PVI alone for patients with
persistent AF with controlled hypertension or without hypertension in a multicenter,
single-blinded, longitudinal randomized clinical trial. The trial will be advantaged by
performing implantable loop recordings (ILR) in all patients, which will facilitate the
calculation of AF burden, now recognized as a powerful predictor of clinical outcome.
With successful completion of this pilot program, we hope to launch a large-scale trial
with cardiovascular and death events as endpoints.
The primary aim of the study:
To determine if patients with persistent AF with controlled hypertension or without
hypertension who are referred for catheter ablation (PVI) and undergo adjunctive RDN have
reduced AF burden at 12 months in comparison to patients who undergo only PVI
The following secondary aims will be tested:
In patients with persistent AF with controlled hypertension or without hypertension who
are referred for catheter ablation (PVI) and undergo adjunctive RDN relative to patients
who undergo only PVI:
To assess safety, blood pressure and autonomic nervous system outcomes
Procedural complications rates
Postural blood pressure changes over time
Ambulatory blood pressure monitor results
Cardiac sympathetic nervous system modulation
To evaluate clinical end points
Frequency of progression to recurrent persistent AF
Referral for repeat catheter ablation of AF
Need for cardiovascular emergency room visits and hospitalizations
To measure effects on quality of life