Renal Denervation and Atrial Fibrillation: Interview with Dr. Jonathan Steinberg

A collaboration between The Valley Health System in Ridgewood, New Jersey and New York, New York, and cardiologists in Siberia, Russia has led to the publication of a randomized, double-blind study showing that renal denervation prevented atrial fibrillation (AF) when combined with catheter ablation. Dr. Steinberg is the Director of the Arrhythmia Institute at The Valley Health System in New York and New Jersey, and a Professor of Medicine at Columbia University College of Physicians and Surgeons of New York. Read more about his findings in this feature interview.

Tell us about the role of hypertension in atrial fibrillation.

There are a number of cardiovascular conditions that change the pathology and physiology of atrial tissue in ways that promote atrial fibrillation. These range from heart failure to diabetes, but the most commonly diagnosed cardiovascular condition that is associated with atrial fibrillation is hypertension. About half of the patients with atrial fibrillation that we see have hypertension preceding the atrial fibrillation.

Describe the purpose of your study and elements of its design.

The study that we did is based on work that originated as a treatment form for resistant hypertension. There is a minority of patients with hypertension that do not have their blood pressure brought under control by medical therapies. The formal definition of resistant hypertension is when three forms of therapy fail to bring the blood pressure to a proper range. A treatment approach called renal artery denervation was developed, which involves ablation within the renal artery to interfere with the sympathetic nervous system, including how it innervates the kidney and how the kidney interacts through the nervous system with the brain, to improve blood pressure control. A number of clinical trials suggested that this approach was very effective for blood pressure control in resistant hypertensive patients, and was a safe procedure. It became clear to us that there may be an opportunity to take advantage of this technique to see if it would have a beneficial effect on the occurrence of atrial fibrillation when combined with a catheter ablation procedure. Catheter ablation has become an important approach for the treatment of atrial fibrillation when medical therapy has not been satisfactory. It is very effective at bringing atrial fibrillation under control in select patients, but it is not always effective and there are certainly some subgroups that are much more challenging to treat even with ablation. Therefore, our initial hypothesis was that if we combined ablation with renal artery denervation, we could positively affect the AF pattern after the procedure has been accomplished. We further hypothesized that the patients who would be eligible to this would be resistant hypertensives, so they might have the dual benefit of having their blood pressure brought under control, and via better blood pressure control or perhaps through a direct effect of the renal artery denervation, have improvement in AF control. Renal artery denervation might directly affect atrial fibrillation because it may reduce the central nervous system sympathetic output that would be involved in generating atrial fibrillation, and by attenuating sympathetic output, the AF patterns may improve.

How many patients were enrolled? Discuss the two treatment arms.

The treatment was applied in a randomized fashion to a group of 27 patients (14 were randomized to standard ablation, and 13 to standard ablation plus renal artery denervation). All patients in both groups underwent a pulmonary vein isolation procedure, which is the standard approach for ablation. Half the patients underwent renal artery denervation. The patients were unaware of whether they had renal artery denervation performed in addition to the ablation; all they knew was that they underwent an ablation procedure. We then followed them for atrial fibrillation patterns after the ablation.

Discuss your techniques for renal artery denervation in this study.

First the patient is imaged, usually by preprocedure magnetic resonance imaging, so we can learn about the renal artery anatomy. Once we were convinced that the patient had a single major renal artery trunk, we would then perform interarterial access and pass the catheter into the renal artery. Once in the artery, we would stimulate the artery with high-frequency output in order to generate hypertensive responses that indicate the renal artery is innervated. We would then begin to longitudinally apply radiofrequency energy in the renal artery adjacent to the kidney to where it joins the aorta. We would do this in a spiral fashion, in an effort to interrupt the renal artery nervous system connections. As we performed the ablation, we would repeatedly test with high-frequency stimulation to see if the nervous system responses were still present. The nervous system responds when stimulated by increasing blood pressure, and when we attenuated or eliminated that reflex hypertensive response, we felt that our procedural endpoint had been met and that the renal artery had become denervated.

How did procedure time compare between the PVI-only group versus the PVI with renal artery ablation group? What about fluoroscopy times?

It is a somewhat longer procedure when you add renal artery denervation to the ablation procedure. It took an average of 8 minutes to do the renal artery ablation. Fluoro times were slightly longer — it took approximately 21 minutes for the pulmonary vein isolation, and 29 minutes for the pulmonary vein isolation plus renal artery ablation.

How many patients in the PVI with renal artery ablation group were AF free at one-year follow-up?

At the one-year endpoint, 9 of 13 (or 69%) in the renal artery group were AF free, versus only 4 of 14 (or 29%) in the control group.

Tell us about the results seen in blood pressure control in patients treated with renal denervation. What changes were seen in their systolic and diastolic blood pressure?

There were marked improvements in blood pressure, but only in the group that underwent renal artery denervation. For example, the systolic blood pressure decreased by about 25 millimeters and the diastolic by about 10 millimeters in the renal artery denervation group, and was unchanged in the control group.

Will further research using combined renal denervation and AF ablation be done?

Yes, we are in the midst of initiating a large-scale randomized clinical trial that will mimic the trial design that I described for the smaller preliminary study, but have more expansive criteria for which patients can be enrolled. Resistant hypertension is not going to be required; it will likely be hypertensive patients who are not ideally controlled, and paroxysmal atrial fibrillation. More information about the trial will be available soon; within weeks we are finalizing the protocol with a sponsor.

What do you find most promising about this treatment option for patients with atrial fibrillation?

It’s complementary to what we are traditionally doing in the EP laboratory, where we focus on triggers and substrate within atrial tissue and the thoracic venous structures that can be involved in triggering atrial fibrillation. We now have an approach that is unconventional in that we are no longer ablating thoracic or cardiac structures — we are now ablating components of the nervous system and accomplishing a form of autonomic modulation, which will affect all of the atrial tissue. Therefore, we believe this will offer a very promising alternative or supplemental technique to control atrial fibrillation compared to what has traditionally been employed in the EP laboratory. It will also give us a great deal of insight into how the nervous system plays a role in generating atrial fibrillation. There may be other uses to this technique for arrhythmias that are dependent on autonomic system modulation as well.