Autonomic Modulation for the Treatment of Atrial Fibrillation and Heart Failure

Discussion With Bradley Knight, MD, and Stavros Stavrakis, MD, PhD

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Interview by Jodie Elrod

Bradley Knight, MD, talks with Stavros Stavrakis, MD, PhD, about his presentation on autonomic modulation for the treatment of atrial fibrillation (AFib) and heart failure at Western AF 2025. 

Bradley Knight, MD: I'm Dr. Brad Knight, editor-in-chief of EP Lab Digest. We're very excited to be here as part of the Western Atrial Fibrillation (AFib) program, which has been going on for many years. It's a fantastic meeting. I'm joined by Professor Stavros Stavrakis from Oklahoma University. He is giving a presentation on autonomic modulation in AFib and heart failure. Can you give us a preview or highlights of your talk, and then I can give you an opportunity to share more about your topic?

Stavros Stavrakis, MD, PhD: Absolutely. Thank you. First of all, I want to say that Western AFib is one of my favorite meetings. There's so much exchange of knowledge. It's phenomenal. So, kudos to Dr Marrouche. 

Bradley Knight, MD: Yes, I agree.

Stavros Stavrakis, MD, PhD: Autonomic modulation for AFib and heart failure is my talk. It would have been nice to have data on both conditions, but we do not. So, I'm going to talk separately about autonomic modulation for AFib and autonomic modulation for heart failure. 

Bradley Knight, MD: Let's discuss each one at a time. When I think of autonomic modulation for heart failure, I think of a few therapies that are already out there. I've been involved for many years with barostimulation, but there are also other techniques with cardiac impulses, vagal stimulation, and renal denervation. What do you consider autonomic modulation, and what is currently available? 

Stavros Stavrakis, MD, PhD: Autonomic modulation is the change in the nerve activity and function by electrical stimulation without injuring or destroying nerves. So, the one that is FDA approved is barostimulation for heart failure. We also have renal denervation, which is approved. The approval is for resistant hypertension, but we have evidence from ERADICATE-AF that it is beneficial in patients with AFib as well. The ERADICATE-AF 2 trial is also ongoing in persistent AFib.

Bradley Knight, MD: There is also cardiac contractility modulation (CCM) therapy. Do you consider that autonomics?

Stavros Stavrakis, MD, PhD: We don't know the mechanism very well, so it's probably in the periphery because it's not directly stimulating nerves.

Bradley Knight, MD: There has also been a lot of interest in vagal stimulation.

Stavros Stavrakis, MD, PhD: I think vagal stimulation is very promising, especially for AFib. For heart failure, we had the large INOVATE-HF study, which was a negative trial. Now, that does not mean that autonomic modulation does not work for heart failure. There is a lot of animal data to support it. It is just that we probably have not found the best way to do it. 

Bradley Knight, MD: In your patients with AFib but not heart failure, do you ever consider any autonomic modulation therapies for them? 

Stavros Stavrakis, MD, PhD: For AFib, I consider it as an alternative option. Some patients come to me saying they want to do this. I tell them it is not FDA approved but it is low risk, especially if it is done transcutaneously, like a tragus stimulation. So, anecdotally, I have a few patients that do it. 

Bradley Knight, MD: That is another one I had not mentioned, tragal stimulation to improve vagal tone. Have you seen any patients benefit from that? 

Stavros Stavrakis, MD, PhD: Yes, as I said, anecdotally, I have patients who have benefited from that. 

Bradley Knight, MD: You defined autonomic modulation more as electrical stimulation than destruction, although renal denervation is kind of a destructive way of modulating autonomic tone. There are other things that we can do in EP such as surgical sympathectomies and stellate ganglion block. We intervene on patients with ventricular fibrillation (VF) storm, things like this, or long QT syndrome. How do you view those therapies? 

Stavros Stavrakis, MD, PhD: They are also autonomic modulation, because we change the function of the autonomic nervous system in general. Like if we do sympathectomy, we take out the sympathetic nerves, so we alter the function of the autonomic nervous system as a whole. 

Bradley Knight, MD: I know there is not direct data on patients with both conditions, but if someone has heart failure and persistent AFib, and maybe they have had a couple ablations or they are not a candidate for an ablation, is there a role for autonomic therapy, and for the therapies that are indicated for heart failure, is there any evidence that they improve their AFib? 

Stavros Stavrakis, MD, PhD: There are some. I saw an abstract that was presented last year on a few patients with AFib and heart failure who underwent barostimulation. So, I think barostimulation is an option, because it has been shown to work separately in both conditions. So, you would think it would work. 

Bradley Knight, MD: I think that there is a lack of data on that, but there is some reason to believe that patients who benefit from barostimulation for heart failure might also have a reduction in their AFib burden, which hasn't been studied by them yet and might have a reduction in ventricular arrhythmia burden too. Do you have any sense of whether that's helpful for ventricular tachycardia or VF? 

Stavros Stavrakis, MD, PhD: Yes, there are also some data that it decreases ventricular arrhythmias in patients with heart failure, so it should work. 

Bradley Knight, MD: What do you think is the future of autonomic modulation in general for an electrophysiologist? 

Stavros Stavrakis, MD, PhD: It is another alternative, taking into consideration the risk-benefit ratio. I think doing it either percutaneously or transcutaneously would be the future, because we minimize risk and increase the risk-benefit ratio. Things like stellate ganglion block can be done with ultrasound guidance. So, maybe I see future electrophysiologists being trained to do transcutaneous barostimulation. This is not available now, but I can see it happening in the future. 

Bradley Knight, MD: Do you consider the following things to be in the category of autonomic modulation? Clearly, when people do endurance training, it increases their vagal tone. Do you think that there are things that patients can do to change their autonomics? 

Stavros Stavrakis, MD, PhD: Sure. Exercise is an intrinsic neuromodulation therapy, meaning it is done by the patients themselves without anything external. So, exercise increases long-term vagal tone and decreases sympathetic tone. 

Bradley Knight, MD: Do you think that is why there is some data on yoga?

Stavros Stavrakis, MD, PhD: Yes, yoga and Pilates would be considered neuromodulation therapies. 

Bradley Knight, MD: Is there anything else you want to share about the future of autonomic modulation? 

Stavros Stavrakis, MD, PhD: I think the future is bright. 

Bradley Knight, MD: Thanks for your time. I look forward to your presentation. 

Stavros Stavrakis, MD, PhD: Thank you!

The transcripts have been edited for clarity and length.