Hi, this is Eric Prostowski and welcome to another segment of EP on EP. It's an incredible delight to have my next guest here because I've known him almost his entire career and what he's done for our field has been remarkable, Dr. Peng Chen, who is currently the Burns and Allen Chair of Cardiology Research at Cedars-Sinai. Did I get it all right? Absolutely. And a former, former, former, your student. For my student. Well, that would be the thing that George Burns would like because he'd consider that a joke. Because now I'm your student. So what we're going to talk about is a topic that you've done incredible research, clinically and basic, which is the autonomic nervous system pain and its interaction with AFib. As a backdrop, just for people who don't know the history, I mean, I'm guessing for maybe a hundred years or more, people have observed that autonomics have had some play in the atrial fib arena, but you've done some really interesting basic work. Let's start. Take us through some of your basic work and then we'll go to the clinical. Well, first of all, thank you, Eric, for giving me this opportunity. I think for hundreds of years, as you know, that there is a suspicion that the autonomic nervous system has something to do with atrial fib and there are very good evidence. But one thing that's lacking, I think, is without direct nerve recording to see spontaneous onset of atrial fib. So the basic science research, what we did is we recorded the nerve activity directly in an animal model of atrial fibrillation and documented that the proximal atrial fibrillation occurs with autonomic stimulation. Spontaneous activation of sympathetic and parasympathetic nervous system together causes too much calcium to go in and also shorten the action potential, resulting in the initiation of atrial fibrillation. Mostly it starts from pulmonary veins. So let me, I didn't mean to interrupt you, but this is a very important observation. I remember reading your paper. It wasn't like only vagal or only sympathetic, right? It was both. Most instances that we observed, atrial fibrillation were both sympathetic, large burst, and also simultaneously vagal nerve was activating. And that together seems to be the cause of atrial fibrillation. And so that's in animal models. So in humans, I'm very eager to record the nerve activity. So we developed a new method of recording. Instead of recording isolated nerve fibers, we record the skin sympathetic nerve activity. As you know, the skin was innervated, and the upper chest of the skin and the neck are innervated by the static ganglion. So we recorded the skin sympathetic nerve activity for humans in patients with proximal atrial fibrillation and the inpatient with persistent atrial fibrillation. And we found that the occurrence of atrial fibrillation and also interesting termination of atrial fibrillation was associated with a large burst of the skin sympathetic nerve activity. So in addition, the activity of the sympathetic nerves directly influenced the rate response, the ventricular rate response during atrial fibrillation. So those studies showing that proximal bursts of sympathetic nerves are associated with onset termination AF and also associated with rate control of atrial fibrillation. So one of the things I learned early in some earlier research I did with autonomics was you couldn't depend, like sinus node, you couldn't depend on a change in the sinus node equaling autonomic changes in other parts of the heart. So how have you been able to think backwards now on what you've measured sympathetic and what's your thought of like, what does that equal, like what's going on in the atrium? Yeah, so this is actually a very important point that your observation is very important. Namely the innervation of the autonomic nerves throughout the body also, of course, come from the brain. But the different segments of the body are innervated and activated differently. So as you said, autonomic nerves in other parts of the body may not be relevant to the sinus rate by itself. In addition, inpatients atrial fibrillation, as you know, often has sinus node dysfunction. And therefore the heart rate variability analysis during atrial fibrillation, during inpatients AF or heart failure with sinus node dysfunction may not be most accurate. So with that, I think this put us in, there's a new method, a way to prospectively and directly measure the nerve activity. I think that is, give us a new perspective. Yeah, no, I think it's very exciting because people only can look at one thing, which is the sinus rate. And they assume that if they're seeing a minimal change or a lot of change, it equals something, first of all, on the heart, which you know is clearly not always the case, even directionally it may be so. And second of all, in a patient with sick sinus syndrome, they may not have the ability to increase the rate, even though lots of autonomics are going on. So I think we've picked a poor surrogate, right? Heart rate variability. And I like the fact you're getting direct. So the next thing is how do we apply this to patient care? And so I would propose something to you. I've had very little success in my career giving someone a beta blocker and having them stop AFib. I may even prevent AFib. So help me on that one. Well, the nerve activity occurs, there are two different patterns of nerve activity. One is baseline nerve activity that's always present and is supporting the physiological function of the end organ. The other will be large burst of nerve activity, which is very large. And I don't think just using the partial beta blockade, either with metobrol or with propranolol, is going to completely block its function. So I think the best approach would be reducing those bursts. So we only have a little bit of time left. How do you plan to do that? Well, there is already data showing renal denervation seems to work in patient's hypertension, as you know. And what I'm interested in now in dog models in humans is trying to do subcutaneous nerve stimulation. Got it. Because subcutaneous nerve directly goes to the static ganglion. When you activate it very fast, the neurons don't like it because too much calcium goes into the cell and it kills the neuron. And the neuron's death signal propagates to the neighbors, very similar to what happens to Alzheimer's. In Alzheimer's, it's called excitotoxicity. But in stimulation-induced neuron death, histopathologically, it looks just like the excitotoxicity. Well, once again, you've educated me and our listeners. And if anyone can figure this out, I know it's you, Peng. So I look forward to your next series of papers, and thank you so much for joining the show. Thank you.

autonomic nervous system

atrial fibrillation

sympathetic and parasympathetic nerves

skin sympathetic nerve activity

nerve stimulation