Hi, I'm Eric Prostowski, and welcome to another segment of EP on EP. With me today is one of the leaders in our field, Dr. Ed Gerstenfeld, who is the professor of medicine at UCSF. Ed, welcome to the show. It's always great to have you. Nice to be here, Eric. So, this may surprise you, but I'm going to talk about PBC cardiomyopathy. No, really? Okay. So, there are so many papers out there that give different numbers, like 20% of PBC, you know, 20% of UVs, 10,000 PBCs, and I want to start with that, in an asymptomatic patient, where do you start to say, yeah, this could be due to the PBCs? Do you have a number? Yeah, that's a good question, and obviously, the number that statistically works on a paper might be different than what we use practically, but we do see a lot of people with PBCs, and one of my cutoffs is, you know, fewer than 5%. I usually just reassure the patient, because I think it's pretty rare that you'll ever see a cardiomyopathy less than 5%. More than 10%, then I think you're, not everybody, but that's where you potentially can run into a problem with a PBC cardiomyopathy. Five to 10, say, kind of watch and wait, I might look at more prolonged monitoring, but less than five, pretty much reassure them. More than 10, I think, is where you start to get into that realm of possible PBC media. So, you use more, I mean, some people like percentage of beats, but you're more of a, you prefer to look at the number? No, percent of beats, so 5% versus 10. Oh, 10% of beats, not 10,000 people. Yeah, well, you know, as you know, a good rule of thumb is most people have roughly 100,000 beats in a day. So less than 5%, I don't worry about, more than 10%, I start to worry about, and that correlates from a number roughly to, you know, 5,000, or fewer, or more than 10,000. I think the next thing is to define the myopathy, right? So it's, I mean, when it's obvious, it's obvious, right? So if someone comes in, their EF is really low, but there's some patients who come in who are minimally symptomatic, where the EF is normal by echo, and then, you know, tell me about your concept on strain, or LVED, I mean, at what point do you say, you know, I'm a little worried there's something going on here? Yeah, no, that's a good question. What I said is, as you know, you know, a drop in ejection fraction can be a relatively late occurrence, right? So when the heart muscle gets weaker, right, the first thing it's going to do is dilate. So I tend to look at diameters, you know, volumes, end-diastolic, end-systolic volume, and if I see the heart enlarge or enlarging, that makes me concerned. I don't think there's clear cutoffs for LV strain, but, you know, you see a young person, right, you expect their EF to kind of be 65, 70, but if I see someone who's a young person with PVCs where the EF's, you know, in the 50, 55% range, that's where I might look at strain to give me a clue. And I have a pretty low threshold these days to also get an MRI and kind of quantify dimensions and function. And if you see, you know, any evidence of LV enlargement, that can be a clue to an early cardiomyopathy. How do you use delayed enhancement on MRI? I mean, I know that people have used it in their approach to ablations, but is that a dichotomizing point for you guys when you're sort of on the borderline? I mean, if there's scar present, will you get more aggressive, that sort of thing? Yeah, I will, because I think that, you know, suggests probably some other underlying cardiomyopathy. There is data that if you have scar and inducible VT, that you are at higher risk potentially for arrhythmias. And so, I do have a lower threshold to bring someone to the lab, particularly if you see non-stained VT on a monitor and if they have delayed enhancement on MRI. Let me go to a different issue. I was fascinated by the wonderful work you guys did, published in Jack, looking at this. I'm trying to figure out the right word. I think you said it was mechanical abnormality, presage. So for people who haven't read your paper, then you'll correct me. So, as I remember your paper, the sinus beat before the PVC was showing mechanical dysfunction, right? The actual sinus beat. Correct. So, why don't you educate us on that? I found it a fascinating observation, and I'm still thinking about it after reading your paper. Oh, I'm glad you did. So, you know, this was a project where we had done a lot of animal work, and we were really just looking to correlate it to humans coming to the lab for afib ablation. And so, we started doing these dyssynchrony echoes. And we were sitting with Nelson Schiller, who's one of our longtime echocardiographers, and it was really his observation. He's like, how come that beat before the PVC looks funny? And we were like, huh. And so, then we started quantifying the synchrony and the strain, and we found, you know, the sinus beat before the PVC, so the PVC hasn't happened yet, actually has lower strain and more dyssynchrony than the other remote sinus rhythm beats. The PVC, obviously, has more dramatic dyssynchrony, but it's an intermediate value. And what it means is the heart somehow knows a PVC is going to happen, right, because the PVC hasn't happened yet, yet the sinus beat before the PVC has some dyssynchrony and decrease in strain. So, there's some premonition going on, you know, why does that happen? We don't know for sure. Two hypotheses, you know, one, obviously, we know the heart functions on calcium-triggered calcium release, so some abnormal calcium handling that's happening before the PVC. Probably the more likely thing, I think, is autonomics. We know from work that it's been shown in frequent PVCs, there's sympathetic hyper-innervation, even that persists after resolution of PVCs. And my sense is that sympathetic firing that leads to the PVC may be leading to some of these mechanical abnormalities that we see before the PVC. So, it would be whatever...my take from your paper, and again, I hope the readers will read that paper, I think it's a fascinating piece of work, is that whatever is causing the PVC is somehow...the sinus beat ahead of time is experiencing whatever that is, or do you think because that sinus beat was dysfunctional a little bit, it caused the PVC? In other words, you know what I mean? It's like if there's a sympathetic...it's like, sort of, are they connected or are they side by side? Yeah, that's a good question, and I think I don't have the answer. My sense is probably that it's whatever is driving the...you know, because the abnormality is fairly subtle. I'm not sure why, you know, a little bit of the synchrony would cause the PVC. My sense is it's whatever process is driving the PVC is occurring, you know, but it's interesting to think that something's...it's already stopped beforehand, and your heart kind of knows it's going to occur, and to think about, you know, if there's some intervention method where we can block that sympathetic surge, maybe we could have... I think it's fascinating. So, did you find...I couldn't remember from your paper, was it localized to any areas? Was it outflow tract versus PAPS or something? Did it matter? Was it a universal concept? What we looked at was more global strain. In some of the animal studies, we've found that, you know, when we create PVCs by pacing, that that segment tends to be the more synchronous one, but we didn't find, you know, a clear region that kind of precipitated the PVC. All right. So, before we end, I'd like to get your view on what you consider a success in the lab. You go after the PVCs because...I mean, obviously, they're symptomatic. You're going to try to help the patient, but in these patients where you feel their dysfunction is there because of them, you started with your 10% or whatever. Not everybody gets 100% elimination of PVCs, okay? So, but at what point are you okay, and you say, you know what, they used to have whatever 15,000 a day, now they're having 6,000 a day, do I have to go back or am I going to be okay? That heart's going to start to, you know, remodel itself back to normal. Yeah. Because as you know, obviously, the best cases are someone's got a single, you know, monomorphic PVC, 98% of their PVCs, but some people have more than one, and you have to target all of them. And we try to, but we try to focus on the dominant PVC. And this was, you know, looked at...Mark Dayal was the first author when we were in the Penn group. And in the group where we were able to reduce the PVCs as we started initially to fewer than 5% or less than 5,000 per day, we also had sort of an 80% reduction. But if you can get it down to less than 5%, those people seem to still have recovery of LB function. Good. So even if you can't, you never...I always tell people, because they, you know, focus on their Holter, oh my God, I've got still 2% PVC. Right. They do focus. You're right. More than a friend. As long as you're, you know, below 5%, often LB function will recover and that's probably good enough. Yeah. And I love that because you'll know...you're saying, well, you had 26,000 PVCs before we started and you had 798. And they're like upset over the 798. It's like, okay, I'm not going back in for 798. No, no. I think nowadays we see lots of people who...Apple Watch, you know, will pick up PVC and come in based on an Apple Watch referral. And then as you know, a harder group are the people who are completely asymptomatic with normal LB function. Right. And then when do you target those? I mean, as always, it's fun to interview on these subjects. Thanks for the work you're doing and keep it up. Okay.

PBC cardiomyopathy

diagnosing cardiomyopathy

PVCs monitoring

ablation therapy

individualized treatment approaches