Hi, this is Eric Vrstovsky, and welcome to another segment of EPIMP. I am really delighted to have Pasquale Santanginelli with me today from the University of Pennsylvania. He's Associate Professor of Medicine there and an absolutely terrific electrophysiologist who I specifically wanted him to cover today this whole area of PBC ablation and normal heart. So, Pasquale, welcome. Thank you, Eric, for having me. I'm delighted to be here. Now, we're going to start off maybe with the simplest question and maybe not so simple. What do you call a normal heart? Thank you for the question. It's really, I would say, a moving target. I mean, historically, we've been defining a normal heart with a normal 12-lead ECG in sinus and a normal echocardiogram. And there's been actually historical data on that showing a fairly good prognosis in patients with idiopathic PBCs with that definition. A small subgroup of patients, though, they have a higher risk. It's a very small subgroup, but it's there. So more recently, we've been interested in doing MRIs in patients with idiopathic PBCs defined, again, as a 12-lead ECG in sinus being normal and a normal echo. And we did find in a small subgroup of patients, we do find LV scar, which actually, the more you look, the more you find. There are some papers that show up to 50-70% prevalence of LV scar in patients with the apparently idiopathic PBCs. So for us, it was really an impractical criterion to decide which patient is at risk. So more recently, we've been looking at the pattern of the scar. And it turns out that if you have something that is defined as a ring-like pattern, so you have three contiguous segments in the same short axis slice, which is typically located in the mid-marcal segments, this group of patients, which again, in our registry, which includes seven centers and about 700 patients, was about only 10% of those have a higher risk of malignant arrhythmias over follow-up. Again, it's a very small defined subgroup of patients. The large majority with a normal echocardiogram and a normal ECG do well. I actually read that paper, and I'd recommend the readers to read it also. Why don't you give us the reference so they can pull it? It's a great paper. Yes, the paper has been published a month ago in April in circulation. And again, it's a registry. The first author is Daniela Muser, which really did most of the work and includes seven centers, 686 patients, seven centers in the US, Japan, and Europe. And we did MRIs in an unselected group of patients with idiopathic arrhythmias, ventricular arrhythmias. Yeah, it's a great read. Before we get into the meat of things, in retrospect, was the scar at all related to where the PVCs were found when you ablated? Not really, not necessarily. We have patients with a typical idiopathic outflow tract PVCs with scar being located in the mid wall of the LV segment. So there wasn't really a one-to-one correlation. For patients that presented with multiple morphologies and red bundle morphology PVCs, we did find some correlation, although it's always a little bit complicated because we didn't map all of these patients invasively. It was only an observational study done with MRIs. Thanks, Musqually. So now let's go to the next part. Okay, so we've defined the substrate and you've done a great job on that. Let's talk about which ones are you going to ablate? It may be simple. The simple ones are like really symptomatic and you want to ablate them, but what about the ones who are not that symptomatic but have a high PVC burden? And you could take that in two ways, a high PVC burden and LV dysfunction and a high PVC burden, but a normal LV. Take those three groups. Which ones are you comfortable ablating? Yes, so again, this is also a very, I would say, controversial topic still because ablating asymptomatic PVCs for patients would normally have for protecting them against the future possible risk of PVC-induced cardiomyopathy. It's always complicated because, first of all, PVC-induced cardiomyopathy is reversible. So by definition, you can wait for it for happening and then you can ablate them at the right time when the LV starts dilating first and then the ejection fracture decreases and typically you can have a full reversal with that. So being too proactive is always a little bit of a difficult task because, of course, you always have to weigh that against a small risk in experienced centers, but there's always some risk of vascular access and, of course, possible risk of perforation, etc. Very small, but it's always there. But anyhow, going back to your question, there is some data from our center from Michigan that has really, Frank Bowman has done most of the work on this, that shows an association between a very high PVC burden, if you count a percentage of 25% on an ECG monitor, and from our center also some other markers of PVCs, including a QRS width during PVC and also the QRS width in sinus rhythm, which again typically does, even if a patient has a normal EF, typically corresponds to an initial form of a cardiomyopathic substrate that can be more vulnerable to the PVCs. So in those patients, the threshold is lower, although it's always a shared decision making with the patient because really we have no conclusive data that we should treat these patients aggressively. One thing for sure, if you decide to treat them, just, in my opinion, go with ablation. I mean, there is no reason to try medications, beta blockers, or other type of medications. If you go for treatment, just go for something that knows that works, and medications really have very dismal outcomes in terms of the long-term success in suppression of PVCs in most patients. So for sure symptomatic, we both agree there, correct? The little bit more gnarly area might be decreased LB function, but still high burden. I mean, that seems, I think, a good choice. I would throw out one thing for consideration from all of us. We know with tachymyopathies, like with AFib and other examples, the ventricle is never absolutely normal again. So I would ask us all to think about it. If you had a really high burden and they're asymptomatic, once they develop a bit of a myopathy, yes, you can get the EF back up, but there are a lot of people who think it's never a normal heart again. So I just think, just food for thought in that area. I totally agree, Eric. It's really, there is also some data from Ed Gassner and his group about the development of fibrosis, microfibrosis mostly, with PVCs. It tends to be reversible. The question is how much is reversible? Right. Yes, you're right. But again, on the other side, I think we need more data on proactive ablation. I agree. So now we've come to, let's jump into the heart and ablate. And I'm going to ask you just about two areas because I think certainly in our group, and we have some very fine people doing ablation and one of them, one of your stars that we were able to snag away. Let's talk about the LV summit area first. How do you personally approach that? You start with the ECG and then you're in the lab. Talk to us about your methodology and maybe some things like ice versus cath. Just tell us what your approach is. Thanks, Eric. This is really, I think it's one of my favorite areas just because it has a lot of challenges and I think there's still a lot to learn. I mean, first of all, the definition of the LV summit is purely anatomical and really comes from the McAlpine definition, which is the highest portion of the LV epicardium, which is bounded by the bifurcation between the LAB and the circumflex artery at that triangle and bisected by the junction between the great cardiac vein and the anterior interventricular vein. That small triangle in the septal portion of the LV epicardium is the LV summit. Now, that area is very close to the coronary venous system, to the coronary cusp region, specifically the left coronary cusp and also the junction between the right and the left, the RVOT, the most left aspect of the RVOT, and also, of course, the LV endocardium. So my approach is to divide roughly patients in a red bundle and just look at V1. This is going to be inferior axis and I divide them in red bundle versus left bundle morphology depending on the predominant forces in V1. In case of a left bundle LV summit PVC, typically it's left bundle and early transition. We're talking about the LVOT type of arrhythmias. Those are the most complicated ones because tend to originate more septally, very close to the junction between the bifurcation between the left LAD and the circumflex artery. That area is called inaccessible just because we cannot put any catheter there because we have the coronaries on the way and also because there is a thick layer of fat in that location. Those are the most challenging ones because we have to really approach them from different vantage points, which are defined typically anatomically with mapping but also with intracardiac echo. You can see because there's a lot of variability in between patients. So we try to really, the approach that works the best is to put our catheter as close as we can regardless of the activation time and the pace map that has nothing to do with success there. You have to go as close as you can to the area of the site of origin that you cannot ablate because it's too close to the coronary vessels. And then if you add it within a striking distance, which with radiofrequency typically is within 10 millimeters with long lesions, you can make it work. And when I say we can make it work, you get 50% success, which is really quite good for LV-SUMMIT. We reported our early series with epicardial direct mapping for LV-SUMMIT, we reported a success rate of 20% and acute success rate and actually long-term was about 17%. Again, epicardial direct mapping, even if those are epicardial PVCs or VTs, doesn't really work because you have too much fat in the atrioventricular groove and also you're too close to the coronary vessels. The red bundle morphologies are the easier ones because typically are away from the bifurcation and being away from the bifurcation, you're away from the fat layer, you are closer to the accessible area and you can typically target those more successfully and that's the way you approach that. Do you use ice throughout the ablation? Yeah, we do use that all the time, mostly to define the anatomical proximity between the putative site of origin that we map and the closest sites can be the RVOT, can be the coronary cusp region of the LV endocardial site, but also since prolonged lesions are necessary in these conditions, specifically when we ablate from adhesion sites, you really want to monitor ecogenicity at the site of ablation because that predicts the areas that you may have a steam pop, so we're very careful to treating our power depending on what we see on intercardiac echo as well because you typically need prolonged lesions to make this work when you're working from specific vantage points. And 30, 40, 50 watts, do you have a like a hey I don't want to go above that number? Yeah, so we work mostly in time than power and impedance drops and the approach is actually interesting for the atria, which is a small tissue, it's like a thin tissue, we go high power short duration. For the ventricle, we actually reduce the power because we need to prolong the duration to increase the depth. If you go 50 watts after one minute, you for sure, and most of the time you have good contact, you go have a steam pop. You have to prolong the lesion duration. We typically use the impedance trend and we target about 10 percent from the drop from baseline and typically you can achieve that with 35 watts to 40 watts max in most patients and you can keep that power throughout the lesion. You will see late suppression of PVCs typically when you are working from vantage points. Late suppression means beyond typically 30 seconds, sometimes 60 seconds, so you stay on for longer time, typically two to three minutes is necessary to have a longer lasting suppression. And even if it goes away, do you tend to put a couple other lesions in the area? Are you happy if you put one in there and it went away to say I'm done? Yeah, so typically again, when we're working directly from the site of origin, which is very rare, we do only one lesion at the origin. When we're working from vantage points, we tend to ablate from multiple vantage points that are close enough, assuming that it's safe and also depends on the time to suppression. If you have a relatively early time to suppression, you were within striking distance, you were also actually very close typically to the focus, you don't need to do much more. If you have a very late suppression, I tend to do a little bit more from opposite side when possible, just to make sure that I can achieve a lasting success. Again, we haven't looked at this approach really in terms of a study and I think it's an interesting question that you asked, so maybe we'll look for that. All Penn needs is one more idea for a study.

ablation

normal hearts

arrhythmias

ring-like scar pattern

MRI