Hi, this is Eric Brestowski. Welcome to another session of EP on EP, and today we have a wonderful academic and practicing electrophysiologist with us, Dr. Sam Asabatham, who's told me he wants his title to be electrophysiologist of the Mayo Clinic. Talk about a underrated title, Sam, but that's what you want to be called. We're going to give it to you. We're going to discuss an area of, I think, great clinical importance still undergoing evolution and one in which Dr. Asabatham has been one of the leaders, and it's the malignant mitral valve prolapse syndrome. So Sam, welcome to the show. Thank you. Thanks, Eric. Sam, let's start off with sort of just defining this syndrome. Lots of people have prolapse, but how would you define the malignant mitral valve prolapse syndrome? Thanks, Eric. So as you know, this malignant mitral valve prolapse syndrome is a diagnosis that sort of came together in an after-the-fact manner. So one of the early people to recognize this was my colleague, Mike Ackerman, who was actually evaluating patients for possible long QT syndrome, that is, people who had unexplained sudden death and who happened to have mitral valve prolapse and didn't have long QT syndrome, and started characterizing what is it about those individuals. And that became the form first of the syndrome. Instead of all mitral valve prolapse, there was a preponderance of people who had bi-leaflet mitral valve prolapse and, in addition, had complex ventricular ectopy. So part morphology, part electrophysiology. The complexity of this ectopy was either it was frequent, it was more than one morphology, with at least one of the morphologies or origin of the PVCs appearing to come from the mitral valve apparatus. The third component was maybe the reason why some of these patients were referred to a long QT clinic, is they had abnormal repolarization. The T waves were not normal. They were flat. They were, you know, giving the appearance of the QT being longer. So abnormal T waves, frequent ectopy, and bi-leaflet prolapse. That was where it all kind of started. Since that time, it's been getting more and more defined. The big addition is the added morphology feature of mitral annular disjunction. So mitral annular disjunction, where the mitral valve, instead of being inserted right on the annulus, is actually inserted on the atrium, giving rise to some abnormal-type tissue that's ventricular to the point of attachment of this annulus. So it's kind of like an inverse of the Epstein anomaly, where instead of being the tricuspid valve too ventricular, the mitral valve is too atrial. And this is usually kind of the tetrad of like malignant mitral valve prolapse. But within this syndrome, there have been three additional features that have been brought to light. One is it's not just complex ventricular ectopy, but polymorphic non-sustained VT. So there's a PVC, and then a couple others, changing axis or morphology. And the last has been imaging with MRI that shows abnormal late gadolinium enhancement. Usually in the submitral apparatus, papillary muscle was around the area of the mitral valve. But in some patients, nothing even close to the mitral valve, suggesting that what really they may be having is a cardiomyopathy. And as part of that cardiomyopathy, they have abnormal support to the mitral valve. So today, it's varying contributions from each of these that we'd call malignant mitral valve prolapse syndrome. That's a great overview, Sam. Let me let you dig down a little bit into this, though. And let's start with the MAD, the mitral annular disjunction. I really hadn't paid much attention to that over the years. For me, it was a more recent observation. Obviously, it's been around, I'm sure, for years. But the earlier descriptions, and even my experience with patients over the years who unfortunately had a cardiac arrest with mitral valve prolapse, it was very billow-less valves. And they would have that fibrosis under the leaflets in the earlier descriptions. But it's changed now, right? In other words, I remember reading your papers and others that you don't really have to have dramatic mitral regurgitation as part of the syndrome. Is that correct? Yes. So the bileaflet prolapse, large floppy valves probably play a role in the ectopy just from contact, just hitting against the outflow tract, back, and the annulus on the papillary muscles. This would be Barlow's contact lesions, for example. But the extent of regurgitation is not a predictor for malignant nature of ventricular arrhythmia. So really, those decision-making for what to do with the valve kind of goes in parallel. Based on the regurgitation, do you need surgery? And how much is the valve morphology itself contributing to the ectopy? And then there's this knotty problem with the MAD. You mentioned it could be part of the syndrome. But there are good data out there showing patients who have only MAD and have suffered a cardiac arrest. You know so much about the anatomy. You've done a lot of work in this area. How do you put that together? Is this a form first? Is it part of a spectrum? How do you look at that? Is it OK to draw a quick picture here? If you could do it, sure. Oh, yeah. So if this is atrium, this is ventricle, and this is mitral valve normal, mitral valve prolapse would be in systole. It's bellowing back like this. If instead of this point of attachment, it's attached right there, then even if it's not bellowing back, it's still prolapse. So by definition, this displacement would have been something just called prolapse in years gone by. It's just the mechanism is different. It's actually the point of attachment is further back. Now, this tissue here is actually like atrial tissue, but it's a continuum. And it seems to give rise to arrhythmias, both atrial arrhythmias and ventricular arrhythmias. So it's hard to envision mitral annular disjunction without some kind of prolapse. But if in patients with prolapse, there's annular disjunction, this is becoming clearer and clearer that that is an important risk factor. And in fact, in the patients, which is a small minority who've had ablation studies, the arrhythmia, the abnormal electrograms, the site of ablation is often right underneath this disjuncted valve. That's great. That's wonderful, Sam. Well, let's go now to the more practical problem, I think, of when and how to screen for patients who may be at risk for sudden death. As you well know, any person who's been in the business for a while and gets set patients, it's so common to see an echo report with mitral valve prolapse. And it might be minimal, right? And then you sometimes see the usual 7-millimeter MAT on a report. And the patients are asymptomatic. So I guess the question for you is, and I know kind of what I do, but I don't want to talk about me. I want to talk about your approach. When do you start to delve in and say, hey, I've got to look at something else? Because I think you would agree with me. You can't do MRIs on every patient. There's got to be a way that you select out those. So give us your approach when you start to say, hey, I've got to do more. Yeah. Of course, the easy case is when someone has had a malignant event already or a malignant sounding event. So we'll forget about those. So to me, there has to be either worrisome symptoms, worrisome arrhythmia, or worrisome morphology, usually a mix of more than one. So most common patient where this would be is they knew about mitral valve prolapse maybe already, but now start getting palpitations. And if you did a Holter monitor or monitored them, they either have frequent or close coupled or polymorphic ectopy. And that would definitely be an alert level to say mitral valve prolapse plus complex ectopy need to look more carefully. So maybe MRI, maybe more carefully defining how much non-disjunction there is, how much disjunction there is, and so on. The other is occasional patients. And I would say this may be 10% of the patients just guessing is they never really complained of palpitations that much. That doesn't bother them. But for some reason, they got monitored or had a stress test and had a very malignant looking polymorphic VT that spontaneously stopped. Patient hardly felt it. But when you and I would look at it, this is like a scary arrhythmia, clearly polymorphic, rapid. And then they have mitral annular disjunction. They have mitral valve prolapse. Those are patients who at least need careful counseling to state both what we know and don't know about the syndrome and to consider a defibrillator, at least consider MRI. And in some patients where it's a tough call, there's some symptoms, malignant looking arrhythmia, but MRI is equivocal. Could even consider an EP study to see is there sustained arrhythmia that's inducible. We're going to get into treatment in part two of your interview, Sam. So let's hold off on that. Let me just ask you something that I've been doing, only because I've been interested in this, as I think, you know, we've talked about it over the years for probably better part of a couple of decades before it was more well-defined only because I had some patients sent to me and had not done well. And I tried to look into it in my own experience and tell me if this is something you agree with as far as far as a easy screen. I haven't found any patient yet with normal T waves in 2, 3 and ABF who fit the malignant pattern. That's just been my experience. I don't know if that's yours. I don't mean they have to be, you know, deep downward T waves, but I've never I just haven't seen a patient that's totally normal to 3 and F. And so I sort of use that as a initial screening test. But what's your experience been? It's very interesting. You know, I think it's all most patients with the syndrome do have funny looking T waves, you know, but I've never really thought about the opposite. Does a normal T wave kind of say low risk? It makes a lot of sense. I have just not paid attention to that from that angle. So now I've given you yet one more. It's a very interesting. It's very interesting way to look at. So, Sam, I'm going to stop at this point only because I want to regroup with you for part two and discuss therapy. Thank you, as always, for being so informative to our audience. Thank you very much.

Dr. Sam Asabatham

malignant mitral valve prolapse syndrome

bi-leaflet mitral valve prolapse

mitral annular disjunction

polymorphic VT