Cardiovascular Diseases and Cardiac Surgery

Overview

In this Heart Rhythm Webinar Series challenging case discussion, Mayo Clinic cardiology experts Samuel J. Asirvatham, M.D., Abhishek J. Deshmukh, M.B.B.S., Siva K. Mulpuru, M.D., M.P.H., Ammar M. Killu, M.B.B.S., and Christopher V. DeSimone, M.D., Ph.D., and guest panelists Melanie C. Bois, M.D., and Narayan (Guru) G. Kowlgi, M.B.B.S., discuss inflammation and rhythm disorders.

For more information or to refer a patient, visit Mayo Clinic Medical Professionals — Cardiovascular Diseases.

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SAMUEL J. ASIRVATHAM: Well welcome, everyone, to our heart rhythm clinical discussions webinar series. Thank you for those of you who sent in some questions. Please do feel free at any time to bring in questions or present anything that you feel would be relevant.

Today's discussion topic is looking at arrhythmias in a specific set of patients, those with inflammatory type causes for structural heart disease. We have Dr. Deshmukh, Dr. DeSimone, Dr. Mulpuru and Dr. Killu here with us, along with Dr. Guru Kowlgi, who will present an interesting case. And today, a featured part of the session will be a part with Dr. Melanie Bois, a cardiac pathologist who will show us some of the sequelae of what we see in autopsy hearts in patients that we try to intervene on as electrophysiologists.

So to get started, what are we actually thinking of here? We've got a set of diseases that have some unique features. We talked earlier in this webinar series about patients with structurally normal heart beating, and these were a unique set of patients, locations like the outflow tract, the fascicles and a common set of patients we deal with. Very important in understanding that group and complexity is just anatomy of the normal heart, something that we discussed in some detail. We had some questions and discussion further on it, and we'll bring up cases that we present through the course of this series.

But we also have conditions where we have abnormalities. For example, when we have a patient mapping PVCs, but then when we look at the signals, the ventricular electrograms and sinus beats, ventricular electrograms during PVCs, multiples areas in the heart, the signals aren't normal. Yet unlike the substrate VT discussion and approach we had, where we have a known etiology, like ischemic heart disease, or familial inherited problem like laminopathy, we have a border line type of condition.

It's mostly normal, except there's an ongoing process. So this is a challenging group of patients because we need to have a thorough understanding of anatomy [INAUDIBLE] structurally normal heart, VT and atrial arrhythmia, but we also need to understand dynamic pathological changes. It's challenging for treatment, challenging to understand, and to try to facilitate this process we will go through a few cases, and then we'll look at some actual pathology to try to understand a little bit more about this disease process.

Now do we have Dr. Kowlgi on with us here?

GURU KOWLGI: Yes I'm here, Asirvatham.

SAMUEL J. ASIRVATHAM: If you want to introduce yourself and tell us what you'd like to share.

GURU KOWLGI: Sure. Hello, everyone. My name is Guru Kowlgi. I'm one of the final year EP Fellows here at Mayo Clinic. Happy to be here. I will be presenting a case which will base the discussion thereafter, so I can share my slides ir--

SAMUEL J. ASIRVATHAM: Sure.

GURU KOWLGI: Good. OK

Can you all see this?

SAMUEL J. ASIRVATHAM: Yes.

GURU KOWLGI: OK, so this patient is a 50-year-old male, had comorbidities including hypertension, had systolic heart failure with the ejection fraction of 47%, was known to have frequent PVCs. He also had obstructive sleep apnea. He was on CPAP therapy, had morbid obesity, and had undergone Roux-en-Y gastric bypass surgery a few years ago, and he was a non-smoker. And he had symptoms of dyspnea and palpitations and occasional chest pain. His chest pain was somewhat atypical, did not have any exertion features, and had this burning discomfort for many years.

So he was evaluated in cardiology clinic for an abnormal stress test. This was his baseline ECG. And as you all can see, he had sinus rhythm but had some evidence of conduction disease, has right bundle branch block, has a left axis deviation likely left anterior physical block and sinus bradycardia. And this was his Holter monitor. He had about 19% PVCs, and the PVCS were all unifocal. It looked like a right bundle branch morphology and B1 transitioning and B5, we had one in a prior ECG that looked like that as well. And then some of these had some runs on long sustained ventricular tachycardia, but the initiating beat was similar to this PVC and then he had a slightly different morphology of the VT.

And then he had a stress test done at one of our satellite facilities. And on the left panel, you can see resting images and the right is peak stress, this was an exercise stress test. He went about eight minutes, had submaximal heart rate response, but you can see there were some wall motion abnormalities. And I'll play this one as well. So he had both apical, lateral wall and also some basolateral wall abnormalities here on wall motion.

So that was his initial presentation. And then he was evaluated in cardiology--

SAMUEL J. ASIRVATHAM: So the evaluation was here, patient with conduction system disease, not previously known. VT and PVCs, PVCs one morphology, VT nonsustained, maybe another morphology.

GURU KOWLGI: Right.

SAMUEL J. ASIRVATHAM: Suspicion of coronary disease because of an abnormal stress test. And then I assume the patient had an angiogram, right?

GURU KOWLGI: He did, yes.

SAMUEL J. ASIRVATHAM: And if you could just tell us findings on that, in general.

GURU KOWLGI: Yeah, I did not have any obstructive pulmonary disease on his angiogram.

SAMUEL J. ASIRVATHAM: So if I have to summarize this patient, your thought process is, why is there this seemingly new onset conduction disease, ventricular arrhythmia, more than one location?

GURU KOWLGI: Right.

SAMUEL J. ASIRVATHAM: Wall motion abnormalities, rest and stress but normal coronaries?

GURU KOWLGI: Correct.

SAMUEL J. ASIRVATHAM: Yes, if a patient presents like this to you, your thought process on what you'll be thinking about?

GURU KOWLGI: Yeah, so this is, so when I see evidence of conduction disease and ventricular arrhythmias in a relatively young patient, he's 57, always like to think of certain conditions, like one of them would be cardiac sarcoidosis, and then in this patient, there was no familial history. But some other rarer conditions could be lamin cardiomyopathy, is where you can have conduction disease and have ventricular arrhythmias. So those are a couple of things I think of.

SAMUEL J. ASIRVATHAM: Very nice. So really what has clued you in towards, OK we need to think about an inflammatory process? Is either the presentation of conduction disease or ventricular arrhythmia, but not fitting a pattern and you're thinking, why are they kind of going together? Do you want to tell us what happened with this patient?

GURU KOWLGI: Yeah, so this patient unfortunately, so after this evaluation was completed, a few months later was found unresponsive by his wife at home, and EMS was called and by the time he was brought in he was declared dead on arrival and then had an autopsy.

SAMUEL J. ASIRVATHAM: So this patient passed away without any further specific evaluation?

GURU KOWLGI: Right.

SAMUEL J. ASIRVATHAM: And we're going to discuss some of the autopsy findings in this patient coming up in just a little bit. But if I now go to the individual aspects, the VT and the conduction disease, maybe we can discuss a little bit, see what questions we get from the audience, and then we can come back to looking at what the autopsy findings are and what we learn when we do ablation on patients like this.

So maybe do you want to try to talk to us about this ECG?

GURU KOWLGI: Sure. Sure. Yeah. So I'm looking at this ECG, just atrial rhythm, it looks like it is biphasic and B1 upright in the inferior [INAUDIBLE] looks like sinus rhythm. And then there doesn't seem to be any correlation with the ventricular rhythm so appears to be sinus rhythm with complete heart block. And the underlying ventricular rhythm, the QRS is also slightly wide, negative and B1 notched in one and aVL, sort of a left bundle junctional escape.

SAMUEL J. ASIRVATHAM: Outstanding. So this is probably one presentation where electrophysiologists have to get clued in. So we have conduction system disease, but although we don't have VT on this tracing, we have suggestion that this patient has got ventricular scar. You very nicely pointed out the change in wavefront, the glitch or the notch in different parts of the QRS, on the QRS complexes here. So even though there isn't VT, we're thinking here conduction block could be multiple reasons, but there's also scar in the ventricle. So that's like a surrogate for VT plus conduction disease, much like your patient thinking about this.

Now Abhishek, you put together a very nice slide of potential causes for AV block of relevance to electrophysiologists when we see. Do you want to give us a brief look at how you use this information?

ABHISHEK J. DESHMUKH: Sure, absolutely. So whenever, so this ECG, what you showed was on a 50-year-old professor actually who was having exertional shortness of breath when he was giving long lectures and going for walks. So whenever that happens, he got an ECG that showed complete heart block as we saw. Young patients, complete heart block, it's almost like a class to a recommendation that we have to rule out certain inflammatory cardiomyopathy. But generally, when we think of complete heart block in patients with younger patients, you know degenerative disease, Lyme's disease can be seen, even COVID now is causing some AV block and bradycardia. Apart from that, prior history of radiation is important. And beyond all this, sarcoid is really the main condition which we really need to be aware of to make sure that we are not missing.

Now the key thing with sarcoid and some of these inflammatory cardiomyopathies is that they can cause AV block and they can also cause VT, so both are extremely concerning. And as we picked up from the ECG, the fact that the patient had fractionated QRS, the patient does have underlying substrate to have a ventricular arrhythmia. Now going forward-- Yeah.

SAMUEL J. ASIRVATHAM: No, go ahead.

ABHISHEK J. DESHMUKH: Now the thing which becomes challenging, that when we see these patients, if the ejection fraction is normal, you know what kind of device to offer.

SAMUEL J. ASIRVATHAM: Maybe we'll come back to that.

ABHISHEK J. DESHMUKH: OK.

SAMUEL J. ASIRVATHAM: But if we just stay like, let's say for our trainees, new electrophysiologists, you sometimes get a big list like this and we have to have some method of how we're looking at it. Maybe I'll just share mine.

So advanced AV block, anybody can get it. But typically you're going to see it with the degenerative population. So you're going to know the age of the patient, and you'll see other features, A-fib, atrial scar, atrial enlargement, things that go with age. And you have the age of the patient advanced AV block, probably we don't think too much more.

Things that would be classic scenarios, which should make you think of a condition, one is rapidly evolving conduction disturbances. Bundle branch block one day, complete heart block another day. One condition there we have to think is giant cell myocarditis. So VT and heart block, like sarcoid with this condition, but it's a rapid, not a subacute, it's an acutely evolving syndrome, to make us think about that.

Now Abhishek, you included Lyme disease as a cause of block. We have Chagas, we also had ankylosing spondylitis, all cases that we see with this type of presentation come to us because they also make it VT. So some just clinical clues to this, Lyme disease tends to be higher level AV blocks, so it tends to be QRS is OK, we don't see some bundle branch block. Ankylosing spondylitis, very, very similar to the type of block, type of EKG that you get with sarcoid, the difference is the well. You will always have some aortic regurgitation, when heart block is as a result of ankylosing spondylitis. So there it's just combining some auscultation or knowledge that they have some disease of the aortic valve.

Beckers and dystrophies, the QRS is abnormal. Classic feature here is the appearance of right ventricular enlargement because of posterior scar, taller with in V1, sometimes very slow process, nothing evolving like with an inflammatory cardiomyopathy. Radiation, as you pointed out, very similar to what we get in many of these, but difference is heart unusual to get sole myocardial or conduction system disease. You'll see multiple viral involvements may be coronary involvement as well.

Last point I'll make is with sarcoid. You can start with AV block and then get bundle branch block in the escape rhythm. Whereas in Chagas disease, you start with bundle branch block, vascular blocks, and then can progress towards complete AV block. So that's one angle, that's one place that we get this type of clue to try to avoid where we're getting to a patient that we missed the diagnosis and passes away suddenly.

The other is VT, and that's something we're accustomed to and many of your questions are on. We'll come back to that. But I'd like here to just first of all, thank Dr. Melanie Bois, who is going to talk us through and show us the autopsy heart to see what the lesions look like, how the diagnosis is made in the autopsy laboratory, but also to give us some clues when we're thinking about mapping or ablating VT. So I'll play here a--

So Dr. Bois, really want to thank you for giving us a chance for seeing the actual gross anatomy, gross pathology in patients that we evaluate and ablate for sarcoidosis. So looking at what we have here, do you mind pointing out to us what you see in this patient that looks abnormal, and we'll pair this with a similar section in someone with ischemic heart disease?

MELANIE BOIS: Absolutely. So when I start to think about what looks abnormal, I think the best way to start is to really identify normal. So here, this coloration here is a normal color in the myocardium, in this particular specimen. Now the specimen is fixed, and it has been fixed for several years, so it will start to lose a little bit of its coloration.

But I'm looking just at this side. What I start to see are some white areas here, here, right in here, that are representative of either scar or active inflammation within the myocardium itself. Now just looking at this by itself, I would think that it could be an ischemic event that could cause this, or it could be a multifocal myocarditis that's really only manifesting at this mid ventricular level in this location. But the subepicardial nature of it starts to clue me in that we might have something going on, with relation to an inflammatory disease rather than a ischemic heart disease.

SAMUEL J. ASIRVATHAM: Well, maybe I'll point out a few things for the electrophysiologists here. So one thing that we notice is we need to understand very accurately what the overlap areas of the right and left ventricular are, because it's this septal area with various amounts of depth that we see the lesions that cause or promote re-entry with ventricular tachycardia.

Note for example, we intuitively understand this region as interventricular septum, and think about ablating from the right or the left ventricle. However, look at this overlap area, so-called anterior crescent and posterior crescentic regions of the right ventricle. You really have to insinuate the catheter between the trabeculations, and if you do and get to this location, mapping this region becomes quite straightforward. Trying to ablate that same region from the left ventricle with present biotechnology, is biophysical methods, is very, very difficult.

Note also that the catheter wedged in this location to pick up voltages from this myocarditis region will simultaneously record signals from the right ventricle, giving us a false negative with normal electrograms, but looking at the quality of the electrograms, we can see the slow conduction around this region. But what else could we compare this with what we would see in ischemic heart disease?

MELANIE BOIS: Absolutely. So in ischemic heart disease, looking just for orientation purposes, we have the anterior left ventricle here, lateral, inferior, posterior, interventricular septum, right? And in this particular instance, we have a scar that has formed within a vascular territory, in this case the left anterior descending coronary artery territory. There's also very little star forming in other vascular territories, which helps us to understand that this is what we're seeing in ischemic heart disease. Also note that advanced remodeling that has formed, where there's dense fibrosis within this area, indicating that remote myocardial infarction.

SAMUEL J. ASIRVATHAM: Well, as a nonpathologist, when I just examine that scarred region, I see what looks like some normal tissue there. Would that be what we'd expect to see when we look at this histologically as well?

MELANIE BOIS: It depends on the degree of the infarction. So you can have subendocardial infarctions, which would result in scar tissue in this location, and then other normal myocardium, further out in the midneural and subepicardial regions. A transmural infarction, on the other hand, would effect the entirety of the left ventricular wall, in this case, and would mostly be representative of scar tissue in this location. We will have some insinuating normal monocytes that have survived that ischemic event, but the majority of it will be scar [INAUDIBLE] along with some fatty infiltration.

SAMUEL J. ASIRVATHAM: So this is a critical image for electrophysiologists to look at and compare. First, notice the sharp demarcation of visibly normal and abnormal size. This is what we see with our catheter. In other words, the voltage cut off that you use to record the electroanatomic map is much more forgiving with ischemic heart disease, with its gross abnormal, versus areas that are completely normal. So if we take, for example, a window between .05 millivolts, as low as that, to say one millivolt, we'll get a tremendous differentiation of the area that we need to concentrate for substrate modification.

On the other hand, with the example that Dr. Bois showed us before, there's really no area that's transmurally abnormal, or perhaps even transmurally normal. So the gradation in voltages, differences between affected and unaffected sites, are much more gradual, much more nuanced. So to really tease this out, we have to rely on the quality of the local electograms, rather than [INAUDIBLE]. This is one of the limitations of substrate ablation, entirely based on bi-polar voltage.

Note also there will be a tremendous difference between a catheter placed here, looking at unipolar voltage in this region versus this region, but not that different in bipolar voltages. On the other hand, with the ischemic heart infarction patient, we'll have no real difference in either unipolar or bipolar signals here or here, and a major difference between bipolar or unipolar signals here or here.

Now I notice that, Bois, that as we move away from this obvious kind of infracted area, it just looks like there are streaks of scar, streaks of abnormality. Now for the genesis of arrhythmia, we really need viable tissue to be able to sustain the arrhythmia. I'm just curious, what is it that keeps these living myocardial cells viable after an infarct has happened? The reason I ask this is one of the debates in electrophysiology is whether the remaining tissue that we see is fragmented scars, fragmented signals within scar is Purkinje that has a higher threshold for ischemic death compare, or is it actually myocardium that survives? Any thoughts that we need to keep as it is when we see something that looks alive, even though the rest is obviously scarred and dead?

MELANIE BOIS: It's a very interesting question, one that is clearly very nuanced with regard to the literature and evolving research as well. I think what we're seeing can be variable, again depending on the degree of the ischemic infarct and the genesis of it and whether or not the patient was reperfused at the time of the event. So reperfusion injury can happen along the borders of the ischemic event and can lead to patchy myocyte survival and patchy myocyte death, depending on the insult to that particular cell. So I would think that honestly you have a mix of normal myocytes, as well as Purkinjes that have managed to survive.

SAMUEL J. ASIRVATHAM: Thank you.

So we'll come back to Dr. Bois, who's kindly looked at several cases from a pathology perspective, and we'll come back to talk about that. But I want to look first, before we go back, at some of the other side, the other side of where we get a presentation that clues us in to a inflammatory process, is an evolving ventricular arrhythmia syndrome.

So maybe this is a patient, I know Guru, you're familiar with this tracings and we'll get your help with this, but very similar to the case you presented as well. But conduction abnormality, acute development conduction abnormality, so it's not going to think [INAUDIBLE] disease and a Graves' disease. Some things going on to all of this. And as right before your eyes, as the day is the minutes to hours progress, you not only have evolving conduction abnormalities, but you start developing ventricular irritability, and then you get Frank ventricular tachycardia.

So this specific type of rapidly evolving, rapidly evolving. So this is not something that is going up for days or months. Thought processes and your approach, maybe we'll get Dr. Killu's perspective on this type of syndrome. If you have this evolving, your thoughts on how you approach this. Ammar?

AMMAR M. KILLU: Yeah, so sorry, I wasn't sure if you were asking Guru still. So when I see this, I do worry about an active myocarditis. So some severe inflammatory process going on within the hardware, there is a giant cell myocarditis, something like that. So needs very prompt and aggressive management, often a multidisciplinary approach I think. So that would be one of the main things that I would be worried about in this kind of situation.

SAMUEL J. ASIRVATHAM: And so Ammar, when you say multi-disciplinary approach, you're saying that with giant cell for example, this can go so bad so quick. You want to have heart failure advanced therapies, support transplant all available, and probably rheumatologists, pulmonologists, who may be more expert than us and immunosuppressive therapy involved. Those would be the big two, I think, isn't it?

AMMAR M. KILLU: Yeah absolutely. Because it can really be, I mean you've shown the slides here, but before your eyes, as you said, it can happen. So it just needs to be all hands on deck, I think, to really try and optimize the outcome for the patients.

One thing I would, as well, sorry, is I've seen something similar with checkpoint inhibitors and I think someone mentioned that in the texts, with the medications we're seeing for patients with melanoma, for example. So just important, I think, to be aware of that.

SAMUEL J. ASIRVATHAM: Yes, do you want to expand a little bit on that to see what the times or time course of that syndrome and prognosis would be?

AMMAR M. KILLU: Prognosis isn't great, or I should say it's actually poor, but it can be reversible. Treatment requires immunosuppression as well. But it can't evolve very quickly. I've had one patient in the last couple of years where they presented with syncope and they had advanced AV block but then rapidly started developing ventricular tachycardia. Diagnosed quickly, or at least the suspicion was there. Started treatment very early, but unfortunately the outcome wasn't good, but it can also evolve quickly in similar fashion to this, at least in the rare cases I've seen.

SAMUEL J. ASIRVATHAM: So one of the things, and this is why I believe Dr. Kowgli presented this to our group was early in the pandemic, there was this recognition that some patients with COVID-19 did get cardiac involvement, and that involvement was myocardial and conduction disease. And this is in keeping with what we see in other types of myocarditic processes. On the one hand, we may have repolarization abnormalities, this kind of mimic of an aseis syndrome. Other hand, we have just heart block, AV block coming in pretty early, and that clues us in to just like it would in other times into a possible inflammatory cause. And then the same thing of this pairing with ventricular tachyarrhythmia and conduction block, but with other features of inflammation. The instability, the dynamicity of the course, and some inflammatory changes that may involve the pericardium as well.

Now generically, we can think about inflammatory myocarditis as like viral versus autoimmune, but within viral also there may be some differences. For example, in patients with coxsackievirus, a very common cause of myocarditis worldwide when a virus is identified, you tend to have simultaneous involvement of atria nodal tissue and ventricle. So early in the course, sinal atrial block, sinus arrest, along with bundle branch block. Not so common and very rare in sarcoid, for example. Very rare returns of myocarditis to get permanent sinus node involvement. That might clue you in onto this diagnosis.

Another unique syndrome also tends to occur endemically sometimes is part of a viral myocarditis. Big thing here is endothelial involvement, so Purkinje is affected more. Other evidence of endothelial dysfunction, and one of the ones that's easier to biopsy because it is an endothelial dominant type of disorder.

A couple points we should remember, it's not always VT and heart block. Myocarditis tends to produce inflammatory types of straights in many places, plus the patients may be very sick. They may have ARDS, they may have other critical illnesses as part of their clinical course. So multifocal atrial tachycardia is something that can complicate the course in these patients, and the real risk in this dynamicity is you have these multiple sites that can each produce maybe nonsustained VT, but they can all do it at the same time. So this is like an exponentially severe EP study going on continuously in this patient population, and exactly why Dr. Killu pointed out, the minute you sniff the diagnosis you're going to get ready to get supportive therapies transplant, LVAD, because this is a tough one for us to try to manage with the catheter.

I should also point out that in patients with inflammatory carditis, they may have a pericardial syndrome that involves the ganglia. So these patients after they recover may be left with things like inappropriate sinus tachycardia, or parts like syndrome, or even myocardiogenic syncope that they never had before but comes after this myocarditis critical illness type syndrome. And both aspects of that are probably playing a role.

Now one of the questions that we had related to kind of substrate mapping approaches in patients with inflammatory disease. And maybe I'll ask Dr. Mulpuru to get us started and that thinking any things that we should be aware of or think specifically when we're thinking about electrogram interpretation, substrate in patients with inflammatory that you use, compared to how you do it in other syndromes.

SIVA K. MULPURU: So as you showed in the autopsy specimen, the scar is kind of patchy. It's good to get some sort of imaging, either a cardiac MRI or PET scan, so we know where to focus our efforts in the EP lab. Once we get to the EP lab, it's good to use some sort of electroanatomic mapping system to tag areas of abnormal electrical signals that correspond to our imaging abnormalities, and it is those areas we should try to, if you're trying to take a biopsy, those are the areas we should try to target for a biopsy.

As far as ablation is concerned, these patients are quite sick. In an acute phase, we really don't take them to the lab, let acute heart failure manage them. After the scar, after the scar forms but the situation has stabilized, that's the time to take them to the lab if they are having a recurrent arrhythmias. One exception is PVC induced ventricular fibrillation. If the patient keeps on having multiple episodes of ventricular fibrillation refractory to other therapies, we may have to do a very focal targeted ablation, just targeting that clinical PVC, and hoping that we at least reduce the burden of those BF episodes.

SAMUEL J. ASIRVATHAM: Fantastic, thank you. So maybe I'll go to this here. And if you see other questions also, let me know, but here's kind of a slide that Dr. Deshmukh put together. So very nice kind of pictorial view of what this patchy kind of involvement can be, just more fixed, more scar than the heart of the patient that Dr. Bois looked through. So can easily kind of get that idea that we're going to have some unique electrogram correlates in these patient populations that were not used to seeing in others, this interspersing of normal, abnormal type tissue coming so close together.

Now just in terms of distribution, Abhishek, I know this is a slide that you put together. With sarcoidosis, in your mind do you have some key areas you look at which are very likely to be abnormal with sarcoid, or is it like Siva pointed out, we just need detailed imaging and mapping.

ABHISHEK J. DESHMUKH: I think certainly, starting off with the ECG what we saw, I think from there itself we can start to in our minds think about where the abnormal substrate is going to be, looking at the fractionated QRS is. Certainly imaging is going to be very, very helpful. But as you saw on the autopsy specimen, certain areas, even if we map endocardially, we may certainly miss it because it is so patchy in involvement, and certain areas we may not be able to clearly map to know whether this is, whether we have any abnormal signals, such as deep into the septum, or epicardial substrate, if you have not done epicardial mapping. So I start off with imaging and then try to hone on my mapping more in that direction to at least try to get some insight into the clinical arrhythmia, what is going on.

And then finally, the VT morphology is certainly helpful, the other device interrogation and the tracings are going to be helpful and all those kind of clues you in to map which area of interest, beyond mapping everything else.

SAMUEL J. ASIRVATHAM: So one of the things, like a dictum in our field, is in the right ventricle, when we think, does the patient have sarcoid or do they have right ventricular cardiomyopathy? The two diseases, where we may have some familiar things like ultratech tachycardia, but it's not in a normal heart. One of the victims is sarcoid is a septal disease, right ventricular cardiomyopathy is a free wall disease. But I think it's important from the picture you shared here that this is, it's not that sarcoid doesn't involve the free, it just has a predilection for the septum, especially the high interventricular septum, the region of the ventricular crest, and it's the reason why we get bundle branch block and AV block so commonly with sarcoid. And it's unusual to have sole free wall involvement, so you won't get this without getting this.

Unlike right ventricular cardiomyopathy, where it's extremely unusual to get septal involvement, and pretty much unheard of to get septal involvement before free wall. So now Guru, do you have an ice image of a patient from VT ablation to show us this septal involvement.

GURU KOWLGI: Yes I do, Asirvatham, I can share my screen. Can you see this?

SAMUEL J. ASIRVATHAM: Yes.

GURU KOWLGI: So in this image, you can see the crest of the interventricular septum here, and in this patient, mapping was performed in this region and ablation was performed, substrate based ablation on the septum.

SAMUEL J. ASIRVATHAM: So I would guess if you ablate where you're showing, you're going to get AV block. Was it, was the reason you ablated there, the patient already had AV block from those lesions?

GURU KOWLGI: Yes, patient already had AV block and had a CRT device implanted.

SAMUEL J. ASIRVATHAM: Yes, so this brings up an important point. One of the hardest VTs to ablate is high ventricular crest, crest of the interventricular septum VTs, very difficult because you're going to get AV block. But the flip side of that is the most common scenario to get VT from there is sarcoidosis. And in those patients, the reason they're getting the VT from there is the inflammatory lesions. So good that they have either really bad conduction to begin with, or actually have AV block so we're able to ablate in that region.

So maybe I'll kind of show the equivalent image for that region that you've shown us from pathology.

So this is kind of what you showed us. Let me go ahead. So it's really this, so interventricular septum, and you showed beautiful image from your ablation case of [INAUDIBLE] this region. So in this ventricular septum, when you go to its highest point, you're above the septal leak of the tricuspid valve. So this is actually approached from the atrium. And when you approach it from the atrium, you're above the valve, you're on the septum, that's conduction tissue territory. So the atrioventricular septal region, high point crest of the interventricular septum, almost pattern mnemonic of sarcoidosis, you should expect to see things here and you should expect to see VT here.

The problem is we may fail to recognize it for several reasons. One is the patchy involvement could result in an exit of the VT, fairly far away from where the circuit is housed. So we're focused on these regions. The second is we forget this is ventrical, where we keep the tricuspid valve, we go up above that, we're feeling that we're on the atrial side, but this actually, this region is approached from the atrial side.

Now Siva, I see there's a question from the audience about the role of biopsy in sarcoidosis. What are we using to target the area for the biopsy? And maybe I'll have you comment a little bit on that, and then let's see if we can get this slide to come up here.

SIVA K. MULPURU: Right. So you know biopsy, it has to be sarcoidosis, one disease state where you have to do a targeted biopsy, unlike other conditions like amyloid joint cell where there is more of a global involvement of the myocardium. With sarcoid, if you just go and take pieces just from the RV apical septum, you may miss the actual involved areas.

So one way to pick the abnormal myocardial regions is to use the electroanatomic mapping tools. Here in the picture, you can see there is an ablation catheter, you create an electroanatomic map, looking at the quality of the signals and also the voltage amplitude of the signals. And usually, if you have a patchy scar, and in the border zone where there is fractionated signals, you know, where the voltage is transitioning from scar to normal, but still not completely normal, those are the areas we should target.

Here I believe the catheter is coming from the internal jugular vein. And sometimes we use an alligator clip, I think you have it in the other slide to see, also try to map from your bioptome, so you can use that as a marker and display the electrograms using that bioptomes--

SAMUEL J. ASIRVATHAM: So talk us through the setup for this Siva, how would you do this?

SIVA K. MULPURU: OK, so here we could see that you are the black clip of, it is almost like a pacing cable that we are using. We are connecting that black alligator clip to that metal spring there, which is in continuous connection to the distal tip. It's almost like a unipolar electrogram if you record this and you use A [INAUDIBLE] and central terminus, or if you connect the red alligator clip to a patient, like a needle on the patient's body, or a forceps that is in contact with the patient. This is almost like using it to obtain unipolar electrograms here.

SAMUEL J. ASIRVATHAM: OK so you connect this up like this, and then you'll have this maybe touching something metal in the patient, and then this is what we're using to biopsy. So what will, maybe we'll ask Abhishek who put this together for us, what would you look at, Abhishek, to kind of say, I'm going to do a biopsy here.

ABHISHEK J. DESHMUKH: So first of all, when we are mapping we need to identify how the normal myocardial signals look like. And then, as we are mapping along, say on the septum, the clues what I look for is if we start to see any fragmented signal or if we have a His bundle catheter, then I'm seeing that the delay between the near-field and the far field ventricular signal, what you can get from the His bundle is quite further apart, so that will tell me septal delay. Then as you're going down the septum, if you start to see these abnormal signals, then at least I tagged them on the voltage, I tagged them on the mapping system as you have seen on the left, the pink dots, and then, or the green dots, and then if I find a safe location predominantly on the septum, then we biopsy that.

Now mind well that sarcoid, as we talked, likes to hang out more in the septum, so overall specificity and sensitivity of getting the diagnosis is a little bit better with sarcoid, compared to other inflammatory cardiomyopathies, but this is generally the approach I would use. And then really depending on the clinical situation, if we are really compelled to biopsy the left ventricle or RV free wall, at least I would shy away from RV free wall, but certainly we have done even LV biopsies for these patients.

SAMUEL J. ASIRVATHAM: Fantastic, thank you. So if we go to another question that had to deal with, we'll try to get as many of these questions as possible, but about intercardiac electrogram maneuvers, specific in these populations. Maybe I'll use this patient as an example. This is a patient with recurrent VT and a known inflammatory myocardial process. So the diagnosis was already known. The question is, how are you going to deal with the VT? So maybe Guru, maybe I'll ask you to comment, and Chris, feel free to chime in as well. Looking at this, what's your thought process for planning the ablation procedure?

GURU KOWLGI: Yeah so this looking at the ECG, white complex tachycardia, I'm looking at V1 first and very wide notched fragmented QRS, and then sort of transitions in V3. There's very slurred onset, tells me it's taking time to engage the conduction system, and then sort of left bundle early transition inferior access and rightward axis. So I would think of something on the septum. Yeah, it's tall. Inferiorly, it's a positive but not very tall suggesting high in the outflow tract, so maybe basal septum.

SAMUEL J. ASIRVATHAM: So very nice. So few things, very important things that Guru has pointed to us. One is we're used to saying that when we have a delayed up stroke in the VT, we're used to thinking that's epicardial, and that could be true, but what Guru said is probably more accurate. It's not so much epicardial, but you have trouble engaging the conduction system. Epicardium is away from the conduction system so we see this in epicardial VTs, but if we're in a region where we don't have conduction tissue, like near the annulus where we have a paucity of Purkinje tissue, mitral annulus lateral, tricuspid annulus lateral, or the conduction tissue itself is severely diseased, and this is exactly the subset of inflammatory myocarditis. We have VT and we have really bad conduction systems. So we expect to see VTs which have this epicardial look because conduction system is bad. So even if you engage it, you're not going to get much from it.

You also pointed out that you have multiple late fragmentation. And this is a clue to us that we're going to see more than one VT, because late in the VT, somewhere away from the exit, we have slow conduction and we have scar. So this is not going to be the pathology section, like what Dr. Bois showed us of a discrete scar, like the patient with the infarct. It's going to be more like this patchy substrate that we have.

Now the intercardiac signals can be pretty unique as well. It may be, and I ask you, Guru, as well, maybe talk us through what you see in this. So for orientation, we have the ECG, got a his bundle recording site catheter, we've got an ablation catheter somewhere, in this case in the right ventricle, and then we have the coronary sinus seated nicely in this CS atrial pace.

GURU KOWLGI: Yeah so we can see two pacing spikes, the first pacing spike is followed by atrial signal from the coronary sinus, so I think that is an atrial spike. You see P waves that are on the surface. And then a second pacing spike with the positive QRS in B1, so could be left ventricular pacing. And then another intercardiacs, on our his catheter we see two sets of signals. I think that first one is too late to be an atrial signal, probably both our ventricular signals, and could be suggesting delay across the septum. And then we actually see a change in our QRS vector from the third and the fourth beat, so with that there's more delay, especially noted in the proximal his.

SAMUEL J. ASIRVATHAM: So if I ask you Guru, if I understand right, what are you interpreting this signal to be? Because this becomes the key when we're mapping, either during VT or during substrate is dynamicity of the signals. We'll have to figure out which signal are we going to use, whether that's entrainment, whether that substrate, whether that's activation mapping. So what do you think this signal is?

GURU KOWLGI: I still feel it is also a ventricular signal. It could be on the other side of the septum.

SAMUEL J. ASIRVATHAM: So it's not at all tagging with the A. So we would have to say this is ventricular. But if this is ventricular, why aren't we seeing it in this beat here?

GURU KOWLGI: I feel there are two components in that beat as well, they just closer together.

SAMUEL J. ASIRVATHAM: Outstanding. Outstanding. So these are exactly what we need to keep our eyes open for. Just spontaneously, even with that late, we can have this amount of change as a result of conduction. So instead of being together here, they're going to come apart here.

And notice the QRS changes, as you pointed out as well. So this hump here is hiding inside the QRS, just like the signal is hiding in the ventricular electrogram. So these are signs of it's not just slow conduction, but dynamicity. And what do we mean by that? Maybe I'll use the board here to kind of come back to explain that.

But we have, when we see two signals like this separate, that could be a fixed block. So we have a catheter that's somewhere around here, and that's picking up a wavefront that comes towards this, needs to skirt around and come to this location. So it's a fixed block.

On the other hand, if sometimes it looks like that, other times it's together, it's not a fixed block. It's so close to being a block, means it's very slow, easily decremental conduction. So could go through or could block.

So just from these type of signals, we know we're dealing with substrate for VT. It's slow conduction, so close, so slow it can block, and it can do it with very little change in rate. Meaning, we don't even need a close couple PVC to potentially cause this change in wavefront and could get us started with a VT type process.

So this becomes also important when we're doing entrainment, so I think one of the questions dealt with entrainment issues. When you have, are you all able to see the screen here?

So this is an example also of how you can have these changes happen in real time, change with ablation. So here you have, eyeballing this, you've got pacing during the VT. Stop pacing, VT resumes. Pacing speeded everything up, and has a morphology very similar to the VT that we have as well.

But few things become issues when you have this type of substrate, like we see this interspersing of normal and abnormal tissue so close together that you see this type of phenomenon. If you have these late signals here, your QRS is going to look different for when you have those late signals to when you don't. So even though you may have concealed fusion during the tracing, the QRS could look different because these bystander's sites may have decremental tissue. So you really in the circuit, but downstream you may block to chunks of myocardium or not. So the QRS could keep looking different, even though it really is one circuit and you really are in that circuit.

So how to get around it is you'll have to fix your reference on parts of the QRS that doesn't change, or an electrode placed at a site that doesn't change and use that for your interpretation of entrainment. So I hope that kind of answers the question from our colleague who brought that up.

Now let's just look through some of the other questions here and maybe we can do one more and then we'll do the rest while we-- So there's one question here that says about sarcoid related idioventricular rhythms. So this is a very nice question and this is a very practical question. Patients with, this is true also with the checkpoint inhibitor therapy patients, it's also true with COVID recovered patients and for sarcoid. You treat and you get this slow VT, and you don't know whether you slow the VT, whether it's a drug you're using, but you also know because it's a conduction system inflammation. You can get this inflammatory related idioventricular arrhythmias. Maybe Chris, I can ask you to kind of get us started on that, and then we can maybe answer this and the other questions when we do a recorded session at the end of this session.

CHRISTOPHER V. DESIMONE: Sure. I think it's tough because it can be, I think, any of the things you mentioned. So it can be kind of this cool down or warm up phase of that inflammatory process. It could be your drugs, it could be your treatment. So I'm not sure, I would kind of watch and monitor to see. I wouldn't make any rush to judgment of interventions yet.

SAMUEL J. ASIRVATHAM: Yeah, I definitely agree. So just to say like here's the quandary, so normally we would say that if we have an idioventricular rhythm, well don't worry about it. It's slow, we can overdrive pace it, we can leave it alone, but in this subset of patients that part of their inflammation is the conduction system, an ideal ventricular rhythms come from these bundle branches so I think the doctor probably has had a quest patient like this, and we've certainly had patients like this, where it's tough because on the one hand, we have to think this is a manifestation of ongoing inflammation. So we have to look for other correlates, other things with inflammation, and see does this mean we have to give better immunosuppressive therapy? And that's often the clue and the treatment that helps in these patients.