All right, so my name is Jeremy Moore. I'm the director of the ACHD electrophysiology program at the UCLA Medical Center. I'm going to be talking about ventricular tachycardia, substrate mapping, and ablation for those core concepts in EP for Tetralogy of Fallot. Here are my disclosures. I'm going to start with a little bit of background, and then we'll get into contemporary practice after that for how to map and ablate ventricular tachycardia for Tetralogy of Fallot. Some of the earliest studies for VT and Tetralogy go all the way back to when the primary modality was epicardial mapping in the operating room. It was recognized very early that the mechanism of tachycardia was reentrant and that postoperative sequelae were generally the culprit mechanism for these reentrant VTs. This is an early study by Horowitz in 1980 showing with SOC electrodes, closely spaced electrode samples, one could map out a reentrant circuit on the RV free wall, particularly the RV outflow tract where ventriculotomy had been created in a counterclockwise direction. This early description of RV outflow tract VTs was one of the early mechanistic descriptions. It wasn't very long after that that studies of intracardiac catheter-based studies showed, again, reentrant VT, but now related to the RV inflow septum. You can see in this study from 1983, we have the development of fractionated electrograms on the hispundal catheter with the onset of VT with diastolic activity. This second major category of inflow, septal VT, was described also very early on in the 1980s. This became the two dominant mechanisms of ventricular tachycardia for Tetralogy of Fallot. Not long after, in 1986, there was a first description of a successful catheter ablation approach. This was direct current shock ablation. This was performed in the RV outflow tract between the ventriculotomy and the pulmonary annulus in a case report out of Japan that actually worked long-term, kept the patient out of VT long-term. Very early, again, descriptions of successful catheter ablation for Tetralogy. This was supplanted by more descriptive and much larger studies out of the group from Toronto in the early 1990s, again, with a surgical mapping approach. This is a description of endocardial SOC electrodes and epicardial SOC electrodes as well, showing the mechanisms of VT in a large number of patients. Again, an understanding of the reentrant mechanism, both in the RV outflow tract and the septal inflow area, were key to these early descriptions. Some of the early investigators also looked at how to localize the culprit isthmuses related to VT, and pace mapping was one of the early ways that operators could determine where the VTs were localized in these patients. In this study here, you can see a nice left bundle branch VT, and then pace mapping at the suspected exit site of the circuit, and then catheter ablation performed successfully in that area. I'll talk a little bit more in the contemporary practice, how we can use these same kinds of techniques in the modern era. Some of the pathophysiologic understanding of what caused VT came out of the surgical literature. This is a nice study where a patient with an RV outflow tract aneurysm and a reentrant VT around a ventriculotomy. The histopathology showed surviving myocardial bundles in areas of scarring and fibrosis, and these areas of surviving myocyte bundles correlated very nicely with diffractionated electrograms and diastolic activity that was seen during this VT. Describing the correlation between histology and clinical VT and tetralogy is related to these kinds of pathological findings. Some of the further work showed that linear ablation, not just a single point lesion or a couple of point lesions, but a linear ablation between an area of scar and a nearby anatomical isthmus was really a good way to definitively eliminate reentrant VTs for tetralogy of Fallot, and so this concept of a line of block was pretty instrumental very early on in the literature. A nice series came out in 1996 with nine patients with tetralogy of Fallot, so pretty big for that era, where the operators were able to localize the VTs. Seven of them were from this RV outflow tract area and two from the septal inflow area, and using a variety of techniques that include pace mapping, entrainment techniques, and activation mapping were able to successfully ablate these VTs in tetralogy. Again, this is only 1996, so again, very early, this was described as a successful approach for tetralogy. A third isthmus was described in 1997 at the basal RV free wall between a transannular patch and the tricuspid annulus, and I'll talk about the various isthmuses that we described today, but this was sort of the third type, and this group also suggested that one demonstrate bidirectional block after ablation, after linear ablation between two non-conducting barriers. So a lot of the things that we do today really are borrowed from years of experience very early on in our descriptions. And then finally, now in 1998, we have the early reports of three-dimensional mapping and local activation time mapping to define the entire circuit of a VT wavefront. This was Bill Stevenson's report from 1998 and showed very nicely how you can have reentrant VT in tetralogy of Fallot. This one last one I'll show you real quick. This is a basket electrode catheter in the RV outflow tract from 2006. This is actually – we have some of the mapping systems today used by basket catheters, and the operators put this in the RV outflow tract. They found essentially they could map the entire circuit, entire activation sequence of the entire circuit with this basket electrode catheter. And with the ablation catheter placed between the pulmonary annulus and the VSD patch, you can see in this lateral view here, they had diastolic activity. This is that septal inflow VT that is commonly seen in tetralogy of Fallot, and this is the critical isthmus for this type. So a very early report, but again, very much what we see today. I think the modern era of substrate-based mapping really was introduced with Katja Zeppenthal's description of nine patients with tetralogy of Fallot in 2007. And based on the surgical approach, which is well conserved for patients with classic tetralogy of Fallot, there's a very well-conserved series of surgical interventions, and this results in a limited number of anatomical isthmuses that can cause ventricular tachycardia. And she defined these – number one, and this is that basal inflow area that I'd spoken about just briefly a minute ago, but between the transannular patch and the tricuspid annulus was defined as isthmus number one. Between a ventriculotomy and the pulmonary annulus is isthmus number two. Between the pulmonary annulus and the VSD patch was labeled isthmus number three. And between the VSD patch and tricuspid annulus, isthmus number four. This is essentially all of the potential isthmuses that one could find in tetralogy of Fallot related to the surgical approach to this lesion. Importantly, isthmus number one is really not commonly implicated in the modern era because the patch tends to be very remote from the tricuspid annulus, and this isthmus is generally not targeted for catheter ablation. It's not very narrow. It's usually not pathologic in terms of its myocardial characteristics. Likewise, isthmus two is less commonly seen these days because ventriculotomies were essentially abandoned in the 80s. And isthmus number four between the VSD patch and the tricuspid annulus is technically not even present in the vast majority of tetralogy patients who have perimembranous VSDs. In fact, for tetralogy of Fallot, this isthmus is only present in around 10% of patients. And after the surgeon places a patch here, that may disrupt any remaining myocardial bundles in this area. Really, in the modern era, what we're dealing with is almost not exclusively, but by and large, very commonly, isthmus number three between the pulmonary annulus and the VSD patch, so-called septal infundibular isthmus, is by far the most commonly targeted isthmus in the modern era. And it's important to understand the relationship between that isthmus and the surrounding structure. So that isthmus you can actually get to from the RV endocardium to, again, the pulmonary annulus and the VSD patch. The aortic root sits right across from this area, and one can relatively easily go retrograde into the aortic root, place the catheter against the same isthmus in the right coronary cusp, and provide counterlesions for the same isthmus. So it's good to understand this important relationship because it can be useful for ablation. So this is actually a postmortem specimen showing this isthmus between the pulmonary annulus and VSD patch. One can get the catheter here from the RV endocardial side, but also retrograde into the aortic root, obviously being cautious with the aortic valve and the coronary. But one can place lesions here to get a transmural effect across this isthmus. Catheter ablation for Tetralogy of Fallot, unlike other forms of congenital heart disease, and in fact other structural heart disease-related VTs, can be curative. If one is able to show that the VT is related to one of these anatomical isthmuses and completely interrupt all conduction permanently through that isthmus, then this can be a curative approach. And it's beyond the scope of this lecture, but in select cases, VT ablation can be performed in lieu of defibrillator placement in, again, select patients with careful expertise. The other basic and sort of important issue related to substrate mapping for Tetralogy of Fallot is the physiologic characteristics of the anatomical isthmuses. We look at length, we look at width, those do predict whether an isthmus is likely to support re-entrant VT, but it turns out that conduction velocity is the most important characteristic, and a conduction velocity below two standard deviations below the mean, which is half a meter per second, turns out to be a very good discriminator of inducible versus non-inducible VT. So one of the things we'll do when we look at these anatomical isthmuses, when we're doing our 3D mapping and our substrate-based approach, is to determine the conduction velocity through the isthmus. Importantly, when one does this, you need to be very careful, because you want to only look at the diseased area in question. So as per the original description and using our 3D mapping systems, we want to look for normal electrograms immediately adjacent to abnormal fractionated electrograms when we're making these measurements. So we go from normal electrogram to normal electrogram through an abnormal area, and we measure that distance linearly and divide it by the conduction time. As shown here, one can then make a measurement of the conduction velocity through the respective anatomical isthmus. This, again, is the septal and fundibular isthmus between the pulmonary annulus and VSD patch. If your mapping system has a way of automatically annotating fractionated signals, as shown here, this area has been highlighted. One can simply measure from either side of this fractionated area to measure the conduction velocity. So this can be expedited by some of the modern mapping systems. Now, importantly, when you're making this measurement, I think you need to be aware of the pattern of activation of the RV. In most patients with Tetralogy of Flow, we have complete right bundle branch block. In some patients, there's either incomplete or otherwise normal-appearing QRS complexes. When that happens, the RV free wall is going to be activated relatively rapidly. So as shown here, you can see the right bundle branch is activating the RV free wall, and so you have nearly simultaneous activation of the septum and free wall and collision of the wavefront in this septal and fundibular isthmus. And when that happens, it's really not possible to measure the conduction velocity accurately. And so what we and others do typically in this situation is we're going to pace from one side while we make the conduction velocity measurement. And I think what I like to do is put a catheter out in the coronary sinus, get it out towards the AIV. It's very stable here, and you can pace near the septum. And then in this is actually the same patient I just showed a moment ago, where we now can see very clearly there's a conduction isthmus here, anatomical isthmus with slow conduction velocity. So this would be a useful technique when patients have incomplete or narrow QRS complex. Another thing to be gleaned when you're mapping these patients is the VT morphology. In general, we see the right bundle or left bundle morphologies, and this can point you very quickly to the likely origin of the tachycardia. Right bundle branch VT essentially occurs when there's an exit site near the septal portion of the right ventricle. If this is endocardial, typically you'll see right bundle branch pattern with precordial concordance and usually an inferior axis. If the exit site's more epicardial, closer to the summit or the epicardium near the aortic root, you may see a right bundle pattern with pattern break in V2. It's very common for these sites of origin, but oftentimes, again, an inferior axis. But right bundle branch VTs are generally speaking exiting from the RV septum. Left bundle branch VTs, on the other hand, are almost always exiting into the right ventricular free wall, and despite being the opposite complex, still use the septal infundibular isthmus in both of these cases, both right bundle and left bundle morphology VTs. It's important to understand, and this has been well-described, if the transannular patch is very small, you'll typically have an earlier transition in the pericordium, so left bundle early transition. And if the patch is very long onto the RV free wall, the wavefront has to take a longer course down towards the apex before turning around. Typically, you'll see a much later pericordial transition, V5 or later. Finally, if you have a ventriculotomy circuit, you generally will have left bundle branch VT. However, the pericordial transition will be dependent on the direction of the wavefront and also this will depend on whether you have a second dual loop re-entry through the septal infundibular isthmus. And so, a little less predictive when you have ventriculotomy circuits for the QRS morphology depending on if there's a co-existent circuit at the same time. In some patients, we'll have both VTs through the septal infundibular isthmus, so this one's going clockwise, but you can see counterclockwise in both right bundle and left bundle VTs in the same patient depending on which way the circuit is going. Getting to the sinus rhythm EKG, the QRS duration can give you a lot of information in advance of the procedure. It's been well described that, again, that septal infundibular isthmus, depending on how it conducts, can activate the RV free wall in different ways. If it conducts normally, the RV free wall will generally be more rapidly activated than if there is slow conduction or block through the septal infundibular isthmus. When there's slow conduction or block, the RV free wall is activated unidirectionally and it takes longer to activate the RV free wall. So in patients who have right bundle branch block at baseline, more than 120 milliseconds, if the QRS is longer than 150, that turns out to be the best cutoff, there's usually a pathologic abnormality in that septal infundibular isthmus. If the QRS duration is 120 to 150, usually it implies that the septal infundibular isthmus is normally conducting and that turns out to be predictive of inducible VT. So for patients who have slowly conducting anatomical septal infundibular isthmus, QRS duration over 150 is usually present and it's associated with inducible VT, whereas the same is not necessarily true for patients with QRS duration less than 150 milliseconds. So this is a kind of a sensitive but nonspecific indicator of inducible VT because it tells you what's going on with that septal infundibular isthmus. A second sort of feature is the QRS morphology and sinus rhythm that can also tell you a bit about that septal infundibular isthmus. I think understanding just how the ventricles are activated in Tetralogy Fallot provides the basis for this. So with complete right bundle branch block, you have essentially activation of the ventricles in series, the left ventricle followed by the right ventricle. If you look at an isochronal map, which we've shown here for biventricular mapping, the QRS complex in V1 is initially just left ventricular activation, again with right bundle branch block. This middle component is both right and left ventricular activation. And then the most of the R' wave is really created by our right ventricular activation. And getting a little more specific here, this nadir in the QRS complex tends to be related to the RV septum being activated. This transition point where the wavefront is kind of slowing down and changing direction correlates typically with the beginning of RV free wall activation. And then the peak here is the most anterior part of the right ventricle being activated by the wavefront. That's where V1 sits, just anterior to that right ventricle. And so this can tell us what's happening with the septal inflandibularism. So when there's good septal inflandibular conduction, the RV free wall is activated very rapidly. You have two wavefronts activating it rapidly, and it's also being activated in an inferior and superior direction by these two wavefronts. So if you look at the EKG in this scenario, you have a nice, healthy-looking R' wave without any fragmentation. And AVF, the inferior lead, is relatively isoelectric because you have cancellation of the forces here, both superior and inferior. If you have produced block, this is the same patient now after catheter ablation. If you produce block in this isthmus, the RV free wall is activated very differently. It's a unidirectional wavefront. Your RV free wall is being activated more slowly, and you have just pure superiorly directed activation of the basal RV free wall. And this creates a blunting and a fragmentation in V1 as well as a late terminal S wave from the superior activation in AVF and the inferior leads. So these two findings can be very helpful for understanding if you have either block or very, very slow conduction through this anatomical septal inflandibular isthmus. This finding can appear during catheter ablation. So this is with successive lesions in the septal inflandibular isthmus, and you can see the development of these large terminal S waves in the inferior leads, which is a clue that you've produced block in that isthmus. Sometimes you see this abruptly during a single lesion. So this is 10 seconds into a lesion. We have development of split potentials here, blunting of the R prime wave, and deepening and widening of this terminal S wave. And so these are clues that you've produced block in this septal inflandibular isthmus, and this can be used actually longitudinally during follow-up to understand whether the patient still has the same kind of conduction through that area. Another useful tool for VT ablation and tetralogy is the CT scan. And for patients in particular, those that are going for transcatheter pulmonary valve, CT scans, high-resolution CT scans are performed as a matter of routine for deciding whether the patient's a good candidate for the transcatheter valve. And so you can utilize these studies best to understand the areas you may need to ablate. First of all, calcification in the area of the VSD patch and the transannular patch are very common. One or more of those are seen in about 75% of patients. And then you can make, with 3D multi-planar reconstruction, you can actually make very detailed measurements of the wall thickness in the critical isthmuses that you anticipate having to ablate. And so we found that this is very, very useful for understanding what to expect during the upcoming procedure. So if you focus on panel B here, you can see the wall thickness overall. These are the various isthmuses that have been described. Isthmus number three, again, the septal infundibulitis, this is most common. On the median is 4.2 millimeters here, but you can see that some patients do have much thicker septae, much thicker tissue in this area, and these can be very challenging to ablate. So good to know this ahead of time. Wall thickness also does have a correlation with the type of conduction. So the thicker wall thickness correlates with normal conduction, whereas thinner myocardium correlates better with block or slow conduction. And then finally, the CT scan can also tell you about the coronary arteries. Some patients, about 5% of patients will have major anomalies of the coronary arteries, which can be useful, especially if we're going to go retrograde into the aortic root, like I mentioned earlier. But also rightward, clockwise rotation of the right coronary is pretty common in Tetralogy, and that can place the right coronary potentially in jeopardy as you're targeting the septal infundibular isthmus. So here's an example of a CT integration during this case, and you can see that we're planning out this thick septum here with an anomalous coronary, and you can see we're planning out how we're going to do our ablation based on these anatomical features. This is just a figure showing how the proximity of the endocardial lesions with this clockwise rotated right coronary artery, again, you can have this proximity effect in some of these cases. So it's important to know this ahead of time. Whenever you're doing these cases, I think it's good, especially if you're ablating within the aortic root, to understand the coronary anatomy. The CT scan can be a nice adjunct to that, but you should also be thinking about using ice or potentially selective coronary angiography to know exactly where the coronaries are whenever you're ablating within the aortic root. As far as the workflow for this mapping and ablation, just take you through a quick case. This is a patient came in with left bundle branch VT, you can see here there's a late transition beyond V6 and left superior axis. This would be consistent with a counterclockwise loop through that septal infundibular isthmus, and sure enough, when you map the patient's substrate here, there is a slowly conducting isthmus in this region. If possible, we like to use entrainment of the VT to show a good post-pacing interval that's equal to the tachycardia cycle length with concealed fusion as shown here, and ideally we want to see that there's a stem to QRS that's equal to the electrogram QRS, suggesting that you're not in a bystander site but in the critical isthmus itself. If the patient's unstable with their VT, we do typically use pace mapping as a secondary option to show where the VT exit site is in this case, and if you have a 10 out of 12 you can feel pretty comfortable, especially if you have slowly conducting anatomical isthmus, you can feel pretty comfortable about blading that isthmus if it's related to the VT. And then just another example there. Finally, as you finish your ablation, I think it's, again, you need to show that the isthmus is completely eliminated. Not only the patient should be non-adducible, but the isthmus needs to be completely eliminated. So this is an example of a case where we've been pacing septally, we can see conduction going through the septal and fundibular isthmus. After ablation, we remap the same side of activation here and show that there is bidirectional block. This is showing a block in the septal to lateral or posterior to anterior direction. We'll commonly use differential pacing for the other side to show that the opposite is true, that the other is blocked in the opposite direction. But showing bidirectional block is really key for these patients and should be done for every case. Finally, I'll talk briefly about pulmonary valves. With the advent of transcatheter valves, pulmonary valves, and surgical valves, it's been described that we can have isthmuses that are covered by the valve and make it either difficult or impossible to perform catheter ablation at the VT isthmus sites. Just some experience from our center where we've had cases that have been ablated, and six months later, we've mapped and found that the isthmus is completely covered by the new transcatheter valve. This top one is a harmony valve here. This bottom here, we had performed an ablation in a sort of a ventriculotomy-type isthmus here, and six months later, it's covered by the Altera device that's been placed in this area. So this is a real phenomenon. I think it can make these patients quite challenging. One of our original cases where we had a patient present with monomorphic VT, it was nearly impossible to ablate to this covering of the harmony valve here. So in order to sort of circumvent this issue, there is some real rationale to performing preemptive EP studies before these transcatheter surgical valves go in. I think we focus oftentimes on the right ventricle itself and the effect of the pulmonary regurgitation on the RV size and function, and the valves are put in with good reason, but I think at the same time, there is this abnormal degenerative remodeling involving the myocardium that we're not as able to easily identify, and it's important to understand that that's happening concurrently. And so in order to avoid the situation where we have VT that's not targetable, it's good to be able to target these in advance. So in conclusion, I think I just wanted to point out the two main reentrant subtypes that were originally described in the 1980s as the RV outflow tract and the septal types, and we really still see that those are the most common today. First successful VT ablation was in 1993, and we've gotten much better at this ever since. And using substrate-based mapping, isthmus number 3, is ultimately the most common target. Mapping ablation should really focus on the substrate with our scar maps, conduction velocities, and VT morphology, the confirmatory maneuvers, and ancillary studies such as CT scans and the surface ECG. So thank you for your attention.

Ventricular tachycardia

Tetralogy of Fallot

Substrate mapping

Ablation

RV outflow tract

Catheter ablation