So, the last one is Evaluating Risk Beyond Tetralogy of Fallot by Frank Fish from Vanderbilt. So, Frank, thank you very much. Frank Fish Thank you. Thanks to the meeting organizers for the opportunity to be here. I say that sort of whimsically because as I struggled to think about this talk, I realized that I could probably put up a blank slide because in some ways we know a lot about tetralogy, but don't know about some of the other things as well as we'd like. There we go. They said I had no, one of my partners is our compliance officer. He says I have to list all this stuff. So, what I'm going to talk about is the stuff that keeps us up late at night, and I've got a lot of stuff. I figured that since there's not a lot of great data, the best way to deal with that is just to have a lot of slides. So, I'll try to go through this quickly, but, you know, we all have these stories that haunt us. A 15-year-old athletic male, just a simple VSD repair during infancy. Everything looked good. Did have right bundle branch block. Partner came to me. He had frequent PBC, moderately frequent PBCs. Looked like they're coming from more of a benign outflow tract area. He put him on a treadmill. They suppressed his exercise, but he noticed during recovery he had a single three-beat run. He ordered an MRI, really had little, if any, scar, but after much coaxing, I agreed to take him to the EP lab. We did a standard study. We didn't use isopryl, but did a standard study, and he was non-inducible with three extra stimuli, three cycling links, two sites. Two years later, of course, he had a cardiac arrest while playing basketball and was left with some neurologic injuries, and so I think part of this talk is, you know, what could we have done better or, you know, how would we better understand to identify this guy might have been at risk for this event. So I think everybody here understands the problem, but looking at the adult congenital populations, sudden death accounts for only about 20% of the late deaths in adult congenital patients, and among those that have sudden death, about 80% or so is estimated to be arrhythmic. Several studies, which I think I've deleted a slide because I have too many already, band then heart failure and other cardiovascular causes account for a large proportion of the remainder. One of the few cohort studies that are out there, published just recently from the Australian group, looked at death records and found 1.2% of their total adult congenital cohort experienced sudden death over a period of about 15 years. This translated to an incidence of 0.4 deaths per 100 patient years for all comers. If they excluded patients with mild to moderate aortic valve disease, it actually increased to 0.7 per 100 patient years, but I think as we start to think about our ability to identify risk factors, considering the diversity of patients we have, the numbers that it will take to tease this out to our satisfaction are huge, and the challenges, of course, are that we have a high diversity of lesions, a diversity of surgeries even for common lesions, compound that, the effects of age, which clearly are important for the arrhythmias these patients develop. And so even with large populations, the largest cohort that's been followed and has been the subject of several, I think, important publications, almost 30,000 patients in that cohort, and even then, the ability to identify risk factors in all the different anatomies is tenuous. And I think another challenge that we have in this group is I think we share some of the blame, because I think we tend to think, like electrophysiologists, we like to focus on the EKG, the monitoring, the EP study, the stuff that we do, and we'll leave, with rare exceptions to the previous talker, we leave that other stuff to those other guys, the imaging, management of the heart failure, the genetics, Prince, I think, stepped out, so I can say that. And then we also, I think, tend to sort of capitulate on looking at the non-medical morbidities, which may play a factor. We know that lesion complexity is an issue. This just is looking at on the, on this side is the freedom from sub-cardiac death in one large cohort for simple versus moderate versus complex lesions, and then similarly, this is maybe not quite as clear-cut, is likelihood of ICD discharges with simple, moderate, or complex lesions. But lesion complexity plays a factor, and it's very difficult sometimes to know how best to factor that in, and we also know that the more complex the lesion, sometimes the more challenging the intervention, once we start to think about primary prevention of what that may entail. We worry a lot about exercise. The Australian group looked at the circumstances of death, at the time of death, and what they found was that exercise was really, played a small role in the occurrence of sudden death in their cohort. Morbidities are also important, and this just looks at the pace, again, this is from the Australian study, looked at the, I'm having trouble with this mouse, figuring out, because it's here, just the prevalence of various comorbidities and how they might impact the risk of sudden death was looked at, and I think we have to take these things into account when we're thinking about what to do about our patients. This was the large study that's, most of these investigators are from the Netherlands, I think they had three different databases that they combined and came up with this data, and we have our little list of things we all feel like we know must be issues, but these, when they did a multivariate analysis of a very large population combining an array of lesions, these are what fell out. Supraventricular arrhythmias, QRS duration, and the incremental risk was small, but that was per 10 millisecond increments, QT dispersion, which I think is tedious and a very difficult thing to measure, but there was also a contribution there to risk, and then, you know, obvious candidates of dysfunction, both the sub-pulmonary and systemic ventricles. So there were other clues that they found that were embedded in their data, they pointed out, this must be thinking out of the box, so if it's in red, it's sort of like, well, that's kind of out of the box, there really isn't a very good box for this, though, this topic, but sudden death patients were more likely than their, each of these patients, by the way, had two controls for each of the sudden death patients, and the sudden death patients were more likely to have heart failure symptoms, but not really arrhythmia symptoms in this particular cohort, but they were more likely to be on antiarrhythmic meds and heart failure meds than their controls. They also published a paper, a follow-up paper, one of a couple, looked at changes, it may not be the absolute values, but it may be the change, or the rate of change, in some instances, that may identify a patient who is becoming a patient that you need to think about intervening prophylactically, primary prevention. And so they looked at the change in systemic ventricular function from any degree of dysfunction to severe, had a very high odds ratio, increase in curious duration, had a rate of more than five milliseconds of incremental prolongation per year, had a modest p-value, and then QT dispersion, which, because of the nature of it, it was difficult to sort of even tease out how they did it, but what they looked at was that if the QT dispersion was increasing over time, it also was highly significant in terms of patients being at risk. So I think we all understand that, you know, it's nice to look at the tetralogy data and apply that to certain lesions, which are tet-like, I would say, like, you know, repair truncus or pulmonary atresia, VSD, where you have, you know, a ventriculotomy, something done to the outflow tract, a VSD repair. I sometimes, I just recently had a patient say, I didn't have tetralogy, and I have to explain, I know, but surgically, you kind of do. But lesion-dependent risk stratification beyond tetralogy, what we're talking about, is really important, and, you know, it's apples and oranges many times. We know that in the tetralogy group, non-sustained VT does correlate with both inducible and clinical VT, but when looked at in a more heterogeneous population, it's not predictive overall of risk of sudden cardiac death outside of that group. And I think, likewise, the role of VT study, particularly as a risk stratifier, varies tremendously. I think it's got tremendous utility in the tets, but patients and patients with prior VT, particularly if you contemplate thinking about ablating, it's obviously important. But Paul Carey showed nicely that inducible VT did not correlate at all with sudden cardiac death risk in the transposition patients. Just highlighting that it's lesion-specific. This is from the Australian group, and it just, you know, we go from ASD patients who have a very low risk of sudden death over time to the eisenmakers, which have a very high risk. Sorry about that. It's time to move on to eisenmakers at the bottom. And this is just displaying the data from another group that sort of highlights it again. And this is looking at all-cause mortality in an adult congenital cohort, and the red is a sudden death. And so we have big, broad bars. I think MARFans realize that these sudden deaths are likely not arrhythmic, but the point is, is that how large a role sudden death plays in the overall mortality of patients varies tremendously from lesion. So we'll try to talk a little bit about what can we say or what can we try to say. I think most of the, most people would accept that sudden death risk in a systemic RV is associated with ventricular dysfunction and AV valve insufficiency. There's some data that prolonged cure restoration probably carries some risk. Atrial arrhythmias, I think, in the atrial switch patients in particular, probably play a tremendous role. We've seen at least three patients in our practice recently who came, had a VF arrest, and then after an ICD was implanted elsewhere, they then had inappropriate, if you will, shocks for a rapidly conducted atrial flutter. And that was well described by the Boston Group in a tragic case many, many years ago with antidepressant pacing as well. Functional RV ischemia, I think, is emerging as a factor that may be even more important than we sometimes recognize. But clearly, induction of VT at electrophysiology study for this lesion hasn't been proven predictive, at least in the group from Cary, and this is their data. And they looked at a cohort of patients who had ICDs. Some were primary prevention, some were secondary prevention. None of the eight patients who had inducible VT who received a primary prevention device experienced an appropriate shock. And they saw high rates of inappropriate shock for ATAC, to highlight what we talked about a moment ago. But this is their beta blocker patients had a high degree of protection appeared from VT, VF, as compared to those who didn't receive a beta blocker. And that could well be related to the ischemia. So Paul's group also reported on a couple of patients who underwent bio autopsy after a sudden cardiac death and found to have massive myocardial infarction and evidence of chronic severe endocardial ischemia. Sudden death in arterial switch population, fortunately, seems to be fairly low. And most of the coronary deaths occur fairly early post-op. But realize that you may have a patient, as we recently ablated, who had an infarction at probably three weeks of age, based on the outside data we had. And now has had multiple episodes of VT and recently underwent VT ablation. And so what happened as an infant, in her case, put her at risk for later problems. CCTGA, the point I want to make here, there's a role for mild or moderate systemic tricuspid valve insufficiency, although the data's fairly sparse in number. The experience that we've had that I wanted to mention here, since we're thinking out of the box, two patients that we had excellent response to cardiac resynchronization. These were two of our earlier patients. And clinically did great. Both had VFRS that were documented on their pacemakers at rest. And so we've, since then, taken to CRT-ICD only in this population, not CRT pacemakers. How much more time do I have? Am I out now? Yeah. Okay. Let me see if there's anything else I really want to say. Fontans, sudden death is really not that big a risk. I mean, this is the large cohort from the Mayo Group. And you can see freedom from sudden death was really pretty good. And I think the sudden death risk in the Fontans, we worry a lot about it. You see the patients with the non-sustained BT, but the sudden death risk is dwarfed by the other problems that develop with liver and heart failure, et cetera. I don't know what they think in Mayo Clinic these days. So risk stratification and single ventricle, I think, given the overall low recurrence of sudden death, I'd be fairly cautious in recommending any primary prevention strategy in this population in an asymptomatic patient. And certainly not a proven role for EP study that I'm aware of in the patient that comes in with a run of non-sustained BT on their pacemaker interrogation. Probably the last thing I'll say, Eisenmengers, it's interesting, the European Society of Cardiology recommendations of Eisenmengers is not an exclusion in the 2014 HRS adult CHD. It's a class 3 indication. But I certainly have a couple of patients that I follow that have Eisenmengers that are really pretty well compensated. Their stats are in the 80s. They get around. They do pretty well. And I think that particularly in this era of the SICD, if we should rethink whether that's an appropriate exclusion for these patients that may have a number of functional years. MRI, the only thing I wanted to say is preliminary data from one group didn't correlate very well to risk stratification. But I think there are other strategies that are underway to try to look at this in other detail. And there are other MRI modalities. We heard about one. We had a case recently of a patient that had VT syncope resolved, but he was wearing a monitor at the time. So we went and took him to the EP lab, put an ICD in, had just a few slow voltage everywhere. Very difficult time finding a place to put a lead. And he underwent a fiddle map protocol with his MRI, which I'd never heard of before, even though I'm from Nashville. And it was a way to see very, very thin areas of fibrosis. And he had this throughout his right ventricle. And he's a critical PS patient. And so you can imagine this was probably even prenatally acquired. So genetics may have a role. We'll need huge populations, huge databases to tease that out because of all the complexity. And so I'll just leave with this last statement. If risk stratification that we derive from the TET population doesn't translate to the patient with D-transposition, do we really think that the applying dilated cardiomyopathy guidelines to our population is really going to work any better? I would suggest the answer is probably no. So we need more data. We need better data collection to try to solve this problem. And I think it's important that we involve not just a PACES-derived thing. It really needs to be across the board. Because if we drive it ourselves internally, I think there's the risk of having a huge selection bias by the fact that we'll populate our studies with symptomatic patients who had events and not see what else is out there. So I'll stop there. Sorry, everyone. We have time for one quick question. Go ahead. Thank you, Frank. That was great. Sunita Ferns from the University of Florida. So I guess my question was related to what is your threshold for, say, monitoring these patients? So what is your threshold for, say, monitoring these patients better with an implantable loop? Especially, not specifically, you're monitoring these patients better with an implantable loop. Not specifically the high-risk TETs that don't meet criteria for an ICD, but more so across the board with complex adult congenitals. Because we know that, say, EP studies for TETs, absence of proof is not necessarily proof of absence. They've had negative studies. You're worried about them. How often do you implant loop recorders? Well, my practice has been evaluating symptoms. I haven't done it routinely for surveillance. I think when we look at patients that have implanted devices, pacemaker and ICD, but pacemaker patients, I mean, even simple congenital heart block, structural heart, you follow those patients long enough. If I had a loop recorder in me for five years, I would probably find a run of non-sustained VT. I think that it happens. And I think that if we, it's my own opinion, but I think if we do, you know, 24-7 surveillance on every single patient, we're going to find a whole bunch of people that have runs of non-sustained VT that may or may not be meaningful. And I don't know. You asked for my threshold. My threshold is still symptom evaluation. Great. We'd like to thank all the speakers in the sessions, and thanks to Mitch and Susan for putting this together. And thanks to Dr. Crabill and the AEPC.

evaluation of risk

tetralogy of Fallot

adult congenital heart disease

sudden cardiac events

arrhythmias