So the next presentation is from Mary Gliva, Washington University in St. Louis. Good morning, and thank you for the invitation to present a heart failure case. Okay, so my case is all kind of gray in the guidelines, and I'll be interested to see what people's opinions are, and then I'll let you know what happened. So I call this basically my free consult from Dr. Ellen Bogan and Dr. Gillis. Okay, so I also have a 59-year-old male who has heart failure. He's class three, he's non-ischemic, and he has atrial fibrillation. And we were asked to consider both, but at different times, CRT and a PVI for persistent atrial fibrillation. He had a prior heart failure hospitalization about four months ago. He had AF at the time. His heart rate was in the low one teens, but he had a thrombus on transesophageal echo, and he opted to be treated with dabigatran. And he comes back later, repeat TE, thrombus is resolved, and we start dofetilide. And he gets cardioverted, and he goes to sinus rhythm, and he feels a whole lot better. However, he did require norepinephrine for blood pressure support during the brief cardioversion. And after three or four weeks, he comes back into the clinic because he doesn't feel good, and he thinks he's back in AF, and he wants to know what we should do next. So his past medical history over the years of having an ICD and being followed in our heart failure center, he's had variable ejection fractions, and variable mitral regurgitation, and variable atrial fibrillation. His initial ICD, I will show you on a chest X-ray, was notable for high DFTs, so he has extra wires in different places. And he had a prior treatment trial of amiodarone, and thought that it either gave him stomach upset, he couldn't remember if he took it with food, or he got short of breath. But we never had any clear changes in his DLCO to suggest that his shortness of breath was amiotoxicity, and may have just been heart failure. Socially, he last worked in the winter of 2018. He had remote history of drug use, but was clean, and he's a non-smoker. And he's on guideline-directed medical therapy with all the right medicines. He's not on Entresto, but was on everything else, and doing well relatively. And then anticoagulated with Zubigatran, and treated with dofetilide. On physical exam, his blood pressure was 76 over 50, which was a bit concerning, but his pressures run 85 to 90 on his heart failure regimen at home. He had reasonable oxygen saturation, and he was of reasonable size. But he was dyspneic, his JDP was elevated, he didn't have crackles, didn't have an S3, or he didn't have a murmur, but he had an S3, and he had some peripheral edema, but he was mentating. Creatinine was about baseline, he wasn't anemic. And there's his presenting electrocardiogram, which demonstrates atrial fibrillation, and a QRS duration that is modestly prolonged, and a single PVC, which was not frequent for him. So I wanted to admit him to the hospital. The day I saw him in clinic, and he declined. He had to go home, take care of his little one, get some things set up, but he did agree to come in in a couple days. He had a chest X-ray done, and I'm not sure that my pointer shows, oh, it does show up, good. So he had a couple extra leads. This lead right here in the middle of the spine, which is very posterior, was an azigous lead. It's actually retracted a little bit from implant. But as you can imagine, it probably wasn't successful enough when this was put in years ago, and he now also has a tunneled subcutaneous lead for defibrillation. Fortunately, he's not had a lot of ventricular tachycardia requiring ATP or shocks. Here are some selected still images from his echocardiogram. The one on the left is the transthoracic showing kind of a significant turbulent flow across the mitral valve, and on the TE image, you can see that the flow also is a bit eccentric and goes back towards the pulmonary veins. I'll tell you that his effective regurgitant orifice was large, and his regurgitant volume fit into the moderate to severe mitral regurgitation classification. So here's kind of where he was, and you can also notice that he wasn't that tachycardic in atrial fibrillation when the imaging was performed. So I wanna stop now and then address some discussion points. So what are we supposed to do now? Is there a rule for another antiarrhythmic drug trial? If so, what drug? Should we do any other device intervention, and what is his risk? Should he get an AF ablation? Should he have an AV node ablation? Or should he have cardiac contractility modulation? So all of these things were kind of going through my head as we admitted this gentleman to Barnes Hospital, and I wanted to kind of start the discussion about an antiarrhythmic drug. So Dr. Ellen Bogan, what do you think about another drug trial? Well, I think like most patients who have heart failure, if you can get them in sinus rhythm, they clinically tend to do better, and this patient certainly is an AFib with suboptimal rate control, and not a lot of blood pressure to push down in terms of increasing beta blockers. So I think there would be a role. The problem is I think it would be a waste of time to treat him with any other drug other than amiodarone. He's failed dofetilide. You're a class three agent. There really, we have very few drug choices these days for patients who have AFib and heart failure, and they're really the class three drugs, primarily in the class three drugs. You didn't do well with dofetilide, and so I'll both work on the IKR channel, and your only other option that I see is amiodarone, which is a multi-channel blocker. You name the channel and it blocks it, and I think the question is whether it's worth giving him another trial. Okay, then I was gonna kind of address each of these points in sequence. So the house staff says to me, quote, but amiodarone isn't indicated for atrial fibrillation. It's like, ooh, I forgot that. They were actually right. So, you know, we just looked around in the New England Journal, and there's well-established rule of amiodarone for atrial fibrillation, and then the trial on the bottom is a VA trial of amiodarone versus Sotolol, and amiodarone was better for long-term rhythm management, and I bring this up because we always think about Sotolol, but for him we didn't because of his creatinine clearance, and also because our heart failure doctors aren't fond of Sotolol. The ejection fraction tends to be on the lower side, but I thought another trial of amiodarone was also reasonable, even though he was 59 years old. We talked about it. I didn't want to do it long-term, but I felt that he said sinus rhythm made him feel better, and therefore I felt compelled to try and get him to sinus rhythm upstream if possible. So, my next question. Yes, I mean, I think, just a final sentence, and that is, you know, you did what we do all the time, and that is get him in sinus rhythm and see how much better they function, and you did that, even though it only lasted a couple weeks, and he felt a lot better, and you're right, you know, amiodarone's not a great long-term drug for a 59-year-old patient, but this guy, this patient has a very poor prognosis, so his long-term, long-term for him is not really all that long-term. We'll talk more about what it really looks like. I'm sure we'll get to that. And if I can make an additional comment, you mentioned that when you saw him initially, his average heart rate was 91. It would be interesting to know if, at times, he's well above 100, and remember, amiodarone has some important rate-controlling effects independent of whether you restore sinus rhythm. That, in this case, might be beneficial. Good point, good point. Sometimes I'll put holters on people and look how many hours that they have an average heart rate greater than 100 or 110. I didn't do that for him, but that would have been a good thing to do. So he has an existing ICD system. He's got two ICD leads in his left subclavian, and then he has this other lead that's underneath the skin, and so our heart failure doctor said, well, you could upgrade him, and we could, and this is a figure stolen from the replace paper that looked at complications with ICD upgrade procedures, and overall, the major complication rate was 14%, which is not small, and for him, I think, given the longevity of the leads that he's had in for 10-plus years, the size of the leads, that his likely wasn't going to be a rather quick procedure had we proceeded with that, and I wanted to just comment a little bit about potentially the risk of epicardial LV leads in certain patients. I think in the replace registry, there were eight patients who died who had upgrades to CRT, and I think, if I remember correctly, four of them had gone to the operating room for epicardial LV leads, and those four had significant comorbidities, like the lung disease that was mentioned previously, and when people have renal dysfunction, heart dysfunction, regurgitant lesions, they don't tolerate general anesthesia. Maybe they wouldn't tolerate single lung ventilation that was required, and so I backed away from even considering an LV surgical lead placement in almost anybody unless the surgeons are going and have the chest open for another reason and can access the correct location. So replace, 10-plus years ago, still was kind of an important consideration in discussing with him what his risk of upgrade were. Okay, so I'm getting a little ahead of myself, so I'm gonna go back for a minute. So I would also say that I would not touch this guy for an upgrade. I think, first of all, I think we're electrophysiologists, and heart failure doctors look at the EKG, and they read the QRS's 136 milliseconds, and they say, hey, don't you guys, don't you folks have guidelines? Isn't the guidelines say QRS duration greater than 130? This guy is class three, heart failure, almost class four, or ambulatory class four. Why don't you upgrade him? And I would say that we know that there are non-responders, 20% of our patients. This patient has non-responder written all over him, assuming he survived the implant. We saw the patient sort of decompensated with just general anesthesia for cardioversion. So I think doing a upgrade in a patient whose electrocardiogram shows a nonspecific IBCD, we know from MATIC-CRT that if we do a secondary analysis, sub-analysis, that the patients who were actually harmed, harmed by IVICDs were the nonspecific IBCDs like this patient. And looking at that QRS, I bet you you could map every branch of his heart, and you wouldn't find a laid area to put it. So this would be a guy that I would, this would be a patient I would never want to take to the lab for an upgrade, because this patient has written non-responder in caps all over. Well, those are really good points, and certainly the need for norepinephrine with a simple cardioversion gave me chills, and I was not very excited about upgrading him. So what about his atrial fibrillation? Casal AF, the cabana sub-analysis, should we consider an AF ablation in a patient like this? Hoping that we could use amiodarone for a short period of time, and then give him the substrate change that would help him maintain a more durable sinus rhythm. Well, I think we should probably be doing more AF ablations in patients who have heart failure. We know that the risk of pro-arrhythmia is considerable, and we know, of course, amiodarone has a lot of long-term side effects. But again, I think you have to look at the whole patient, and looking at this patient, with that amount of MR, left atrial enlargement, putting him through a procedure, and I think this is where, I think it was smart to do all that imaging. MRI would be useful also to look at left atrial size. I think it's probably the best way to look at left atrial size, left atrial volume. but I think it would be like swimming uphill, hard to do for mere mortals. So I look back at CASEL-AF to see how many patients actually are essentially what this guy was, ambulatory class four. Not very many. So I was not real excited about the ask for an AF ablation. I thought that was not going to be doable with a good hemodynamic outcome. So then we think about the AV node ablation. Should we do an AV node ablation and upgrade the guy to CRT at that time? We certainly know that that gives us better control of the heart rate, and it works for heart failure with controlling AF and getting 100% good by the pacing based on QRS morphology. What do you think about doing an AV node ablation and then a HYST lead or the CRT lead? Does this person's lack of candidacy based on just CRT upgrade sway you away from doing an AV node and conduction system lead? It sure does, actually. I think even if he already had a conduction system lead in, I'd be somewhat reluctant to do an AV node ablation in this patient just because I think from listening to your story he sounds like he is decompensated, sort of ambulatory class four, and I feel somewhat uncomfortable. Maybe a heart rate in the 100 to 110 beat a minute range may be somewhat physiologic in this patient who's somewhat decompensated. And he's so – this patient is so tenuous that obviously you never, ever do it in somebody like this, but even if he had a great HYST bundle lead, I would be concerned. You know, it comes up a lot, as you point out. Is it tachycardia-induced cardiomyopathy? Is that contributing to it, or does he just have – does this patient really just have a very bad cardiomyopathy? My gestalt from hearing the story is that he has a very bad cardiomyopathy. I think if you ablate and pace this patient, even with a HYST bundle lead, he's probably going to do very – probably do no better and possibly worse, and I think when you make these tough clinical decisions, you should always remember the golden rule, you know, physician golden rule, first do no harm. So, you know, and then, God forbid, this patient gets infected, then, you know, he's really up the creek without a paddle, so I would not do an AV node ablation, I think, in this patient. Okay. Well, you can see the future. So I'm going to skip ahead of this and ask the experts here what they think about cardiac contractility modulation. So this is a technique and a device. It's actually FDA approved and it's used in patients who are not candidates for CRT. We just heard that this patient has likely a suboptimal response to CRT. So could he respond to cardiac contractility modulation, which paces in the absolute refractory period at high voltage, high pulse width, in attempts to change subcellular calcium handling, and this chest x-ray that I pinched from one of the papers kind of shows how many leads and wires are in for patients who have defibrillators who get CCM. This is the CCM device with an atrial lead and then two septal RV leads, and this person also had other leads in there, and all I could think about is this is a lot of hardware in the central venous structure for anyone. The lead placement is relatively standard, and there's been a proposal where a CCM type device could fit in our heart failure management. So ambulatory class fours, ejection fractions that are low, non-left bundles put us over to the left-hand portion here, and an injection fraction that his was roughly 25-ish, 24-ish percent would fit into a category where we would consider CCM or one could consider CCM. So I wanted to ask the panel their thoughts of where CCM fits in our device arena. So I'll give you my opinion. I'll be interested to hear what Dr. Gillis has to say, but we participated in one of these clinical trials a number of years ago, and I've implanted a number of these devices. And as you pointed out, you not only have to place a couple leads, but you have to place them in such a position so that when you paste one, you increase the dPDT. So it's not just throwing two more leads into the heart, so throwing more leads in the heart. So secondly is, the most benefit from looking at the clinical trial is really in class three patients. There are relatively few ambulatory class four patients in that trial, and it improves exercise tolerance. There's no mortality data at all. So in this sort of patient teetering on the brink here, I don't think those were the patients in the clinical trial that were studied, and I think it would be too little too late for this patient. Okay. So putting all this together and thinking about how we were going to proceed with this guy, I came up with this schematic, which obviously I needed to treat his heart failure. And I was going to go ahead with amiodarone and cardioversion in attempts to try and get sinus rhythm, see how he did, consider an upgrade, and then potentially talk about his atrial fibrillation and stop amiodarone. But then the TMR business comes in there as well. My rationale was he felt better in sinus rhythm, and if I could do a CRT, I could potentially help optimize his heart failure and decrease his mitral regurgitation. And the whole goal was to see if we could get him to a place where he could tolerate the longer PVI procedure. But I also felt that down the road he was likely going to need an E-clip. But despite all of this sketching and trying to figure out what road we're going to go, things didn't actually go that way. And you look at this and think, how long is this going to take to make this guy better? There's a lot of different procedures, a couple anesthesia experiences. Does he really have the reserve to tolerate something that is complex and complicated? So here's what happened. We diuresed him with IV Bumex. In atrial fibrillation, he was relatively rate controlled. I did not see heart rates greater than 100. He did increase his creatinine, but he also increased his lactate. And he also required dobutamine. So we put him on dobutamine, had to increase the dose, and we couldn't wean it. So he went for right heart cath. And the right heart cath demonstrated that he still was a little volume up. His index was OK. His wedge was a little elevated, but we couldn't get him off the dobutamine. So now, clearly, upgrade to CRT off the table. And his cardioversion on dobutamine, with a history of requiring norepinephrine, did not make anyone ecstatic to do this. And unfortunately, despite an initial rally on dobutamine with correction of his lactate, he then had an increase in his lactate on dobutamine. And we had to kind of retool where we were going. And what he ended up getting was the non-dischargeable cardiac support with a balloon pump. And what I put up here are the new UNOS allocation guidelines for organ heart transplantation, because this changed last fall. And I hear, at least in our region, one of the reasons things changed was because they were always requested to have this exception for these intractable ventricular arrhythmias. Not this patient. But they felt that they needed to, for that and other reasons, come up with other ways of figuring out where transplant fits in the mix. So he became status two for transplant. And there was a consideration of a durable VAD for him. And when we were having these discussions, I was kind of retroactively very grateful that I had not ablated his AV node. And I told the heart failure team that, you know, had I done the AV node ablation and put in a His-lead or whatever, and then he goes for a VAD, now I've really put him at risk, because leads don't always work well post-VAD. And I've made him pacemaker dependent for no good. So I'm very personally reluctant to ablate people's nodes who may have a VAD in their future, because they need a heartbeat. And what eventually happened for him was that he got a transplant. And he was transplanted relatively short term. His drug use history was not an active problem. He was a non-smoker. He was compliant. He did what he said. And his BMI was acceptable. So he probably had the best outcome for this. And I want to kind of wrap up by saying that careful deliberation of the full spectrum of treatment options is necessary in these complicated heart failure patients. And it was probably foolish of me to have this long, involved, trained plan of EP procedures, when really what he needed was a thoughtful approach to what's his best durable result for his heart failure. And definitive therapy may be the better option in the absence of contraindications. And I'm really glad that I didn't have to put him on amiodarone and he got his heart failure fixed. And I think my last point is that maybe cardiac contractility modulation is entering our device space. And it's certainly been proposed for people who are not candidates for CRT. But as Dr. Ellenbogen points out, the papers on this technology have been around for 10 plus years. And this device has kind of taken a slow road into our toolbox. So that probably further remains to be seen. So I would like to stop there and see if there's any other discussion or questions. Thank you. Questions from any members of the audience? I do think it's important when you see people like that. That patient I wrote down LVAD as soon as, you know, after I heard the presentation. But I think it's really important to, you know, do what's appropriate for the patient to get them at a point so they have a quality of life and they can function. And I think a lot of the teaching points here are you could have done a lot of stuff that would have made him a lot worse a lot more quickly. And knowing what not to do is sometimes just as important as knowing what to do. And that's really an important lesson to learn. It reminds me, one of my partners is the son of Dr. Seymour Schwartz who wrote Schwartz' textbook of surgery. And he has a saying that is a good surgeon knows when to operate and a great surgeon knows when not to operate. That's a great saying. That adage is part of this. But unfortunately my treatment of him kind of made the heart failure a little bit worse but brought everyone around to see that the things that we were asked to do probably weren't appropriate. Yes? Just one point. For patients with non-left bundle branch block, QRS between 130 and 150, I too am reluctant to put in CRT. But sometimes I'll order an echo strain imaging just to see if I can show if there's any delay in the lateral wall or in the lateral papillary muscle. Do you think that's reasonable or do you do that? Absolutely. I think it's a great suggestion. Very thoughtful. But to reiterate your point, you know, sometimes our heart failure colleagues will try to push us to undertake interventions that are not, as we've discussed, are not always ideal for the patient. And we have to recognize sometimes that we can't help a given patient with electrical therapy. That's a really nice segue. I'm Dawn from Penn and I'm an advanced heart failure doctor. And we have a lot of collaboration with our EP team. I wondered, you have an excellent heart failure program as well as EP at WashU. And so I wondered how collaborative this was because these are very difficult decisions and we do often take full responsibility for the patients the majority of the time. And so I wonder the kind of dialogue that existed for this kind of patient. Yeah, that's a great question. So we do work very closely with our heart failure team. And what I had actually done was like, let me try. This is what I'm going to try. Let me diurese him. See if I can tune him up a little bit. See if we can go down the amiodarone load. I'll call you when I need you. And unfortunately, I needed them rather quickly. And I needed them to actually consider temporary mechanical support when the lactate was going up. But his liver function wasn't normal at that point and he was therapeutic on Dabigatran. And we were like, oh, if we're putting Empel in this guy, he's doubly anticoagulated. This was not good. And they, of course, we bided some time for about 24 hours and then were able to do the things. But he was looking in the face of urgent mechanical support. So we do work very closely. And I cannot function without them. And I was very grateful to them for their help and getting him what he needed. So it was really co-management for the sake of the discussion and the learning. I kind of left that part out.

heart failure

atrial fibrillation

thrombus

dabigatran

dofetilide

mechanical support