Talking Tall Rounds®: Collaborative Approach for Hybrid EP Procedures

Podcast Transcript

Announcer:

Welcome to the Talking Tall Rounds series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Edward Soltesz, MD:

Good morning. I'm Ed Soltesz, I'm one of the cardiac surgeons here in the Heart, Vascular and Thoracic Institute at the Cleveland Clinic. For Tall Rounds today, you're going to hear from surgeons and electrophysiologists who are working together in a hybrid approach for managing complex atrial fibrillation patients. As you all know, atrial fibrillation is a growing problem, not only in the US, but worldwide. It is estimated that by the year 2030, there will be over 25 million patients a year with atrial fibrillation. Many of these patients have been managed medically some have been managed with catheter-based ablation and few have been managed with surgical approaches to atrial fibrillation.

Today, we're going to talk about the hybrid approach. It's an approach that's growing in interest throughout the country and world. We're going to take a look at what is the best of both worlds for some of these patients, understanding that many of these patients' complex physiology demands a bit of surgical approach as well as the electrophysiological catheter-based approach. You'll hear from surgeons and our electrophysiologists on how they've been working together to combat this very complex issue. We will begin and frame our discussion today with a case presentation.

Karolis Bauza, MD, PhD:

Good morning, everyone. The case is of a 57-year-old female with past medical history significant for obstructive sleep apnea, hereditary telangiectasia, esophagitis and history of neck fusion due to degenerative disc disease. She presented with exertional fatigue and dyspnea and was ultimately diagnosed with paroxysmal AFib. Shortly after the diagnosis, she underwent catheter ablation at an outside institution in July of 2020. It failed, so she was started on TIKOSYN after this, but developed severe lightheadedness with post-conversion pauses. Thus, in December of 2020, she underwent repeat isolation of her pulmonary veins as well as reablation of the left atrial roof line, cavotricuspid isthmus and SVC.

Unfortunately, two months later, her arrhythmia has recurred again. And at this point, she was referred to Cleveland Clinic where in March of this year, she underwent third catheter ablation. All four pulmonary veins, the posterior wall of LA and cavotricuspid isthmus were reablated. And the right sided ablation was extended more septally. She continued to have paroxysmal episodes of symptomatic AFib every one to two weeks, lasting up to five and six hours. Thus, she was referred to Cleveland Clinic for cardiac surgery evaluation. On the pre-OP testing, transthoracic echo showed normal biventricular function, mildly dilated left atrium and trace mitral valve regurgitation. Spirometry was within normal limits and cardiac stress test was negative for inducible ischemia or myocardial scar.

CT of the chest showed mild left atrial enlargement, mild ostial stenosis of the left inferior pulmonary vein, which is a feared complication after multiple catheter ablations, but no left atrial or left atrial appendage thrombus. Thus, in July of this year, the patient underwent Convergent plus procedure, during which her epicardial posterior wall of left atrium as well as lateral wall of SVC, both were ablated using surgicals of xiphoid window approach. During the same surgery, the patient also had the left atrial appendage ligated with a clip introduced via the left thoracoscopic surgery. She was discharged on postoperative day three in normal sinus rhythm and remains arrhythmia free. Thank you for your attention.

Tyler Taigen, MD:

Hey, good morning, everyone. I'm Tyler Taigen, one of the electrophysiologists here, and I have given the task to present the CONVERGE clinical trial from a few years ago. I was a PI on the trial and so maybe have some extra insights. Probably many of you in the room are familiar with the trial. The rationale initially for this trial, I think was brought out with the case presentation, is based on the idea that AFib is very common. A lot of our electrophysiologic approach though focuses on pulmonary vein isolation, as was the case with the presentation there initially. And yet, 70% of the cases of the millions of cases in the world are non-paroxysmal. And as the disease progresses from paroxysmal to persistent, it becomes more complex. Less just about the pulmonary vein triggers, more about changes in the posterior wall from those signaling factors you can see with calcineurin, elevated CRP, leading to fibrosis and inflammation.

And so the approach with our treatment needs to expand, I think, beyond just the pulmonary veins. That's really where this started, is how can we get more done than just the pulmonary veins for these advanced cases. This is an example of that. This is a three-dimensional electro-anatomic map of a patient that has a fairly normal-sized left atrium and had paroxysmal AFib. The purple that you see is a representation of the amplitude of electric potentials. Purple is pretty healthy, large amplitude. And then red that you can see in that inferior pulmonary vein is low amplitude or even absent. This is an example of someone with a persistent, actually longstanding persistent, atrial fibrillation where there's this variation in color and amplitude. Some of these are small and fractionated, and so obviously more complex disease here than with the normal size left atrial paroxysmal AFib.

So the hybrid convergent procedure and CONVERGE clinical trial is designed to address this. The idea with the trial was to have a surgeon go in with an epicardial approach, that you'll hear more about, and deliver those lesions that you see on the cartoon there are blue along the back wall and some of the reflections. And then right after that, the electrophysiologist would go in and deliver catheter-based endocardial lesions which are shown in red. And then the idea of course is to compare one to the next. So this was published in 2020 in Circ. A&E.

The design was two to one randomization, where 102 patients were randomized to the Convergent arm to get both and then 51 patients to the endocardial arm. These were followed over 12 months with echoes, halters, clinical assessment and then a long-term follow-up at 18 months. Inclusion was basically adults that were under 80, had to have persistent AFib or longstanding persistent AFib, so generally a sicker population than what we normally have in these trials, left atrial diameter less than six, and they had to have been refractory intolerant to at least one antiarrhythmic. These weren't reduced, so it was a little different than the case presentation. These were de novo ablations and the patients did not need concomitant cardiac surgery and had fairly normal EFs.

So the study protocol again was in the hybrid arm to deliver the epicardial lesions first and then the patient doesn't go anywhere right away. The electrophysiologist goes in and get access the way we normally do and then makes sure that the veins are fully isolated. In addition, deliver a cavotricuspid isthmus ablation. The reason for that was that in the initial experience, there was more typical atrial flutter, and so that just became part of the protocol. The control arm, the endocardial catheter ablation was to do a pulmonary vein isolation, and then this roof line that you can see connecting the upper pulmonary veins as well as the CTI line. There were not allowances for CFAEs or complex fraction aid electrogram ablations unless there was a specific arrhythmia, so it wasn't intended to ablate along the posterior wall.

So the trial endpoints, the primary effectiveness endpoint, which is pretty standard, was freedom from atrial arrhythmias, absent class one and two antiarrhythmics except for previously failed, and then importantly, no increase in dosage of antiarrhythmics that a patient was on. So they could be on, for example, TIKOSYN, stay on TIKOSYN the whole way through, and as long as the dose didn't increase from 250 to 500, that would count. So they didn't all have to come off the medicine. There was a secondary endpoint for reduction from baseline AF and then a primary safety endpoint, which is a little bit unique in that it wasn't based on comparing the two groups. It was a pre-specified endpoint of 12% as a safety endpoint.

Baseline characteristics are fairly equal across the groups. The patients had AF for about four and a half years on average. There were, as you can see, two prior cardioversions within the 12 months for the hybrid group and three for the endocardial ablation group. So this is the Kaplan-Meier curve showing a convincing difference with the hybrid convergent procedure of about 17 absolute percent compared to the endocardial catheter ablation group. And even more pronounced in patients that had longstanding persistent AF, 65% were free of AFib versus 37% in the catheter ablation group. With respect to primary safety endpoints, overall, it was 7.8%. This is, again, just for the hybrid group. And you can see with the different safety endpoints that were met, including tamponade and a couple patients with stroke and phrenic nerve injury, this was met because the pre-specified endpoint was 12%, so obviously less than that.

So notable limitations I think for the trial were that the endocardial ablation arm did not include posterior wall isolation. That is, I think, standard of practice here to do that. It's not always possible to get it because the esophagus is obviously directly behind that, but that would be our approach and was not the approach here. Primary safety endpoint, again, importantly was pre-specified and not compared between groups, and this was almost a six-year enrollment for 150 patients. So clearly, that's a limitation.

Conclusions we're that the trial comparing effectiveness and safety was better for the hybrid approach than for the endocardial approach alone by an absolute reduction of 17% with that and that the study demonstrated improved maintenance of sinus rhythm and acceptable endpoint with a hybrid approach. So I think takeaway points for me with this were the importance of durable transmural posterior wall ablation and isolation in addition to the PVI for treatment of advanced atrial fibrillation, similar to that first slide that I showed with some of the more complex physiology. And then importantly, and that's really what we're here to talk about, the successful team-based approach with collaboration between electrophysiologists and cardiac surgeons. With that, I'll conclude.

Ayman Hussein, MD:

So I'm Ayman Hussein, I'm one of the cardiac electrophysiologists here. I've been working directly with our surgical colleagues on this complex AFib program and I'll talk to you about how to select patients for the hybrid Convergent procedures. I'll start with highlighting some of the current challenges in AFib ablation. I'll cover the CONVERGE trial briefly, just focus on some technical aspects of it. And I'll then highlight our practice at the Cleveland Clinic in terms of ablation target, surgical referrals and I'll touch on the Complex AFib Clinic that we're working with. So when we think of AFib, we think of AFib nowadays as a spectrum, as a continuum of disease rather than the traditional definitions which categorize it to paroxysmal and persistent. That said, not all paroxysmal AFib patients are the same, not all persistent AFib patients are the same, and this kind of definition misses the true pathophysiology in the background, which is highlighted by AFib burden and disease progression.

But generally speaking, we think that in early stages of the disease, the arrhythmia is primarily driven by triggers, and these are the pulmonary veins. As the disease progresses, there is an increasingly important role for the substrate, mostly the posterior wall, but in addition to left atrial substrate tissue. Whereas with more advanced atrial fibrillation, there is advanced electrical and anatomical remodeling that leads to persistence of the arrhythmia. And it is particularly in these advanced disease substrate patients that the hybrid ablation actually has a role. We know that in patients with paroxysmal atrial fibrillation, doing pulmonary vein isolation might be enough, even though in our practice, we tend to include the posterior wall and we achieve good outcomes. We also know that in patients with persistent AFib and longstanding persistent AFib, the outcomes remain suboptimal due to the substrate. And therefore, that's the population which benefits from hybrid ablations.

Over the past 20 years, there have been a lot of publications, a lot of studies, trying to identify the source of persistent atrial fibrillation and to improve the outcomes of persistent atrial fibrillation, with various mapping and ablation strategies, including rotors, complex fractionated electrogram mapping and ablation, dominant frequency and others, but none panned out. And we're back actually to ground zero and starting point in terms of doing mainly anatomical, even though there are some studies in the pipeline focusing on fractionated potentials and extra PV triggers.

So the CONVERGE trial as a highlighted by my colleague, Dr. Taigen, was done with focus on drug refractory persistent and longstanding persistent atrial fibrillation. But as he mentioned earlier, the main limitation is that the endocardial catheter ablation arm did not include ablation of the posterior wall systematically. And looking at the outcomes, I can tell you that based on our record and for AFib ablation outcomes, catheter-based outcomes, that persistent and longstanding persistent freedom of recurrence after ablation is better than what's reported here in the trial in the catheter arm, which highlights the importance of the posterior wall, which again we routinely do.

So the first image on the left here is from the CONVERGE main publication. This is after an epicardial ablation and before endocardial. Red is scar. So the transmurality of scar actually is evident with epicardial ablation, now we're mapping the endocardium, and we detect this scar at the posterior wall. As you can see, it doesn't reach all the way to the roof. That's because of the recesses and the pericardial reflections, but that's when the catheter-based ablation, the endocardial ablation, takes over and completes encirclement and full isolation of the veins and the posterior wall. This is, on the right here, an example of a catheter-based ablation from here, from the Cleveland Clinic, showing that after ablation of the veins and the posterior wall, we have complete electrical silence. Which technically if you compare this to panel B here, on the left, that's the same technically electrical endpoint with complete electrical silence of the veins and the posterior wall. The question remains though, what happens in the epicardium after endocardial ablation only? Are we missing any substrate? And in some patients who have persistent AFib despite multiple ablations, maybe we are missing some substrate.

So how do we select our patients and how do we approach these catheter ablations at the Cleveland Clinic? So for a first time, PVI and posterior wall ablation. For redo, we typically target three isolation of the pulmonary veins, we do posterior wall and in addition to empirical or areas with fractionated electrograms, such as ablating of both the right atrium, the left atrium and in areas with abnormal signals or potentials. Empirically, we may target the vein of Marshall or ligament of Marshall, we may target the appendage, we may target the roof. We ablate septal to the pulmonary veins, inferior to the right inferior pulmonary veins, and sometime within the coronary sinus. But as I mentioned earlier, all advanced mapping over the past 20 years did not improve targeting the substrate and we're technically limited to anatomical mapping nowadays.

How about redo after index ablation at CCF? Actually most of the time, as I can share actually with you, when we go back in after an ablation that we did, most of the time, those veins and the posterior wall are mostly done and there is little to nothing to be done. And in such case scenarios, maybe we're missing some more substrate that is beyond the pulmonary veins and the posterior wall, maybe we're missing some epicardial component. And that's when Convergent comes in. At the Clinic, and I'm sure Dr. Soltesz will cover that in details later, we're doing a Convergent Plus, which is the Convergent approach in addition to a left atrial appendage clip and ligament of Marshall. The clip has the stroke prevention benefit possibly, but there's also some arrhythmia control benefit because some of those arrhythmias or a-tach that trigger AFib could be originating from the appendage and the clip may result some scarring around that area and electrical isolation of the appendage. The ligament of Marshall is a known contributor to AFib in many cases.

So who are the candidates? Persistent and longstanding persistent AFib, sometimes as a first line, but often as a redo after failed endocardial catheter ablations, especially in patients with silent PVs and posterior wall and trying to focus on additional targets beyond the pulmonary veins. In patients with severely dilated atria, those are patients who may not achieve arrhythmia-free survival with endocardial catheter ablation only. We can consider it also in patients with limited endocardial ablation due to the esophagus being in the way. Whereas the advantage with an epicardial approach is that the probe points away from the esophagus towards the atrium and the radio frequency is going towards the atrium only. So it could be applicable in patients in whom posterior wall ablation was not possible due to the esophagus.

Here at the Clinic, we've been working directly and closely with our surgical colleagues on this Complex AFib Clinic, which targets offering state-of-the-art mapping and ablation for difficult AFib cases. Some of them are served with catheter-based ablations, some of them are served with hybrid ablation, but many can go directly to surgery and depending on what they have otherwise in terms of valve disease or other surgical indications. In this particular clinic, working on prospective data and outcomes collection, with great opportunities here to move science forward and improve the care of our AFib patients. With that, I thank you so much.

Announcer:

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