Hello, HRS. My name is Emile Daoud, and I'm chief of the Cardiac Electrophysiology Program at the Ohio State University in Columbus, Ohio. These are my disclosures. This is the title of today's webinar, Role of Atrial Fibrillation Ablation in Patients with Heart Failure and Reduced Ejection Fraction. I'd like to thank HRS for inviting me to participate in the webinar series. So let's look at some of the basic questions when addressing atrial fibrillation in patients with reduced ejection fraction. First, do we expect heart failure patients to have improved hemodynamics if they're on sinus rhythm, even if we compare that to patients with rate-controlled atrial fibrillation? And so if we answer those questions as yes, then the next question is, does the technique of pulmonary vein isolation enhance the likelihood for freedom from AFib when compared to antiretroviral therapy? Is pulmonary vein isolation feasible in terms of risk-benefit ratio in patients with reduced ejection fraction? So let's look at this bit of the physiology between AFib and heart failure. As a background, we all have a good appreciation that there's a tight relationship, tight adverse relationship with atrial fibrillation and heart failure. So of course, with onset of atrial fibrillation, there's loss of atrial contraction. The rapid ventricular rate results in significant adverse physiology. There's also the irregular ventricular activation. Functional MR results in heart failure, as well as there's several comorbidities that coexist with atrial fibrillation and heart failure, diabetes, OSA, hypertension, ischemic disease, which can participate in these processes. Then, of course, with heart failure, volume overload, altered atrial refractors, triggered activity, increased stretch and interstitial fibrosis leads to atrial fibrillation. And so there's this downward spiral. This was seen in a recent study published regarding the interaction between atrial fibrillation and heart failure in the Framingham study. And what they found that AF begets heart failure and vice versa. So when you look here on the table on the left, these are patients with heart failure in black and the patients without heart failure in red. And this is the instance of new onset atrial fibrillation. So of course, you can see that in the patients with heart failure, the new onset of atrial fibrillation is much higher. And then also vice versa, when you look at here in the patients who have a history of atrial fibrillation, whether it's reduced or preserved ejection fraction compared to patients who do not have atrial fibrillation, the instance of heart failure, new onset heart failure is significantly greater in those patients with atrial fibrillation. So the heart failure is associated with new onset AFib hazard ratio of 2.18. Atrial fibrillation is associated with new onset heart failure hazard ratio of 2.3. And the presence of both of these were associated with greater mortality versus the absence of both of these conditions with a hazard ratio of 2.7. So almost three times greater risk, particularly in patients with heart failure and reduced ejection fraction. So clinically, we see this and in this study confirms that there is a tight adverse relation between AFib and heart failure. So let's look at a case example. This is a 56 year old gentleman with prior myocardial infarction, three year history of worsening heart failure. He's had AFib persistent for five years and good rate control, ejection fraction of 20%. New York Heart Association class three to four symptoms with these other comorbidities is on a good medical therapy. The echocardiogram here shows an ejection fraction again of 20%. We look that there's significant moderate to severe mitral regurgitation. So the question is, how do we proceed with managing this patient's do we continue rate control and refer for advanced heart failure therapies, amiodarone and cardioversion, refer for mitral valve repair with intraoperative maze, AV node ablation and biventricular ICD, or ablation of the atrial fibrillation. We'll get back to that case report. Let's look at some of the therapies for atrial fibrillation and so we can understand the role of ablation. So this is a probably the most encompassing trial looking at the use of amiodarone, class one drug propafenone and class three drug Sotol in patients with atrial fibrillation, the Canadian trial of AFib. What we found was that, and again, clinically we recognize this, that there's a high recurrence rate of AFib even in the presence of a good antiretroviral drug therapy. In the class one and class three group, the recurrence rate is about 40, 45% in one year. With the amiodarone, it's a little bit better, but about 75 to 80% recurrence rate. The trend, however, continues to decline over time. Of course, the primary concern with antiretroviral drugs is the prorythmic risk. This is a Holter monitor from one of my patients that I treated with a class one agent and they had fortunately non-sustained torsad. Additionally, the risk of antiretroviral drugs is borne out in clinical trials. This is the last one, dronetarum, use in patients with severe heart failure. This was a double-blind or randomized trial. The primary endpoint was death from any cause or hospitalization for heart failure. Importantly, this was not an AFib trial, but it does demonstrate the risks of entering the drugs in patients with reduced ejection fraction. The trial was stopped early because of an increased mortality associated with dronetarum. I think we all appreciate that we want to avoid drug therapy, particularly in patients with reduced ejection fraction due to poor efficacy and increased risk of side effects, including prorythmia. This really boils down to the options of managing patients either as a rhythm control with ablation or rate control without conversion to a sinus rhythm. Let's look at some of the rate versus the rhythm control trials. Obviously, the largest and most well-known is the AFIRM trial published in New England Journal of Medicine in 2002. They randomized over 4,000 patients to rate versus rhythm control. The importance is that they had no symptoms. Rate control was resting heart rate less than 80 and a six-minute whole walk exercise rate less than 110. Rhythm control was either class one or three agent, but two-thirds of the patients were treated with amiodarone. Importantly, when you look at this study, the mean ejection fraction was 55 percent. The AFIRM study was not in patients with reduced ejection fraction. These are the major outcomes of the study. What they found was there's no difference in mortality stratified by ejection fraction. This is the overall mortality of rate versus rhythm. Then they stratify the outcomes by different categories of ejection fraction. Even when you look at the low ejection fraction group patients, the rate versus rhythm category are nearly identical. Then we see the same findings associated with either overall hospitalization for ejection fraction, and then same findings for near-car association class and six-minute hallway walk test, meaning that regardless of which group of patients you looked at, and particularly even the low ejection fraction group patients, you do not see any difference in mortality, hospitalization, near-car association class, or six-minute hallway walk test. Let's look at another study. This is the AFCHF study, also in the New England Journal of Medicine article. This was a study that looked particularly at patients with reduced ejection fraction. They had over 1,300 patients with heart failure. Ejection fraction was less than or equal to 35 percent in episodes of atrial fibrillation. They were randomized to rhythm versus rate control. In the rhythm control, they had sinus rhythm in up to 80 percent of patients, which is rather remarkable, and 82 percent of the patients were treated with the amiodarone. Again, similar to what we found with the AFFIRM study, when you look at death due to any cause, stroke, worsening heart failure, or composite outcome, and you compare rhythm control to rate control, you can see that the lines are superimposed with identical outcomes with any subgroup or any sub-outcome category, again, including the composite outcome. The trouble is, if we know in our heart that sinus rhythm is better for patients, particularly those with heart failure, why do we not see any benefit when we try rhythm control? I think we are familiar with this. The trouble with these studies was that rate versus rhythm control populations, they had nearly similar treatments, meaning that when you look at the AFFIRM, patients that were considered rate control patients, 35 percent were, in fact, in sinus rhythm. In the rate control patients, 15 percent crossed over to rhythm control patients. In the rhythm control patients, 37 percent were actually in AFFIRM. The trouble was that the rhythm was different in only about 30 percent of the patients in these trials. What you were doing, you were comparing AFFIRM in sinus rhythm in the rate control group versus AFFIRM in sinus rhythm plus the antirethnic drug in the rhythm control group. Any adverse effect of the antirethnic drug was negated by any benefits of sinus rhythm. Again, the end therapy, meaning whether they were enough, sinus rhythm or AFFIRM was not that significantly different between the two patient populations. Hence, the outcomes were nearly identical. In summary, at this point, medical therapy, antirethnic drug, and rate control, antirethnic drug, of course, is an issue of poor success and pro-rhythmic risk. When we look at the rate versus rhythm control trials, the important point is, one, there's no improvement in mortality with this. These trials were poor design. Importantly, they did not include what we know as being the best approach for rhythm control, which is ablation therapy. Let's look at the effect of ablation therapy. Ablation of AFib in patients with heart failure, one of the early studies was a non-randomized study. They had 58 patients with heart failure, AFib, and reduced ejection fraction that were in good medical therapy. The mean ejection fraction was 35%. They had AFib for six years. More than 90% were persistent or considered permanent. They compared the outcomes of this ablation procedure to a control group, which was matched for age, gender, type of AFib, but not heart failure. In this group, in the control group, the ejection fraction was 66%. All subjects underwent ablation. They looked at ejection fraction, LV dimensions, symptoms, exercise capacity, and quality of life. What they found is, at first, you could achieve successful ablation of AFib in the heart failure patients. It was 78%. In the controls, it was 84%. The heart failure did not adversely impact the outcome of ablation procedure. Terribly important is that within the heart failure patients, there was an absolute, not a relative, but an absolute increase in the ejection fraction of 21%. Remember, they start off with a reduced ejection fraction. Now, you add on another 21%. That's a huge increase. When you look at ablation of AFib, you can see that there are multiple favorable responses. Not only do you see an improvement in ejection fraction with normalization, you see an improvement in fractional shortening, a reduction in diastolic volume, and a reduction in systolic volume. The conclusion from this study is that, indeed, ablation can, in these patients with reduced ejection fraction, can be successful and can achieve favorable remodeling. Again, this was a non-randomized study. Let's look at the CHF study, which I think is a great study looking at really probably the two main alternative therapies for rate versus rhythm control in patients with heart failure. They took 81 patients with AFib and depressed ejection fraction. It was about a 50-50 split in persistent paroxysmal. They're good on medical therapy, mean ejection fraction 28%. Again, they have already failed to enter the drug therapy. It's either ablation or rate control. They were randomized to AF ablation versus AV node ablation with biventricular ICD. When you look at the patients undergoing AF ablation, the six-month success rate without antiretroviral drug was about 70%. The primary endpoints we see were significant improvement in ejection fraction with the patients that had ablation. Again, these are compared to patients with AV node and biventricular ICD, so the rate control is outstanding in these patients. Then you also see a significant improvement in the six-minute hallway walk test. The fallout, though, was rather short of about six months. The trial did imply, however, that even with the ultimate rate control, meaning AV node ablation, you can see significant benefit with maintaining sinus rhythm. This is a randomized trial of catheter ablation versus medical treatment called the CAMTAF trial. It's randomized 50 patients. These are patients who all had rate-controlled persistent AFib, reduced ejection fraction. They were randomized to continued on medical therapy versus ablation. Ablation with sinus rhythm was 73% successful at 12 months. It did require multiple procedures, and they looked at multiple outcomes in hemodynamics and ejection fraction. This is a busy slide looking at all the different parameters, but on the far left of each of these graphs is the preablation medical versus catheter ablation group. The catheter ablation group here is in the dark line, and you can see for each graph, ejection fraction, BMP, Minnesota living with heart failure score, the quality of life score, near-car association class, peak VO2, that with each parameter, the ablation group has significant improvement in the parameters. So the ejection fraction significantly goes up, BMP goes down. The living with heart failure score improves by demonstrating a reduction in the score. Quality of life scores improve. Near-car association class gets the lower class improving. And then importantly also, there's a significant increase in the peak VO2. So this was also notable in that this is, again, this is a little bit hard to read, but this is one month here. This is three months here. So the improvement is rather quick. There's an immediate positive effect of the benefit of sinus rhythm. This is ablation versus amiodarone. Again, a very common treatment for patients with persistent AFib in the ATAC trial. They had 203 patients with a reduced ejection fraction. They had a dual chamber ICD or CRTD. So this helped keep an excellent log of AF episodes. The rejection fraction was less than a 40%. They randomized either catheter ablation or amiodarone, and they looked at the end points of ejection fraction in six minute hallway. When you look here, is in the ablation group of the ATAC trial, there was freedom from atrial fibrillation at one year is 80% versus about 45% in patients randomized to amiodarone. And what we found in these trials now is first we talked about medical therapy, entering the drug and rate control. Well, we also now look at small studies. Ablation is indeed feasible in heart failure patients, and they get the same results as patients without heart failure. And in these trials, there seems to be a better outcome versus enter the drug as well as versus AB node ablation and biventricular ICD implantation. So some of the concerns of doing an AFib ablation in patients with heart failure is how many procedures we need to do? Are these patients too ill? Can we achieve good results? And these preliminary studies do indeed show not only can you achieve results compared to ablation in patients with preserved ejection fraction, but that the results of ablation result in significant improvement in our heart failure patients. So what about the question regarding mortality in patients with AFib and reduced ejection fraction? So the CASLAF is obviously an important clinical trial published in the New England Journal in 2018 that looked at management of atrial fibrillation in patients with heart failure with catheter ablation with a particular focus on mortality. So let's look at this study. These are patients, again, mostly persistent AFib, 70%, mean ejection fraction was 26%, neocardial association two to four. They all had an ICD or CRT with an atrial lead. So again, this was excellent monitoring for any AFib recurrences. And they're randomized to medical therapy, so which could be the rate of rhythm control versus ablation of the atrial fibrillation. And the composite primary endpoint was total mortality and heart failure hospitalization. So this is a good study that kind of included the gamut of therapies, either rate of rhythm control or ablation, and looking at the important outcomes, which were total mortality and heart failure hospitalization. So when you look at the composite outcome, death of any cause and heart failure hospitalization, you can see that here, the ablation group here in blue did significantly better than compared to the medical therapy group. Important to note that the curves start to diverge somewhere around six months. So it's not an immediate effect. There is some time for the benefit of sinus rhythm to result in favorable remodeling and outcomes. When you look at the subcategories of outcomes, when you look at death of any cause, again, there's benefit with ablation, but interestingly, the curves did not split until you're out about three years. So this is terribly interesting to me. So the effect of ablation with regards to mortality is not immediate like we see with the other hemodynamic parameters, such as ejection fraction or VO2, or changes in dimensions of the left ventricle, but rather the mortality benefit takes, here it was three years before you start to see a split in the curves, also implying the slow insidious onset of the adverse effects of the atrial fibrillation in the medical therapy group. When you look at the heart failure hospitalization, that effect is early. Within six to 12 months, you see a splitting of the curves. Again, in favor of ablation. The primary outcome was the composite. We know that that was significantly different, but when you look at all the other secondary outcomes, it was also in favor of ablation. So death from any cause was significantly reduced with ablation, as well as heart failure hospitalization, cardiovascular death, and cardiovascular hospitalization. Important comment was that stroke was not reduced. It was the same in both in ablation therapy and the medical therapy, which probably really implies the significant success of our direct oral anticoagulants. Let's look at another study regarding atrial fibrillation ablation in patients. The heart failure and mortality was the BANA trial. They had obviously patients that had both paroxysmal and persistent AFib. I identified out of the total population, 778 patients, 35% of the total population that had heart failure, either neocardic association class two to four. When you look at this group, it's important to note that the majority, 51%, had a preserved ejection fraction, but about 50% did have a reduced ejection fraction. Only 9% had an ejection fraction less than 40%. They looked at the composite of all-cause mortality, stroke, serious bleeding, cardiac arrest, and then heart failure, mortality, and cardiovascular hospitalization. So we looked at the primary endpoint in patients with a heart failure, again, neocardic association class two to four, and this is a mixed bag of preserved ejection fraction and reduced ejection fraction. You see that by the intention to treat principle, there was a reduction of the composite endpoint of death, stroke, serious bleeding, or cardiac arrest in favoring ablation therapy here in the red compared to the medical therapy. We see the same outcomes when you look at all-cause mortality. Has a ratio of 0.57 favoring ablation here in red, so reduction in all-cause mortality compared to drug therapy. Now, unlike the Kambana trial, I'm sorry, unlike the CASEL-AF trial, you can see that the mortality data has early divergence quite soon once the patients are enrolled and undergo ablation. In the CASEL-AF, if you might recall, we saw the splitting of the mortality curves occurring at three years. And then, of course, what we've seen time and time again with all these clinical trials is that the freedom from AF is significantly better in the heart failure patients who undergo ablation. Again, we're seeing that number of 70% success in the ablation group at about one year compared to drug therapy, which is about 45% success at one year. So in the Kambana trial, in patients with reduced, I'm sorry, in patients with heart failure, both preserved ejection fraction and reduced ejection fraction, ablation therapy compared to antiretroviral drug resulted in significant reduction in all-cause mortality, reduction in AF recurrence, improvement in quality of life, but no difference in heart failure hospitalization. So let's go back to our case study. If you remember, this is our patient, a young gentleman with an ischemic cardiomyopathy who had this, oops, let me try that again, get it to play, this reduced ejection fraction with a severe MR. So with this understanding now from the publications, we, of course, endorsed AF ablation. And the first ablation, we did wide-area circumferential ablation. The patient had a recurrent atypical left atrial flutter. We brought him back for a second procedure. At the second procedure, we did post-pace interval mapping. Yes, this is a little old-fashioned compared to high-density mapping, but nonetheless, we did find the successful ablation site here just below the left inferior pulmonary vein and resulted in termination of tachycardia and resumption of sinus rhythm. And then three months post-ablation, this is our, again, pre, this is the post. You can see the ejection fraction improved, the MR is resolved, and the outcome was outstanding for this patient. Again, this is all managed by AF ablation. So what we talked about, again, brief summary here of the up-to-date, meaning that we know that there's poor outcomes of medical therapy. We know that ablation is feasible in heart failure in the small studies. And now the large multi-center randomized trials of ablation of AFib and heart failure show superiority to antiretroviral drug and to ray control. Importantly, the outcomes are not only maintenance of sinus rhythm or freedom from AFib, which were proven on multiple other studies, but also these studies extended the results to include a reduced all-cause mortality and hospitalization. So with this pretty compelling data, why is there reluctance to bring these patients to the electrophysiology laboratory? In general, there seems to be a concern regarding the likelihood for successful ablation, the perception that perhaps these patients are too complex, too ill, the left atrium is too dilated, there's too much MR to give any reasonable chance of restoration of sinus rhythm. Well, this is one other study that I wanted to talk about. These are 377 consecutive patients undergoing radiofrequency ablation. And this is an older study in 2004. The ejection fraction was 36%. And what I wanted to really focus in on, this study initially concluded, or the first major finding in the study was that the patients with reduced ejection fraction had a higher recurrence of AFib. So the freedom from AFib at 14 months was 73% with a reduced ejection fraction versus 87% in the normal ejection fraction was significantly different. But what was interesting in this study and I think helpful for us when they looked at the patients who had a repeat second pulmonary van isolation procedure, the cure, that's a tough word to say, but nonetheless, they said total cure off enter of the drug, including a second procedure was not significantly different. So maybe that these patients with heart failure, like our case example, may require additional procedures. But even with that, given the safety of the procedure and the significant benefits of mortality and hospitalization as well as freedom from AFib and the favorable remodeling, there's significant benefits for AFib ablation compared to the alternatives of medical rate control or entering the drug therapy. Lastly, I just want to look at this meta-analysis. This is in the Annals of Internal Medicine. There was six randomized control trials in 775 patients of catheter ablation in patients with heart failure. And what you found here is when you, again, we look at all-cause mortality and heart failure hospitalization, all-cause mortality favored, strongly favored ablation with a 50% reduction in mortality and the heart failure hospitalization is about a hazard ratio of 0.6. Also, both of these favoring ablation. And then when you look at the other outcomes of AF recurrence, of course, favors ablation, there's no difference in complications in the procedures of AF ablation versus the medical therapy. So we often assume that when you take a pill, it'll be less complicated than an ablation procedure, and that did not bore out in this meta-analysis. And ablation increases VO2 max, again, another significant improvement in quality of life and functionality. So in summary, certainly AFib and heart failure are quite common, and it's a significant health issue with progressive adverse physiology. There are multiple randomized control trials that confirm the benefit of sinus rhythm and confirm that ablation is better than antiretroviral rate control. Again, rate control has been studied both with medical therapy and with the best rate control, meaning AB node ablation. We've seen that with ablation and restoration of sinus rhythm, there's an improvement of all-cause mortality, ejection fraction, six-minute hallway walk test, quality of life, favorable LV remodeling, and heart failure hospitalizations. So I think the greatest disservice of literature and training is perpetuated as a focus upon symptoms, and that successful rate also there's a perception that successful rate controls blocks the adverse effects of atrial fibrillation. I completely disagree with that. Heart failure and the low ejection fraction are the grave symptoms of the AFib. Even though the patient may say, I don't notice my AFib, the fact that they are having heart failure and the fact that their ejection fraction is reduced is their symptom. Of course, we have many examples of disease that are considered asymptomatic until severe, and yet we know that intervention, particularly early, is proper. And we've learned that lesson with heart failure and reduced ejection fraction where even before patients develop clinical episodes of heart failure, you want to initiate medical therapy. So in conclusions, patients with heart failure and reduced ejection fraction who have recurrent AFib, either proxismal or persistent or longstanding persistent, should be offered and should undergo AFib ablation, even if it may require repeat procedures with the hopes and the intent that your results when achieving sinus rhythm will result in improvement in ejection fraction, an improvement in mortality, improvement in heart failure hospitalizations, and improvement in symptoms and functionality for your patients. Thank you very much.

webinar

atrial fibrillation

AFib ablation

heart failure

reduced ejection fraction

treatment options