All right, well, thank you very much for the opportunity to speak today. So a little bit of a timelague for you to look at my disclosures. All right, so I'm Jim Freeman, I'm hailing from Yale. Thank you again for the opportunity to be here today. I'll be talking about the benefits of early AF rhythm control. And actually judging by the answers to the questions, I've got some work to do. So this will be exciting and fun. I always like to start this talk just by talking about the significance of atrial fibrillation. I know people are probably aware of this, but it's important to reiterate that this is the most common cardiac arrhythmia. It impacts about 15 to 20% of Americans over the course of their lifetime. There's an increasing prevalence in all age groups. Hospitalization with atrial fibrillation as a primary discharge diagnosis is increasing. And it worsens outcomes, including both mortality and stroke. About a quarter of all strokes in the United States annually are from atrial fibrillation. And then of course it causes symptoms and decreases quality of life. So the data on rhythm control as opposed to rate control for atrial fibrillation was really the affirmed trial for many years. And it showed really equivalency of those two paradigms. But it didn't really look at the issue of early rhythm control. And there were some design issues associated with that trial. And so the investigators of the East AF Nat 4 trial decided to conduct a trial. It was a large study, 135 centers, almost 3,000 patients with early atrial fibrillation. This is really important. The median time since diagnosis to the beginning of their enrollment in the trial was 36 days. So these patients truly were early in their disease course. And then they were followed over five years. So again, a really important aspect of this study was the five-year follow-up. Their primary outcome was a compositive cardiovascular death, stroke, heart failure hospitalization and ACS hospitalization. And then the second primary outcome was number of nights in the hospital. And this study showed a statistically significant improvement in the patients treated with early rhythm control with a hazard ratio of 0.8. And then importantly, when you look at the composites of that primary endpoint, both death and stroke were also statistically significant despite relatively low numbers. And then it's also important to note that only about 20% of the patients in this study were treated with AF catheter ablation after two years in the early rhythm control arms. So the vast majority of these patients were treated with rhythm control antiarrhythmic drugs. There were some downsides associated with rhythm control. And I think it's really important to raise this, particularly because of the issue that we talked about that the vast majority of the rhythm control was done with antiarrhythmic drugs. So serious adverse events related to antiarrhythmic drugs were higher, higher rates of toxic effects associated with antiarrhythmic drugs, higher rates of bradycardia and higher rates of device implantation because of the bradycardia. And then interestingly enough, also higher rates of hospitalization for atrial fibrillation. So it may be that these patients were being watched closely or had more issues associated with their antiarrhythmic drugs but they were hospitalized for atrial fibrillation more frequently. So catheter ablation is an increasingly used paradigm for rhythm control of atrial fibrillation. And as a reminder for the audience, there are really two broad paradigms for doing catheter ablation. The first is a radiofrequency energy delivery catheter, generally point catheters at this point. And then you can use a cryo balloon catheter that uses a nitrous oxide delivery system to freeze tissue. And in either case, the goal here is to electrically isolate the pulmonary veins which harbor electrical triggers. And by electrically isolating the pulmonary veins, you render those triggers incapable of propagating out to the atrium and initiating atrial fibrillation. So it's really about controlling the triggers of AFib. And so there have been a number of studies looking at the use of cryo balloon ablation as first-line therapies that were published in the last year in particular. So actually two of those studies were published in the New England Journal of Medicine and one was published in EuroPace. The studies were all moderately sized, about 200 to 300 patients. And they all looked at this issue of cryo balloon with pulmonary vein isolation versus medical management. And they universally showed that the rates of recurrence of atrial fibrillation with these therapies was markedly better with pulmonary vein isolation, all with about a 50% relative risk reduction. And they showed marked improvements in quality of life as measured by the AFEQT and decreases in healthcare utilization. Importantly also, the rates of adverse events associated with therapy were as good or better with therapies. So it's important to kind of raise that as we look back to some of the adverse events associated with primarily rhythm-controlled drugs in the EAST-AF trial. I wanted to highlight in particular Jason Andrade's study published in the New England Journal of Medicine. Because the unique aspect of this study was that they implanted implantable loop recorders. And Jason, I should say, shared this slide with me. And so with implantable loop recorders, you get a continuous monitoring for atrial fibrillation, a true sense of AFib burden. So historically, AFib trials, these rhythm-controlled trials have used a freedom from atrial fibrillation metric. So any substantial, any episode of greater than a few minutes often is considered a failure. Whereas burden sort of takes in the totality of the AFib that patients have. And I think this is probably where the field needs to go. And you can see here a marked reduction in burden. So when you look at burden as a metric, you see that the vast majority of patients, well over 95% of patients, have a marked reduction in AF burden. So then if we look at atrial fibrillation catheter ablation and we start to think about hard outcomes associated with ablation. So we know that ablation's better at achieving rhythm control. But can we impact hard outcomes? And probably the best trial in this space is the CABANA trial. It's about 2,200 patients from 126 centers with symptomatic atrial fibrillation. And they were randomized to catheter ablation versus medical management. Now this is not an early rhythm control study. This is just a study looking at catheter ablation versus medical management. The primary endpoint for this study was death, disabling stroke, serious bleeding, or cardiac arrest. And actually they did not achieve statistical significance when they looked at this primary endpoint in this trial. Though there was a trend towards improvement with catheter ablation. But the important thing to note is that there was about a 30% rate of crossover. So about 30% of the people that were supposed to be treated with medical management ended up getting a catheter ablation. And so that, of course, is going to bias the results towards the null. And I think appropriately in this circumstance, they also published a per-protocol analysis. And obviously you lose randomization when you do per-protocol because the patients that got treated with ablation were supposed to be in the medical therapy are maybe sort of healthier and more capable of undergoing a procedure. But with that caveat in place, they started to see a widening of the curves by six months. And by 12 months, there was a statistically significant difference in this primary outcome of death, disabling stroke, serious bleeding, and cardiac arrest. And then the next sort of issue to look at is the issue of catheter ablation and whether we can influence heart outcomes in patients with systolic heart failure. So the data gets very good for improvement in heart outcomes when we look at patients with systolic heart failure. And so probably, there have been a number of trials in this space, but probably the best study was the CASEL-AF study. And the CASEL study had a primary endpoint of all-cause death or heart failure hospitalization. And for that primary outcome, there was a marked improvement associated with catheter ablation. And then when you looked at the secondary endpoints, including death, heart failure hospitalization, cardiovascular death, and cardiovascular hospitalization, there were statistically significant improvements for all of these. Notably, LVEF was noted to increase by about 8% in patients who were treated with catheter ablation at five years. The one caveat to this trial that I think is important to point out is that patients with very severe heart failure, so when their EF is less than 25%, and with New York Heart Association Class IV symptoms, these patients probably had an attenuated benefit associated with rhythm control using catheter ablation. So there may be a group of patients that are just too far gone, too sick with their heart failure to really benefit from rhythm control. And so, in conclusion, the EAST-AFNet4 trial was a study that showed that early rhythm control has been now shown to be associated with improved cardiovascular outcomes. Early rhythm control with catheter ablation as a first-line therapy has been shown to be superior to medical rhythm control for improving the burden of atrial fibrillation symptoms and quality of life, and that was shown in three moderatized studies all published in the last year. And then there's increasing data showing AF ablation is associated with improved heart outcomes, so like death and stroke, compared with medical therapy, and I'd say the data is particularly strong in patients with systolic heart failure. Thank you very much. Thank you.

atrial fibrillation

early rhythm control

cardiac arrhythmia

antiarrhythmic drugs

CABANA trial