I am Hakeem Ayinde from the Cardiology Associates of Fredericksburg, and today we're going to be talking about the evolution and benefits of rhythm control. I have no disclosures. Today we'll talk about the historical perspective of rate and rhythm control. We'll talk about updated data on rate and rhythm control and clinical outcomes of rate versus rhythm control. Now, ever since the pivotal study of Heisiger et al., where they described the distribution of HR fibrillation triggers back in 1998, we have struggled with, you know, questioned how best do we actually achieve this rhythm control, number one. Number two, in which patients do we offer this rhythm control to? And then, is there any benefit of rhythm control versus rate control? So on one hand is rhythm control. We have options like capillary fibrillation, options like antiarrhythmic therapy, and we also have the rate control, which we have the negative dermatropic medications, where the goal is to keep the heart rates within a certain rate and it doesn't go too high. Now the landmark study of rate and rhythm control was published in 2002. It was called the AFIRM trial, and this was a study where they looked at 4,060 patients' average age of 70, and the question was, okay, if we randomize them to rhythm control versus rate control, looking at heart outcomes like mortality, what do we find? The mean fall off of this population was 3.5 years. Now when you look at the rhythm control, the rate control arm, here you'll see that majority of the medications for the rate control were digoxin, so about 49% initially received digoxin, about 47% received beta blockers, and about 30% received diltiazem for rate control arm. Now for the rhythm control arm, most of them, about 38% received amiodarone and 31% received sotolol. So between amiodarone and sotolol, we had almost 70% of these patients on these two medications. A small proportion were on propafenone, procainamide, quinidine, flecainide, but these were really small numbers. Now these patients were followed for an average of 3.5 years, longest follow-up was about six years, and what it showed was that there was no difference in long-term mortality in the rate control arm versus the rhythm control arm. Now when you look at the side effects, the adverse effects that were suffered, so primary endpoint was death for adverse events, there was no difference, and the secondary endpoints also was no difference. That was a composite of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, and cardiac arrest. Now when you tease these things apart, one thing you'll see is that there was numerically more torsades de portes among the rhythm control group. There was more ventricular fibrillation, ventricular tachycardia, no, I'm sorry, I meant there was more pulse-less electrical activity, bradycardia, or other rhythm among the rhythm control group. And finally, the rhythm control group were more likely to be hospitalized at the baseline. But overall, looking at it, when you pull all the adverse events together, there was no difference. So at that point, the takeaway from that was, you know, there's no difference between rhythm and rate control, you just kind of pick, you make a decision based on, you know, what you think was good for your patients, what was nuanced at that point. And there was even a big meta-analysis that combined studies published between 2000 and 2009 comparing rhythm and rate control. This was published by Caldera et al. in 2012, and it also confirmed what a firm showed, which was there was no difference between rate and rhythm control. So, well, maybe that's the end of the story. Except this study back in 2004 raised a couple questions. This was a secondary analysis of the AFIRM trial, and the two things that stood out was when they looked at predictors of mortality among these patients that were in the AFIRM trial, they found two things that stood out. Number one was that sinus rhythm was associated with a 50% reduction in mortality. The second one was that antiarrhythmic drug use was associated with approximately 50% increased risk of mortality. So it begs the question, maybe this antiarrhythmic medications, maybe in order we would, the idea was, yeah, getting to sinus rhythm was a good thing, but maybe the tools we used in getting there was the problem. Well, fast forward many years, we had a paradigm shift with the East AF NET trial. Now keep in mind that if you look back at the guidelines, the AFIRM guidelines from 2013, back then they were like rhythm, so catheter ablation was recommended for patients who had failed antiarrhythmic medications and all that. And that was just because we didn't have really good, we didn't have strong data for it. So fast forward here, 2020, we had this publication about how about looking at early rhythm control? Patients who have atrial fibrillation diagnosed within the past year for the first time, if you can control their rhythm early, get them on a rhythm control plan early within a year of diagnosis compared to RIT control, is there going to be a difference? That's the question that the East AF NET 4 trial answered. So in this trial, they screened about 2,800 patients, 2,789 patients underwent randomization. And so the idea was you were going to be on rhythm control. Now here rhythm control included medications and ablation. Now interestingly, when you look at the initial therapy, only 8% initially underwent catheter ablation. Majority of the patients, about 36%, were on flecainide. So amiodarone was used in about 19% of patients, dronaderone in about 17% of patients. Now fast forward down two years down the road, you see that about 19% had received ablation, about 35% were not on any medications. This is compared to the RIT control arm. And let's see what we found. Now here, so primary outcome measure was early rhythm control compared to usual care and composite endpoints were death from cardiovascular causes, stroke, hospitalization for worsening heart failure, hospitalization for acute coronary syndrome. Well, we had at five years, you could see the curves separating early within a year. And at five years, we had a 21% reduction in primary composite outcome, which included a 28% reduction in cardiovascular mortality, and a 35% reduction in stroke. Now the patients in the early rhythm control arm were more than three times more likely to be in sinus rhythm at two years of follow-up. And this study showed us that not only was rhythm control safe, because they found that there was no difference, when they compared safety outcomes, there was no difference in the rhythm control arm versus the RIT control arm. So rhythm control improved cardiovascular mortality, improved stroke at no cost to us because the safety outcomes were similar between both arms. Now so the ECF trial established that early rhythm control. Now early rhythm control here, again, we define as rhythm control within a year of AFib diagnosis, is superior to RIT control. Now does the method of rhythm control matter? Remember that in ECF NET4, they used a combination of medication and ablation. So but in this case, now with all the evolution in technology of capital ablation, how does this stack up against anti-arrhythmic medications? Some of the trials that answered this question was, there were some early cryoablation trials. Three of them in particular, there was the cryo first, stop AF first, and early AF. And what these trials looked at was, you know, now that we've decided that early ablation appears to be, early rhythm control appears to be of benefit. So if we now decide, okay, we're picking just early rhythm control, so early ablation versus early anti-arrhythmic, what do we find? And consistently across these trials, the cryo first, stop AF first, and early AF, we saw that meta-analysis of these three trials showed that there was a 39% reduction in recurrence atrial tachyarrhythmias, atrial fibrillation, and atrial tachycardia compared to anti-arrhythmic medications. And when they looked at adverse outcomes, the safety outcomes were similar to anti-arrhythmic medications. Early capital ablation did not pose a danger to patients compared to early anti-arrhythmic use. Now, to put this together, the things we see here that the benefits of rhythm control when we compare it to rate control will be number one. Rhythm control reduces the risk of major adverse cardiovascular events, as we saw from the HDF NET4 trials, improve symptoms and quality of life, reduce AFib progression. And this is the data from the AF NET4 trial showing the first thing I mentioned, reduction of major adverse cardiovascular events, 21% reduction in primary composite endpoints. This is data from the CABANA trial showing that quality of life, so CABANA trial is a trial that compared rhythm control to rate control, no, compared capital ablation to rhythm control medications, anti-arrhythmics, and showed that capital ablation had better improvements in quality of life compared to anti-arrhythmic medications. And finally, the ATTEST trial, so the ATTEST trial specifically looked at capital ablation versus drugs for rhythm control in AFib progression, meaning progression from paroxysmal AFib to persistent AFib. And what they saw was that people that underwent capital ablation, they were 10 times less likely to develop atrial fibrillation, atrial tachycardia, compared to anti-arrhythmic medications. So this right here summarizes what I just said. Reduce risk of major adverse cardiovascular events, improve symptoms and quality of life, reduce AFib progression. Now this here, I will be remiss if I don't mention the updated guidelines, the 2023 ACCAHA ACCP HRS AFib guidelines. And when you see a patient, number one is, you know, when we talk about goals of therapy with rhythm control. So one of the things they point out here is patients with LV dysfunction and persistent AFib or high-burden AFib. What they see here is that, what they say is, you know, when you look at AFib alone, when you look at heart failure alone, now when you put them together, the outcomes of these patients who have AFib and heart failure are way worse than patients with AFib alone or heart failure alone. They do recommend, you know, try to get these patients to sinus rhythm because AFib, the presence of AFib may, you know, if you've ruled out any other condition that's causing this heart failure, think about AFib as probably a driver for the heart failure. Very important to get them to sinus rhythm. The other things we've mentioned here, if you look at this two-way guideline here, you know, rhythm control can be useful to improve symptoms, reduce hospitalization, stroke mortality, reduce progression of AFib, which we've discussed. And then the other big thing about the guidelines are that now the only rhythm control modality that is a class one recommendation is catheter ablation. And when you look at it, so we have three, so there are three options right there. So number one is when you look at, it's a class one recommendation for, you know, if you found drugs to be ineffective, contraindicated, not tolerated, or not preferred, then, you know, you can proceed with catheter ablation to improve symptoms. Number two, this also comes to patient selection. You know, you have younger patients, fewer comorbidities, this might be a patient where you just go straight to catheter ablation as a first-line therapy to improve symptoms and reduce progression of AFib. And finally, atrial flutter is another one. It's a class one recommendation. You see atrial flutter, catheter ablation is useful for these patients. So in summary, I'll say early rhythm control is superior to rate control. And again, early rhythm control here is defined as diagnosis that when you do rhythm control within a year of AFib diagnosis, it is found to be superior to rate control in reducing major adverse cardiovascular outcomes, symptoms, and progression of atrial fibrillation. The other takeaway here is that catheter ablation is a first-line rhythm control strategy in selected patients. Thank you.

atrial fibrillation

rhythm control

catheter ablation

AFib progression

cardiovascular mortality