It’s No Longer a Debate: Don’t Be Late to Ablate

[00:00] stage only one extra game

[00:20] They're not been asked for volunteers. They said they overbooked the rebels. They said they had to sell them off. They reversed. There were people in the pain. They had been in the hotel. There were people in the pain. I don't know. They preferred student pain.

[00:40] And then have your book out. It's that age you can have on the other side. This is your first check. I'm going to do it. Forget it. Maybe you're like the top of the movie after the eye run. You can have it at the left. Yeah, actually for no reason. Here it comes, that audience can you grab the book?

[01:00] Okay, okay, okay. Okay, okay. Okay, okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay. Okay.

[01:20] Okay, now I'm going to start.

[01:40] Okay.

[02:00] Okay, okay, welcome everybody, we'll get started. I'll just highlight a few announcements. As usual, you can see faculty meeting next week and then some additional outside speakers will be coming. Quick break for Passover and then some fellow talks as well.

[02:20] And now I will hand it over to Dr. Rosenfeld, who will introduce our speakers today.

[02:40] Tréjo Parevis. Dr. Essin was born in Nigeria, started university in Canada, and then matriculated at the University of Alabama, Birmingham. She received her MD degree at Meharry Medical College where she was elected to AOA. Dr. Essin did her internal medicine.

[03:00] medicine training at Yale, staying for cardiovascular medicine fellowship, and is now a third year fellow. She's been active in mentoring and diversity initiatives, and her research interests have focused on myocardial infarction in diverse populations.

[03:20] Next year, Dr. Essin will be pursuing a career in general cardiology, focusing on comprehensive cardiovascular care and prevention. Dr. Trejo Pare, this is from Columbia, where she received her MD degree from the University of Antipasic.

[03:40] to Yale to be a research fellow starting in 2017, which is when I first met you. And she next did her internal medicine training at UConn, receiving the Harold N. Williams Award for Academic Excellence in Ambulance

[04:00] care. Dr. Trejo Pareilles has returned to Yale for cardiovascular medicine training in 2022 and currently serves as chief fellow. She has published a number of papers on a variety of cardiovascular topics and has also been active in mentoring.

[04:20] medical education, and promoting excellent cardiovascular care. I'm very happy to say that next year she'll be pursuing a clinical cardiac EP fellowship right here at Yale. So also on a personal level, I would really like to thank both Caro.

[04:40] and Camilla for their courage and persistence during their journeys to Yale, where on a daily basis they contribute so much to patient care and to our community. And I know where today with their combined interests on general cardiovascular care and optimizing that and electrophysmally-based care.

[05:00] physiology will provide us with a really wonderful and interesting grand rounds.

[05:20] So our topic is titled It's No Longer a Debate, Don't Be Late to Ablate. And the goal of this talk today is to increase awareness and enhance knowledge on the importance of early rhythm control and the role of ablation as a first-line therapy in selected patients with atrial fibrillation with the aim to.

[05:40] improved clinical care. And we hope that at the end of this talk will have helped you guys understand the pathophysiology of atriomyopathy in the natural course of atriofibilation, to understand the evidence supporting early rhythm control and ablation over anti-rhythmic therapy for managing atriofibilation, and to gain.

[06:00] into the clinical outcomes of patients undergoing early atrial fibrillation ablation based on patients' profile. So to put everything in perspective, we are going to start with our case. He's Mr. C. He's a 47 year old man who's presenting to emergency department with a chief complaint of a

[06:20] week of exertional dyspnea and palpitations. He has a history of AF, hypertension, diabetes, and obesity. In regards to his AF diagnosis, he was diagnosed in 2020 in the context of an emergency department visit due to symptomatic AF. He was treated with intrabenal beta-palparectin.

[06:40] blockers and restore sinus rhythm. After that, he had two additional ED visits in 2022 and 2024, also for symptomatic AF. He underwent cardioversion at that time and then was discharged. Since the time he was diagnosed with AF, he has been on anticoagulation with a DOAC, which he has tolerated well for a short time.

[07:00] Chatsvast of 2, which portends at 2.2% stroke risk per year. This time, he reports limited adherence to DOG due to lack of breath. On further review of systems, he reports recurrent episodes of palpitations and shortness of breath for the past six months for which he has used

[07:20] as needed beta blockers but has not noticed any improvement. In the emergency department, he's noted to be in AFib with RVR in the 120s. Otherwise, he's stable from a blood pressure and a respiratory status perspective. An exam, he's warm and eulogic. He undergoes further testing with a C.

[07:40] ABC and a BMP, which is unrevealing, and he also gets a trans-toracic echocardiogram that shows normal left ventricular systolic function and mildly enlarged left atrium. He receives intravenous metoprolol 5 milligrams times 3 with improvement in heart rates from 120 to 100.

[08:00] However, he remains symptomatic and continues to complain of palpitations. So the emergency doctors consult cardiology and their recommendation is to admit for TEE followed by cardioversion. So he's admitted the day after he undergoes TEE that shows no evidence of intracardiac thrombosis, he undergoes

[08:20] dose cardioversion with successful restoration of sinus redem and his discharge home on a doac on an increased beta-blocca dose and his recommended outpatient follow-up with cardiology for further management. We are going to bring back this case later in the course of this presentation, so keep it in mind.

[08:40] To accomplish our learning objectives, this is our agenda for today. We will talk about key aspects of atrial myopathy in AF. We will also go over key findings of landmark clinical trials in the management of AF, particularly those that have focused on comparing red end control to red control.

[09:00] early versus quote-unquote late rhythm control, and a f ablation versus drug therapy. As we do this, we will also go over how guideline recommendations have changed over time based on this trial data, and we will start with the 2006 guidelines. We will briefly talk about cost effectiveness and cost value of AFM.

[09:20] fibrillation and we will finish by sharing our conclusions. So to begin, what is AFib and why does it occur? Atrial fibrillation is a disorganized irregular rapid atrial rhythm with rates between 300 to 500 beats per minute. AFib often stems from ectopic action potentials that are most

[09:40] commonly generated in the pulmonary veins or from reentrant circuits that are due to insufficitial fibrosis. And the pulmonary veins are particularly vulnerable because of their high resting membrane potential, the stretch-activated channels, and the pattern of the cross-myofibre

[10:00] including genetic, environmental, autonomic, and metabolic factors. And over time, AFib leads to structural, architectural, contractile, and electrophysiological changes affecting the atria, which then contributes to atriomyopathy and in turn perpetuates atrial fibrillation. So we have categorized

[10:20] the etiologists of AFIP into local factors, those that are originating from the heart itself and into systemic factors, those that are outside the heart but contributes to atrial fibrillation and we'll explore both categories. And in terms of local factors, we know that AFIP has electrophysiological, contractural, and structural changes in the atrial.

[10:40] myocardium that drives the progressive nature of the disease and contributes to atriomyopathy. And there have been studies in animal models that have shown how rapid atropacin can alter atrial vulnerability. In a study of 22 drugs, rapid atropacin at 400 beats per minute for six weeks,

[11:00] via a transvenous pacemaker and a right atrial appendage, led to by atrial enlargement, prolonged P-wave duration, prolonged intra-atrial conduction time, and a reduction in the atrial effective refractory period. It also led to mitochondria proliferation due to disruption of sarcoplasmic reticulum, and that led to

[11:20] increase spontaneous and sustained AFib episodes. And additionally, atrial staining can occur even after brief episodes of AFib, anywhere from one to 30 minutes, and following cartovergion. And this is due to loss of myofibrils and due to glycogen deposition in myolytic spaces. And the recovery of atrial contraltility after

[11:40] restoration of sinus rhythm is variable and dependent on the duration of AFib. Another animal study showed how maintenance of AFib can prolong AFib episodes. In this study of 12 goats, automatic maintenance of AFib by an external atrial fibrillator led to

[12:00] increase in due stability by a single premature stimulus, which led to atrial effective refractory period shortening, also led to prolonged afib duration and stability. And these electrophysiological changes were known as to be reversed within one week after a restoration of sinus rhythm. Additionally,

[12:20] Ion channel remodeling also plays a role in atrial myopathy. The increase of calcium influx and spontaneous release from sarcoplasmic particulum and also to decrease in the transient outward potassium current and L-type calcium current all contribute to atrial fibrillation progression and atrial myopathy. In this figure,

[12:40] just shows how AFib induction with a fibrillation pacemaker can occur. So these are sinus episodes, and when a one-second burst of stimuli is given, AFib is quickly re-induced, and these is occurring in their short episodes of self-term induction.

[13:00] permeating AFib episodes. And then this second figure shows how AFib induction with the pacemaker prolongs over time. In this control subject, who has been exposed to AFib for about six seconds, a single burst of stimuli led to induction of AFib, which quickly terminated after five seconds.

[13:20] seconds. And then after 24 hours in AFib, the duration of AFib increased to 20 seconds before termination. And then after the subjects had been in AFib for two weeks, we see sustained atrial fibrillation. And this just demonstrates the progressive atrial remodeling that happens with AFib.

[13:40] In terms of systemic factors, this figure just highlights the strong link between atrium myopathy and comorbidities that are associated with metabolic and hemodynamic stress. These factors include smoking, sanitary lifestyle, unhealthy alcohol use, obesity or hypertension, diabetes, heart disease.

[14:00] failure, sleep apnea. And as these stresses progress, they contribute to structural remodeling, which creates a more favorable substrate for AFib persistence. And in essence, we can say that the persistence of AFib reflects the substrate for AFib. And in particular, large fibrotic and fatty atria

[14:20] are more likely to sustain AFib. So to summarize, although we've been saying is that AFib is a complex disease that's influenced by both genetic and environmental factors, and it leads to electrical remodeling, structural remodeling, and autonomic remodeling. And in terms of

[14:40] of electrical remodeling, there's calcium dysregulation and ion channel dysfunction that results in decreased action potential duration, decreased atrial refractory period, and slowed conduction velocity. And in structural remodeling, that's most commonly seen in left atrial enlargement, which correlates with atrial fibrosis.

[15:00] and that results in increased automaticity. And then changes in the cardiac autonomic nervous system can contribute to both early and delayed after the polarization and these all lead to focal ectopic firing and a reentry prone substrate that helps to sustain atrial fibrosis.

[15:20] So therefore, we can say AFib begets AFib and prevention of AFib with rhythm control would be ideal. But have we proved that rhythm control is actually better and how has our thinking changed over time? And over time, our approach to the management of AFib and rhythm control is different.

[15:40] evolved significantly. Rhythm control was not always the consensus. In fact, early strategies often equated rape and rhythm control. But today's recommendations are built on years of research that has deepened our understanding of the natural course of the disease and the benefits of rhythm control in selected patients.

[16:00] This timeline here just provides a broad overview of key landmark trials that have shaped our current guidelines. And if we look back at the patient Camilla presented initially, the recommended management strategy would vary depending on the error in which this patient was encountered. So throughout this talk, we'll take some time to review some of this pivotal studies.

[16:20] and understand how our perspective has shifted from an era where rate was considered to be equivalent to rhythm control to where we are today where we recognize the distinct advantage of rhythm control in specific population. So to begin we'll start with two landmark trials that

[16:40] were published in 2002 that shaped our initial understanding of rate versus rhythm control. This is a firm in race. A firm trial was a randomized multicentered study of about 4,000 patients. The mean age was 69, and this patient's had AFib and a high risk of stroke. And the rate control

[17:00] arm received rate-lowering medications in the rhythm control arm, underwent cartoversion and received anti-avitment drugs. And the primary endpoint was overall mortality. And after a mean follow-up of about five years, there was no difference in mortality between the rate and rhythm control arm. In fact, the patients in the rate control arm had fewer hospitalizations.

[17:20] patients because of the lower adverse drug side effects. And the study concluded that rhythm control offered no advantage and there was actually potential advantages of a rate control approach. And then the RACE trial was a randomized perspective study of 522 patients who had persistent AFib at the end of the day.

[17:40] after a prior cartoverstion. And the distribution of the primary endpoint was death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, need for pacemaker, and drug side effects. And after a mean follow-up of about two years, the primary endpoint events. So we can see here, we're similar.

[18:00] rate and rhythm control arm. And the study concluded that rate control was non-inferior to rhythm control for prevention of death and morbidity from cardiovascular causes and may be appropriate for patients with recurrence of persistent AFib after cardiophysia. So what did our guidelines reflect

[18:20] at that time after these studies. If you look back at the 2006 AFib management guidelines, we see a clear emphasis on rhythm control as the primary strategy of rate control as the primary strategy and rhythm control was reserved for specific scenarios. Cardiversion was reserved for raptor, ventricular,

[18:40] response with symptoms or when symptoms were unacceptable to patients. Antirabatmat drugs were advised to enhance cartovergion success in cases of repeated attempts of cartovergion. And catheter ablation was considered to be reasonable for preventing rare occurrence, but only in patients who had normal or malle-enlarged left

[19:00] at the atrium. And importantly, ablation carried a class 2a recommendation at the time of the 2006 guideline. And by the time we arrive at the 2014 guidelines, we see a shift in emphasis. While rate control was still recognized as an appropriate strategy, new insight

[19:20] led to the expansion of the role for rhythm control, particularly in cases where there was tachycardia-induced cardiomyopathy. Additionally, catheter ablation gained a stronger support, and it was now being recommended for symptomatic AFib in patients who had failed prior anti-arithmic drugs. And importantly, ablation was a great-

[19:40] it to a class 1a recommendation reflecting the growing evidence base and the effectiveness in rhythm control strategy. So guidelines have increasingly focused on rhythm control, but for a long time whether rhythm or rate control was better remained inconclusive. So this is a

[20:00] summary of some of the most relevant clinical trials that compare rhythm control, including ablation and antiarrhythmic drugs with rate control. This included 18 trials and a total population of more than 17,000 patients. In terms of the patient's demographics, patients mean age was 68.

[20:20] Most of them were males over 60% and 31% had paroxysmal AF. The primary outcome was cardiovascular death and the secondary outcomes were all cause death, stroke, and heart failure hospitalization. And they showed that a mean follow-up of 28 months, a rhythm control strategy was

[20:40] associated with better outcomes in terms of cardiovascular death, stroke, and heart failure hospitalization with a HSA ratio of 0.8. Notably, they also saw that within the rate control arm, more ablation use was associated with better outcomes in terms of cardiovascular death. Specifically, the risk of cardiovascular disease is not as high.

[21:00] there was a hazard ratio reduction per every 20% increase in the use of ablation. So although over time, the emphasis on rhythm control has become stronger in both ablation and drugs and options, when we look at the timeline of when anti-arrhythmic drugs became first FDA-owned drugs.

[21:20] approved, we see that it was a very dynamic field before the early 2000s. However, when we compare that to the timeline to when we first heard about different ablation techniques, we see that after the early 2000s, the research has mainly focused on different ablation technologies and there has not been

[21:40] really any advances in the drug field. Software learning that patients with AF do better with rhythm control over rate control, naturally the next question was, what's the better rhythm control approach? Is it ablation or drugs? And to answer that question, we are going to go over the key findings.

[22:00] of these three Larmax trials that compared ablation with drug therapy in the patient population in whom ablation was acceptable at that time. And these were the patients in whom drug therapy had previously failed. So before going into the trial data, we wanted to go over some of

[22:20] the general aspects of AF ablation. As Cara explained earlier, the pulmonary veins play a critical role in generating AF, and because of the critical role, a variety of ablation techniques have been used for electrical isolation of the pulmonary veins from the left atrium.

[22:40] or PVI has become the standard approach for a first ablation procedure in patients with AF. There are different technologies that can be employed for PVI, which include radiofrequency that uses thermal energy, cryoablation that uses cold temperatures, and pulse field ablation, which is the newest electrical product.

[23:00] newest emerging technique that uses electrical pulses. In addition to PBI, it is not uncommon that additional ablation procedures are employed, and this is a summary of the most common lesion sets marked in red. Of note, the data on these supplementary ablation techniques is not as strong.

[23:20] as PVI. Starting with the trials, the first trial was Thermocool AF. This was a prospective multi-center trial that included patients with paroxysmal AF who had had at least three episodes of symptomatic AFif within the six months prior to enrollment and they had previously failed.

[23:40] at least one anti-arrhythmia drug. Patients were randomized in a 2 to 1 ratio to ablation with radiofrequency or drug therapy. And they were followed for 9 months. And arrhythmia recurrence was monitored with trans-elephonic monitoring for all symptomatic events and at scheduled times, weekly for the first time.

[24:00] first eight months and then monthly for the entire follow-up time. They enrolled over 160 patients. Most of the patients were male, over 60%. The mean age was in the mid-50s, and the median AF duration and the time of enrollment was 5.4 to 6.2 years.

[24:20] These are the Kaplan-Meier curves for some of the most important endpoints, which include protocol-defined treatment failure, defined as recurrent symptomatic AF or change in antiretomy therapy after the three-month blanking period, symptomatic atrial arrhythmia, and any atrial arrhythmia. The continuous

[24:40] represents catheterablation and the dotted line represents antiarrhythmic drug therapy. And as you can see, a nine-month follow-up in patients with symptomatic AF who had failed at least one antiarrhythmic drug previously, pulmonary vein isolation with radiofrequency catheterablation was

[25:00] associated with less treatment failure and less recurrence of any atrial arrhythmia. They also noticed that patients who underwent ablation experienced a greater quality of life. This was first noted during month 3 of follow-up and the benefit was sustained during the 9 months. And lastly, they

[25:20] also reported that ablation was safe. There was no significant difference in measure-related adverse events at one month. The second trial is STOP-AF, the pivotal trial. This was a prospective multicenters randomized trial that included patients who had had at least two episodes of symptomatic

[25:40] AFib within the two months prior to enrollment. They were randomized in a 2 to 1 ratio to cryoablation versus drug. Arrhythmia recurrence was monitored with weekly trans-elephonic monitoring and holders at 6 and 12 months regardless of symptoms. They enrolled over 300 patients,

[26:00] Most of them were male, over 70%, and almost 80% had paroxysmal AF. This is the Kaplan-Meier quorf for the intention to treat primary effectiveness endpoint, which was continued treatment success. The continuous line represents the ablation arm that used cryovalent.

[26:20] and the dotted line represents the drug group. And as you can see, the patients who underwent ablation experienced freedom from treatment failure almost 70% versus 7% within the drug arm. So the authors concluded that at one year follow-up in

[26:40] In patients with symptomatic paroxysmal AF, for whom at least one antirhythmic drug had previously failed, cryo-balloon ablation was an effective alternative to drug, and they also showed that ablation was safe. Last, we wanted to highlight Cabana. This was a large multicenter randomized clinical treatment.

[27:00] trial that included patients from 10 different countries, including the US. Patients had symptomatic KF, they were 65 years or older and had at least one risk factor for a stroke. They had to have at least two episodes of pyroxysmal AF within the six months prior to enrollment or one year before.

[27:20] episode of persistent AF within the six months prior to enrollment. They enrolled over 2,200 patients. 42% had paroxysmal AF, 57% had persistent AF, 63% were male, and the median age was 68 years. This is a Kaplan-Meier question.

[27:40] for their primary endpoint, which included a composite of death, disabling stroke, cardiac arrest, or serious bleeding. In blue, we can see the drug therapy arm and in orange we see the results for the ablation arm. And for the primary endpoint, they did not see a benefit of catheter ablation when

[28:00] compared to drugs. However, when they performed the intention to treat analysis for the endpoints of recurrent atrial fibrillation after the three-month blanking period and cardiovascular mortality or cardiovascular hospitalization, they saw that patients who underwent ablation experienced better outcomes. And they also reported

[28:20] that that ablation was safe. So what have we learned? That in patients with AF, particularly those who have not responded to drug therapy, either due to a high burden of recurrent AF or adverse effects to drug therapy, ablation is associated with a lower risk of recurrent symptomatic AF.

[28:40] lower risk of hospitalization from cardiovascular cause, and lower cardiovascular mortality. They also experience a greater improvement in quality of life when compared to using another anticharrhythmic drug. Now that we know that ablation is both safe and effective in patients who have failed.

[29:00] prior anti-arithmic drug, but what about ablation as a first-line therapy, which we can regard as an earlier ablation, quote-unquote. And the role of catheter ablation as first-line therapy for rhythm control has evolved over time. There are several multi-centred randomized control trials that have demonstrated the superiority over the years.

[29:20] anti-arithmic drugs in patients who have symptomatic parxis small atrial fibrillation and these trials are listed on the right. And this table is a summary of the six key landmark randomized controlled trials that have compared catheter ablation versus anti-arithmic drugs as first-line therapy, published between 2005

[29:40] in 2021. The sample size varied between 32 and 149. The mean age of the patients were in the mid to late 50s slash early 60s. They had mildly enlarged left atrium. They had preserved ejection fraction in this group and they had proxysmor afib. And they underwent and

[30:00] with either radiofrequency or cryobalamin. And the primary endpoint was afib recurrence and afib burden and follow-up was an average of one to two years. And results show that the recurrence of any

[30:20] atrial arrhythmia was significantly lower in the ablation group. And this trials collectively highlight at the advantage of ablation in demonstrating higher success rates in maintaining sinus rhythm and lower affip recurrence compared to antiarrhythmic drugs. And what about special populations? In studies of

[30:40] Very young adults who are less than 35 years of age with both symptomatic, parxis, small, persistent AFib, catheter ablation has been shown to be both effective and safe. And structural heart disease and obesity were key predictors of AFib recurrence in that group of patients. And studies comparing radiofrequency catheter ablation in the elderly

[31:00] population, a study looked at octogenarians greater than 80 versus younger patients who are less than 50, ablation for symptomatic afib was both safe and effective in that group. But some studies highlighted the need for those elderly patients to be fit, something that's termed elderly fit.

[31:20] And to also point that paroxysmal afib ablation in the oxogenarian population was similar in terms of clinical effectiveness with the younger patients, but when it came to non-paroxysmal afib, it was less effective, but still clinically effective, and just highlighting the fact that it's very crucial to select the appropriate

[31:40] elderly patient for ablation. And in terms of ablation for heart failure, we know that AFib and heart failure frequently co-exist together in a vicious cycle and they perpetrate each other where we can say AFib begets heart failure and heart failure begets AFib. And this interplay just really makes it crucial for us to

[32:00] to ensure rhythm control in that group of patients. In the non-randomized control trials of catheter ablation in patients with AFib and heart failure with preserved ejection fraction that have reported improved quality of life and survival benefits with sinus rhythm restoration. And a recent observational study further demonstrated that catheter-driven sinus rhythm

[32:20] restoration led to both improvement in the invasive hemodynamic parameters and exercise capacity in patients with preserved ejection fraction. And then in patients with reduced ejection fraction and heart failure, several studies have demonstrated the potential benefits. This table highlights randomized controlled trials

[32:40] instead of compared catheter ablation versus medical therapy in that group of patient. These are data published between 2008 and 2023. Sample sites varying from the 40s to the 700s. The patient had a mix of paroxysmal afib and persistent afib, a big chunk of the patient.

[33:00] had persistent AFib. Their New York Heart Association class was 2 and 3. They had baseline reduced ejection fraction. It was a mix of ischemic and non-ischemic etiology for their reduced ejection fraction, but most commonly non-ischemic. And they had at least moderately enlarged left atrium.

[33:20] was anywhere from six months to about four years, and the results show that ablation reduced aphid burden in this group of patients. A pooled analysis of the data showed both reduce aphid burden, decrease hospitalization, and improve survival in patients with heart failure with reduced ejection fraction.

[33:40] Beyond the rhythm control, it frequently led to LVF improvement in some of this patient, which just highlights the broader role and the broader impact of cardiac function of ablation. I want to take a couple of minutes to highlight the CASEL-HTX trial, which was an open-label single-centre study that was-

[34:00] done in Germany. It investigated catheter ablation plus guideline-directed medical therapy versus guideline-directed medical therapy alone in patients who have symptomatic heart failure and end-stage heart failure who have been referred for heart transplantation. And the primary endpoint was the composite of death from any cause, alvat implantation.

[34:20] and urgent heart transplantation. And this primary endpoint was significantly lower in the ablation arm. And this just also highlights the potential role of ablation and improvement outcomes in even the sickest of heart failure patients. So to summarize, in patients where sickest

[34:40] Since 1960 to 70 years old, with parcystomol persistent AFib, with New York Heart Association class 2 to 3 and reduced ejection fraction, and at least moderately enlarged left atrium,

[35:00] decrease all cause death. However, proper patient selection is key to maximizing the benefits from affib ablation. And these are indicators for the greatest improvement in LV ejection fraction. That's a lower NYHA class, non ischemic etiology for their heart failure, persistent affib and narrow QRS.

[35:20] absence of CMR-detected atrial or ventriclevibrosis, postcard diversion, ejection fraction, and New York Heart Association class improvement, absence of severe atrial dilatation, and afib preceding their heart failure diagnosis or simultaneous diagnosis of their afib and heart failure.

[35:40] So after this point, we have reviewed the data on rhythm being superior to rate control approach and on ablation being superior to anti-arrhythmic drugs, which ultimately leads us to think of ablation as a first-line therapy. However, what does first-line really mean in terms of timing? So ist ablation a first-line therapy?

[36:00] was the first study to look into timing from AF diagnosis to rhythm control. The East AVNet investigators aim to test whether a strategy of early rhythm control could be associated with better outcomes in patients with early AF than evidence-based usual care. For this, they designed a parallel group

[36:20] Open-blinded outcome assessment trial. They included patients that were 75 years or older who had diagnosis of early AF, which was the teramine as within a year prior to enrollment. Patients had also one cardiovascular condition if it was TIA or a stroke, or at least two of the following.

[36:40] 65 years or older, female gender, heart failure, hypertension, CAV, diabetes, CKV, or LVH. They randomized over 2,700 patients to rhythm control and to usual care. Within the rhythm control arm, most of the patients were diagnosed with a severe illness.

[37:00] of the patients received treatment with drug therapy, antiarrhythmic drugs, during the initial randomization, about 8% of the patients underwent ablation and at year 2, 20% of them had undergone ablation. Within the usual care arm, most of the patients were treated with rate control medications

[37:20] year 2, about 7% had undergone ablation. Notably, the median time of AF diagnosis at the time of enrollment was 36 days. That means that rhythm control was implemented pretty early in the course of AF. These patients were followed for 15 years.

[37:40] 5.1 years, and these were the outcomes. The primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization from the compensated heart failure, or ACS. And this is the table that summarizes the data on the primary outcome. In the last column, we see the treatment effect,

[38:00] expressed as a hazard ratio with a confidence interval in parentheses. So for those patients who underwent rhythm control, they experienced better outcomes when we talk about the primary endpoint with a hazard ratio of 0.7. And when we look into the separate components of the primary outcome, that benefit is so important.

[38:20] stain for stroke and death from cardiovascular causes. And this is the graph for the primary outcome. So the East Avnet authors concluded that patients who underwent early rhythm control was associated, had lower risk of adverse cardiovascular outcomes than usual care.

[38:40] So we just there from East Avnet that redem control is better. And we had also learned that ablation is better to drug therapy when we talk about redem control. But when we talk about ablation, what is early? So to answer this question, we are

[39:00] going to look into the data on DAT or diagnosis to ablation time. So this comes from a meta-analysis that included six observational studies and over 4,900 patients. And this is a forest plot for the relative risk on AF recurrence after ablation with pulmonary

[39:20] vein isolation. They perform a random effects model and they reported a relative risk for shorter DAT defined as within a year after ablation of 0.7, which essentially translates to the fact that a DAT of one year or less was associated to a 27.

[39:40] lower risk in atrial fibrillation recurrence postablation. So by now, we hope you are convinced that early rhythm control is better and that within the rhythm control approaches, ablation is the way to go. However, it is also important to keep in mind that ablation may not be the best approach for all people.

[40:00] patients and that actually there are certain patients in whom ablation should be avoided. These populations include patients with advanced infiltrative cardiomyopathies, patients with untreated severe mitral valve disease. And in general, all those patients where we anticipate the

[40:20] ablation will not be successful due to an overwhelming atrial substrate or underlying physiologic processes that are going to perpetrate a high risk for afib and just make very challenging maintenance of sinus redden. So this table is taken from the 2023 ACC HRS guidelines and is

[40:40] It's a very good overview on the factors that favor rhythm control. So these factors include patient's preference, young age, although as Kairo mentioned, there's data that patients even in the 80s can benefit from ablation, shorter history of AF, which also translates into shorter DAT, smaller left atrium.

[41:00] size, more symptoms, difficult to control heart rate. And there are certain subpopulations in whom ablation may actually derive greater benefit, particularly those with left ventricular systolic dysfunction. So the 2024 electrophysiology clinical consensus statement that

[41:20] was released last year in which the European and the American Epi Societies participated, also talk about pre-procedural factors that can help us determine risk for AF recurrence after ablation. These factors include AF type and duration, left atrial size, electrocardiac type, and atrial type. Okay.

[41:40] cardiographic predictors, and preprocedural imaging of atrial structure. These may provide relevant prognostic information and will help guide a patient's selection to determine candida c4 ablation. So in terms of AF type and duration, we know that although postablation rhythm monitoring

[42:00] significantly varies when we compare different clinical trials. In general, patients with paroxysmal AF tend to have less affib recurrence after ablation when compared to those with persistent AF. And in terms of DAT, shorter diagnosis to ablation time also translates to less affib recurrence.

[42:20] In general, the data suggests that per each year increase in DAT, there's an increase in AF reparance of 20%. In terms of left atrial size, we know that this is an indicator of atrial myopathy and so it can perpetrate AF. Studies have looked at this.

[42:40] look into different parameters to evaluate left atrial size. There are linear parameters and also volume, which is better. And actually, volume has been shown to be an independent predictor of recurrent A-fiff post-tabulation. There are also several ECG predictors that can be used to evaluate left atrial size.

[43:00] evaluate atrial substrate, particularly P wave duration, P wave dispersion, and specifically a P wave duration of more than 150 milliseconds on a 12-litre amplified ECG has been shown to identify those patients with persistent AF who are at higher risk to have recurrent AF if following PVI.

[43:20] These P-wave indices also help identify the extent of the low voltage substrate in the atrium. And lastly, atrial structure assessed by different very procedural imaging. So the two specific structural changes that have been studied are atrial fibrosis and lipids.

[43:40] left atrial epicardial adipose tissue, which help identify those patients with advanced atrial remodeling and thus those who are less likely to respond to a fever ablation. Atrial fibrosis can be detected with LGE, with cardiac MRI, and it has been shown to be an independent predictor of AF recurrence status post-PVI.

[44:00] and left atrial epicardial adipose tissue, which can be quantified with cardiac CT, has also been shown to have a negative impact of AF ablation outcomes, particularly it has been associated with a higher risk for AF recurrence following ablation.

[44:20] reviewed some of the most relevant data explaining why a f ablation as early first-line rhythm control should be preferred. We know that early rhythm control with ablation in selective patients is associated with better cardiovascular outcomes in terms of mortality, hospitalizations, and

[44:40] that also leads to improved quality of life. And we know that the impact of catheter ablation is a class effect. So it is irrespective of the ablation technology use. All this to say that invasive intervention early in the natural course of AF results in favorable outcome with shorter D-Cids.

[45:00] the DAT related to the increased likelihood of arrhythmia recurrence, repeat ablation, and adverse cardiovascular outcomes. So we hope with the data we presented so far that you're convinced that ablation should be first-line. But what is in the current guidelines? According to the 2023

[45:20] ACCAHA guidelines for atrial fibrillation management. Viribium control is recommended. Specifically, catheteroblation is recommended as a first-line therapy in selected patients with paroxysmal AFib. Additionally, for patients where anti-abidemic drugs are not an option, whether due to contraindication or patient's preference, catheteroblation

[45:40] ablation remains a recommended strategy for rhythm control. And while catheter ablation as a first-line therapy in patients with persistent AFib has not been fully evaluated, we know that its effectiveness in reducing the burden and recurrence in both parxismal and persistent AFib are similar. So according to the 2024 European

[46:00] Heart Rhythm Association and Heart Rhythm Society consensus statement, catheter ablation remains a beneficial option for patients with both paroxysmal and persistent atrial fibrillation. And this just reinforces the role in rhythm control strategies. So we know we should be referring for a

[46:20] ablation, but what do we need to do before referral? It's imperative that we manage risk factors to optimize and improve the outcomes of ablation. So optimizing heart failure medications, encouraging moderate to vigorous exercise, blood pressure control, diabetes control, complete cessation of tobacco use.

[46:40] a healthy BMI, minimal to no alcohol consumption, and treatment of sleep apnea with CPAP. So these are all factors that, you know, we should take very seriously before referring patients for ablation. So before we conclude, we'll briefly discuss the economic value and healthcare utilization.

[47:00] of catheter ablation. A key consideration in catheter ablation for AFib is the cost effectiveness, and this evaluates which intervention provides the highest value for the cost associated. The value of an intervention is measured in quality, which is quality-adjusted life years.

[47:20] measures both the quantity and quality of life that it's gained from an intervention. And the incremental cost-effectiveness ratio, or IHSA, compares the cost-effectiveness of an intervention against the best available alternative. And it takes into consideration the cost of the new intervention.

[47:40] minus the cost of the alternative divided by the quality of life gain from the new minus the quality of life gain from the alternative and it comes up with a value. And according to the ACC and AHA guidelines, an ICER of less than 150,000 per quality gain

[48:00] is considered to be cost effective and an ICER of less than 50,000 per quality gain is considered to be highly cost effective and somewhere in between is the intermediate value. So studies have shown that capital ablation for symptomatic AFib provides intermediate economic growth.

[48:20] economic value compared to anti-arrhythmic drug with an iser of around 58,000 per quality gain. So while ablation is costly upfront, it provides significant value by improving symptoms and clinical outcomes. And the initial higher cost of ablation may be offset over time by the reduction of cardiovascular disease.

[48:40] hospitalization. And then when evaluating the cost-effectiveness of first-line cryoablation versus drugs for symptomatic paroxysmal affib, data from these three studies, cryoafers Stup AF and early AF, showed an average ICRF around 24,000 per call again, which is highly cost-effective.

[49:00] And then the CABANA trial further supports the economic value of ablation. In the overall cohort, it was around 57,000 per quality gain. And this was driven primarily by the quality of life improvements in that sub-study. And then in the patients with a heart failure and a heart failure subgroup, it was around

[49:20] around 54,000 per quality gain. And this was driven by both quality of life and survival benefits in that heart failure. So these findings just highlight that catheter ablation is economically attractive. It's an attractive alternative to drug therapy, particularly in heart failure patients where we see an improvement in.

[49:40] not just quality of life, but also in their survival. So essentially, if we're able to totally alter the natural history of AFib, which is what early ablation does, we can offset the long term costs of ablation by reducing need for lifelong anti-arbitrate drugs, hospitalizations, and complications that are so

[50:00] associated with atrial fibrillation. So, going back to our case, in summary, a young man with cardiovascular comorbidities with history of paroxysmal AF, symptomatic, who required multiple hospitalizations due to symptomatic AF, and who has carried that

[50:20] diagnosis of paroxysmal AF for a couple of years. These are the options that we have to manage him. And we hope that after attending this presentation, all of you answer option E, which includes a promotion of lifestyle modifications as well as talking to the patient about PVI and referring

[50:40] to EP if appropriate. As a bold part, more than 12,000 patients carry diagnosis of atrial fibrillation within the Yale-New Haven system and expectedly will lack human resources within the cardiology and EP departments to see all those patients. So it is very important not only that early but also well triaged.

[51:00] referrals are done for optimal care of these patients. To conclude, AF induces electrophysiologic contractile and structural changes that lead to disease progression, which we want to avoid. And so early rhythm control and early rhythm control with ablation is preferred.

[51:20] An ablation for atrial fibrillation is disease-modifying and more effective than anti-abithmic drugs and therefore improperly selected patients will prevent disease progression and related long-term adverse outcomes. Early AF ablation lowers the risk of recurrent atrial tachyrhythmias, reduces AF-

[51:40] burden, improves the quality of life, reduces symptom burden, lower the rates of hospitalizations, improves mortality, and overall reduces health care utilization.

[52:00] importance of early rhythm control and catheter ablation as first-line therapy to facilitate timely referral and early intervention. So, before we finish, we wanted to share a project we have been working on for some time called Atrial Harmony. This has been a team effort on which me

[52:20] and other trainees from these and other institutions have participated, mentored by some of our amazing electrophysiology attendings. The app is not ready yet, but we anticipate we will be launching in June 1st. This is a tool designed to help physicians and healthcare providers take care of patients with

[52:40] It is primarily tailored for internal medicine and primary care physicians and providers and early cardiology trainees. It includes different modules to help decide on anticoagulation, to help with decision making, to determine bleeding risk, to decide

[53:00] and rate and rhythm control, determining which agents, monitoring, dosing, including ablation candidacy, and the tool is grounded in the recently released 2023 HRS, ACC, and H8-violence. This is a screenshot of the RVR assist module for inpatients.

[53:20] So for those who are interested, you are welcome to scan the QR code and subscribe to get updates when it releases on June 1st.

[53:40] for her amazing mentorship. It was an honor and a pleasure to work with you, Dr. Rosenfeld. Thank you so much. And also special thanks to Mr. Richard Weiss as Dr. Rosenfeld's husband. His assistants with our title wish we loved. We really want to just honor that. Thank you all. Thank you.

[54:00] Thank you. That was excellent. I'm going to be great to learn about that website upcoming. I will pass it over for questions now. This isn't really a question so much as a comment. First of all, fast-forward.

[54:20] fabulous tour through the data on afib ablation that was really super, both of you. And you know, I think a firm, in general, it takes trials like, you know, supposedly 10 years to get into practice. A firm took a day and has done a disservice to afib patients for a decade, over a decade now. And so I think the fact that

[54:40] I think the fact that you're trying to get out there, the concept that in fact rhythm control through oblation is better is just so important. And you know, I just want to say one other thing about cabana. So cabana showed a negative outcome as far as the primary outcomes, but the quality of life was better from the get-go. And one of the most interesting

[55:00] comments I heard about Cabana was a panel that included, it was shortly after Cabana, and it included a patient advocate who started sapefib.org, sort of a well-known patient in the field. And people said, you know, Melanie, what are your constituents saying about Cabana? And she said, the main thing I hear is outrage.

[55:20] that a study that showed improved quality of life is being called negative. And I think that tells us what patients care about. And I'm so glad that the medical aspects have caught up so that patients can benefit from this.

[55:40] that you actually recommend that we do a lot of secondary prevention or blood pressure. And you mentioned the diabetes. Is there any study going on to see the effect of GLP1 receptor agonist have any effect for the erython? Yes. In fact, I was at a session that I was at a couple

[56:00] years ago. So I think there is one showing that there's improvement. There's an improvement. Yes. There's the answer. So you talked about pulmonary vein ablation. Did you look at all a ganglion at plexi ablation because there are advocates for that.

[56:20] that as well.

[56:40] if you want to look at that to answer that question. I don't know. Most of the trials really don't include PVI and kind of additional ablation techniques are left at the discretion of the side investigators, but we didn't see anything on the combination of it. And overall the data for all those additional things that you do before, besides PVI.

[57:00] is much less strong than just the data for PBI.

[57:20] mean. So congratulations, you did a great job and it's really a great honor that Dr. Rosenfeld was here for you guys. And I think just kind of echoing all the data that you guys mentioned specifically for patients with amyloid, the raid control is really not an option until it has to.

[57:40] to be because we have nothing left. But a lot of the patients, particularly those in early stage amyloid that get ablated, have a wonderful quality of life. I would say probably symptomatically feel better even than being on TTR stabilizers and whatnot because that is really just a key component.

[58:00] into the pathophysiology of their symptoms. So great talk.

[58:20] Let's go to our title so you can include it.

[58:40] Just tell me a story.