Good day, I am Hakeem Ayinde, cardiac electrophysiologist at the Cardiology Associates of Fredericksburg, Virginia. Today we'll be discussing strategies for rhythm control. I have no disclosures. We are going to talk about options for pharmacotherapy. How do we choose an anti-rhythmic drug based on a patient's characteristics? We're going to talk about ablation approaches, what are the current ablation modalities we use, their strengths, their weaknesses, and finally we're going to be comparing evidence on ablation versus anti-rhythmic drugs for rhythm control. The Vaughn-Williams classification of anti-rhythmic drugs at baseline has four classifications. Now there are more, but for just basic knowledge, we have four classes. Class 1, 2, 3, 4. Class 1, the sodium channel blockers, which are subdivided into class 1A, 1B, 1C. Class 1A, they moderately block fast sodium channels. An example is quinidine, procainamide, disoperamide. Now think of procainamide specifically, it's important to know that for AFib, the active form is called NAPPA. There's metabolism of procainamide to the active form and it is metabolized in the kidneys. Now we specifically use this for pre-excited AFib to control rates. So when you have a patient with rapid pre-excited AFib, this is a medication to consider. Class 1B medications, lidocaine, maxillitine, are typically used for ventricular arrhythmias. We do not use them for atrial arrhythmias, so we're going to skip that. Class 1C agents, so they do have significant sodium channel blockade. Good examples are the flecainide and the propafenone. I'll say they are the workhorse of rhythm control for paroxysmal AFib. Now flecainide is typically excreted. It's metabolized in the liver and excreted in the kidneys. Propafenone is also metabolized in the liver. So we have metabolizers, you know, metabolism of propafenone depends on, there's some polymorphisms there where you can have slow metabolizers or fast metabolizers. So that's something to note. Now some people use this as a pill in the pocket. You take a high dose when you go into AFib to acutely convert AFib on an outpatient basis. Now a quick thing to note here is that there are studies that have shown that kidney function does not affect propafenone levels that much. So when we're going to pick this medication, like if somebody has liver disease, you want to avoid both medications, flecainide and propafenone, or if it's just kidney dysfunction, you might be able to use propafenone. We have to worry about flecainide because you need to excrete it through the kidneys. Class II agents are Sotolol beta blockers, and Sotolol falls under the category. Class III are potassium channel blockers. Again, Sotolol, so Sotolol is a beta blocker as well as a potassium channel blocker, so it falls under Class II and III. Ibutelide is a pure potassium channel blocker. It's IV medication given in hospital for terminating AFib or HL flutter in the acute setting. Dufetilide is an oral potassium channel IKR blocker. Dronetarone and amutarone actually have properties of all four classes, so we actually should put them under other class. Now the thing to note about Dufetilide, Sotolol is excreted in the kidneys, so kidney function is very critical. Potassium, magnesium levels are critical in these medications because they do prolong QT. And then your Class IV agents are your non-dihydropyridine calcium blockers, verapamil, diltazum. You want to avoid these drugs in patients who have low liver ventricle ejection fraction. Now let's focus specifically on the common drugs we use for AFib management. Class I C agents are a frequent go-to for paroxysmal AFib, flecainide, propafenone. These medicines are usually well-tolerated by many patients. There's risk of toxicity in patients with liver disease, kidney disease for flecainide, or patients with conduction disease. So you have to be careful if you see somebody who has a white QRS. These medications, because of how much they block sodium channels, they can, people who have conduction disease, they can actually cause hybrid conduction blocks. You monitor QRS within these patients to determine whether you need to back up on the pill. So I will sometimes stop this medicine if the QRS gets really wide. Especially at faster heart rates, because they do cause rate-dependent sodium channel block. Now the class III drugs like sotolol and dufetilide, you have to, significant, they do prolong the QT. So you worry about TORSAD in these patients. Dufetilide has a black box warning that it has to be initiated in the hospital. So you have to be in a steady state before you discharge the patients on the appropriate dose. You want to avoid these medications when patients have bradycardia, because bradycardia is more likely to promote risk of TORSAD. Significant kidney disease, because these medicines are excreted in the kidneys. And when you initiate them, you have to monitor your EKG closely. Class drugs like mutarone, dronetarone. Mutarone has the highest efficacy for rhythm control, but it also has the highest toxicity. In fact, in general, one thing to know is all these antiarrhythmic drugs have what we call a narrow therapeutic window, therapeutic index. The effective drug, the effective dose is not far from the toxic dose. So a lot of times you don't have a huge margin with these medications. So you have to be careful when you escalate doses. So with mutarone, you have to, because of side effects, you monitor thyroid, liver, lungs, eyes, even concussive neuropathy also. What we advise is for mutarone, if you can choose other drugs, you want to stay with mutarone, especially for paroxysmals. Now, when you've tried other medications that have failed and mutarone is the only choice you're left with, just if you have a good monitoring strategy, you might try it. And we also say try to use the lowest effective dose for long-term control. Dronetarone is similar to imutarone, and the black box warning for dronetarone is you do not want to use it in people with permanent HIV or people who have symptomatic heart failure. There's actually increased risk of mortality in this group of patients. Now, this is a summary slide for things to watch out for, for antiarrhythmic drugs. In general, they all tend to promote bradycardia. So if a patient is bradycardic, that's probably not a patient you want to use antiarrhythmic drugs on. Conduction system disease, a lot of these drugs do worsen conduction disease. So you have to be careful in introducing antiarrhythmic drugs in patients. Antiarrhythmic drugs in patients who have sinus node dysfunction or some level of conduction disease. Prolonged QT, most of them, it's hard to prescribe most of them, especially class 3, class 1C agents in patients who already have prolonged QT. Hypokalemia, hypomagnesemia, these drugs may be poor rhythmic in patients who have hypokalemia, hypomagnesemia. When you have renal impairments, you want to, so flecainide is excreted in the kidneys, so you want to watch if you're on flecainide, perhaps stay away from it. Sertol, Defedolide, you have to watch. These are also excreted in the kidneys. When a patient has a significant hepatic impairment, now then you have to worry about amiodarone, flecainide is another one, and also propafenone. LV dysfunction, so there was a CAST trial that, you know, patients who had recent MI when they were admissed that class 1C agents had a high risk of mortality. So in general, we tried out what class 1C agents in people who have significant lip ventricle dysfunction or significant scarring in the lip ventricle, what we say, just structural heart disease. And then you also watch out for drug interactions. For example, Sotolol is one that does interact with delpazumab, rapamil, so you want to look at these drug interactions when you're prescribing antirhythmics. Amiodarone and digoxin also do interact, so you want to stay away from that combination. Now we're going to switch gears to ablation. So this is the pivotal trial that looked at the distribution of atrial fibrillation triggers, and most triggers were found to be localized in the pulmonary veins. So published by Heisiger et al. in 1998, this is really what started our approach to a universal foundational approach for a-fib ablation where we do pulmonary vein isolation. Now we're going to talk about the basic, so there are three common modalities we currently use for atrial fibrillation ablation, radiofrequency ablation, cryoablation, and pulse field ablation. Radiofrequency ablation is the oldest modality of all three, and at the current state of the technology, we generally use irrigated catheters. So current is delivered through the catheter, and at the catheter tissue interface, there's heating from conductive and resistive heating, and this heat destroys the local tissue. We do watch for changes in impedance, a sudden drop in impedance kind of tells us that we've achieved a durable lesion. These catheters have contact force, so it gives you feedback on how much you're pushing. So that's a good safety feature. And so we deliver spot lesions, and you just kind of go step-by-step spot lesions until you go around each pulmonary vein. Now, so I'll just talk about the major limitations of this unique limitations of each modality. For radiofrequency ablation, the feared complication is a thermal injury of the esophagus, leading to atrial esophageal fistula. This tends to, it's rare, it's been reported, one in 1,000 to up to one in 10,000. It really varies by study, but it's really rare, but it's a feared complication because mortality exceeds 50% when it happens. And the other problem is it happens really late, like two to six weeks after ablation, so it's something that may not be picked up early. The other things about radiofrequency is it needs a high degree of operator skill delivering spot lesions compared to some other modalities. And also when you're delivering the spot lesions, making sure that each lesion is transmural so that you're not leaving gaps because these gaps are what can cause flutters, atrial tachycardias, after ablation. And before we used to have a risk of pulmonary vein stenosis, but now that we've learned to ablate more entirely instead of inside the vein, this is now a rare occurrence. Then we'll move to cryoablation. So cryoablation is a single-shot type of ablation where you, so it's a balloon-based technology where you seal the entrance of the vein and deliver really cold temperatures. If you form ice crystals in the cells and there's osmotic lysis and death of these cells. Now, the major limitation of cryoablation is injury to the phrenic nerve when you're freezing around the right pulmonary veins. It's quoted as around 4% of cases people do develop phrenic nerves injury or palsy. Now, the good news is most of these do resolve like of 100% of cases that get phrenic nerve injury, only 2% of them have symptoms at one year. And at two years, that goes down to 1%. There's a small risk of atrial spondylolisthesis with cryoablation as well. Now, the most recent technology here, what's the new kid on the block is the pulse field ablation. And here it uses, so this is, we call this, generally we call this a non-thermal ablation where what we're doing is we deliver very high voltage. And so this high energy creates pores. So it creates holes in cells and these cells lose their membrane function and die by apoptosis. The most important safety, the way to look at pulse field ablation is we're still learning, it's still new technology and we're still learning about it. But one of the critical things we've found is safety. And I think that's number one. So when you look at the feared complications of cryo and RF ablations, the ablation of pulse field, when we do pulse field ablation, we tend to spare, it's very cardioselective. So we, it spares our surrounding structures. So there's no injury to the esophagus. And there's also, we also spare the phrenic nerve. So being cardioselective is one very good safety feature of it. Now, what are the possible complications of pulse field ablation? When we look at a manifest 17K study, you know, we saw a few things that were interesting and most common of that was a gas bubble formation. And there's about a three to 9% incidence of silent cerebral events. I mean, this may not be, this have not been shown to cause clinical strokes because the strokes in that study was about 0.12%. So yes, we see gas bubble formation, but what does it really mean clinically? We're not clear yet. There was some trans-infrenic nerve paresis when people did, when people use it around the SVC, but generally for left-sided pulmonary vein isolation, we didn't see that. Coronary spasm, if you deliver energy close to coronary arteries, this, you can cause spasm. The incidence was about 0.14%. So we tend to administer nitroglycerin when we're doing pulse field around the coronary arteries. Red blood cell hemolysis leading to acute kidney injury occurred in about 0.03%. And we found out that this is more likely to happen if you're delivering pulse field and we don't have good tissue contact and you're pretty much delivering pulses in the blood pool. Now, the ADVENT trial did look at pulse field ablation versus thermal ablation, meaning pulse field on one hand and on the other hand, you have your cryoablation and your radiofrequency ablation. And they found out that at one year after three month blanking period, the efficacy was the same. And they also had similar 2% clinical complication rates. Let's switch gears now and compare, since we've talked about radiofrequency, we've talked about cryo, we've talked about pulse field. So with this modality, how do we stack up against our current antiarrhythmic drugs? There are a few studies that looked at, I'll just pick a few of them. The CABANA trial was published in 2019. This was a very large trial that looked at ablation on one hand and, so ablation on one hand and antiarrhythmic drugs on the other hand. Primary outcome was a composite of total mortality, disabling stroke, serious bleeding, cardiac arrest. And the secondary outcomes were cardiovascular hospitalization, medical costs, resource utilization, cost effectiveness, quality of life, composite of adverse events. Now what they saw was that there was no difference in primary endpoint of a composite of mortality, stroke, bleeding, cardiac arrest. But there was a 17% reduction in a composite of the cardiovascular hospitalization and all cost mortality compared to, meaning catheter ablation superior to antiarrhythmic drugs in that regard. They also found that catheter ablation provided better improvements in AFib related symptoms and quality of life. Now we'll look at a CAPTAF trial. This was a trial that compared ablation to antiarrhythmic drugs on quality of life. And what they found was that ablation had a 3.8 times greater improvement in overall quality of life compared to drug therapy. They're looking at the secondary outcomes also. They saw there was a less, on the ablation arm there was less cardiovascular, less cardiovascular hospitalization, less reablation. And finally, there's the ATTEST trial. The ATTEST trial was a trial that looked at, it was the AFib progression trial. So you took patients that were paroxysmal AFib and at three years, did they progress to persistent AFib if you A, give them catheter ablation or B, give them antiarrhythmic drugs. Secondary outcome was rate of recurrence of arrhythmias, AFib ATAC, rate of repeat ablation. Now what they found was patients who had catheter ablation were 10 times less likely to progress to atrial fibrillation or atrial tachycardia. And at three years, only 2.4% of patients in the ablation arm progressed to persistent AFib compared to 17.5% in the drug arm. And then there was, there's this also, there's this meta-analysis of early cryo-trials published in 2021, looking at patients who had, so early AFib now, now we're going to early AFib. So you have early AFib, do you get early ablation, meaning within a year of diagnosis, do you get rhythm control with antiarrhythmics early? And looking at the outcomes, there was a 39% reduction in recurrence of atrial arrhythmias in the ablation arm compared to the drug arm. Now all this put together led the recent guidelines, 2023 guidelines for AFib, the HCCHR, HCCP guidelines where AHA, and now for the first time, catheter ablation is the only class one recommendation for AFib rhythm control. So when patients, in patients who have symptomatic AFib, where drugs are not effective, drugs are contraindicated, they're not tolerated, or per patient preference, a catheter ablation is useful to improve symptoms. And then also you look at patient characteristics, generally younger patients, fewer comorbidities, you know, this rhythm control with catheter ablation is useful as a first line therapy to improve symptoms and reduce progression to persistent AFib. And then patient with atrial flutters, you know, atrial flutter is something that's fixable, catheter ablation is a class one guideline. So I will summarize here, and what I want you to take away here is, you know, when you pick a patient for antiarrhythmic drugs for patients, you wanna look at certain clinical characteristics of the patient, the LV function, look at the renal function, the hepatic function, or the drugs the patient are taking for drug interaction in order to choose the right antiarrhythmic drug because we wanna make sure we're safe. Number two, when we look at ablation, thermal versus non-thermal ablations, meaning a PFA, which is a non-thermal versus thermal, like cryo and RF, recent studies have shown that possibly this thermal and non-thermal ablations appear to have similar safety and efficacy. And finally, catheter ablation is superior to antiarrhythmic drug therapy in reducing death, cardiovascular hospitalization, and AFib progression, and also improving quality of life. Thank you.

atrial fibrillation

antiarrhythmic drugs

catheter ablation

pulse field ablation

Vaughn-Williams classification

cardiac electrophysiologist