Treating Atrial Fibrillation with Medications — Mintu Turakhia, MD, FHRS

September 8, 2015

In his talk about Treating Atrial Fibrillation with Medications at the 2015 Get in Rhythm. Stay in Rhythm.TM Atrial Fibrillation Patient Conference, Dr. Mintu Turakhia of Stanford University covered:

  • How does the doctor decide what medications to recommend?
  • Rate control vs. rhythm control
  • Whether rhythm control should be used without overt symptoms
  • What drugs can be used
  • How structural heart disease vs. no structural heart disease relates to drug choice
  • AF and heart failure

Video watching time is approximately 25 minutes. Click the Treating Atrial Fibrillation with Medications link below to watch the video.

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About Mintu Turakhia, MD, FHRS

Dr. Turakhia is a cardiac electrophysiologist, outcomes researcher, and Assistant Professor of Medicine and of Health Research and Policy at Stanford University. He is

Chief of Cardiac Electrophysiology at the Palo Alto VA Health Care System and is an Associate Investigator at the Center for Innovation to Implementation.

In his clinical role, Dr. Turakhia performs complex catheter ablation (primarily for AF), device implantation, and left atrial appendage occlusion. Dr. Turakhia has an active clinical research program, with funding from AHA, VA, NIH, the medical device industry, and foundations. His research program aims to improve the treatment of heart rhythm disorders, with an emphasis on atrial fibrillation, by evaluating quality and variation of care, comparative and cost-effectiveness of therapies, and predicting outcomes such as stroke.

Dr. Turakhia has extensive expertise in using large administrative and claims databases for this work. His other research interests include technology assessment of new device based therapies and the impact of changing health policy and reform on the delivery of arrhythmia care. Dr. Turakhia has over 70 publications and is a Fellow of the American Heart Association, American College of Cardiology, and Heart Rhythm Society.

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Video Transcript:

Time markings are approximate

Thank you all. How’s everyone doing? Good. It’s a tough, tough act to follow John. It is tough. I’m going to do my best. I want to thank Mellanie and all at for having me here. It’s a real privilege to be here, and Mellanie hit me up for two talks, and I happily obliged. So you’ll have to hear me twice, but luckily, you’ve have a break in between.

What I’m going to do is give you an overview on how we, as physicians, who really have focused our lives on afib think about treatment. The point is not to overload you with information. You can read this. You’ll have the slides. The materials will be there. The point is going to give you a framework of how we think. There will be more detail than I would ever expect any audience to take in, but it’s there for you to come back to and digest.

[00:01:00] The reason that I thought this was important is to really lay out how the advice you’re going to get now is even different from the advice you may have received two, three years ago.

And this is true for rate and rhythm control, and also for preventing strokes. So the first thing you have to deal with when we’re dealing with afib is which path are you going to go down? There’s a fork in the road. Rate control in afib is when you really focus only on keeping the heart rates in a reasonable range so that you don’t experience symptoms or other consequences, typically of the extremely fast heat rates that can occur. And those may occur at rest. They may occur with exercise. They may occur unpredictably and may be triggered by many of the things you heard Dr. Day talk about in terms of triggers. And sometimes those triggers are not just those that provoke you into afib. They may provoke the heart rates to behave erratically as well.

[00:02:00] Rhythm control is when, as Dr. Day said, you really make it a commitment to keep the heart in normal sinus rhythm and thereby avoid the consequences of the fast and unpredictable variation in heart rates that you have. So the problem we have sometimes is the inherent bias that we think one side of the road is sunny and one side of the road is cloudy, but in truth, this fork may emerge in your life multiple times. How many of you have seen more than one doctor for your AFib? How many times, every time you go to a doctor, something changes, they change something? Yeah, not an uncommon situation, okay? So the reason we think about rhythm control is when the AF is causing symptoms, and the symptoms vary, and all of you know this better than your doctor or better than me. The problem is the way we, as health care providers, think about what these symptoms are.

[00:03:00] Sometimes what happens is, a physician who has a lot of things to care for and has to make sure that all of you, not just the upper chambers of your heart are functioning, may not have the time, resources or understanding to go through all of the symptoms. And it’s hard to connect the dots if you don’t know what AF could possibly cause. So sometimes some doctors may ask you if you have palpitations, and if you don’t, you must not have symptoms of afib, and that’s not true. What we see here is that there are many different things that can happen. The fatigue, the weakness, the tiredness we just head from a patient, can be a real problem for patients. And that’s often expressed in different ways. That can be someone just becoming irritable.

I had a patient’s spouse complain that she knew when her husband was in afib because he just got grumpy. And she commented, when he was wearing the Holter monitor when he was grumpy. And it tracked. When he was in afib, her notes matched spot on.

[00:04:00] So these symptoms can be very, very subtle. What we have not done a good job of is figuring out a way to quantify these symptoms or in some way measure them in the same patient. There are questionnaires, scales and instruments. This one comes from Europe, and many of us acknowledge that the way the European societies have started to think about afib in some ways exceeds the framework that we have in the U.S. There’s good and bad, and a lot of good doctors will take some from here and some from there and piece it together.

But the EHRA scale really talks about disability and symptoms, and it’s a functional scale of what is interfering with your daily life. So should rhythm control be used without overt symptoms? Again, this is one of those things where you have to connect the dots. And you’re all here because you know about AFib, it must have an impact in your lives.

[00:05:00] But in some patients, heart rates are not so obvious if they’re out of range. Now, this is a patient that has good heart rate control, and this is a monitor that he wore, and this is a two-day snapshot. And what you can see here is that this general range of 60 to 100 is where you kind of want people’s heart rates to be, and you can see where the average is, which is a single dot, and where the range was for that day. He felt mostly fine, but he even triggered some diary events that you can see up here, and he was in afib 24% of the time. Now, this person has good heart rate control, and he felt fairly well, so rhythm control may be fine, but some patients may have very fast heart rates, and feel perfectly fine. And that is a situation where, although they’re not overtly symptomatic, we as their providers are concerned that those heart rates can cause problems.

[00:06:00] And as part of that, the heart failure, the inability for the heart to squeeze and work as that pump to give the rest of your body the blood that it needs, that even may not be so obvious. Now, afib can cause heart failure a lot of ways, and the important thing to understand is that prolonged periods of excessively fast heart rates, and in some cases, not excessively fast heart rates, diminish the heart’s ability to contract. And that is in the acute phase very quickly while it’s happening, but also in the chronic phase, even after that AF episode were to terminate. And the way that’s seen is in two ways, but the most common is that the ejection fraction declines. That means your systolic function of the left ventricle, that’s what we call it, the squeeze of the heart has weakened. Most of the time, it’s reversible.

And the other thing to note is that patients who have diseased hearts for other reasons, prior heart attacks, coronary disease, maybe a thick heart from hypertension, may be the ones that are most vulnerable.

[00:07:00] And as heart failure develops, you get in this vicious cycle where the heart progressively becomes dependent on atrial function. So sinus rhythm isn’t just happiness on an EKG, that means that the upper chambers, the atria, are squeezing in synchrony [with the lower chambers, and your pump is working on four cylinders and not just two. And what happens in heart failure is that those lower two cylinders, the ventricles, end up not working as well, so that the upper two cylinders, the atria, need to squeeze a little bit more.

And that works in two ways. The systolic dysfunction, which is a squeeze of the lower chambers and the left ventricle in particular, and the diastolic dysfunction, which is the ability of those lower chambers to relax to allow the blood to come in. And if the heart is thick from high blood pressure or other reason, it stiffens. And when it stiffens, it can’t relax, and if it can’t relax, the atrium has to squeeze and supply more.

[00:08:00] This is nothing to really stare at for very long, but it tells you the mechanisms that we now see in terms of how the fast heart rates can lead to heart failure. There are many ways that this happens, and this is a massive area of understanding, where we’re just starting to really learn the cellular and the energetic and biochemical mechanisms for this. And what does happen over time is you, as I said, get in this vicious cycle. The terms here are not important, but what you have to appreciate is that afib causes heart failure, and heart failure causes afib. One can beget another, and our goal is to help you break that cycle.

So how does the doctor decide what to recommend? How does a doctor decide what fork you should take and what to advise you on?

[00:09:00] And the problem with this is that a lot of this decision-making is a matter of perspective, and any time we say it’s a matter of perspective, you have to worry that there’s some bias thrown in there that may not really reflect an objective decision that’s personalized for you. William Evans and Peter Swann wrote this in 1953 after they observed 20 patients, all men. “…The condition did not jeopardize life in a single instance and did not prove even a handicap to the majority.” “Longevity is unaffected.” “Reassurance should be the uppermost in treatment…” “…Continuous digitalization,” digoxin, which we’ll talk about, “…is the ideal treatment,” and an urge to reinstate sinus rhythm should be suppressed.” 1953, okay?

Good thing you’re here today in 2015 and not in 1953 because you know what would have happened in terms of your treatment here. This is wrong. So the road not taken is a matter of perspective.

[00:10:00] And in some ways, a matter of your perspective, but also your doctor’s perspective. We looked at this and looked at 163,000 patients who had a new diagnosis in the VA of afib, and we asked a simple question. If they went to a primary care or general medicine doctor, or if they went to a cardiologist, which includes an EP, electrophysiologist, was the initial treatment different? And if you adjust for everything, and we even adjust for their travel time, how far they had to go, and balance the group so that the distance to the cardiologist was the same as the distance to the primary care doctors. And what you can see is that the cardiologist, if they were seen by a cardiologist, they were almost twice as likely to be prescribed rhythm control drugs.

And the gap actually got worse over time. So it could be that some patients self-selected themselves even though we tried to adjust for that, but the almost 2x difference suggests that this is clearly a matter of perspective.

[00:11:00] And what does that mean? Well, perspective is in how we interpret the evidence, and how I as an EP and my colleagues as a cardiologist and even amongst us friends and colleagues, interpret in evidence is going to vary based on the lens we’re looking through. And what has happened in some circles is, there’s been a lot of weight on older data that really has lost relevance. This trial is a trial that’s often quoted in circles outside of EP, the AFFIRM Trial, occurred almost 15 years ago now, where they looked at rate versus rhythm control.

Both groups got anticoagulation, but they looked at this and looked to see, was there an outcome difference whether you started with antiarrhythmics or whether you started with rate control medications.

[00:12:00] But the important thing to note is it doesn’t really generalize to most people with afib, because they threw out or didn’t enroll anybody with symptoms. So when you look the data of AFFIRM and you show that, in fact, the people who are on rate control had a trend towards better survival, you’re missing the point because this excluded people with symptoms. So the reason I’m passing on to you is that you educate your peers, and sometimes your providers, about the way we’ve moved away from some of these trials. And you’re going to hear more about ablation and rhythm control trials in the afternoon. I don’t want to go through too many of those drug trials because you’re going to hear about that later.

Again, in the AFFIRM Trial, they also said there was no difference in quality of life. Well, that’s because they didn’t have a problem with quality of life when they enrolled in the trial. So this is not relevant, but somehow, this data and this trial, with its catchy name, gets brought on and it gets talked about and talked about and talked about again.

[00:13:00] And my colleague, which you’ll see, Dr. Sanjiv Narayan, I’m so glad he has called his trial FIRM and his approach FIRM, because we need to get away from AFFIRM. So the severity of afib should also influence decisions, and antiarrhythmics have inherent risks that exceed risks of rate control, to the extent that sometimes doctors may rightfully, or not, become concerned about using these drugs. But the willingness to try rhythm control really is one where it depends on the potential benefit, and the severity of AF can influence that potential for benefit.

So you have to weigh the risks and benefits of the therapy, okay? The problem was the next one, this button, “Trust me, I’m a doctor.” So the doctor would look at the scale, figure out what’s right for the patient and make a decision, and we’re just not there anymore.

[00:14:00] In fact, we now have volumes of text and information talking about interpreting benefits and risks, teaching doctors how to do this. Shared decision-making, partnering with the patient and making that decision together. And in fact, the top-line recommendation from the AHA/ACC/HRS, the professional American society guidelines, about what to do in afib is, first and foremost, it should be a shared decision-making process. It’s not about the individual drug. It’s not about this or that. Some of those things are important, but top-line recommendation is partnering with your patient.

So let’s again get back to the severity issue. You heard a little bit about this from Dr. Day. The severity and the way we think about the afib is more of an issue of how it behaves and less of an issue of how much or how often you have it, the duration or the burden.

[00:15:00] Paroxysmal afib is when it comes and goes on its own, but unpredictably, and that’s a huge problem. Persistent afib is when it starts on its own, but as you heard from a patient, it doesn’t go away on its own. Something has to be done, often a cardioversion. And permanent afib is a tricky term, because there’s a judgment implied in the term and we don’t love it, but it means that you’ve tried and tried and tried, and you can’t get someone out of it.

And the reason this is defined by behavior and not burden is, if someone comes to my office and tells me that they’ve been in afib for the last six months, I’m doing a disservice by calling that permanent. We don’t know what that is yet. We haven’t challenged it with behavior. And sometimes what we will do in a patient who has symptoms is to see how the afib will behave just so that we can classify this to help prognosticate treatment.

[00:16:00] In the natural time course of afib, this is classical, every patient’s different, is you may have afib that you don’t even know about, short, little burst, couple seconds. Oh, that felt funny. Oh, I felt a little flutter. Maybe it was something I ate. Maybe it was the ice cube I swallowed, don’t know. It then becomes more symptomatic as it gets longer, and then over time, months, years, longer sometimes, become persistent or even permanent.

And we have developed a classification around this scheme. There are flavors of how this has been modified, but this is really how, again, we think about the behavior. Now, it’s not just about characterizing your symptoms and how it works, but actually, these provide some insight into the mechanisms and what’s going on, and in turn, how we might ablate it, which you’ll hear about in the afternoon.

[00:17:00] Paroxysmal afib typically occurs in healthier hearts that are irritable, and often, you can succeed by taking away the irritability. And if the irritability is gone, the heart has a tendency to avoid going into this on its own. Once you have persistent afib, and you need something, that shock to get out, you have to do more, and permanent AFib may be that it’s very difficult to affect that because the heart is, in fact, scarred. What that does tell us is there’s a window of opportunity for attempting rhythm control. You really have to time this well so this also influences how we think about what to do.

Okay, what drugs can be used? There are a lot of drugs and a lot of choices. There are antiarrhythmic drugs that are shown here on the left. There are rate control drugs, shown on the right, and we don’t want to get into too many of the details because it really varies on what you can use.

[00:18:00] I’m going to give you a framework on how we think about it, but there are a lot of different options here, and there’s no one right drug. The way we have evolved to think about rhythm control is we look at patients and determine whether they have structural heart disease or not. And if they don’t have structural heart disease, you have greater latitude in using certain drugs.

What has changed, again, in the last couple of years is, we’ve made a clear distinction about what we want to use first-line, and what we want to use second-line, such as amiodarone not being used first-line. And the reason we care so much is that there are drugs on the left, these are all antiarrhythmics used for many reasons, they all have problems. You have a lot of serious acute and chronic adverse effects, and we have to think very carefully about what we use. Two of these drugs, sotalol and dofetilide to maintain rhythm work extremely well, and again, this is informational, but nothing you should know.

[00:19:00] The point is that they have a lot of problems. You have to bring patients to the hospital for dofetilide, and more commonly, we’re now doing that for sotalol for up to three days to load them to make sure it’s safe, so this doesn’t happen.

This is called Torsade de Pointes, or a form of polymorphic ventricular tachycardia that is because the body is seeing exceedingly high levels of these three drugs. So you have to watch these drugs and do them carefully. This is essentially equivalent to sudden cardiac death, and that’s what you, of course, don’t want. So there is appropriate reservation, but an experienced, capable physicians and health care systems that are resourced, you can get on these drugs and be very safe and not have problems.

Let’s talk a little bit about amiodarone. So amiodarone used to be a favorite in many people. It’s easy to prescribe, it rarely causes arrhythmias, and it’s well-tolerated in the short term.

[00:20:00] The problem is, it deposits everywhere. It stays in your body and can take months or longer to be eliminated. Every time you take amiodarone, a little bit of iodine is released in the bloodstream, and there are some dose-dependent effects, especially on the thyroid, the lung and the liver. It also interferes with warfarin. So we now don’t use this first-line unless there are no other options really remaining, which can happen.

Dronedarone is a new drug, relatively new, that is supposed to have been amiodarone without the badness of it. It has no iodine released. It has no accumulation effects, but now, we’re learning it’s actually not terribly

effective in most patients and can provoke heart failure, so it’s fallen a bit out of favor in the U.S. as well.

Let’s talk about rate control. How do we decide what to use first-line?

[00:21:00] This is highly variable, and you need to ask your doctor why they are recommending what they’re doing because there is not a ton of evidence in terms of whether beta blockers — metoprolol, atenolol, others — or calcium-channel blockers — diltiazem, verapamil — are better. It’s a personalized decision based on how well someone’s going to tolerate them, and in some cases, whether heart failure is a co-existing condition.

So again, we think about how to do afib rate control the same way. We have certain first-line drugs based on other accompanying diseases, and we try to avoid amiodarone, which rarely can be used just to control the rate. So this, again, is a matter of discussion and personalization. What about digoxin? Well, digoxin’s got a lot of press lately. We’re partly to blame for that. We did a big study that got some press back in last August where we looked at 160,000 patients and found, in newly diagnosed afib, not long-standing afib, but new afib, and we wanted to see if there was a problem with the drug. And we found an increased risk of mortality with digoxin.

[00:22:00] This was not a randomized trial, and you don’t prove that it was definitively the cause, but it got a lot of press, and there’s been a lot of studies afterwards. And the point of this isn’t that you should stop your digoxin. It isn’t that it’s going to necessarily kill patients. It’s an observational study. There are many potential causes. The point of the study is to have a conversation amongst us as physicians and amongst our patients and us as physicians about what really are the best choices. Maybe this is right, but could there be other options that could do just as well, if not, a better job.

How fast or slow should my heart beat? There’s no right answer. It’s highly individualized based on symptoms and avoidance of extreme heart rates. And the trials of strict and lenient control just haven’t been very good.

[00:23:00] So we have guidelines, and again, I’m showing this to you to give you insight on what we think, what we’re held to in terms of accountability. In patients with AF-related symptoms during activity, the adequacy of heart rate control should be assessed during exertion, adjusting treatment as necessary to keep the rate within physiologic range. Don’t just look at your resting heart rate, see what it does with exercise.

So I’m going to close here. There’s a lot to digest, and we’re going to have a little bit of time for questions. I will be at the break, but the choice of rate or rhythm control is a highly, highly personalized decision that is guided by symptoms, which may not be apparent, quality of life and now, the impending risk of heart failure. That’s something that’s relatively new.

So one is, are you in tune with your symptoms. Are the things that are nuisances in your life there, and could they be associated with afib? And the second point is more important. Is your doctor in tune with you to personalize this decision.

[00:24:00] And within each of these strategies, there are numerous drugs that could be chosen based on individual circumstances. There is no decision, this is not a permanent fork in the road. You may revisit this many, many times over the course of your life. No decision is final, none irrevocable, and the best decision here really is one that’s made through a shared decision-making process with you and your doctor. Thank you.