Diagnosis and Treatment of Atrial Fibrillation
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Welcome to listeners from around the world, and thank you for tuning in to this JAMA Clinical Review Podcast. I am your host, Mary McDermott, Deputy Editor of JAMA, and I'm here today with Dr. Amelia Benjamin, who is Professor of Medicine and Epidemiology at Boston University and a cardiologist at Boston Medical Center. Dr. Benjamin is an author of a JAMA review on the topic of atrial fibrillation.

Welcome, Dr. Benjamin, and thank you so much for joining me today. Greetings to those around the world, and thank you for having me. So let's get started. And maybe you could tell us first, exactly what is atrial fibrillation from a pathophysiologic standpoint?

We know that atrial fibrillation, sometimes people pick it up as an irregularly irregular rhythm, and it really represents both electrical and structural remodeling. The electrical and structural remodeling happening in the atrium. It can also happen from ectopic atrial premature beats that originate in the pulmonary vein sleeves, which is just where the pulmonary veins attach to the left atrium.

It can also happen from autonomic dysfunction, such as in sleep apnea. And can you tell us about how common it is in the United States and also who is at risk?

Yeah, one of the fascinating things, I've been studying atrial fibrillation since the 90s, and we know that the incidence, prevalence, and the lifetime risk have been increasing in the United States and around the world. The best data comes from the United States, Australia, China, and Europe.

We have areas where we don't have as much data, but virtually all of the studies who have looked at it have been showing an increasing trend. The trend probably is increasing because populations are aging and people are surviving longer

with their cardiovascular diseases so they have more time to develop atrial fibrillation. So atrial fibrillation increases with advancing age and there are several risk factors that predispose to it. There's a genetic predisposition and there are clinical factors that predispose to it.

When you look at a risk prediction algorithm such as the CHARGE-AF risk prediction algorithm, we know that people who are at low genetic risk and low clinical risk, sort of lowest third, have only a 20% chance of developing atrial fibrillation late into their 90s. On the other hand, those who are at high genetic and high clinical risk

have about a one in two or 50% chance of developing atrial fibrillation before they pass. In terms of risk factors, they're the classic risk factors, most of them, such as advancing age, current smoking,

obesity, blood pressure, diabetes, physical inactivity, also alcohol use, as well as cardiovascular conditions such as heart failure, myocardial infarction, valvular disease, some other sort of one-off conditions such as sleep apnea and hyperthyroidism.

And are any of those risk factors stronger or more important, would you say? Probably the most important risk factor is advancing age. What I like to say is that what we all want to do is we want to be healthy, healthy, healthy, and have a spectacular, terrible last six months of our lives. That's called compression of morbidity. And

ideally we will be healthy and postpone when we get atrial fibrillation because there is a genetic predisposition to it.

And how is it typically diagnosed? First of all, 10 to 40% of the time, it's asymptomatic. People don't know and they show up at their doctor or they have some kind of device like an implanted cardiac device, pacemaker, an ICD implantable cardiac defibrillator device, and it's just picked up routinely. Sometimes it's picked up because people have complications.

About 10 to 40% is completely asymptomatic. However, many people present with symptoms, palpitations, shortness of breath, chest pain, presyncope, or exertional fatigue. People tend to be more symptomatic when they're younger, less symptomatic when they're older.

Is it underdiagnosed? That's a great question. One of the things that we get concerned about is sometimes people first get diagnosed with atrial fibrillation when they show up with a significant complication, such as heart failure, a stroke, or a myocardial infarction. That is undesirable. And so in that context, it tends to be underdiagnosed.

How about wearable devices? People are wearing Apple Watches, for example. Are those accurate methods to detect atrial fibrillation?

That's a great question. I don't believe we cited this in the publication, but when we think about wearable devices, there's been a recent study in the Journal of American College of Cardiology, EP, that was published in 2023, and they looked at five smart watches, and they found the sensitivity ranged anything from 58 to 85%. The specificity ranged from about 69 to 75%.

So, the bottom line is that if one has atrial fibrillation detected by a smartwatch, it's important for it to be confirmed by a 12-lead ECG or Holter or a patch monitor. And when we look at the Apple Heart Study, only about a third of those who received a smartwatch notification subsequently were diagnosed with atrial fibrillation using a patch monitor.

Now, they may have actually had atrial fibrillation, but they probably had the type that was paroxysmal that came and went, and it just didn't happen to be detected by the patch monitor. So related to that, do most people with atrial fibrillation present with continual atrial fibrillation, or what proportion of the disease is intermittent?

That's a great question. We probably don't really know what proportion is because there's a lot of atrial fibrillation that's paroxysmal, that's undiagnosed. Sometimes people show up and they have permanent atrial fibrillation, meaning that they are never destined to get out of atrial fibrillation. Sometimes people have persistent and they can get out of atrial fibrillation. They have paroxysmal, they can get out of atrial fibrillation.

or they just have little bursts of atrial premature contractions. And then related earlier, you mentioned that drinking alcohol is a risk factor. So if someone's had any level of atrial fibrillation, like intermittently, for example, what do you tell them about how much alcohol is safe to drink?

We were just participating in the American College of Cardiology, American Heart Association, American College of Chest Physicians, and Heart Rhythm Society guidelines. They came out at the end of 2023, about a year ago. And it is now recommended for people who are at risk of atrial fibrillation at any of the stages, either have a predisposition to it genetically or from risk factors, have pre-AF,

which is stage 2 atrial pathology without diagnosed atrial fibrillation, stage 3 with the diagnosed paroxysmal or persistent AAF, or stage 4, which is permanent AAF. Regardless of the stage of atrial fibrillation, it is important to modify one's risk factors. And in particular, it's a good idea to modify alcohol use.

you can say, well, is there a safe amount of alcohol? Our understanding about alcohol and its health benefits have really been changing over time.

For people who have atrial fibrillation, there now is a randomized controlled trial that has studied it. And people who have atrial fibrillation, if they want to prevent it from coming back, they might want to consider being either abstinent or dramatically decreasing their alcohol consumption. Well, let's move on to adverse clinical events associated with atrial fibrillation. Why is it so important to diagnose and treat atrial fibrillation?

We do have management strategies that can prevent complications of atrial fibrillation, so it's important to diagnose atrial fibrillation early. Stroke is the most feared complication. It has a lifetime risk of about one in five, and we have a lot of strategies that we can discuss later that can prevent the onset of stroke.

What has received less attention, which actually occurs more frequently, has a higher relative risk, a higher lifetime risk, is heart failure. The lifetime risk of heart failure after a diagnosis of atrial fibrillation is about 40%. And is it thought that the atrial fibrillation is contributing to that, or is it they both have similar risk factors?

all of the above. Heart failure is fascinating because atrial fibrillation can cause heart failure and in fact if somebody shows up with heart failure and rapid atrial fibrillation one of the things we ask ourselves is is the heart failure from the rapid atrial fibrillation? Sometimes

converting them and getting them into a stable rhythm can make their cardiomyopathy or heart muscle disease go away. On the other hand, the opposite can happen. Heart failure can cause atrial fibrillation. So the directionality is bi-directional. They very commonly complicate each other's life course. And we don't have as strong strategies to prevent the onset of heart

failure or the onset of atrial fibrillation in people with either condition. I think that's an important area for future research. Okay, so your review in JAMA talks about different treatment strategies, and you talk about ablation, and then you also talk about rhythm control. Instead of ablation,

Can you just give us an overview of how do you decide who's a candidate for one treatment or another? Before I move on, though, I'd like to add a couple more potential complications just to put it on people's radar. The first is we know that there's an increased risk of myocardial infarction, emerging data that's pretty strong that there's an increased risk of chronic kidney disease,

cognitive decline, and dementia. And most importantly, there is an increased risk of all-cause mortality. So atrial fibrillation, it used to be viewed as kind of a benign nuisance condition, and now we understand it's associated with a lot of bad outcomes. Can I just ask you a quick question about that? Please. I'm interested in how atrial fibrillation might cause chronic kidney disease and cognition problems. Do we know?

Short answer is we don't have all the mechanisms. Part of it is what you already alluded to is atrial fibrillation is reflective of a lot of cardiovascular risk factors that are also associated with those other conditions. However, if we adjust for those other conditions, it still is associated and

When you look at Mendelian randomization studies, which looks at the genetic load for any given condition, there's a suggestion that there actually is an increased risk, although that's a little bit more controversial. In terms of the pathophysiology, it may be shared genetic load, it may be shared risk factors. There may also be issues around perfusion with atrial fibrillation and microemboli. All of the above may be operative.

Do you want to move on to treatment? So, you know, the first thing is, is the old adage, somebody hemodynamically stable. If they're not hemodynamically stable, and particularly if their atrial fibrillation is new, you need to take care of that rapidly. That's pretty uncommon. Most people are hemodynamically unstable, and you have time to really think through what is the best strategy.

If people are hemodynamically stable, they need to show up and go to a hospital. Similarly, if they have a stroke or a complication, heart attack, heart failure, et cetera, they need to show up for a hospital evaluation. If they don't, somebody shows up in the office and they're not symptomatic or they have minimal symptoms, then you can start with first-line therapies.

The first decision point is oral anticoagulation. We know that oral anticoagulation in the indicated individuals is associated with a 60 to 80% reduction in stroke risk, and that is really key to the management strategy. When do you decide somebody is a candidate for ablation? So then the next decisions are, do you want to pursue rate control or rhythm control?

A rate control strategy is you want to make sure that somebody's heart rate's under 100 to 110. And you can do that with beta blockers or non-hydropyridine calcium channel blockers, such as daltiazab or verapamil. If you're going to pursue a rhythm control strategy, your decision is antiarrhythmic drugs or ablation. And typically, people will favor a trial of antiarrhythmic drugs and decide

Being honest with you, when you get to that point, probably good to consult an electrophysiologist about the best strategy because there's a lot of, if you have this condition, do this. If you have that condition, do that. Although it also is written out if you're in a rural area or somewhere where you don't have access to a cardiologist or electrophysiologist.

In terms of who should receive ablation, there were a couple of studies that came out that really showed no clear superiority to ablation versus a rhythm control, rate control strategy. More recently, there have been some studies that have looked at early rhythm control and early ablation, meaning in the first year of having atrial fibrillation.

And it is now thought that it's considered a class one recommendation that people who are very symptomatic or people who have heart failure with reduced ejection fraction benefit from a strategy of ablation. And the ablation can prevent the complications and there are some suggested, depending upon the context, where it may even improve longevity.

Can you talk more about your approach to anticoagulation for atrial fibrillation? What are the considerations and what's first-line therapy there?

So that's an important question and we know that depending upon the health system, many patients who should be on oral anticoagulants are not on oral anticoagulants. And this is a combination of many, many different factors, social drivers of health, as well as health system issues and also individual decisions.

We know that oral anticoagulation, as I mentioned earlier, is associated with a 60 to 80% reduction in stroke risk. The class one recommendation, meaning that it is strongly recommended, is people who have a risk of stroke or thromboembolic events of about greater than or equal to 2% a year should be on oral anticoagulation.

that translates into a CHADS-VASc score of about greater than or equal to two in men or greater than or equal to three in women. The ACC/AHA guidelines do not weigh in and say there's a clear superiority to the CHADS-VASc score versus other scores. The stroke risk scores are not brilliant.

And a lot of it really depends upon shared decision making. And so the class one recommendation is greater than or equal to 2% a year.

The 2A, meaning this is reasonable, is a risk of having a stroke of greater than or equal to 1 to less than 2% per year. And then you need to actually spend time with the patient and talk to them about what do they want to avoid, really engage in shared decision-making.

The other thing that I want to mention that the guidelines came down firmly about is if there is no other indication for aspirin, aspirin is considered not beneficial and potentially harmful.

if it is the strategy that you're using to prevent stroke because it doesn't really prevent stroke and is associated with an increased risk of bleeding. In terms of a specific agent, if people have mitral stenosis or mechanical heart valves, warfarin is preferred. If people don't have that context, then direct oral anticoagulants are preferred.

And do you have a preferred DOAC that you use? So the market share is really moving towards a Pixaban. There are not, at this point, head-on-head comparisons. So a lot of it is speculation and network meta-analyses, etc. There are a couple of contexts where, at this point, a Pixaban and Rivaroxaban are the only

FDA approved DOACs for people on hemodialysis. Interestingly enough, the ACC AHA did not come down this way, but the American Geriatric Society came down and recommended the use of apixaban over rivaroxaban for people that are older adults. And that's partly because of the somewhat increased risk of rivaroxaban for bleeding.

Again, they make a caveat to that. If you need a once a day daily DOAC, then rivaroxaban is reasonable. So it sounds like apixaban may be preferred primarily because of reduced risk of bleeding. We cannot say at this point because there have not been head on head comparisons. We can't say which is the preferred DOAC.

All right. I also wanted to ask, since atrial fibrillation is so common among older people, would someone with a history of falling be okay with anticoagulation? Or do you try to avoid anticoagulation in someone like that? That is a really important question. And there have been studies that you have to fall over 200 times to not make a

being on an anticoagulant worth it. That's because guess what? The people who are falling are also people who are at increased risk of stroke.

Again, though, it comes down to shared decision making. And for many older adults, the thing they fear most is not bleeding. They really fear having a stroke. And so even if somebody's falling, many people will recommend and a lot of patients would prefer to be on an oral anticoagulant. This has really been informative. Is there anything else that you'd like to add?

Yeah, I want to add two more things. The first thing is that in the United States and even in countries with universal health coverage, there are really substantial inequities by social drivers of health. And multiple analyses have demonstrated that there are inequities in the diagnosis and the management and the outcomes by demographics such as sex, race, ethnicity, income, insurance, and really important

importantly, by rurality. And we need to think about how do we improve our systems of care so everybody gets great care. The other thing that I wanted to emphasize that we talked a lot about both in the guidelines and we talked about in the JAMA article is we need to start thinking about atrial fibrillation as a life course phenomena, similar to heart failure.

You know, with heart failure, we don't treat people's blood pressure when they develop heart failure. We think about preventing heart failure or pushing it off as long as possible by treating risk factors early on. So there is no stage where it isn't important to engage in active lifestyle and risk factor management.

In addition to treating blood pressure and cholesterol and making sure people maintain normal body weight when possible and exercise, does that mean that you recommend people minimize alcohol? So people who are at risk of atrial fibrillation, there's probably a lot of other reasons to limit your alcohol consumption. But people who are at risk for atrial fibrillation, we recommend that people consider limiting their alcohol consumption and certainly never doing binge drinking alcohol.

One thing that I did want to mention is that it's actually the only risk factor where it's not clear that it's related to atrial fibrillation are lipids. And there have been many dealing randomization studies and meta-analyses where it really isn't clear that lipids are a risk factor for atrial fibrillation. However, the other risk factors such as current smoking, obesity, blood pressure, diabetes, physical inactivity, and alcohol use are all related to atrial fibrillation onset.

I've been speaking today with Dr. Amelia Benjamin about her JAMA review on atrial fibrillation. You can find a link to the article in this episode's description. For more of our podcasts, please visit us at jamanetworkaudio.com. You can subscribe and listen wherever you get your podcasts. This episode was produced by Shelley Stephan at the JAMA Network.

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