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Treating Atrial Fibrillation with Anne Curtis, MD
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How does management of AF differ when patients have a decreased ejection fraction? Would conversion to sinus rhythm be a top priority or would rate control?
Dr. Curtis: Choice of antiarrhythmic drug is one consideration in patients with a decreased ejection fraction who you want to keep in sinus rhythm. Some drugs, such as flecainide and propafenone, are contraindicated when someone has a decreased ejection fraction.
Amiodarone might be a drug you would try early in someone with advanced heart failure, or as your only drug, simply because you can’t use the other ones. Dronedarone is an agent that can be used in milder forms of heart failure and when there is some structural heart disease, but in advanced heart failure you can’t use dronedarone either.
Rate versus rhythm control is a decision to be based on the constellation of patient characteristics, not simply ejection fraction. If a patient has recurring episodes of AF even on antiarrhythmic drugs, perhaps you shouldn’t keep trying. Maintenance of sinus rhythm becomes more difficult the lower the ejection fraction and the larger the left atrium.
When a patient has a low ejection fraction, I don’t believe I have to jump through hoops to maintain sinus rhythm for its own sake. The choice depends more on the symptoms and what happens when the patient goes into arrhythmia. If a patient with a large left atrium were in heart failure but totally asymptomatic from the AF, I probably would go with rate control, because my only other option if drugs have failed might be an ablation strategy, which is always more difficult in patients with enlarged left atria. The lower the ejection fraction, the larger the left atrium, and the more persistent the AF, the more difficult it is to achieve sinus rhythm long term with catheter ablation.
What should the clinician know about the differences between dabigatran and warfarin?
Dr. Curtis: The most important differences are the advantages dabigatran has over warfarin. Ease of dosing—150 mg twice daily, as long as the patient doesn’t have very poor renal function, with no blood test monitoring. Warfarin requires having to draw the internationalized normalized ratio (INR) blood test and make adjustments in the dose. Dabigatran presents no drug-drug interactions. All of that makes getting a steady anticoagulation level easier with dabigatran. I think it’s overall better tolerated. We have better adherence with it.
The downside is that we don’t really have a specific antidote to dabigatran. With warfarin, we can give vitamin K or fresh frozen plasma and reverse it quickly if we run into trouble with bleeding. With dabigatran, people do use fresh frozen plasma, but we depend more heavily on the drug simply wearing out naturally, over the course of a couple of days. In very severe instances of bleeding, we might even have to think about dialysis. I don’t consider it a major negative, but it is something to be aware of.
Should dabigatran be used first then, instead of warfarin, in patients with nonvalvular atrial fibrillation?
Dr. Curtis: I certainly offer it to patients. If patients have already been on warfarin for a long time and they’re doing well, I don’t see a need to change. For some patients, the cost difference has to be taken into consideration as warfarin is generic and dabigatran may have a high copay. Cost of the drug isn’t the only consideration when we’re looking at what it costs to manage a patient. When you add in all the blood-test monitoring and everything else that has to be done with warfarin, I think the higher price of dabigatran is actually a pretty good tradeoff.
Can you define “nonvalvular atrial fibrillation” for the clinician? Should the significance of the valvular regurgitation be determined by echocardiography? If so, what would be the criteria?
Dr. Curtis: What most people think of as nonvalvular atrial fibrillation is moderate to severe valvular regurgitation. When a patient has a clearly evident heart murmur on physical examination, most cardiologists will get an echocardiogram.
Now, if a patient has mild to moderate valve leaks in a couple of valves, that doesn’t by itself tell me that that’s valvular AF and that I should avoid using, for example, dabigatran. Mild to moderate valve leaks are not a big issue to me.
Something that’s called “moderate to severe” on an echocardiogram and, importantly, changes in chamber size and function, can help indicate the relevance of valvular regurgitation. So, if a patient has mild to moderate mitral regurgitation, for example, and their chamber sizes are normal, I’m not reading that as AF on the basis of mitral regurgitation; it’s probably either pulmonary vein foci or a result of hypertension or other problems.
Once patients are converted to normal sinus rhythm, how long should anticoagulation therapy be continued?
Dr. Curtis: Guidelines recommend a minimum of 4 weeks afterwards for a patient who would not otherwise need to be anticoagulated except for recent cardioversion. Because of stunning of the left atrium, you need to keep that patient on anticoagulation at least that long.
On the other hand, if a patient has a CHADS2 risk score of 2 or greater, based on congestive heart failure, hypertension, age older than 75, diabetes and history of stroke or TIA, then you should keep that patient on anticoagulation anyway. Once somebody has demonstrated that they can have AF, you have to consider them to be at risk for it again.
Where does radiofrequency ablation fit in the paradigm for AF treatment?
Dr. Curtis: I think the current AF guidelines by the American College of Cardiology and American Heart Association are very helpful here, because they split treatment recommendations into classes I, IIA and IIB, based on the underlying substrate. So, for example, if a patient has paroxysmal AF and either a normal heart structurally or mild left atrial enlargement and mild left ventricular dysfunction and has failed at least one antiarrhythmic drug, that’s considered a class I indication, because the results are the best with that group of patients. I have no problem at all offering ablation to a patient who is symptomatic and failed a drug.
You have to be realistic about the outcomes to be expected with ablation in more severe or more persistent AF. So, for example, if a patient has marked left atrial enlargement and persistent atrial fibrillation—meaning they have to be cardioverted to get out of AF—then the results get worse with ablation. It becomes more of a IIA or even IIB problem depending on the degree of persistence of the AF and the structural abnormalities in the heart, because the results start to get worse.
The primary success rate of ablation, by which I mean that the patient has long-term control with no antiarrhythmic drugs, with a single procedure, is about 50% in patients with persistent AF. I spell that out, and if the patient is willing to accept a 50% success rate, that’s great. If those patients wind up having to have a second procedure, they’re not going to be surprised.
Whatever you decide to do, act before the AF becomes permanent. Once a patient has been in AF persistently for a year or more, the results with ablation become that much worse. Talk with patients when, even if expected results may not be terrific, they’ve got the best shot of having a good long-term outcome, rather than getting so late in the course that the odds go way down and it becomes less favorable to do the procedure.
Which patients would not be candidates for radiofrequency ablation?
Dr. Curtis: Somebody who’s been in atrial fibrillation persistently for more than a year wouldn’t be a good candidate for ablation. Good centers have results where only about 30% of such patients remain in sinus rhythm long term after the procedure. Many of these patients need multiple procedures. Sometimes the arrhythmias that are generated when someone has a partially successful ablation are even tougher to deal with, such as left atrial flutters. I wouldn’t recommend ablation for a patient with a giant left atrium of, say, 6 cm. The ability to get contiguous lines to ablate the pulmonary veins and then create the other lines that might be necessary is extremely difficult.
Another important category that’s not talked about much is a patient who cannot be anticoagulated. Patients who undergo an ablation procedure, even if they would not otherwise be candidates for long-term anticoagulation, need to be on warfarin or dabigatran for at least a couple of months afterwards. If someone has an absolute contraindication to anticoagulation, then you don’t want to introduce lesions in the left atrium and induce a prothrombotic state that might put them at risk for stroke.
Dronedarone versus amiodarone: Which would you recommend first in a patient with AF? What are the main differences between the two drugs?
Dr. Curtis: In a patient with AF for whom I would recommend drug therapy, I would go to dronedarone first for two reasons. Dronedarone has a shorter half-life, so I can take the patient off it faster if I need to. Also, dronedarone has less toxicity than amiodarone. It does not contain iodine, as amiodarone does, so we don’t see thyroid toxicity, and dronedarone doesn’t contribute to pulmonary toxicity. Finally, if a patient doesn’t see a benefit with dronedarone, I can easily move to amiodarone.
On the other hand, amiodarone is a more effective drug than dronedarone. In a head-to-head comparison of dronedarone with amiodarone, amiodarone was more effective in maintaining sinus rhythm. So I tend to use amiodarone when other drugs have failed and I’m trying to give one last good effort to keep somebody in sinus rhythm—that’s one situation. Another is in heart failure, where the only other drug option is dofetilide, which requires in-hospital managing. If you want to treat a patient in an outpatient setting and they have atrial fibrillation and heart failure, amiodarone is the better choice.
Has minimally invasive mitral valve repair shown any efficacy in restoring sinus rhythm in patients with AF?
Dr. Curtis: The data don’t really assess mitral valve repair by itself. Many patients who have mitral valve repair do have preexisting atrial fibrillation.
When someone’s having minimally invasive mitral valve repair, they’re also typically having AF surgery done at the same time to isolate the pulmonary veins, which is a minimally invasive procedure as well.
If someone had a tendency toward AF already, doing the mitral valve surgery ought to arrest the progression of left atrial enlargement and keep the problem from getting worse on a structural basis. Although electrical remodeling may have already occurred, it wouldn’t restore the heart to normal, and I think that’s why so many surgeons like to try to address the AF at the same time.