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Atrial Fibrillation

The incidence of atrial fibrillation increases as the population ages and some studies, including the Framingham study, suggest that a patient 70-years-old and older is 10% or more of those patients have atrial fibrillation. Patients with significant left ventricular dysfunction or going into congestive heart failure due to atrial fibrillation or people with angina who are having significant ischemia due to the rapid rate of atrial fibrillation are unstable. In that case it is not unreasonable to quickly cardiovert them emergently.

I think it is important to recognize what kind of energy you should use. There is an increased risk of shocking somebody into ventricular fibrillation with a lower energy because the lower energy will incompletely depolarize the entire heart. So itís our recommendation that if you are trying to convert somebody out of atrial fibrillation.

If somebody is somewhat stable and you choose acute rate control there is a variety of agents that you can use. There are the IV calcium channel blockers, most notably in the past was their practice to give boluses up. More often now with diltiazem where you can put somebody, after giving them an initial bolus, then on a drip, titrating to the heart rate that you want. This is quite effective, however this is not great for the long term rate control of the management of patients. Because your hospital administrators will come to you and say this costs way too much. And once somebody is stable you can convert them over to an oral agent. There are many IV beta-blockers that work good. Itís a misconception about IV digoxin. Thereís a lot of people who have been practicing medicine for awhile who think that they give patients digoxin intravenously converts people convert to sinus rhythm and digoxin reverted them. But if you look at the trials there is a significant percentage of patients who present with atrial fibrillation that converts on digoxin. In all the trials that compared IV digoxin to placebo in the acute atrial fibrillation syndrome.

What happens if the patient is stable, youíve the rate controlled, now what are you going to do with them? The decision whether to electrically cardiovert them or not. Clearly if they have been in atrial fibrillation for greater than 48 hours - some people say greater than 24. We usually use 48 hours - an anticoagulation is indicated. Pharmacologic therapy for a conversion: intravenous drugs like cocaine or ibutilide, or oral agents. There is electro-cardioversion, both external and internal. And key is anticoagulation for 1-3 months post-cardioversion.

So if somebody has been in atrial fibrillation for more than 48 hours or if you donít know how long, the question is what do you do? The standard of care in the past has been anticoagulation for 4-6 weeks prior to cardioversion. There has been some work done using TEE, transesophageal echocardiography to help guide cardioversion. This is what you are looking for. This is the TEE showing the left atrium here, and I think this is not very subtle, this big clot sitting in the left atrium here where if that were to slide off somewhere you can image.

So what are the benefits of the TEE guided approach? Well one, you have early cardioversion for those who no thrombi are seen. So you have a shorter duration of anticoagulation. Itís important to think about it. So you see someone in the ER who is anticoagulant and we bring them into the hospital, start Coumadin and you send them out. When does the clock start ticking to how long they have been anticoagulated? Is it as soon as you give them Coumadin? Or is it as soon as their INR is therapeutic? You know what happens in week three when the INR goes down to 1.2? Do you have to restart the whole clock again, or what do you do? So there are some issues with anticoagulation. Obviously there are issues with bleeding on Coumadin also. You have a more rapid return sinus rhythm, more rapid return of atrial function and a question of fewer thromboemboli. In studies that have looked at TEE guided therapy cardioversion, if you demonstrate there is no clot in the left atrium with TEE.

What are the costs of TEE guided cardioversion? Obviously the procedure cost and morbidity and discomfort of it, so I think it depends on the patient. If you have a patient who would like to get back to sinus rhythm quickly I think this is a good approach. Itís something that should be considered if you have

I just wanted to touch briefly on electrical cardioversion. I mentioned my pet peeve about lowering energy for atrial fibrillation. What do you do with a patient who youíve shocked now with 360 joules four times? And you canít get them back into sinus rhythm. So you have a 38-year-old guy who weighs 320 pounds. Heís in new atrial fibrillation. You shock him a bunch of times, heís still in atrial fibrillation. Do you just give up and say, "Well, the guy is just in atrial fibrillation. Weíll just anticoagulate him and rate control and that will be that." I think the answer is no at this time. What weíve been doing is something called internal cardioversion now in people who you are unsuccessful with external cardioversion.

For chemical cardioversion, there are a couple of drugs available now in the United States. The standard one that has been around for years is procainamide. We usually give it as a 15 mg per kilogram bolus over about 20-30 minutes. This is a lot quicker than recommendations and as long as you have good nursing staff that is monitoring the patient, watch out for hypotension, QRS prolongation, you can usually do it safely. Getting it a little more rapidly this way increases the efficacy. You get this higher peak plasma level which increases your chance of a converted patient.

Newer agents that are out there. There is a drug called ibutilide, which is a class III antiarrhythmic in that it prolongs the action potential duration and it does that by keeping the sodium channels open and prolonging the flat phase of the action potential. You can see here in a study that looked at atrial fibrillation and atrial flutter, that in increasing doses you can convert people with this drug, although the success rate isnít great or even very much better than procainamide. But itís much easier to give. You give it as a 1 mg bolus over 10 minutes and you can give up to two of those. The one problem with it, since it is a class III agent and it prolongs the action potential, you have the risk of torsade de pointes. In some studies it suggests that with ibutilide there can be up to about a 9% incidence of the induction of some ventricular arrhythmias. So if you give this agent, you have to realize that this is a possibility. In my experience the patients who were most likely to get into trouble with this are the ones that are going to be bradycardic after you convert them. So somebody that is cruising along in atrial fibrillation, they may be going relatively fast, they are on all kinds of drugs to rate control and convert them, to sinus rhythm, they are slow. The QT prolongs more and those are the people at high risk. As with any antiarrhythmic drug, the group of patients that are at high risk for torsade is women. And older women and small women. The studies have suggested that it has to do with body size but there also seems to be some genetic or some gender differences between the two. And the incidence of torsade in women is always higher in all these drug trials. So thatís just something to consider. After you give this agent you have to monitor the patient for four hours to watch for these arrhythmias.

So now the question comes, after youíve dealt with an urgent or emergent or acute situation, what do you do over the long haul to treat atrial fibrillation? Well, one, obviously you treat the underlying causes if present if someone is thyrotoxic, you want to treat that or other reasons for having atrial fibrillation. Rate control we talked about. Iím going to spend some time next on anticoagulation and then the maintenance of sinus rhythm in selected patients. Thereís more slides on this in the handout that goes into a little bit more detail, but what this is is a kind of summary slide in some of the stroke prevention trials in patients with atrial fibrillation and anticoagulation. And you can clearly see in a whole wide variety of studies a significant reduction in the risk of stroke in patients receiving Coumadin versus controls, with kind of a wide range. But clearly it is really unequivocal now that Coumadin is good in atrial fibrillation.

The question we come up with is, are there a subset of patients who require Coumadin and subsets of patients who donít? How do you decide? There has been some data that looks at that. The _ two trial tried to look at a low risk group, so no prior events, no hypertension, no history of CHF, LD dysfunction, no mitral regurgitation, and they broke the population up into younger patients and older patients and they found that the event rate on Coumadin was actually a little bit more - although this wasnít significant - than the event rate on aspirin. And it was a higher event rate, as you can imagine, in the older population. So the low risk group, patients essentially with structurally normal parts, aspirin is probably as good as Coumadin.

Then they tried with the high risk patients. These were patients with prior embolic events; systolic hypertension, women greater than 75, LD dysfunction, CHF, mitral regurgitation, and what they found was they tried to compare Coumadin with a low dose Coumadin and aspirin and they found clearly that in patients at high risk Coumadin is the best thing out there.

So if we kind of try to distill some of these studies and some of the other ones that I didnít show, what do we do? What are the recommendations? This is not complete and there are still going to be patients that you have to deal with it. Itís really going to be a judgment call. Basically if there is a strong contraindication to warfarin - you canít give it to people with GI bleeding, or bleeding all over the place, theyíve got a bleed in their head, or for whatever reason, they are falling down all the time - then aspirin should at least be instituted. And obviously trying to keep them in sinus rhythm will be important to try and decrease the stroke risk. If they have known atrial fibrillation, especially if they are young, some people suggest nothing. I usually recommend people go on aspirin just because of the low toxicity and side effects and potential benefits. Low risk patients, aspirin is okay. If there are one or more risk factors, I go with Coumadin. If they are greater than 70 - which is a risk factor - but otherwise low risk, the question is, what do you do? We know that the risk of bleeding on Coumadin goes up with age. We know that age is an increased risk factor for having a thromboembolic event. So itís kind of a balancing act. If you have somebody with an absolutely normal heart, that is greater than 70, itís unclear right now if there is not a contraindication to warfarin, I will go with Coumadin in those patients, but shoot for maybe a little bit lower INR. I donít know if there is a right answer yet or not on those patients.

I think this is something thatís very troubling and I was very surprised when I saw it. This data. People who looked at the national patterns of warfarin use for atrial fibrillation - and you can see over the years - has increased in patients. These are patients, not of all comers because weíve seen some patients in whom Coumadin is probably not indicated. This is in patients in whom there is a clear indication for anticoagulation with Coumadin in atrial fibrillation. And you can see there has been an improvement but the scary part is that if you look over here at this axis itís not even 50% of patients that should be anticoagulated are. I think this is very important. The significance of a stroke in a patient, both the quality of life, mortality, cost, is really traumatic and it is something that we really need to pay careful attention to.

Iíd like to move on a little bit and talk about other treatment goals. So what are our goals in treating atrial fibrillation? Well obviously alleviating symptoms are important, preventing ischemia, improving hemodynamics and obviously we always like to prolong life and prevent sequelae. But at least to date there is no data that supports the reduction in stroke or a prolongation in life with antiarrhythmic maintenance with sinus rhythm. I think we all assume that patients are better off maintaining sinus rhythm. And that prompts a lot of people to treat that. But there is no data. There is a study going on hopefully to answer this and itís called the EFUN trial, and what is does - it is an NIH sponsored trial, begun in 1995, looking for quite a few number of patients and basically randomizing people between rate control and rhythm control to see if we can identify differences. Primary end point, which I think is always good to have as your primary end point, is total mortality. Secondary end points though will also include quality of life, cost and other composite clinical end points such as stroke and heart failure and things like that. So I think this study is really going to give us some good information on helping to direct us.

In the meantime, our options are, one; trying to convert someone to sinus rhythm and maintain sinus rhythm, and Iíll talk about that in a few minutes, or to leave them in atrial fibrillation. Obviously anticoagulate them and then achieve rate control. What can we use for rate control? Thereís pharmacologic means for rate control, digitalis, beta-blockers, calcium channel blockers or even amiodarone and there are non-pharmacologic measures. I would say one important thing, if you choose rate control for your patient, or if you have a patient who is in chronic atrial fibrillation, when you choose rate control make sure you have achieved rate control. So just seeing somebodyís heart rate when they are sitting in your office or when you are seeing them in the hospital and they are lying in their bed, is not adequate. If somebody is sitting there with a heart rate of 70 when they are lying in bed, say okay, they are rate controlled. What you really need to do is see what is going to happen to their heart rate when they get up and start moving around. This is obviously more important for young active healthy people who have atrial fibrillation. But itís also important for older patients. Thereís a few ways to address this. In the hospitalized patients what I like to do is hit the stairs before they leave the hospital, so when they are still in telemetry, or even just taking their pulse, have them go up and down a flight or two of stairs and see what happens to their heart rate. If they are already at home and you are seeing them as outpatients a Holter monitor there for them for 24 hours while they are doing their usual activities of daily living, see what happens to their heart rate. Make sure they are under control. The other thing you do is put them on a tread mill test. See what happens to their heart rate. Iíve seen plenty of patients where people thought they had been adequately controlled, when the get on the treadmill, they have a Holter and the heart rate titration at 150-160, 180 beats per minutes and that is not good for the patients. So I think that is an important caveat, if you choose rate control as your treatment of choice.

So, we look at the different agents for rate control. Thereís digitalis, the one thatís been used for years and years and years. Itís okay if the patient has a history of congestive heart failure. He may get some double benefit ventricular function, and for rate control. But itís very poor for the active patient. What you find is that there is excessive flowing during sinus rhythm at rest, if they

In patients with CHF or LV dysfunction - we are going to talk about this a little bit more - clearly the drug of choice is amiodarone. You can consider a non-pharmacologic approach which we are going to talk about, and again, clearly avoid the 1Cís and also probably the 1Aís. This is the group of patients that have the highest risk of proarrhythmia from these drugs. You donít see that with amiodarone, in fact it may be a benefit in suppressing ventricular arrhythmias.

For patients with LVH or hypertrophic cardiomyopathy again the class 1C drugs are good. Disopyramide is good especially in patients with hypertrophic cardiomyopathy, because itís a negative inotrope. Sotalol and amiodarone are also good drugs. And consider a non-pharmacologic management. In some patients with hypertrophic cardiomyopathy may benefit from ablating the AV node and pacing the ventricle. We are going to talk about that a little bit. We talked about the results with the other drugs and I didnít show a slide of any of the other drugs because they all look the same. Fifty-percent in one year maintenance of sinus rhythm.

Amiodarone is different. And for years amiodarone was reserved malignant ventricular arrhythmias because of the significant toxicity associated with long term use. The toxicities include pulmonary fibrosis, thyroid disease, liver disease, lung disease, it turns people blue. They walk around looking blue. But what we found is that over time that our experience in using amiodarone in atrial fibrillation has been a good one. These toxicities tend to be both dose and time related and the dose that you need for atrial fibrillation is often just one pill a day, 200 mg a day, and at that dose many people could tolerate it for a long time without any problems. And you can see, compared to other agents like quinidine or Norpace, patients failed quinidine, so again the patients who used it selected out to be drug failures, not even to all comers. There still is a significant success rate with amiodarone. Anywhere from 70-80%. So itís a very effective drug. Amiodarone is a very useful treatment.