Atrial Fibrillation

Atrial fibrillation Janet Wong, M.D.

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Emergent/urgent Cardioversion € Poorly tolerated atrial ablation: •

Significant hypotension

•

Pulmonary edema

•

Significant ischemia

€ DC cardioversion: •

Minimum 200 J. synchronized shock

Atrial fibrillation is the most frequently occurring cardiac arrhythmia, and it is the main problem that we have to deal with when it comes to cardiac arrhythmias. There is a 2% risk of atrial fibrillation over 20 years, and the risk increases with age. By the time people reach 75, there is a high prevalence of atrial fibrillation. The risk also increases with other associated diseases like hypertension, coronary disease, and diabetes. The main thing we worry about is the risk of stroke in people with atrial fibrillation. People can be very symptomatic and have functional limitations due to rapid ventricular rate, loss of AV synchrony, variability of ventricular response, and tachycardia-induced cardiomyopathy. Poorly tolerated atrial fibrillation is characterized by significant hypotension. If their BP is 50, you are going to want to treat it as an emergency. So you have someone that comes in, their blood pressure is maintained, but they are developing severe pulmonary edema or they are complaining of crushing chest pain with ECG changes, I think you are not wrong in that case to urgently DC cardiovert those people. Atrial fibrillation is probably the most difficult arrhythmia to electrically cardiovert. Certainly harder than ventricular tachycardia, often harder than ventricular fibrillation. It usually takes high energy. There are two reasons to start with a higher energy. A shock of 50 joules externally stimulates skeletal muscle and that's what makes it painful. A shock of 200 joules or 300 joules or even 360 joules hurts just as much. It doesn't hurt any more. So, you are not saving your patient any discomfort by using a lower energy. When you shock somebody, you should always recharge the defibrillator immediately because when you shock somebody there is always the risk you are going to put them into VF. The risk of causing VF with the shock is related to the energy. The lower the energy, the higher the risk of VF because you have incompletely depolarized the heart. You can decrease the number of shocks if you use a higher energy and you can also reduce the risk of causing VF. I routinely start at 200 to 300 joules, and if I have a big barrel-chested person or an obese person, I just start with 360.

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Acute Rate Control €

IV calcium channel blockers • Diltiazem 20 - 25 mg bolus, then 10-15 mg/hour infusion • Verapamil 2.5 - 5 mg bolus

€

IV Digoxin

What if the person is stable and you want to just control them medically when they come in? The rate can be controlled with a variety of agents. One group of agents is the IV calcium channel blockers. IV diltiazem is the drug of choice because of the ease of use. After you have loaded the patient with a bolus, which is usually 20 to 25 mg, you can start the patient on an infusion of 10 to 15 mg/hour, and you can titrate the infusion rate to achieve the appropriate heart rate. This strategy is very effective in the short term at controlling ventricular rate. You want to convert people over that can take p.o. medications early on if you are going to continue to need to rate control them. IV beta blockers work very well. IV Inderal, IV metoprolol; the shortacting one is esmolol which is difficult to dose. Diltiazem is easier for that reason. IV digoxin is not usually recommended for acute rate control because the onset of action is very long; it can take hours before you rate control someone. Digoxin is not good at rate control in somebody with a high catecholamine state. IV digoxin is no longer used for acute rate control. There is no difference in conversion rate with IV digoxin. Rate control that in atrial fibrillation in the setting of the WPW syndrome. In WPW, there is an accessory pathway connecting the atrium to the ventricle which bypasses the AV node. The problem with that is that the AV node limits the number of impulses that can reach the atrium from the ventricle, maybe in a young healthy person, to 200 to 220 beats per minute. The accessory pathway doesn't have that same function and can let 250, even 300, beats per minute through to the ventricle. The hallmarks of WPW in atrial fibrillation are a wide QRS complex that is an irregular tachycardia, and you have changing amounts of preexcitation. So, the QRS is almost changing beat to beat by the amount of excitation of the ventricle. If you give typical AV node blocking drugs in these patients, they will block the AV node fine, but the ventricle is still going to be activated rapidly over the accessory pathway. If you give a drug like verapamil, you may increase conduction over the accessory pathway. If you give these patients, digoxin, verapamil, or beta blockers, you can degenerate them to ventricular fibrillation. The treatment of choice for atrial fibrillation in the setting of WPW is electrical cardioversion if the patient is unstable. Procainamide is the drug of choice given intravenously because it may convert the atrial fibrillation, and it suppresses conduction over the accessory pathway, and it will limit the number of impulses getting to the ventricle. A potentially life-threatening complication may occur with the usual rate control medications.

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Elective Cardioversion € > 24 - 48 hours € Pharmacologic •

Intravenous: procainamide/ibutilide

•

Oral loading

€ Electrical •

External

•

Internal

Anticoagulation for three months after cardioversion is recommended because of high-risk of embolic events during this period.

Patients who have been in atrial fibrillation for less than 48 hours can be safely cardioverted without anticoagulation. Elective cardioversion can be accomplished pharmacologically with either intravenous procainamide or ibutilide. Or you can use oral loading of quinidine or disopyramide (Norpace). External electrical cardioversion can be used. Internal cardioversions may also be effective in the patients who are resistant to external DC cardioversions. In atrial fibrillation that has been present for more than 48 hours, after you cardiovert them, you need to maintain anticoagulation due to the high risk of embolic events during that period. Patients that have been in chronic atrial fibrillation, the atria are stunned and they don't contract very well. Patients are at continued risk for stroke even though they are in sinus rhythm for a period of three months after conversion from atrial fibrillation. The standard approach is you put them on Coumadin and wait four to six weeks and then bring them in for an elective cardioversion. The down side is there is a delay in cardioversion. You also end up having more prolonged anticoagulation with the risks attendant with warfarin and you delay the recovery of atrial function. The longer you leave somebody in atrial fibrillation, the longer it takes the atrium to recover. The quicker you get somebody out of atrial fibrillation, the longer they will stay out of fibrillation. Transesophageal echo should be used to select candidates for early cardioversion. Heparin therapy should be instituted and the rate should be controlled, and you do a TEE and you look for thrombus. In patients who do not have a thrombus, you can go ahead and cardiovert. So, you have an overall shorter duration of warfarin therapy--four to six weeks less–and a more rapid return of atrial function, and fewer incidents of thromboembolism. In patients in whom left atrial thrombi was excluded, you can safely cardiovert these people. If you decide to cardiovert somebody you don't always have to shock them right off. What we do in our hospital is often bring them in for elective cardioversion, we will give them a load of intravenous procainamide, and if they don't convert then we go ahead and do the DC cardioversion. The standard dose of procainamide, 15 mg/kg over 20 to 30 minutes. It is probably more effective at this faster rate because you get a higher peak plasma level of the procainamide, and that is probably what accounts for the acute conversions. The patient should be monitored for hypotension, QRS widening and QT prolongation. A new class III antiarrhythmic drug called ibutilide (Corvert) works by prolonging the action potential duration. It works well for up to 50%. With atrial fibrillation, with a 30% conversion rate. There is a significant risk of torsades de pointes with ibutilide. It is much easier to give than procainamide - you can give it quicker. Patients develop polymorphic VTs, sustained in almost 2%, 2.5% nonsustained. Some people even developed monomorphic VT. You can see a 9% incidence of ventricular proarrhythmia in these patients. It is okay to use it; you just have to be aware of this and use it in the proper setting. So, if you give this in the ER, patients have to be monitored closely for 4 hours after you use it. If you use it in the hospital, they have to be in a telemetry setting where you are comfortable with the people on your telemetry floors that they can recognize this and treat it very rapidly. How do you convert somebody electrically? When external cardioversion fails, internal cardioversion with a catheter may be success-

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Treatment of Atrial Fibrillation € Treat underlying cause if present € Rate control € Anticoagulating € Maintenance of sinus rhythm in selected patients

ful. The catheter has a platinum electrode on it is floated into the right atrium, and then you shock between the tip of the catheter and the back patch. So, you are actually shocking from inside the heart. The results have been really encouraging. Significantly more people were cardioverted with internal cardioversion than with external. The long-term outcomes were no different. It is useful in the patients who will benefit from sinus rhythm, but you can't get into sinus rhythm with external shocks. Treatment of atrial fibrillation includes treatment of underlying causes. The most common disorders are thyrotoxicosis and pericarditis.

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Anticoagulation Recommendations € Strong contraindication to warfarin: Aspirin 325 mg per day € Lone atrial fibrillation, less than 65: No treatment or aspirin € Low-risk: Aspirin € One or more risk factors: Warfarin (INR 2.0-3.0) € $70, low-risk: Warfarin (INR 2.0) or aspirin

People who have atrial fibrillation have a 6-fold increased risk of stroke. The very high risk patients tend to be the older patients with diabetes, hypertension, previous strokes and TIAs, CHF, coronary disease, and mitral valve disease. High risk patients greater than 65, with one of these risk factors have a 5% per year risk. The low risk patients are the patients less than 60 with normal hearts, with normal blood pressures and glucoses, and the risk is probably even less than 1% per year. With Coumadin there is an overall 65% reduction in stroke presentations with atrial fibrillation. Anticoagulation is important in atrial fibrillation. There is a significant reduction in the risk of stroke with Coumadin over platelet inhibitors. So, in the general population, including the high-risk patients, Coumadin is clearly better than aspirin alone. In patients that are low-risk, who have essentially structural normal hearts, that have no hypertension, no LV dysfunction, no prior embolic events, even if they are older, aspirin is probably better than warfarin in those patients. High risk patients should be on Coumadin. With strong contraindications to warfarin, you need to put them on aspirin. In patients with lone atrial fibrillation that are relatively young, either nothing or aspirin is recommended. If it is a male patient that is 55 years old, having him take an aspirin a day may have some added benefit in coronary disease, so I like to tell them to take an aspirin anyway. Low-risk patients can be treated with aspirin alone. If they have one or more risk factors, warfarin is recommended with an INR between 2 and 3, usually shooting between 2 to 2.5. Greater than 70 puts them in high-risk; however, those are the people that have a higher incidence of bleeding. What I tend to do in people that have relatively normal hearts even if they are older than 70, I will often use aspirin alone, or if I do use Coumadin I will tend to shoot on the lower side of the INR. You have to individualize it for each patient.

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Treatment Goals € Alleviate symptoms € Prevent ischemia € Improve hemodynamics € Prolonge life in prevent sequelae Maintenance of sinus rhythm with an antiarrhythmic has not been proven to reduce risk of stroke or prolong life

Treatment goals in treating atrial fibrillation include alleviation of symptoms, prevention of ischemia with high heart rates. Some patients with atrial fibrillation due to the loss of AV synchrony and the irregularness of their rate have more CHF and keeping them in sinus will improve hemodynamics. You would like to prolong life and prevent sequelae. There is no data at present that supports reduction in stroke or prolongation of life with antiarrhythmic maintenance of sinus rhythm. Antiarrhythmics in patients that had no history of CHF did not cause a significant increase in mortality. Patients with a history of CHF and no antiarrhythmics, clearly they did less well than those patients that had no history of CHF, but the surprising finding was that if you looked at the survival curve for the patients that both had a history of CHF and were receiving antiarrhythmics to maintain sinus rhythm, their survival is much worse than the other groups.

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Rate Control € Pharmacological •

Calcium blockers

•

Beta-blockers

•

Digitalis

•

Amiodarone

Rate control in chronic atrial fibrillation. There are pharmacologic agents, digitalis, beta blockers, calcium channel blockers and even amiodarone for rate control and there are some non-pharmacologic approaches such as AV node modification or ablation of the AV node and physiologic pacing.

€ Non-pharmacological •

AV node modification

•

AV node ablation plus physiologic pacing

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Pharmacologic Rate Control € Digitalis is indicated if history of CHF •

Poor choice in active patients

•

Excessive slowing during sinus rate or at rest

€ Beta-blockers •

Excellent in active patients

•

Using combination with and antiarrhythmics

•

First choice in thyrotoxicosis

•

First choice in ischemic patients

•

May not be tolerated in patients with CHF or lung disease

•

ISA in patients with tachy-bradycardia syndrome

€ Calcium channel blockers •

Good in active patients

•

First choice in patients with lung disease

•

Acceptable in patients with ischemia

•

May not be tolerated in patients with CHF

€ Amiodarone •

May work when nothing else does

•

Good in patients with enhanced AV conviction

•

May be beneficial in patients with LV dysfunction and/or Nonsustained ventricular tachycardia

If you are going to go ahead with pharmacologic rate control it is important to confirm that the patient is rate controlled. A significant number of patients who their physicians thought were adequately rate-controlled were in atrial fibrillation with rates of 140 to 150 at rest. Before people leave the hospital, I will get them up and put them on the stairs while they are still on telemetry and see what their heart rate does. After I send them out, I will either get a treadmill test, or it is even better to send them home with a Holter monitor and tell them, "I want you to go do all of the things that you are normally going to do." You really want to do surveillance Holters when they are back doing the things that they do because when these people get active, their heart rates often shoot up much higher than you thought. Beta blockers are an excellent choice for active patients. Use in combination with antiarrhythmics is well tolerated. It is the first choice in patients with thyrotoxicosis. It is the first choice in patients with ischemia. It may not be tolerated in patients with moderate CHF or lung disease, although patients with mild CHF should be put on beta blockers. A beta blocker like Pindolol, with intrinsic sympathomimetic activity, may be advantageous in patients with tachy-bradycardia syndrome, where you could avoid a pacemaker. But I am not sure how good that is. Calcium channel blockers, I think, are very good agents for rate control. They are good in the active patients. They are the first choice of patients with lung disease who can't use beta blockers. I think they are the first choice of patients with atrial fibrillation and LVH because of the beneficial effects of calcium channel blockers in these patients and the regression of LVH. It may not be tolerated in patients with CHF. Negative inotropic effects. Digitalis is only recommended in patients with a history of CHF because you have the added benefit in those patients. It is very poor in active patients. The problem with digoxin is that you have excessive slowing of the sinus rate at rest but not good control during exertion. So, you push the dig to a point where someone has a heart rate of 60 at rest and then they get up and start doing things like climbing stairs and stuff and their heart rate goes up to 170 or 140. Digoxin, especially in the active patient, is not recomended. Amiodarone may work when nothing else can control the heart rate. It is good in patients that have enhanced AV nodal conduction is a very rare entity where people go into atrial fibrillation and go very rapidly up to 250 or 350 beats per minute. It may be beneficial in patients with LV dysfunction and/or nonsustained VT where you get the added benefit of reducing the risk of sudden death. AV junctional ablation for rate control of atrial fibrillation. The response of patients is really dramatic, and people do really well with this procedure. Indications include failure of the multiple AV nodal blocking drugs. So, patients that you just can't rate control no matter what you use. Patients in whom even though their rate is controlled the irregularity of the atrial fibrillation still bothers them. Drug intolerance. Patients that when they take the drugs that rate control, they get admitted five times a year with CHF and their heart rate is 150 because they never take their medications. Also, patient preference. What do we do with patients with atrial fibrillation and heart failure? Twenty five percent of patients with heart failure may also have atrial fibrillation. These are the patients that are at highest risk of proarrhythmia from antiarrhythmic drugs. Congestive heart failure

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Chemical Cardioversion

can lead to atrial fibrillation, and atrial fibrillation can lead to and worsen congestive heart failure. Chronic tachycardia is associated with the development of a cardiomyopathy and it appears to be reversible.

€ Procainamide •

15 mg/kg IV over 20-30 minutes (750-1500 mg)

•

Watch for hypotension, QRS widening, QT prolongation.

Ablation and pacing results in an improvement in EF from 25% to 52%. Dramatic increases in injection fraction. With severe LV dysfunction, after you ablate their AV node and put in a pacemaker; it is almost back to normal. I think that is a really important point that people don't fully understand yet. Patients with mean heart rates of 60 to 100 beats per minute on a Holter that had depressed LV function underwent AV junctional ablation and showed a significant improvement in function after this. Regularization of ventricular response. Even if you have somebody rate controlled, the ventricle is being activated very irregularly. Regularization of rhythm provides significant hemodynamic benefits. In patients with AF, an increase in pulmonary capillary wedge pressure were seen with irregular rhythm as opposed to regular rhythm; therefore, both rapid rate and irregularity leads to decreased LV function. If you have patients that are difficult to manage and are having repeated visits to the hospital with CHF and have chronic atrial fibrillation, AV junctional ablation with pacing is something to consider. It may help you manage their CHF.

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Maintenance of Sinus to Rhythm € Pharmacologic € Preventive pacing

Maintenance of sinus rhythm. There is a subset of patients in whom we are going to want to try and maintain sinus rhythm. There are pharmacologic approaches, preventative pacing, implantable defibrillators and ablative therapy.

€ Implantable defibrillator € Ablative therapy •

Surgical

•

Catheter

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Pharmacologic Maintenance of Sinus to Rhythm € Class IA •

Quinidine: diarrhea

•

Procainamide: arthritis/rash/lupus

•

Disopyramide: urinary retention

€ Class IC •

Flecainide: avoided in ischemia/poor LV function

•

Propafenone: avoided in ischemia/poor LV function

€ Class III •

Sotalol: CHF, asthma, bradycardia

€ Amiodarone: end organ toxicity

Pharmacologic agents. The class-I agents are sodium channel blockers. There is quinidine, procainamide, disopyramide. Quinidine is a drug that has been used for years and years, but 40 to 50% of patients can't take it because of the diarrhea. Procainamide maintenance is not recommended because of arthritis, rash, and lupus-like syndromes. Disopyramide (Norpace) is not good in older men because of urinary retention, but it is very welltolerated in younger patients, and in patients with vagally mediated atrial fibrillation. The class 1C agents. Flecainide got a very bad name because of the excess mortality in patients post MI. But I think in patients with structurally normal hearts, it is probably one of the most effective agents that we have for controlling atrial fibrillation. It should be avoided it in patients with ischemia or poor LV function. The same thing with propafenone (Rythmol). A newer agent, Sotalol can be very effective because it offers both rate control and an antiarrhythmic properties, but the beta blocking properties can cause problems in patients with CHF, asthma, and it can cause bradycardia. Amiodarone is a very good drug for controlling atrial fibrillation, but the end organ toxicities are something to be concerned about. Over one year's time on quinidine, about 50% are maintained in sinus rhythm. Propafenone and Sotalol, 50%. With the exception of amiodarone, the antiarrhythmic drugs are all about 50% effective at one year. Amiodarone appears to be the most effective antiarrhythmic at maintaining sinus rhythm. It is 78% effective at maintaining sinus rhythm in people who had failed a type-I antiarrhythmic. Amiodarone versus quinidine, again right around 50% versus 79%. Same thing for amiodarone versus Norpace. Amiodarone is the best drug available for maintaining sinus rhythm. We have had a lot of good success with using amiodarone, and we use it in a lot of patients. Toxicity tends to be dose related. So, in the doses we use in ventricular tachycardia, 400 to 600 mg/day, there is a significant incidence of pulmonary fibrosis and other end organ toxicities. At the dose we use for atrial fibrillation, it is 200 mg/day, which is one pill, or even 200 mg every other day, the incidence of these side effects are very low. The side effects are reversible. In patients that have failed other drugs and patients that have LV dysfunction, amiodarone is the drug of choice. Amiodarone is a very unique drug. The half-life is one month to five months. It is a very lipophilic drug so when you give it to people it immediately gets sucked up into their fat stores. Start with a much higher dose and then we cut the dose back. Start them on 800 mg/day for about two weeks, then I will put them on 400 mg/day for about a month, then cut them back down to 200 mg/day. Results have been very good. Patients have tolerated it well and it clearly works much better than other agents. Anybody over 70 who presents with atrial fibrillation or who has any LV dysfunction, should be started on amiodarone as a first line agent.

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No Structural Heart Disease € First-line agents •

Class IC (flecainide, propafenone)

•

Disopyramide (especially if vagally mediated)

€ Second-line •

Sotalol

€ Third line •

Amiodarone

If you have a patient that has no structural heart disease with lone AF, they are very symptomatic, you don't want to leave these people in AF all the time and make them take aspirin and have them in atrial fibrillation. You can give them drugs to try to maintain sinus rhythm. We have had a lot of success with flecainide in this population. Norpace is very good especially in vagally mediated AF. There is a group of patients who get atrial fibrillation after they eat big meals or they wake up in the middle of the night. Vagal surges change the electrophysiologic properties of the atrium and make it more susceptible to atrial fibrillation. Norpace has some vagolytic effects and may be effective in those patients. Second line, Sotalol is often good in these patients, and you can use amiodarone.

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Ischemic Heart Disease € First-line: •

Sotalol

In patients with ischemic heart disease, the class 1C drugs should be avoided. Sotalol may be a good drug. The beta blocking properties are good for the ischemic patient, and amiodarone is a good agent in those patients.

€ Second-line: •

Amiodarone

€ Avoid class IC

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CHF/LV Dysfunction € First-line: •

Amiodarone

€ Consider non-pharmacologic approach € Avoid class IC

In the patients with CHF and LV dysfunction, you have to avoid those drugs that are proarrhythmic. Amiodarone may be the best drug in these patients because you get the added protection from sudden death. You should also consider the non-pharmacologic approach in these patients because you may see an increase in LV function after you control their rate with ablation and regularize their ventricular response with pacing.

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LVH/HCM € First-line •

Class 1C (flecainide, propafenone)

€ Second-line: •

Sotalol

•

Amiodarone

In patients that have left ventricular hypertrophy or hypertrophic cardiomyopathy, class 1C agents are also good. Disopyramide is specifically good in patients with hypertrophic cardiomyopathy because of the negative inotropic effects. It may decrease the gradient. Sotalol also is very good in these patients, and amiodarone is good. In patients with hypertrophic cardiomyopathy, you should consider non-pharmacologic management, such as ablation, because dual-chamber pacing will decrease the pressure gradient so you get the added benefit of those two things.

€ Consider nonpharmacologic management (HCM)

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Outpatient loading of antiarrhythmic medications utilizing a monitoring device is probably safe and cost-effective. Patients get their first dose of the drug in the hospital, and then were sent out with a loop recorder for 10 days. Every day they transmit a tracing of their heart rate and their QT interval and they also transmit any palpitations or any adverse effects that they had. Prophylactic pacing for atrial fibrillation. It is thought that atrial fibrillation is due to multiple re-entrant wave fronts throughout the atria. Excitation and therefore prolongation of the refractoriness of the tissue in the critical regions of the atrium may prevent the initiation or maintenance of atrial fibrillation. If you stimulate the heart in more than one place, you may be able to prevent these reentrant wave fronts and prevent atrial fibrillation. There are trials that have looked at patients with sick sinus syndrome that got either dual chamber pacers or ventricular pacers alone. The studies showed that in patients that had atrial pacing, it was a significantly much lower incidence of atrial fibrillation that had active atrial pacing suggesting that somehow pacing the atrium will decrease the incidence of atrial fibrillation. Implantable ventricular defibrillators. This is a device that goes in the pectoral region, has two leads in the right atrium. One in the right atrium, one in the coronary sinus and one for R-wave synchronization in the RV apex. It is used to cardiovert people out of atrial fibrillation. It can be done when you have two leads inside the heart like this and you are not shocking externally and you are not stimulating skeletal muscle. The amount of energy required is only in some patients 0.5 Joule or 1 or 2 Joule. So, although in some patients that causes a fair amount of discomfort, in some patients it doesn't and the idea of atrial defibrillators are being tested right now. The big questions are safety. The first patient that has an atrial defibrillator that gets shocked or it fails and they get put into VF and then dies, that will be the end of the whole idea. Surgical treatment of atrial fibrillation. The Maze procedure consists of multiple atriotomies which interrupt all the potential re-entrant circuits. This will restore control of the heartbeat to the atrial pacemaker, which is the sinus node, and it allows activation of the entire atrial myocardium. The long term results are unclear. Atrial flutter. Typical atrial flutter is characterized by the typical saw-tooth flutter wave in the inferior leads beneath the positive flutter wave in lead V1. It is a macroreentrant electrical rhythm confined to the right atrium. So, the electrical wave front goes around the right atrium, up the septum, down the lateral wall and through this isthmus of tissue between the opening of the IVC and the tricuspid annulus and the coronary sinus. If we can create a line of conduction block, the patient should not have atrial flutter anymore. We are now able to terminate atrial flutter and cure people that have typical atrial flutter in about 95% of cases. Antiarrhythmic drugs are not very effective for atrial flutter, and rate control is much more difficult in atrial flutter than atrial fibrillation because it is hard to get a reasonable rate control. When somebody presents with atrial flutter for the first time, cardioversion is recommended, and then the patients are discharged and observed to determine what the natural history is going to be. If they are not going to have atrial flutter for the next five years, no treatment is necessary. The first time they return with atrial flutter, if it is early on, the first line of therapy now is ablative therapy and our success rate is very good and the risk is low.

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