TREATMENT Atrial Fibrillation
Treatment for AF is primarily guided by patients’ symptoms, the hemodynamic effect of AF, the duration of AF if there are persistent risk factors for stroke, and underlying heart disease. Oral anticoagulation in high-risk patients with AF includes vitamin K antagonists or the newer anticoagulants such as thrombin inhibitors (dabigatran) or factor Xa inhibitors (rivaroxaban, apixaban), but not antiplatelet agents (aspirin and clopidogrel), which have substantially less effect.
New-onset AF that produces severe hypotension, pulmonary edema, or angina should be electrically cardioverted starting with a QRS synchronous shock of 200 J, ideally after sedation or anesthesia is achieved. Greater shock energy and different electrode placements may be tried if the shock fails to terminate AF. If AF terminates and reinitiates, administration of an antiarrhythmic drug, such as ibutilide, and repeat cardioversion may be considered. If the patient is stable, immediate management involves rate control to alleviate or prevent symptoms, anticoagulation if appropriate, and cardioversion to restore sinus rhythm if AF is persistent. Anticoagulation strategies for new-onset AF are debated. In the absence of contraindications, it is usually appropriate to initiate systemic anticoagulation with heparin immediately, while evaluation and other therapies are implemented. CARDIOVERSION AND ANTICOAGULATION
Cardioversion within 48 h of the onset of AF is common practice in patients who have not been anticoagulated, provided that they are not at high risk for stroke due to a prior history of embolic events, rheumatic mitral stenosis, or hypertrophic cardiomyopathy with marked left atrial enlargement. These patients are usually at risk of recurrence, such that initiation of anticoagulation is considered based on the patient’s individual risk for stroke, commonly assessed from the CHA2DS2-VASc score.
If the duration of AF exceeds 48 h or is unknown, there is greater concern for thromboembolism with cardioversion, even in patients considered low risk for stroke. There are two approaches to mitigate the risk related to cardioversion. One option is to anticoagulate continuously for 3 weeks before and a minimum of 4 weeks after cardioversion. A second approach is to start anticoagulation and perform a transesophageal echocardiogram to determine if thrombus is present in the left atrial appendage. If thrombus is absent, cardioversion can be performed and anticoagulation continued for aminimum of 4 weeks because recovery of atrial mechanical function after electrical or pharmacologic cardioversion may be delayed and thrombus can form and embolize days after cardioversion. Some patients may merit ongoing anticoagulation after cardioversion, depending on stroke risk profile. RATE CONTROL
Acute rate control can be achieved with beta blockers and/or the calcium channel blockers verapamil and diltiazem administered either intravenously or orally, as warranted by the urgency of the clinical situation. Digoxin may be added, particularly in heart failure patients, because it does not have negative inotropic effects, particularly if use of AV nodal–blocking agents is limited by poor tolerance or is contraindicated. Its effect is modest but synergistic with the other AV nodal–blocking agents, but it is particularly limited when sympathetic tone is elevated. Typically, the goal of acute rate control is to reduce the ventricular rate to less than 100/min, but the goal must be guided by the clinical situation. CHRONIC RATE CONTROL
For patients who remain in AF chronically, the goal of rate control is to alleviate and prevent symptoms and prevent deterioration of ventricular function from excessive rates. β-Adrenergic blockers, calcium channel blockers, and digoxin are used, sometimes in combination. Rate should be assessed with exertion and medications adjusted accordingly. Exertion-related symptoms are often an indication of inadequate rate control. The initial goal is a resting heart rate of less than 80 beats/min that increases to less than 100 beats/min with light exertion, such as walking. If it is difficult to slow the ventricular rate to that degree, allowing a resting rate of up to 110 beats/min is acceptable provided it does not cause symptoms and ventricular function remains normal. Periodic assessment of ventricular function is warranted because some patients develop tachycardia-induced cardiomyopathy.
If adequate rate control in AF is difficult to achieve, further consideration should be given to restoring sinus rhythm. Catheter ablation of the AV junction to create heart block and implantation of a permanent pacemaker reliably achieve rate control without the need for AV nodal agents, but implement life-long permanent pacing. Right ventricular apical pacing induces dyssynchronous ventricular activation that can be symptomatic or depress ventricular function in some patients. Biventricular pacing may be used to minimize the degree of ventricular dyssynchrony. STROKE PREVENTION IN ATRIAL FIBRILLATION
The majority of patients warrant chronic anticoagulation, but selection of therapy should be individualized based on patient profile and risks and benefits of individual agents. Anticoagulation with a vitamin K antagonist is warranted for all patients with AF who have rheumatic mitral stenosis or mechanical heart valves for whom the newer anticoagulants have not been tested. Anticoagulation with a vitamin K antagonist (warfarin) or the newer oral anticoagulants is warranted for patients who have had more than 48 h of AF and are undergoing cardioversion, for patients who have a prior history of stroke, or for patients with a CHA2DS2-VASc score of ≥2, but it may be considered in patients with a risk score of 1. The approach to patients with paroxysmal AF is the same as for persistent AF. It is recognized that many patients who appear to have infrequent AF episodes often have asymptomatic episodes that put them at risk. Absence of AF during periodic monitoring is not sufficient to indicate low risk. The role of continuous monitoring with implanted recorders or pacemakers is not yet clear as a guide for anticoagulation in patients with a borderline risk profile. Bleeding is the major risk of anticoagulation. Major bleeding requiring transfusion or in a critical area (e.g., intracranial) occurs in approximately 1% of patients per year. Risk factors for bleeding include age >65–75 years, heart failure, history of anemia, and excessive alcohol or nonsteroidal anti-inflammatory drug use. Patients with coronary stents who require antiplatelet therapy with aspirin and a thienopyridine are at particularly high risk of bleeding.
Warfarin reduces the annual risk of stroke by 64% compared to placebo and by 37% compared to antiplatelet therapy. The newer anticoagulants, dabigatran, rivaroxaban, and apixaban, have been found to be noninferior to warfarin in individual trials, and analysis of pooled data suggests superiority to warfarin by small absolute margins of 0.4–0.7% in reduction of mortality, stroke, major bleeding, and intracranial hemorrhage. Warfarin is an inconvenient agent that requires several days to achieve a therapeutic effect (prothrombin time [PT]/international normalized ratio [INR] >2), requires monitoring of PT/INR to adjust dose, and has many drug and food interactions, thus limiting patient compliance. The newer agents are easier to use and achieve reliable anticoagulation promptly without requiring dosage adjustment based on blood tests. Dabigatran, rivaroxaban, and apixaban have renal excretion, cannot be used with severe renal insufficiency, and require dose adjustment for modest renal impairment, which is of particular concern in the elderly, who are at increased bleeding risk. Excretion can also be influenced by P-glycoprotein inducers and inhibitors. Warfarin anticoagulation can be reversed by administration of fresh frozen plasma and vitamin K. Reversing agents for the newer anticoagulants are lacking (but in development), and bleeding must be managed with supportive care, with the expectation that clotting will improve over 12 h as the anticoagulant is excreted.
The antiplatelet agents aspirin and clopidogrel are inferior to warfarin for stroke prevention in AF and do not reduce the risk of bleeding. Clopidogrel combined with aspirin is better than aspirin alone but inferior to warfarin and has greater bleeding risk than aspirin alone.
Chronic anticoagulation is contraindicated in some patients due to bleeding risks. Because most atrial thrombi are felt to originate in the left atrial appendage, surgical removal of the appendage, combined with atrial maze surgery, may be considered for patients undergoing surgery, although removal of the appendage has not been unequivocally shown to reduce the risk of thromboembolism. Percutaneous devices that occlude or ligate the left atrial appendage are being studied for safety and efficacy. RHYTHM CONTROL
The decision to administer antiarrhythmic drugs or perform catheter ablation to attempt maintenance of sinus rhythm (commonly referred to as the “rhythm control strategy”) is mainly guided by patient symptoms and preferences regarding the benefits and risks of therapies. In general, patients who maintain sinus rhythm have better survival than those who continue to have AF. This is likely because continued AF is a marker of disease severity. In randomized trials, administration of antiarrhythmic medications to maintain sinus rhythm did not improve survival or symptoms compared to a rate control strategy, and the drug therapy group had more hospitalizations. Disappointing efficacy and toxicities of available antiarrhythmic drugs and patient selection bias may be factors that influenced the results of these trials. The impact of catheter ablation on mortality is not known. A rhythm control strategy is usually selected for patients with symptomatic paroxysmal AF, a first episode of symptomatic persistent AF, AF with difficult rate control, and AF that has resulted in depressed ventricular function or that aggravates heart failure. A rhythm control strategy is more likely to be favored in younger patients than in sedentary or elderly patients in whom rate control is usually easily achieved. Even if sinus rhythm is apparently maintained, anticoagulation is recommended according to the CHA2DS2-VASc stroke risk profile because asymptomatic episodes of AF are common. Following a first episode of persistent AF, a strategy using AV nodal–blocking agents, cardioversion, and anticoagulation is reasonable, in addition to addressing possible aggravating factors, including hypertension, heart failure, and sleep apnea. If recurrences are infrequent, periodic cardioversion is reasonable. Pharmacologic Therapy for Maintaining Sinus Rhythm
The goal of pharmacologic therapy is to maintain sinus rhythm or reduce episodes of AF. Drug therapy can be instituted once sinus rhythm has been established or in anticipation of cardioversion. β-Adrenergic blockers and calcium channel blockers help control ventricular rate, improve symptoms, and possess a low-risk profile, but have low efficacy for preventing AF episodes. Risks and side effects of antiarrhythmic drugs are a major consideration in selecting therapy. Class I sodium channel–blocking agents (e.g., flecainide, propafenone, disopyramide) are options for subjects without significant structural heart disease, but they have negative inotropic and proarrhythmic effects that warrant avoidance in patients with coronary artery disease or heart failure. The class III agents sotalol and dofetilide can be administered to patients with coronary artery disease or structural heart disease but have approximately a 3% risk of inducing excessive QT prolongation and torsades des pointes. Dofetilide should be initiated only in a hospital with ECG monitoring, and many physicians take this approach with sotalol as well. Dronedarone increases mortality in patients with heart failure. All of these agents have modest efficacy in patients with paroxysmal AF, of whom approximately 30–50% will benefit. Amiodarone is more effective, maintaining sinus rhythm in approximately two-thirds of patients. It can be administered to patients with heart failure and coronary artery disease. Over 20% of patients experience toxicities during long-term therapy. CATHETER AND SURGICAL ABLATION FOR ATRIAL FIBRILLATION
Catheter ablation avoids antiarrhythmic drug toxicities but has procedural risks and requires an experienced center. For patients with previously untreated but recurrent paroxysmal AF, catheter ablation has similar efficacy to antiarrhythmic drug therapy and is superior to antiarrhythmic drugs for patients who have recurrent AF despite drug treatment. The procedure involves cardiac catheterization, transatrial septal puncture, and radiofrequency ablation or cryoablation to electrically isolate the regions around the pulmonary veins, abolishing the effect of triggering foci to interact with the left atrial AF substrate. Extensive areas of ablation are required, and gaps in healed ablation areas necessitate a repeat procedure in 20–50% of patients. Sinus rhythm is maintained for more than 1 year after one procedure in approximately 60% of patients and in 70–80% of patients after multiple procedures. Some patients become more responsive to antiarrhythmic drugs.
There is a 2–7% risk of major complications, including stroke (0.5–1%), cardiac tamponade (1%), phrenic nerve paralysis, bleeding from femoral access sites, and fluid overload with heart failure, that can emerge 1–3 days after the procedure. It is important to recognize the potential for delayed presentation of some complications. Ablation within the pulmonary veins can lead to pulmonary vein stenosis, presenting weeks to months after the procedure with dyspnea or hemoptysis. Esophageal ulcers can form immediately after the procedure and may rarely lead to a fistula between the left atrium and esophagus (estimated incidence of 0.1%) that presents as endocarditis and stroke 10 days to 3 weeks after the procedure.
Catheter ablation is less effective for persistent AF. More extensive ablation is often required, including areas that likely support reentry in regions outside the pulmonary venous antra, but individual strategies are debated. More than one ablation procedure is often required to maintain sinus rhythm.
Surgical ablation of AF is typically performed concomitant with cardiac valve or coronary artery surgery and less commonly as a stand-alone procedure; however, for patients with persistent AF, surgical or hybrid procedures may have higher single-procedure efficacy. Risks include sinus node injury requiring pacemaker implantation. Surgical removal of the left atrial appendage may reduce stroke risk, although thrombus can form in the remnant of the appendage or if the appendage is not completely ligated.