Jose L. Baez-Escudero, MD, FHRS and Miguel Valderrábano, MD

1. How common is atrial fibrillation (AF)?

    AF is the most commonly encountered arrhythmia in clinical practice, accounting for one-third of cardiac hospitalizations annually. Its incidence rises with increasing age for men and women, with an estimated prevalence of 5% at age 75 and 15% at age 85. As many as 2.3 million Americans and 4.5 million people in the European Union are estimated to have AF.

2. What cardiovascular diseases are likely to coexist in patients with AF?

    Hypertensive heart disease is the most common preexisting condition. However, systolic dysfunction, coronary artery disease (CAD), rheumatic valve disease, nonrheumatic valvular heart disease, chronic lung disease, and hyperthyroidism are common comorbidities. Patients without identifiable cardiovascular disease or other conditions associated with AF are said to have lone AF. These patients have a favorable prognosis with respect to thromboembolism and mortality.

3. What arrhythmias are related to AF?

    AF may occur in association with other arrhythmias, most commonly atrial flutter or atrial tachycardia. Atrial flutter may degenerate into AF and AF may organize to atrial flutter, particularly during treatment with antiarrhythmic agents prescribed to prevent recurrent AF. The electrocardiogram (ECG) pattern may fluctuate between atrial flutter and AF, reflecting changing activation of the atria. Focal atrial tachycardias, atrioventricular (AV) reentrant tachycardias, and AV nodal reentrant tachycardias may also trigger AF.

4. What are the main anatomic and physiologic substrates for the initiation of AF?

    Available data support both a focal triggering mechanism involving automaticity or multiple reentrant wavelets. The pulmonary veins (PVs) are the most common source of these rapid atrial impulses. Other known contributing factors in the genesis of AF include atrial electrical remodeling, sympathetic and parasympathetic stimuli, the renin-angiotensin-aldosterone system, and inflammation.

5. Which agents are effective in slowing the ventricular response in acute AF?

    In the absence of an accessory bypass tract and preexcitation syndrome (such as in patients with Wolff-Parkinson-White [WPW] syndrome), intravenous (IV) administration of beta-adrenergic blocking agents (β-blockers; esmolol, metoprolol, or propranolol) or nondihydropyridine calcium channel antagonists (verapamil, diltiazem) is recommended to slow the ventricular response to AF in the acute setting, exercising caution in patients with hypotension or systolic heart failure. In patients with AF and systolic dysfunction who do not have an accessory pathway, IV digoxin or amiodarone is recommended. However, digoxin should not be used as a sole agent.

6. How do you decide which antithrombotic therapy is most appropriate?

    Several schemes for stratification of stroke risk can identify patients who benefit most and least from anticoagulation. The most commonly used tool as outlined in the current guidelines is the CHADS₂ score for AF stroke risk scheme (Fig. 34-1), in which patients are stratified for risk according to the presence of moderate risk factors (1 point) and high risk factors (2 points). The use of appropriate anticoagulation is then decided according to the sum of points, as outlined in Table 34-1. A recently updated and modified CHA₂DS₂-VASc scoring system (Table 34-2) has been validated and used in patients who fall in the intermediate risk category. CHA₂DS₂-VASc assigns points for risk factors not included in the CHADS₂ score, such as female gender, age 65 to 75, and vascular disease.

7. Why is antithrombotic therapy so important in AF?

    AF is an independent risk factor for stroke. The rate of ischemic stroke in patients with nonvalvular AF is about two to seven times that of people without AF, and the risk increases dramatically as patients grow older. Paroxysmal and chronic AF are associated with a similar risk of thromboembolism. Anticoagulation therapy is essential in patients with AF to reduce the risk of embolic stroke. Aspirin (81 or 325 mg/day) reduces the risk of thromboembolism by approximately 35%. Warfarin reduces the risk by 65%. Full-dose warfarin is also superior to low-dose (international normalized ratio [INR] 1.2-1.5) warfarin plus aspirin. The risk of a serious bleeding complication while on warfarin therapy (with an INR goal of 2-3) is 1.3% to 2.5% per year. Although the elderly may have a greater risk of bleeding, they also carry a greater risk of stroke and therefore benefit the most from warfarin therapy.

8. What are some alternatives to warfarin for anticoagulation?

    A narrow therapeutic range and the need for regular monitoring of its anticoagulatory effect impair the effectiveness and safety of warfarin, creating a need for alternative anticoagulant drugs. Interactions of warfarin with food and other drugs also hamper its use. Recently developed and FDA approved oral anticoagulants include direct thrombin antagonists such as dabigatran and factor Xa inhibitors such as rivaroxaban. Dabigatran is at least noninferior to warfarin in all AF patients at low, moderate, or high risk of stroke. It is given twice a day and does not require monitoring. The once-daily drug rivaroxaban has also been shown to be noninferior to warfarin for the prevention of stroke or systemic embolism, without additional risk of major bleeding. Antidotes have not been developed yet for these drugs, although strategies for overdose treatment and bleeding (e.g., charcoal therapy and hemodialysis in dabigatran overdose) have been proposed.

9. When should cardioversion be considered to convert a patient from AF to sinus rhythm?

    Cardioversion (CV) may be achieved by means of drugs or direct-current electrical shocks when the patient has new-onset AF that is less than 48 hours in duration. If the duration is more than 48 hours or unknown, the patient should be treated with anticoagulation therapy for 3 weeks before and 4 weeks after CV to prevent thromboembolism. Alternatively, a patient can undergo transesophageal echocardiography (TEE) to rule out left atrial thrombus and, if negative, proceed with CV while receiving appropriate anticoagulation. In cases of early relapse of AF after CV, repeated direct-current cardioversion attempts may be made after administration of antiarrhythmic medication. Administration of flecainide, dofetilide, propafenone, or ibutilide is recommended for pharmacologic cardioversion of AF.

10. How do you approach rate versus rhythm control issues?

    Two landmark studies, the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) and the Rate Control versus Electrical Cardioversion (RACE) trials, found that treating AF with a rhythm-control strategy, involving CV and antiarrhythmic drug (AAD) therapy, offers no survival or clinical advantages over a simpler rate-control strategy. However, these studies primarily enrolled older patients (older than age 65 years) with persistent AF who were mildly symptomatic. Moreover, in the AFFIRM study, fewer than two-thirds of those in the rhythm control arm were actually able to stay in sinus rhythm. Thus, the results cannot be extrapolated to many subgroups of patients, including younger patients; those with new, first-onset AF who may benefit from early conversion to sinus rhythm; patients with persistent AF who are highly symptomatic; and patients with significant systolic heart failure who have a hemodynamic benefit from the atrial kick.

11. Which antiarrhythmic drugs are most commonly used to maintain long-term sinus rhythm and prevent AF recurrence?

    Before initiating any AADs, treatment of precipitating or reversible causes of AF is recommended. The AADs most commonly used have been sotalol, amiodarone, dronedarone, propafenone, dofetilide, and flecainide. Quinidine and procainamide are no longer used because of safety concerns. Flecainide and propafenone should be used in conjunction with an AV nodal blocker agent. These two antiarrhythmics are contraindicated in patients with CAD. Dronedarone is contraindicated in patients with systolic congestive heart failure and should not be used in patients with chronic persistent AF. Dofetilide and amiodarone are most suited for patients with AF and systolic dysfunction. Dofetilide and sotalol prolong the QT interval and are both excreted by the kidney. Their dosing requires titration according to the patient’s creatinine clearance and their administration is usually initiated in a hospital setting with periodic ECG monitoring.

12. When is catheter ablation of AF indicated, and who is the ideal candidate?

    Pulmonary vein isolation (PVI) with radiofrequency catheter ablation (RFA) is the most common ablation procedure performed in current practice. Because it has been shown to be superior to antiarrhythmics therapy alone, PVI appears in the new guidelines as a first-line option for treatment of paroxysmal or persistent AF in patients who have failed an AAD regimen. Patient selection, optimal set of ablation lesions, absolute rates of treatment success, and the frequency of complications remain incompletely defined. The ideal candidate for PVI is a person with nonvalvular paroxysmal AF, who has failed at least one AAD, and who is highly symptomatic. The patient’s left atrium should be less than 5.5 cm in diameter, without other significant cardiac disease. The procedure has also been shown to be efficacious in some patients with chronic AF, as well as in patients with congestive heart failure. Some new technologies, such as balloon cryoablation, balloon laser ablation, and multielectrode catheter RFA, have been recently developed and are currently being studied as alternatives to conventional open-irrigated catheter RFA.

13. What are potential complications of PVI?

    A worldwide survey on AF catheter ablation showed an overall incidence of major complications of 6%. Potential complications include bleeding, hematoma, or fistula at the site of femoral access, periprocedural thromboembolism, cardiac perforation or tamponade, esophageal injury including atrioesophageal fistula, pulmonary vein stenosis, phrenic nerve injury, and radiation-induced skin injury. Development of reentrant and focal left atrial tachycardias, often more symptomatic than the initial AF, may be seen after the procedure and may be transient.

14. What is the role of AV nodal ablation followed by permanent pacing in treating AF?

    The guidelines specifically state that AV node ablation followed by permanent pacing should be used only as a fallback treatment rather than as a primary strategy, because of the risk of long-term right ventricular (RV) pacing. In general, patients most likely to benefit from this strategy are those with symptoms or tachycardia-mediated cardiomyopathy related to rapid ventricular rate during AF that cannot be controlled adequately with AADs or negative chronotropic medications. Biventricular pacing is often used with or without a defibrillator in patients that are candidates for AV nodal ablation and have a history of cardiomyopathy. Although the symptomatic benefits of AV nodal ablation are clear, limitations include the persistent need for anticoagulation, loss of AV synchrony, and lifelong pacemaker dependency.

15. What is the role of left atrial appendage (LAA) occluders in the prevention of stroke in AF patients?

    Percutaneously placed LAA closure devices can decrease the risk of ischemic stroke in patients with AF, without the need for long-term oral anticoagulation, and may be a useful strategy in patients with contraindications to long-term oral anticoagulation. These devices are deployed in the LAA and occlude the LAA, preventing blood from entering the appendage and hence avoiding thrombus formation. The Watchman closure device (Atritech, Inc., Plymouth, Minn.) was studied in the randomized trial Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF), in which patients with the device took warfarin for at least the first six weeks. PROTECT-AF found the device noninferior to standard warfarin therapy for protection against stroke, cardiovascular death, or systemic embolism in patients with AF and a CHADS₂ score >1. This study led to the approval of the Watchman device in Europe. A larger randomized trial comparing the device to warfarin (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device in Patients with Atrial Fibrillation versus Long Term Warfarin Therapy [PREVAIL]) is currently underway.

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