Manual of Cardiovascular Medicine

I.INTRODUCTION. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is characterized by the degeneration of organized atrial electrical activity into a rapid, chaotic pattern. AF accounts for approximately one-third of hospitalizations for cardiac rhythm disturbances. An estimated 3 million people in the United States and 6 million people in Europe have AF. The prevalence of AF is higher in men and increases with age. AF is associated with an increased risk of stroke, heart failure, and mortality.

A.Classification. AF can be classified as new-onset or recurrent (at least two episodes). AF can also be classified according to its pattern as paroxysmal (self-limiting), persistent (sustained >7 days), long-standing persistent (sustained >12 months), and permanent (no longer pursuing restoration of sinus rhythm). It is important to distinguish nonvalvular from valvular AF (rheumatic mitral stenosis, prosthetic heart valve, or mitral valve repair) because this impacts antithrombotic choice. Many of the clinical trials of the new oral anticoagulants excluded patients with prosthetic heart valves, mitral stenosis, and severe valvular disease who were likely to require imminent valve surgery. The term lone AF has been used to describe patients without structural heart disease and should only be used in patients at very low risk for complications of AF such as thromboembolism.

B.Pathophysiology. Multiple disease pathways contribute to AF, and these mechanisms are incompletely understood. The role of the pulmonary veins as a source for triggers of AF is increasingly appreciated. A previous model proposed by Moe et al. in 1962 described multiple reentrant wavelets within the atrial tissue that contributed to the maintenance of AF. More recent data support a focal mechanism involving both increased automaticity and multiple reentrant wavelets that occur predominantly in the left atrium around the pulmonary veins. A new model incorporates these mechanisms of initiation of AF and additional atrial substrate conditions for AF maintenance. In turn, this may be affected by various modulating factors such as autonomic tone, medications, atrial pressure, and catecholamine levels. AF is a very complex arrhythmia, and this mechanistic model simply serves as a conceptual framework on which to build.

C.Risk factors. AF is most commonly associated with advanced age, hypertension, valvular heart disease, congestive heart failure, and coronary artery disease. AF has also been associated with physiologic stress, drugs, pulmonary embolism, chronic lung disease, hyperthyroidism, caffeine, infectious processes, and various metabolic disturbances. AF has also been linked with obesity and obstructive sleep apnea. This phenomenon seems to be mediated by left atrial dilation. Other less common cardiac associations include preexcitation syndromes, pericarditis, and cardiomyopathies. Surgery, particularly cardiac surgery, is associated with a high risk of AF. Persistence of AF has been correlated with elevated C-reactive protein levels, which raises the possibility of a role for inflammation in this condition.

D.Clinical presentation. The clinical presentation of AF can vary widely. Some patients may be asymptomatic whereas others can present with severe hemodynamic instability such as those with ventricular preexcitation. The most common symptoms are palpitations, fatigue, and dyspnea. Some patients may present with chest discomfort or syncope. AF is also commonly found in patients admitted with stroke.

E.Diagnostic testing. The initial evaluation of a patient with new-onset AF includes a detailed history and physical examination to define the clinical type of AF (pattern, frequency, and duration) and to characterize the nature of symptoms associated with AF. Additional evaluation should include the following:

1.Laboratory evaluation should include a complete blood count, comprehensive metabolic panel, magnesium level, and thyroid function tests. Hyperthyroidism should always be considered, especially when the ventricular rate is difficult to control.

2.12-Lead electrocardiogram (ECG) should be obtained to verify AF and determine the ventricular response rate. P-waves are absent and replaced by fibrillatory (f) waves. The atrial electrical activity is disorganized, and the ventricular response rate is usually irregularly irregular. The atrial rate is generally in the range of 400 to 700 beats/min whereas the ventricular response rate is generally in the range of 120 to 180 beats/min in the absence of drug therapy. Special attention should be paid to signs of underlying left ventricular hypertrophy, ventricular preexcitation, and ischemic heart disease because these features can affect management. The ECG may also be used to measure and follow PR, QRS, and QT intervals during treatment with antiarrhythmic agents.

3.Transthoracic echocardiography is usually performed to identify the presence of structural heart disease, to assess atrial and ventricular size and function, and to document coexistent pulmonary hypertension.

4.Additional investigation in selected patients with AF may include ambulatory ECG monitoring or a 6-minute treadmill walk test to document heart rate response to exercise. An evaluation for sleep apnea should be considered in obese patients or if the index of suspicion is otherwise high.

II.Thromboembolic Risk and Treatment. Patients with AF are at increased risk of systemic thromboembolism compared with the general population, and antithrombotic therapy should be considered in all patients. Decisions regarding antithrombotic therapy should be individualized after careful consideration of the risks of stroke and bleeding as well as patient preferences.

A.Anticoagulation strategy with cardioversion. Electrical, pharmacologic, and spontaneous cardioversion carries an increased risk of thromboembolism with most events occurring in the 10 days following restoration of sinus rhythm. Therefore, several factors should be considered when deciding upon an anticoagulation strategy with cardioversion.

1.Duration of AF

a.Patients with AF longer than 48-hour duration represent a particularly high-risk population. These patients merit transesophageal echocardiography (TEE) to rule out left atrial thrombus or 3 weeks of therapeutic anticoagulation prior to cardioversion regardless of CHA₂DS₂-VASc score.

b.For patients with AF less than 48-hour duration that are high risk for thromboembolism, anticoagulation is recommended as soon as possible before or immediately after cardioversion. For patients who are low risk for thromboembolism, either anticoagulation or no anticoagulation may be considered.

c.Duration of anticoagulation. For patients requiring anticoagulation, they should continue therapy for at least 4 weeks after cardioversion. Decisions regarding long-term anticoagulation should be made after careful consideration of the risks and benefits of therapy.

d.Choice of anticoagulant. For patients with nonvalvular AF, anticoagulation with intravenous heparin, low-molecular-weight heparin (LMWH), warfarin, and new oral anticoagulants may be considered. For those with mitral stenosis and AF, warfarin is the only proven oral anticoagulant to date. Recent American College of Cardiology/American Heart Association guidelines support the use of noncoumadin anticoagulants in other forms of valve disease associated with AF based on registry data from multiple clinical trials.

B.Long-term anticoagulation. The decision for long-term anticoagulation in patients with nonvalvular AF should be individualized after taking into account the risks, benefits, and patient preferences.

1.Thromboembolic risk. Current guidelines recommend the use of the CHA₂DS₂-VASc risk stratification score for the assessment of stroke risk in patients with nonvalvular AF (see Table 24.1). The pattern of AF (paroxysmal, persistent, long-standing persistent, or permanent) should not be considered.

TABLE 24.1 CHA₂DS₂-VASc Risk Stratification Score for Patients with Nonvalvular AF
Risk Factor	Score
Congestive heart failure^a	1
Hypertension	1
Age ≥ 75 y	2
Diabetes mellitus	1
Systemic thromboembolism (including TIA)	2
Vascular disease^b	1
Age 65–74 y	1
Female sex^c	1
Maximum score	9
Ischemic Stroke Risk^d
CHA₂DS₂-VASc Score	Percent per Year
0	0.2
1	0.6
2	2.2
3	3.2
4	4.8
5	7.2
6	9.7
7	11.2
8	10.8
9	12.2
Antithrombotic Strategy^e
CHA₂DS₂-VASc Score	Recommendation
0	Reasonable to omit therapy (class IIa, LOE: B)
1	No therapy or oral anticoagulation or aspirin (class IIb, LOE: C)
≥2	Oral anticoagulation (class I, LOE: A)

AF, atrial fibrillation; LOE, level of evidence; TIA, transient ischemic attack.

^aDocumented moderate to severe systolic dysfunction or recent decompensated heart failure requiring hospitalization regardless of ejection fraction.

^bPrior myocardial infarction, peripheral arterial disease, or aortic plaque.

^cIf age <65 years with no other risk factors, female sex does not independently increase risk.

^dFriberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500–1510.

^eBased on January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071–2104.

2.Bleeding risk. Multiple tools exist to predict bleeding risk; however, their clinical application is limited by imprecise bleeding estimates. The HAS-BLED bleeding risk score (hypertension, abnormal renal and liver function, stroke, bleeding tendency, labile international normalized ratio, elderly, and drugs/alcohol concomitant use) is the most commonly used score, but its routine use is not included in current guidelines. Intracerebral hemorrhage is the most feared bleeding complication and has been reported to occur between 0.2% and 0.4% per year in patients taking warfarin.

3.Choice of oral anticoagulant. The use of most new oral anticoagulants should also be avoided in patients with severe kidney disease. For patients with AF, the antithrombotic selection should take into account multiple factors such as comorbidity, dosing frequency, patient preference, cost, tolerability of warfarin, drug interactions, and other clinical characteristics (see Table 24.2).

TABLE 24.2 Choices of Oral Anticoagulants
	Warfarin	Dabigatran	Rivaroxaban	Apixaban	Edoxaban
Target	Factors II, VII, IX, X	Thrombin	Factor Xa	Factor Xa	Factor Xa
Half-life (hours)	20–60	14–17	5–9	8–15	10–14
Dosing frequency	Once daily	Twice daily	Once daily	Twice daily	Once daily
Antidote	Vitamin K	Idarucizumab	None^a	None^a	None^a

^aAndexanet is currently in clinical trials.

4.Nonpharmacologic stroke prevention. For patients who have an unacceptable risk of bleeding on anticoagulation, percutaneous techniques to occlude the left atrial appendage have been shown to be effective. There are several devices available, but the WATCHMAN device is the most commonly used. This device was approved by the United States Federal Drug Administration in March 2015 based on the findings in two randomized trials that compared the device to warfarin therapy (PROTECT AF and PREVAIL). After left atrial appendage occlusion, patients should be treated with 6 weeks of oral anticoagulation and aspirin followed by 6 months of aspirin and clopidogrel. Surgical closure of the left atrial appendage should be considered in all patients with AF who require cardiac surgery.

III.Rate Control. Control of the ventricular response rate is an important strategy in the management of AF, and multiple drugs that slow conduction through the atrioventricular (AV) node can be utilized. It is important to recognize signs of ventricular preexcitation in patients with AF because AV nodal agents in this setting can facilitate increased conduction down the accessory pathway and lead to further hemodynamic compromise. The ideal resting heart rate should be less than 80 beats/min although a more lenient target of less than 110 beats/min can be used as long as left ventricular systolic function is preserved. Heart rate during exercise should also be assessed to ensure adequate control.

A.β-blockers have a rapid onset of action and are available in both oral and intravenous forms. They can be used in both the inpatient and outpatient setting. Metoprolol succinate, carvedilol, and bisoprolol are the preferred agents if patients have concomitant left ventricular systolic dysfunction. β-Blockers should be used with caution in patients with bronchospastic airway disease.

B.Nondihydropyridine calcium channel blockers such as diltiazem and verapamil have a rapid onset of action and are available in both oral and intravenous forms. These medications should not be used in patients with decompensated heart failure or cardiac amyloidosis. Both diltiazem and verapamil are available in short-acting and sustained-release oral formulations.

C.Digitalis is available in both oral and intravenous forms. It is primarily used for rate control when contraindications exist to β-blockers and calcium channel blockers and in patients with left ventricular systolic dysfunction. It may also be used as an adjunct to β-blockers and calcium channel blockers. It is important to remember that digoxin is most effective at controlling the resting heart rate but less effective with activity. Digitalis toxicity is a serious complication of chronic therapy. Cardiac manifestations of digitalis toxicity include all arrhythmias except rapidly conducted atrial tachyarrhythmias. Patients also present with gastrointestinal and neurologic complaints. Digitalis toxicity can be treated with digoxin-specific antibody fragments.

D.Antiarrhythmic medications such as amiodarone can also be used for rate control because of its β-blocking properties if other medications are unsuccessful. Patients must be anticoagulated, given the chance of pharmacologic cardioversion. Dronedarone should never be used for rate control in patients with permanent AF because of increased harm.

E.AV nodal ablation with insertion of a permanent ventricular pacemaker can be used if medical therapy is unsuccessful and should only be considered as a last resort. If possible, the device should be implanted 4 to 6 weeks before AV nodal ablation to ensure adequate pacemaker function prior to procedure. These patients should be followed closely for the development of a cardiomyopathy because of chronic right ventricular pacing in which case a referral for cardiac resynchronization therapy may be necessary.

IV.Rhythm Control. The treatment of any unstable patient where AF is contributing to hemodynamic instability is immediate direct current cardioversion (DCCV). For stable patients with AF, attempts to restore and maintain sinus rhythm utilizing cardioversion, antiarrhythmic drugs, and catheter ablation are commonly used (see Fig. 24.1). Although rhythm control with antiarrhythmic drugs has not been shown to be superior to rate control with respect to mortality, restoration of sinus rhythm is associated with symptom relief and improved quality of life in many patients. Other factors such as young age, new-onset AF, and tachycardia-induced cardiomyopathy also favor a rhythm control strategy.

FIGURE 24.1 Approach to rhythm control for patients with paroxysmal and persistent atrial fibrillation. CAD, coronary artery disease; LVH, left ventricular hypertrophy. (Adapted from the January CT, Wann LS, Alpert JS, et al. ACC/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2014;64(21):2305–2307; American Heart Association, Inc.)

A.Electrical cardioversion. Successful restoration of sinus rhythm is most effectively accomplished with DCCV, which is successful approximately 80% of the time. Whenever possible, DCCV should be performed under sedation with appropriate hemodynamic monitoring and in the presence of personnel skilled in airway management. See Chapter 58 for more procedural details of DCCV.

B.Pharmacologic cardioversion. Flecainide, propafenone, dofetilide, amiodarone, and intravenous ibutilide can be used for cardioversion as long as no contraindications exist. However, the success rate is much lower than DCCV.

1.Intravenous ibutilide is a class III agent that carries a 1% to 2% risk of torsades de pointes, and patients should be monitored after drug administration. Because of this, the use of ibutilide for pharmacologic cardioversion has fallen.

2.As needed, flecainide and propafenone can be used for selected outpatients as long as these agents have been shown to be safe in a monitored setting. This “pill-in-the-pocket” approach should always be used in conjunction with AV nodal blocking agents because these class IC antiarrhythmic agents can promote 1:1 ventricular conduction in patients with atrial flutter. These agents should not be used in patients with coronary artery disease, left ventricular dysfunction, or other significant heart disease.

3.Dofetilide should always be started in a monitored inpatient setting because of its risk for QT prolongation and subsequent torsades de pointes.

C.Drugs to maintain sinus rhythm. A number of oral agents are available for the maintenance of sinus rhythm. It should be kept in mind that the initiation or upward dose titration of antiarrhythmic drugs should be done with caution and, in many instances, should be performed in a hospital setting with cardiac monitoring. This is particularly true for the class III agents sotalol and dofetilide. On the other hand, in patients without structural heart disease, the class IC agents flecainide and propafenone may be considered for initiation on an outpatient basis.

1.Vaughan Williams class IA agents. These sodium channel blockers have seen a decline in use over time primarily because of a high incidence of intolerable side effects but also because of the possibility of increased mortality in patients with structural heart disease.

a.Procainamide is not used frequently due to its gastrointestinal, hematologic, and immunologic (i.e., drug-induced lupus) side effects. An active metabolite of this drug, N-acetylprocainamide (NAPA), is cleared renally and has class III antiarrhythmic properties. Blood levels of both procainamide and NAPA need to be monitored to prevent toxicity, especially in patients with renal or hepatic insufficiency. Procainamide is still used in stable patients with AF and evidence of ventricular preexcitation.

b.Quinidine is not used frequently due to its relatively high incidence of gastrointestinal, hematologic, and neurologic side effects. Additionally, quinidine prolongs the QT interval and has significant drug–drug interactions. Quinidine has no negative inotropic effects and can be used in patients with advanced renal dysfunction when other antiarrhythmics cannot be used.

c.Disopyramide is not used frequently due to its powerful negative inotropic and anticholinergic effects although it is used in patients with hypertrophic cardiomyopathy.

2.Vaughan Williams class IC agents. Flecainide and propafenone are sodium channel blockers that have become the preferred agents for maintenance of sinus rhythm in patients without significant heart disease. The Cardiac Arrhythmia Suppression Trial found flecainide to be associated with increased mortality when used for suppression of ventricular arrhythmias in patients with left ventricular dysfunction after myocardial infarction. Furthermore, these agents are negative inotropes and can prolong QRS duration. Therefore, these agents should not be used in patients with coronary artery disease or structural heart disease and should be used in caution in patients with significant conduction system disease without a pacemaker. In patients with atrial flutter, these agents can slow the atrial rate to the point where 1:1 ventricular conduction occurs; therefore, they should always be administered in conjunction with AV nodal blocking agents.

3.Vaughan Williams class III agents. These potassium channel blockers have become the preferred agents for most patients with structural heart disease. Sotalol and dofetilide should be avoided in patients with severe left ventricular hypertrophy.

a.Sotalol has β-blocking properties and should be used in caution in patients with heart failure. This agent also causes QT prolongation, and drug initiation or dose increase should be performed in a hospital setting with cardiac monitoring. The dose must be reduced in patients with renal insufficiency.

b.Dofetilide is an effective drug for the maintenance of sinus rhythm in patients with heart failure, coronary artery disease, and sinus node dysfunction. This agent is generally well tolerated but can cause QT prolongation especially in the setting of renal dysfunction. Therefore, drug initiation or dose increase should be performed in a hospital setting with cardiac monitoring. The prescription of the drug is tightly controlled, and only those certified in its use may prescribe it. Careful attention should be paid to avoid electrolyte disturbances and concomitant administration with other QT prolonging drugs, thiazide diuretics, and verapamil.

c.Amiodarone has properties of all four Vaughan Williams classes and has a very long half-life (up to 120 days). It is generally reserved for patients in whom other antiarrhythmic drugs are contraindicated or ineffective because of the significant side effects that occur in the liver, lungs, thyroid, and eyes. Patients should undergo periodic screening for drug toxicity. Sinus node dysfunction is also a common side effect.

d.Dronedarone is similar to amiodarone but has less side effects. It is contraindicated in patients with New York Heart Association classes III or IV heart failure as well as recently decompensated heart failure, especially those with left ventricular systolic dysfunction. It can cause bradycardia and QT interval prolongation and should not be used in permanent AF. There is potential for serious hepatotoxicity, and liver function tests should be monitored closely.

D.Catheter ablation to maintain sinus rhythm. The role of catheter ablation continues to expand rapidly and is currently used in many patients to maintain sinus rhythm. Radiofrequency ablation and cryoballoon ablation can both be utilized to isolate the pulmonary veins. When AF is resistant to at least one class I or class III antiarrhythmic agent, current guidelines recommend the use of catheter ablation in patients with symptomatic paroxysmal AF (class I, Level of Evidence: A), symptomatic persistent AF (class IIa, Level of Evidence: A), and symptomatic long-standing persistent AF (class IIb, Level of Evidence: B). Catheter ablation can be considered before a trial of antiarrhythmics in patients with recurrent symptomatic paroxysmal AF (class IIa, Level of Evidence: B) and patients with symptomatic persistent AF (class IIb, Level of Evidence: C). Patients must be on anticoagulation during and after the procedure. A discussion about the risks and benefits of catheter ablation should always occur. For more details about the procedure, refer to Chapter 55.

E.Surgical ablation to maintain sinus rhythm. The surgical maze procedure was first introduced in 1987 by Dr. James Cox and tested the original hypothesis that reentry is the predominant mechanism for the development and maintenance of AF. Known as the Cox-Maze procedure, the original technique used biatrial “cut-and-sew” incisions in critical locations to create barriers to the propagating wavelets that are responsible for the initiation and maintenance of AF. The technique has undergone multiple revisions over the years, and the original “cut-and-sew” technique has mostly been replaced by the Cox-Maze IV, which utilizes radiofrequency and cryothermal devices to create the lines of ablation. The Cox-Maze procedure has not had widespread acceptance as a means of treatment for AF except in patients undergoing open heart surgery. Even in these patients, the additional intraoperative time and complexity of the procedure have limited its widespread surgical application.

V.Specific Populations

A.Postoperative cardiac and thoracic surgery. AF is common postoperatively. The incidence of postoperative AF varies with the type of surgery and is highest following cardiac surgery (between 20% and 50%). It usually occurs in the first 5 days after surgery and is a major determinant of the length of stay and hospital cost.

1.Therapy. Postoperative AF is usually self-limited, and DCCV is not always needed. Patients who develop AF should be treated with β-blockers or nondihydropyridine calcium channel blockers to achieve adequate rate control. There are a variety of antiarrhythmic agents available for cardioversion in these patients. AF carries an increased risk of stroke in the postsurgical patient; therefore, anticoagulation is recommended if AF persists for longer than 48 hours. The choice of antiarrhythmic agent, AV nodal blocker, and anticoagulant depends on the patient’s comorbidities and type of surgery.

2.Prevention. There is evidence supporting the prophylactic administration of certain medications to prevent the development AF in patients undergoing cardiac surgery. Amiodarone, when given prophylactically before or after cardiac surgery, has been found to significantly reduce the incidence of postoperative AF. Sotalol has also been studied, but there is conflicting evidence regarding its effectiveness. Administration of colchicine may also be considered in patients to reduce AF after surgery.

B.Acute coronary syndromes. The incidence of AF following acute coronary syndromes ranges between 10% and 20% at 30 days. AF is more commonly associated with acute myocardial infarction in older patients as well as those with significant left ventricular dysfunction. Patients with AF in this setting have a worse outcome at 30 days compared with those in sinus rhythm. Guidelines recommend urgent DCCV in patients with acute myocardial infarction and AF with rapid ventricular rates and intractable ischemia. Intravenous β-blockade is indicated for rate control to reduce myocardial oxygen consumption, and digoxin or amiodarone is an alternative for patients with significant left ventricular dysfunction and heart failure. Stroke rates are also increased in these patients, and anticoagulation is recommended for patients with a CHA₂DS₂-VASc score of at least 2.

C.Preexcitation syndromes. The most feared complication of AF in patients with ventricular preexcitation is the development of ventricular fibrillation because of rapid conduction of AF down an accessory pathway. The incidence of sudden cardiac death in patients with preexcitation syndromes is around 0.6% per year. The risk factors for sudden death include a short refractory period of an antegrade accessory pathway (<250 ms), short R–R interval during preexcited AF, and the presence of multiple accessory pathways. Immediate electrical cardioversion is recommended for hemodynamically unstable patients. Intravenous procainamide or ibutilide should be used in hemodynamically stable patients. It is critical to avoid AV nodal blocking agents in patients with AF and evidence of ventricular preexcitation.

D.Pregnancy. AF occurs infrequently during pregnancy and usually has an identifiable cause such as mitral valve disease, thyroid disease, or pulmonary disease. The ventricular rate can be controlled with β-blockers, nondihydropyridine calcium channel blockers, or digoxin. Currently available antiarrhythmic medications cross the placenta and are excreted in breast milk and should therefore be avoided if possible. However, amiodarone, sotalol, and flecainide have all been used successfully during pregnancy in selected instances. Quinidine has the longest safety record of any antiarrhythmic agent in pregnancy and remains the agent of choice for pharmacologic conversion of AF. In the hemodynamically unstable patient, electrical cardioversion can be performed without any concern for fetal damage. Anticoagulation should also be given high priority during pregnancy, given the risk of thromboembolic disease during pregnancy. Only those patients with a very low risk of thromboembolism do not require anticoagulation. Warfarin is generally avoided during the first trimester of pregnancy because of its teratogenic effects and also during the last month of pregnancy because of bleeding concerns at the time of delivery. Administration of unfractionated heparin either by continuous intravenous infusion in a dose sufficient to increase the activated partial thromboplastin time (aPTT) to 1.5 to 2 times control or by intermittent subcutaneous injection of 10,000 to 20,000 units every 12 hours adjusted to prolong the mid-interval aPTT to 1.5 times control is appropriate. LMWH may also be considered during the first trimester and last month of pregnancy although there are limited data about clinical outcomes.

E.Hypertrophic cardiomyopathy. Patients with AF and hypertrophic cardiomyopathy have a high risk of systemic thromboembolism. Therefore, these patients should be anticoagulated regardless of their CHA₂DS₂-VASc score. Antiarrhythmic medications such as amiodarone and disopyramide can be used to maintain sinus rhythm and should be used in combination with a β-blocker or nondihydropyridine calcium channel blocker. Sotalol, dofetilide, and dronedarone may also be considered.

F.Pulmonary disease. AF commonly develops in patients with chronic obstructive pulmonary disease. General recommendations include the treatment of the underlying lung disease, correction of hypoxia, and correction of acid–base imbalances. Medications commonly used to treat bronchospastic airway disease such as theophylline and β-adrenergic agonists can precipitate AF and decrease the ability of medications to control the ventricular response rate. Antiarrhythmic medications with β-blocking properties such as sotalol, propafenone, and adenosine can worsen bronchospasm and are contraindicated in patients with severe bronchospastic airway disease. Ventricular rate control is usually achieved with nondihydropyridine calcium channel blockers such as verapamil and diltiazem.

ACKNOWLEDGMENTS: The authors acknowledge the contributions of Drs. Carlos Alves and Edwin T. Zishiri to earlier editions of this chapter.

Guidelines

January CT, Wann LS, Alpert JS, et al. ACC/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2014;64(21):2305–2307.

Landmark Articles

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Haissaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659–666.

Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374:534–542.

Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol. 2003;42:185–197.

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