AF may be classified as lone, idiopathic, first detected, recurrent, paroxysmal, persistent, long-standing persistent, and permanent. Lone AF is used to describe patients experiencing AF without clinical or echocardiographic evidence of cardiopulmonary disease. Idiopathic AF refers to the uncertainty of AF origin with out considering age or underlying cardiovascular pathology. During a patient’s first detected episode of A F, it should be noted whether it is self-limited or the patient symp tomatic with the arrhythmia. When a person has experienced two or more episodes of AF it is considered recurrent, and once recurrent AF is terminated it is referred to as paroxysmal. Paroxysmal episodes are usually self-terminating and, at least initially, do not usually require direct current cardioversion (DCC). Persistent AF usually lasts longer than 7 days and requires cardioversion for its termination. Long-standing per sistent is when AF has lasted for > 1 year. AF becomes permanent once cardioversion, either electrical or chemical, is unsuccessful and presence of arrhythmia is accepted by the patient and physician and hence rhythm control interventions are not pursued.

As with all arrhythmias, the clinical presentation of AF can vary widely and patients may be asymptomatic, despite rapid rates of ven tricular response. Common symptoms include palpitations, fatigue, dyspnea and/or shortness of breath, dizziness, and diaphoresis. Less commonly, patients may present with extreme manifestations of hemodynamic compromise, such as chest pain, pulmonary edema, and syncope. AF is often noted in patients presenting with a new thromboembolic stroke, with reported rates of 10% to 40%.

AF is most commonly associated with advanced age, hypertension, valvular heart disease, congestive heart failure (CHF), and coronary artery dis ease (CAD). The pathophysiology is dependent on the interaction between atrial anatomic and physiologic factors that favor the initiation and maintenance of the arrhythmia. Pathophysiologically, these entities result in left atrial fibrosis, pulmo nary vein dilation, and reduced atrial contractility, which in turn result at a cellular
level in abnormal intracellular calcium handling, atrial myolysis, connexin down-regulation, and altered sympathetic innervation. Structural remodeling results in electrical dissociation between muscle bundles and local conduction heterogeneities facilitating the initiation and perpetuation of A F. This electroanatomical substrate permits multiple small reentrant circuits that can stabilize the arrhythmia and lead to the establishment of AF.

AF has 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 likely underlying sleep-disordered breathing. This phenomenon seems to be mediated by left atrial dilation. Other less common cardiac associations include Wolff-Parkinson-White (WPW) syndrome, pericarditis, and cardiomyopathy. Surgery, particularly cardiac surgery, is associated with a high risk of postoperative AF that depends on the type of cardiac surgery and is highest for mitral valve surgery, which may reach 35% to 50%. Persistence of AF has been correlated with elevated C-reactive protein levels, which raises the question of a role for inflammation in this condition, and atrial natriuretic peptide has been found to be elevated in people with acute A F. This hormone, which is released by myocardial tissue in response to increased wall stress, promotes diuresis and vasodilation. However, with long-standing A F, atrial natriuretic peptide levels remain within the normal range and patients do not experience its useful hemodynamic effects.

1.The role of the pulmonary veins as a source of triggers and/or drivers in AF is increasingly appreciated. A previous model proposed by Moe et al. in 1962 had described multiple reentrant wavelets within the atrial tissue (substrate) that contributed to the maintenance of A F. Recent data support a focal mechanism involving both increased automaticity and multiple reentrant wavelets, occurring predominantly in the left atrium around the pulmonary veins. A new model incorporates these mechanisms of initiators/drivers of AF and atrial substrate conditions for AF maintenance. This in turn 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 to provide a conceptual framework from which to gain insight into it.

2.Paroxysmal, persistent, or chronic AF presents a considerable risk for throm-boembolism; lone AF is presently thought to also increase the risk, but to a lesser extent. The risk of stroke becomes more pronounced with increased age. An increased risk of stroke has been shown to be associated with AF in the presence of any of the following: age > 65 years, history of diabetes, history of hypertension, history of CHF, history of prior stroke, or transient ischemic attacks (TIAs). Left ventricular (LV) systolic dysfunction predicts ischemic stroke in patients with AF who do not receive antithrombotic therapy.

The initial evaluation of a patient with new-onset AF includes at a minimum a detailed history including enquiry about family history of AF and physical examination to define the clinical type of AF—frequency, duration, and precipitating factors—and to delineate the presence and nature of symptoms associated with A F. In addition, evaluation should include the following:

1. A 12-lead electrocardiogram (ECG) to identify the rhythm (that is to verify AF), underlying LV hypertrophy, and presence of preexcitation, and to diagnose the existence of CAD and any other atrial arrhythmias. A 12-lead ECG may also be used to measure and follow PR, QRS, and QT intervals during the treatment with antiarrhythmic agents. In AF the P waves are absent. Atrial activity is chaotic and fibrillatory (F) waves are present. The baseline of the ECG is often
undulating and may occasionally have coarse, irregular activity that can resemble atrial flutter, but it is not as stereotypical from wave to wave as atrial flutter. AF is distinguished from MAT by the presence in MAT of at least three different morphologic types of P waves. Ventricular rhythm is usually irregularly irregular, and if AF is suspected with a regular ventricular response, then heart block with a junctional or ventricular escape should be considered. The atrial rate is generally in the range of 400 to 700 beats/min, while the ventricular response is generally in the range of 120 to 180 beats/min in the absence of drug therapy. Ventricular response may be 180 beats/min or greater in the presence of an accessory pathway.

2. Transthoracic echocardiogram is usually performed to identify the presence of valvular heart disease, to assess atrial and ventricular size and function, and to document coexistent pulmonary hypertension. Echocardiography is also used as a prognostic tool to predict the development of systemic complications from AF and to help in the decision to initiate antithrombotic therapy. Echocar-diographic predictors of increased thromboembolic risk include mitral stenosis, left atrial enlargement, reduced LV systolic function, decreased left atrial appendage emptying velocities, and evidence of spontaneous contrast (“smoke”) or thrombus in the left atrium or left atrial appendage.

3. Tests of thyroid, renal, and hepatic function. Hyperthyroidism should always be considered, especially when the ventricular rate is difficult to control.

4.Additional investigation in selected patients with AF may include ambulatory ECG monitoring (e.g., Holter), or a 6-minute treadmill walk test to document heart rate response to exercise and an evaluation of sleep-disordered breathing should be considered especially in obese patients.

The term “unstable” should include the patient who is highly symptomatic (e.g., chest pain and pulmonary edema), as well as the patient who is hemodynamically unstable. General management of AF centers on three areas: control of the ventricular response, minimization of the thromboembolic risk, and restoration and maintenance of sinus rhythm.

1. Control of the ventricular response. The ventricular response is generally controlled through drugs that slow conduction through the atrioventricular (AV) node. AF that presents in the setting of WPW syndrome usually has evidence of preexcitation on ECG and is treated differently from AF conducting down the AV node alone. As noted previously, intravenous calcium channel blockers, β-blockers, adenosine, and lidocaine are contraindicated in patients with AF and WPW syndrome associated with preexcitation because they facilitate conduction down the accessory pathway, causing acceleration of the ventricular rate, hypotension, and ventricular fibrillation. In the hemodynamically stable patient, class I antiarrhythmic medications such as procainamide may be administered intravenously, which diminishes antegrade conduction down the accessory pathway and decreases the degree of preexcitation and may convert the A F. For patients without evidence of preexcitation, the following agents are available to control the ventricular rate. a. β-Blockers have a rapid onset of action, as well as short half-lives in both the oral and intravenous forms. These medications should be used cautiously in patients who have known decreased systolic function or evidence of heart failure. Intravenous preparations of metoprolol, esmolol, and propranolol have their onset of action in approximately 5 minutes. Orally available β-blockers of varying durations of action can be used for rate control. These include metoprolol and propranolol, as well as atenolol, nadolol, and a number of less commonly used agents. Amiodarone is an antiarrhythmic
medication with β-blocking properties and can be used for both rate and rhythm control in the acute setting. Sotalol is another class III antiarrhythmic medication with β-blocking properties, which can be used for both rate and rhythm control; however, this medication is available in oral form only and is more proarrhythmic than amiodarone.

b.Calcium channel blockers such as diltiazem and verapamil are available in both intravenous and oral forms. The intravenous forms are rapidly effective and have a short duration of effect. In appropriate patients, they provide rapid control of the ventricular response. Both oral diltiazem and verapamil are available in short-acting and sustained-release preparations.

c.Digitalis has long been used for rate control. Given its relatively long onset of action, digoxin is ideally used in patients with decreased LV function or where a contraindication exists to the use of β-blockers or calcium chan nel blockers (e.g., bronchospastic airway disease, asthma, or hemodynamic instability). It may be used as an adjunct to β-blockers or calcium channel blockers in patients in whom these medicines alone do not provide sufficient control of the heart rate. Digoxin is usually effective at controlling the resting heart rate; however, it is less effective at lowering the ventricular response to activity. Because of this it is recommended that if digoxin alone is used in rate control, the patient should undergo monitored exercise and the exertional heart rate verified to be < 110 beats/min.

Digoxin can be administered intravenously or orally. The onset of action of digoxin is slow (1 to 4 hours). Initially dosing of digoxin is 0.25 mg intravenously every 6 hours for a total of 1 mg every 24 hours. Then a maintenance dose is given, which is based on the patient’s renal function. Digoxin is generally well tolerated, although it is associated with adverse effects, such as gastrointestinal toxicity and neurotoxicity, and because of its long half-life (38 to 48 hours) is more likely to be associated with symptomatic bradycardia requiring intervention such as temporary pacing.

d.Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists may decrease the incidence of AF by decreasing left atrial pressure and by reducing the frequency of atrial premature beats. These medications may also reduce atrial fibrosis and decrease the recurrence of A F. Withdrawal from ACE inhibitors is associated with postoperative AF in patients undergoing coronary artery bypass grafting (CABG) surgery, and concurrent therapy with ACE inhibitors and antiarrhythmic agents enhances the maintenance of sinus rhythm.

e.HMG-CoA reductase inhibitors: statin drugs decrease the risk of AF recur rence following cardioversion. The mechanisms underlying this are poorly understood but probably include an inhibitory effect on the progression of coronary disease as well as their pleiotropic anti-inflammatory and antioxidant properties.

f.Antiarrhythmic agents such as dofetilide and ibutilide are effective for con version of atrial flutter and AF but are not effective for the control of ven tricular rate alone. Propafenone, which is a class IC antiarrhythmic drug, exerts additional mild β-blocking effects and may slow conduction across the AV node, although this is seldom sufficient to control the rate in patients with AF and may paradoxically cause an increase in AV nodal conduction and accelerate the ventricular rate response. Flecainide is another class IC agent that is very effective in converting AF in structurally normal hearts but like propafenone requires concomitant AV nodal blockage.

a. Current recommendations regarding the use of antithrombotic therapy to prevent the development of thromboembolism in patients with AF are to
use antithrombotic therapy in all patients with AF except those with lone AF or with contraindications to antithrombotic agents. Lone AF is defined as that occurring in a structurally normal heart, in a patient younger than 65 years. The American Heart Association (AHA) recommends that the individualized selection of appropriate antithrombotic agents associated with the highest risk of stroke in patients with AF include a history of prior thromboembolism (stroke, TIA, and systemic embolism) and rheumatic mitral stenosis. Moderate risk factors for stroke include age older than 65 years, CAD, CHF, female gender, hypertension, diabetes mellitus, and renal insufficiency. Presence of more than one moderate risk factor suggests the use of a vitamin K antagonist with a goal international normalized ratio (INR) of 2.0 to 3.0 or or alternative anticoagulation with dabigatran, rivaroxaban or apixaban. Aspirin in doses of 81 to 325 mg daily is recommended as an alternative to vitamin K antagonism in low-risk patients or in those with contraindications to oral anticoagulation, and more recent evidence suggests that combination of aspirin and clopidogrel is superior to the use of either agent alone in patients who are unable to tolerate warfarin therapy. The guidelines also suggest similar use of antithrombotic therapy in patients with atrial flutter. Table 24.1 outlines one method of selecting the appropriate antithrombotic therapy for any given patient.

Based on the multivariate analysis from randomized controlled trials (RCTs), there have been several clinical scores developed to stratify the risk of systemic complications. The most well known of these is called the CHADS (Cardiac Failure, Hypertension, Age, Diabetes, and Stroke) risk index, which is a point system and assigns two points for history of TIA or stroke and one point for
each of the following risk factors: age older than 75 years, hypertension, diabetes, or recent heart failure. This risk factor index was evaluated retrospectively in patients older than 65 years and with nonvalvular AF, and the stroke risk varied from 1.8% per year in the lowest risk group with a CHADS score of 0, to 18.2% per year for those with an index score of 6. Another thromboembolic risk factor scoring system is the CHA2DS2-VASc, which assigns two points for age > 75 years and prior history of TIA or stroke and one point for each of the following risk factors: CHF, hypertension, diabetes, stroke, vascular disease, age 65 to 74 years, and female gender. Thus, this risk stratification scheme extends the CHADS2 scheme by considering additional stroke risk factors that may influence the decision on whether or not to anticoagulate with a threshold for therapy that is similar to the CHADS scheme. An assessment of bleeding risk is an integral part of patient evaluation prior to initiating anticoagulation. A simple bleeding risk score (HAS-BLED: hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly [age > 65 years], drugs/alcohol concomitantly) has been used to assess the risk of bleeding while on anticoagulant therapy. A score of > 3 indicates higher risk and suggests caution and regular review of the patient following the initiation of anticoagulant therapy.

Following cardioversion, therapeutic anticoagulation should be continued until sinus rhythm has been maintained for at least 4 weeks to allow for recovery of the atrial transport mechanism and for the recurrence of AF. The decision to anticoagulate beyond 4 weeks will be dependent on the CHADS2 score of the patient with long-term anticoagulation being recommended for all patients with a CHADS2 score > 2. For patients with a CHADS2 score of 1, the physician and patient should discuss the merits and risks of longterm anticoagulation versus the use of aspirin alone. If cardioversion cannot be postponed for 3 weeks and the AF has been present for > 48 hours, patients should be anticoagulated (Table 24.2) with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin as a bridge to therapeutic INR or alternatively dabigatran, rivaroxaban or apixaban could be used and the patient should undergo transesophageal echocardiography (TEE) to rule out atrial thrombus; then anticoagulation should be used for at least 4 weeks after cardioversion. b. A number of major trials have attempted to compare the benefits of aspirin and warfarin in minimizing the stroke risk in patients with AF. Overall, warfarin has shown an annual average reduction of 68% in relative risk for stroke, with aspirin showing a reduction anywhere from 0% to 44% (mean, —30%). A recent trial has shown that clopidogrel reduces the risk of embolic stroke similar to that of aspirin and the combination of aspirin and clopidogrel is superior to either agent alone but inferior to warfarin therapy

The decision to anticoagulate patients with AF depends on both the risk of thromboembolic complications and the risk of bleeding. In younger patients at low risk for stroke (younger than 65 years, without other risk factors), and who generally lead active lifestyles that place them at increased risk for bleeding, aspirin may be an acceptable alternative to warfarin. Older patients at greater risk for stroke (age 65 and older, with or without other risk factors) should be anticoagulated with warfarin to maintain an INR of 2 to 3 or alternative anticoagulation with dabigatran, rivaroxaban or apixaban. The risk of thromboembolism increases rapidly at INR levels even slightly < 2, and the risk of bleeding increases at INR levels > 3. Studies of fixed low-dose warfarin and aspirin have shown ineffective protection from thromboembolic risk as compared with anticoagulation with warfarin to maintain an INR of 2 to 3, and thus are not recommended. Patients who have contraindications to warfarin therapy should be treated with aspirin or the combination of aspirin and clopidogrel should be considered if the patients can tolerate it.