CHAPTER 83: ATRIAL FIBRILLATION, ATRIAL FLUTTER, AND ATRIAL TACHYCARDIA

Atrial fibrillation (AF) and atrial flutter are common arrhythmias associated with a variety of cardiac conditions. AF, the most common sustained cardiac arrhythmia encountered in clinical practice, is increasing in prevalence.^1,2,3 These arrhythmias may be associated with deterioration of hemodynamics, a wide spectrum of symptoms, and significant morbidity or mortality. Perhaps because no single therapy has been shown to be ideal for all patients, there are a variety of treatment strategies that may be applied to these arrhythmias. These include no therapy at all, anticoagulation, rhythm control, and rate control.^2,3 This chapter describes the epidemiology, electrophysiologic mechanisms, and approach to management of patients with AF and atrial flutter.

AF is characterized by temporally and spatially varying rapid disorganized atrial electrical activation and uncoordinated atrial contraction. The surface electrocardiogram (ECG) characteristically demonstrates rapid atrial fibrillatory waves with changing morphology and rate, and a ventricular response that is usually irregularly irregular (Fig. 83–1).

Classification

AF has been classified into four categories: paroxysmal, persistent, longstanding persistent, and permanent.³ Paroxysmal AF is characterized by self-terminating episodes that generally last < 7 days (most < 24 hours), whereas persistent AF generally lasts > 7 days and often requires electrical or pharmacologic cardioversion. Longstanding AF has been continuous for at least a year. It is recognized that many patients have both paroxysmal and persistent episodes of AF, and in general, we characterize such a patient by their more typical form of AF. AF is classified as permanent when it has failed cardioversion or when further attempts to terminate the arrhythmia are deemed futile. At the initial detection of AF, it may be difficult to be certain of the subsequent pattern of duration and frequency of recurrences. Thus, a designation of first detected episode of AF is made on the initial diagnosis. When the patient has experienced two or more episodes, AF is classified as recurrent. The term lone AF refers to AF occurring in the absence of cardiac disease or other known etiologic factors, usually in relatively young individuals.³ Most cases of AF occur in patients with evidence of structural heart disease, but there may be no evidence of concomitant disease in others, especially with paroxysmal AF.³ By contrast, > 80% of patients with permanent AF have an identifiable underlying cause.⁴ The definition of chronic AF varies greatly in the literature, and the terminology is best avoided.

Epidemiology

It is estimated that 2.2 to 5.0 million Americans and 4.5 million Europeans experience AF.^1,2,3,5 The incidence and prevalence of AF steadily increase with age, such that this arrhythmia occurs in about 1% of the population < 60 years of age, and more than one-third of AF patients are 80 years old or older.³ Up to 12% who have AF are between 75 and 84 years old.³ The age-adjusted prevalence of AF is higher for men than women, and higher for whites than blacks.³ Familial AF has been described.³ Genetic abnormalities have been reported.^6,7,8,9 In several Chinese families, the defect has resulted in a gain in function of potassium channels and shortening of atrial refractoriness.^8,9

Etiology

AF is associated with a wide variety of predisposing factors (Table 83–1). Reversible causes should be sought and treated, eg, hyperthyroidism, and risk factors such as obesity and obstructive sleep apnea should be modified.² In the developed world, the most common clinical diagnosis associated with AF is hypertension.^2,3 The presence of heart failure (HF) markedly increases the risk of AF. In developing countries, hypertension, rheumatic valvular heart disease, and congenital heart disease are the most commonly related conditions.^10,11

Pathophysiology

The mechanism of AF may be multifactorial, including electrophysiologic and structural abnormalities and even extrinsic factors such as autonomic perturbations.^2,3,12 Different mechanisms may initiate (trigger) and maintain AF in an individual. The most frequent triggers are rapid spontaneous activity arising in the pulmonary veins. Pulmonary vein ectopy is often transient, and persistence of AF after this mode of initiation likely depends on atrial substrate factors.

Atrial Fibrillation Triggers

Spontaneous ectopy from muscular sleeves of pulmonary veins can serve as triggers of AF. Rapidly firing ectopic foci in pulmonary veins have been shown to be the underlying mechanism of most paroxysmal AF (Fig. 83–2).^13,14 The pulmonary vein musculature of patients with paroxysmal AF demonstrates a markedly reduced effective refractory period and conduction delay.¹⁵ Rapidly firing foci can often be recorded within the pulmonary veins with conduction block to the left atrium (Fig. 83–3).^13,14 Discontinuous properties of conduction within the pulmonary vein may also provide a substrate for reentry within the pulmonary vein itself.¹⁶ Although most triggering foci that are mapped during electrophysiologic studies occur in the pulmonary veins in patients with paroxysmal AF, foci within the superior vena cava,¹⁷ the ligament of Marshall,¹⁸ and the musculature of the coronary sinus¹⁹ have been identified. Other sites of initiating foci may be recorded in the left atrial appendage, left atrial wall, or along the crista terminalis in the right atrium.^3,20 For patients with pulmonary vein foci, a primary increase in adrenergic tone followed by a marked vagal predominance has been reported just before the onset of paroxysmal AF.²¹ A similar pattern of autonomic tone has been reported in an unselected group of patients with paroxysmal AF and a variety of cardiac conditions.²² Vagal stimulation shortens the refractory period of atrial myocardium, but with a nonuniform distribution of effect. These factors support the importance of vagal stimulation in the induction of paroxysmal AF. In animal models, these pulmonary vein foci manifest delayed afterpotentials and triggered activity in response to catecholamine stimulation, rapid atrial pacing, or acute stretch.¹¹

Atrial Fibrillation Maintenance

A variety of electrophysiologic and structural factors promote the perpetuation of AF. Moe and colleagues^23,24 proposed the multiple wavelet hypothesis as the mechanism of AF. Wavefronts traversing the atria fractionate into multiple daughter wavelets, the number of wavelets at any moment depends on the refractory period, conduction velocity, and anatomic obstacles in the atria. More recently, rotors or spiral wave reentry have shown importance as a perpetuating mechanism for AF in humans.^{2,25,26,27,28} Ablation of these rotors can lead to termination of AF in some patients (Fig. 83–4).

Li and colleagues²⁹ demonstrated in a canine model of HF that interstitial fibrosis predisposed to intraatrial reentry and AF. Fibrosis of the atria may produce inhomogeneity of conduction within the atria, leading to conduction block and intraatrial reentry,³⁰ a mechanism that has been shown in animal models.^31,32 A variety of clinical studies have demonstrated that patients with AF have delayed interatrial conduction and inhomogeneous dispersion of atrial refractory periods.³³ Long-standing AF results in loss of myofibrils, accumulation of glycogen granules, disruption in cell-to-cell coupling at gap junctions,³⁴ and organelle aggregates.^35,36 Thus, AF itself seems to produce a variety of alterations of atrial architecture that further contribute to atrial remodeling, mechanical dysfunction, and perpetuation of fibrillation, a concept of AF begetting more AF. Of note, recent data suggest the greater the atrial fibrosis, the less likely is success of catheter ablation using standard ablation approaches.³⁷

In a population-based study of elderly patients without AF at baseline, Tsang and coworkers³⁸ demonstrated that AF developed in direct relation to the echocardiographic left atrial volume index. An even stronger predictor of the development of nonvalvular AF was a restrictive transmitral Doppler flow pattern. Thus, clinical evidence for diastolic dysfunction strongly supports the concept that myocardial stretch is an important mechanism of AF in the elderly. Altered stretch on atrial myocytes results in opening of stretch-activated channels.¹¹ Force transmitted to stretch-activated channels in the membrane or via cytoskeletal integrins produces opening of these channels as well as increasing local production of angiotensin II, which in turn increases L-type Ca²⁺ current and decreases the transient outward K⁺ current. Stretch-activated channels increase G protein–coupled pathways, leading to increased protein kinase A and C activity and increased L-type Ca²⁺ current through the cell membrane and release of Ca²⁺ from the sarcoplasmic reticulum (promoting after depolarizations and triggered activity).¹¹

Clinical Manifestations

Clinical presentation of AF may relate to the disease itself or its consequences (thromboembolism and tachycardia-induced cardiomyopathy). Patients may exhibit none to disabling symptoms. Common symptoms include anxiety, palpitations, dyspnea, dizziness, chest pain, and fatigue. Several hemodynamic derangements, including rapid ventricular rates, loss of organized atrial contraction, irregularity of cardiac rhythm, and bradycardia (resulting particularly from sinus pauses when AF episodes terminate) may be the underlying cause of the symptoms. Many patients with symptomatic AF also have asymptomatic episodes.^2,39,40 Several studies have reported a marked reduction in quality of life in patients with AF.^41,42

Evaluation of patients with AF starts with a complete history and physical examination. It is important to identify any reversible causes or contributory factors such as alcohol and obstructive sleep apnea. Electrocardiographic confirmation of AF is key, and capturing the onset may give valuable clues to therapy. In some patients, AF may be caused by another arrhythmia (tachycardia-induced tachycardia,⁴³ for example, Wolff-Parkinson-White syndrome reentry degenerating into AF; Fig. 83–5). Ablation of the accessory pathway responsible for atrioventricular (AV) reentry typically results in no recurrence of AF, especially in younger patients. Very frequent AF may be detected on a standard 12-lead ECG, but in many patients longer- term ECG monitoring with a 24-hour or multiple-day recorder is needed. It is suggested that patients also have a chest radiograph (if lung disease is suspected), echocardiogram, blood count, assessment of serum electrolytes, and assessment of renal, hepatic, and thyroid function.³

The ventricular rate during AF can be quite variable and depends on autonomic tone, the electrophysiologic properties of the AV node, and the effects of medications that act on the AV conduction system. The ventricular rate may be very rapid (> 300 bpm) in patients with the Wolff-Parkinson-White syndrome, with conduction over accessory pathways (wide preexcited QRS complexes) having short anterograde refractory periods (see Fig. 83–5). A regular, slow ventricular response during AF suggests an AV junctional rhythm, either as an escape mechanism with complete AV block or as an accelerated AV junctional pacemaker.

Thromboembolism

Stroke is the most common clinical thromboembolic event in AF, and approximately 36% of all strokes in individuals aged 80 to 89 years are attributed to AF.⁴⁴ Furthermore, strokes occurring in patients who have AF tend to have a higher degree of severity.⁴⁵ Individuals who have AF are not at equal risk for thromboembolic events and several predisposing clinical factors can identify those patients at high risk (discussed later). Most thrombi associated with AF arise within the left atrial appendage.⁴⁶ Flow velocity within the left atrial appendage is reduced during AF because of the loss of organized mechanical contraction.⁴⁷ Compared with transthoracic echocardiogram, the transesophageal echocardiogram offers a much more sensitive and specific means of assessing left atrial thrombi and spontaneous echo contrast, an indicator of reduced flow.⁴⁸ Several factors contribute to the enhanced thrombogenicity of AF. Nitric oxide (NO) production in the left atrial endocardium is reduced in experimental AF, with an increase in levels of the prothrombotic protein plasminogen activator inhibitor 1 (PAI-1).⁴⁹ The lowest levels of NO and the highest levels of PAI-1 were recorded in the left atrial appendage during AF. Patients with AF have elevated levels of β-thromboglobulin and platelet factor 4^50,51; elevated plasma levels of von Willebrand factor (vWF), soluble thrombomodulin, and fibrinogen have been reported in patients with permanent AF with no evidence of diurnal variation in thrombogenicity.^52,53 In the Stroke Prevention in Atrial Fibrillation (SPAF) III study,⁵⁴ increased plasma levels of vWF were strongly correlated with the clinical predictors of stroke in AF (age, prior cerebral ischemia, HF, diabetes, and body mass index). There was a progressive increase in vWF with increasing clinical risk of stroke in this population.

Tachycardia-Induced Cardiomyopathy

In occasional patients, the first clinical manifestation of AF may be congestive HF related to a tachycardia-induced cardiomyopathy.^2,55,56 The left ventricular (LV) dysfunction develops as a result of sustained high ventricular rates during AF. This clinical syndrome generally occurs in patients who have minimal symptoms from AF and who present with shortness of breath. They typically have a sustained high ventricular rate (usually > 120 bpm) for prolonged time periods, often months to years.^57,58 However, the severity and temporal course of its onset varies significantly between individuals. Because the patients do not experience symptoms, they do not seek medical care initially. In these patients, control of the ventricular rate usually reverses the impaired LV function within weeks to months. In our experience, lack of fibrosis on cardiac magnetic resonance augurs return to near or normal LV function.

Hemodynamic Effects

AF produces several adverse hemodynamic effects, including loss of atrial contraction, a rapid ventricular rate, and an irregular ventricular rhythm. The loss of mechanical AV synchrony may have a dramatic impact on ventricular filling and cardiac output when there is reduced ventricular compliance, as with LV hypertrophy from hypertension, restrictive cardiomyopathy, hypertrophic cardiomyopathy, or the increased ventricular stiffness associated with aging. In addition, patients with mitral stenosis, constrictive pericarditis, or right ventricular infarction typically experience marked hemodynamic deterioration at the onset of AF. The loss of AV synchrony results in a decrease in LV end-diastolic pressure (LVEDP) as the loading effect of atrial contraction is lost, thereby reducing stroke volume and LV contractility by the Frank-Starling mechanism. Although there is a reduction in the LVEDP, there is an increase in the left atrial mean diastolic pressure. Patients with significant restrictive physiology may experience pulmonary edema and/or hypotension with the onset of AF. In contrast, patients with dilated cardiomyopathy may experience minimal hemodynamic compromise with AF if their LV compliance is not significantly impaired. The inappropriately rapid ventricular rate during AF also limits the duration of diastole and reduces ventricular filling. The irregular ventricular rhythm has adverse hemodynamic effects that are independent of the ventricular rate. Irregular rhythm may significantly reduce cardiac output⁵⁹ and coronary blood flow⁶⁰ compared with a regular ventricular rhythm at the same average heart rate.

Treatment

Prevention of the disease-related complications (thromboembolism and tachycardia-induced cardiomyopathy) and control of symptoms may be considered the primary goals of AF management. The three major therapeutic strategies in managing AF include prevention of stroke, rate control, and rhythm control (Fig. 83–6). Anticoagulation with warfarin or the newer direct oral anticoagulants reduce the risk for stroke. Therapies to achieve symptom control and prevention of tachycardia-induced cardiomyopathy are often similar. For example, ventricular rate control during AF or maintenance of sinus rhythm may improve symptoms and prevent tachycardia-induced cardiomyopathy. When clinical goals are not met using one strategy, the alternate strategy can be pursued in the same patient. Primary prevention of AF is another area of great importance for research considering the high prevalence of the disease.

Anticoagulation

Risk Stratification

Not all AF patients are at high risk for stroke. The recognized clinical markers predicting increased risk for stroke in AF are prior stroke or transient ischemic attack, hypertension, diabetes mellitus, HF, and age older than 75 years (Table 83–2).³ Other less validated stroke risk factors include coronary artery disease, thyrotoxicosis, female sex, LV dysfunction, and age older than 65 years.³ Mitral stenosis is well known to be associated with high risk for stroke in AF patients and warfarin anticoagulation is indicated in all such patients.

The CHADS₂ stroke risk stratification scheme, which is based on analysis of 1773 patients in the National Registry for Atrial Fibrillation, gained considerable favor and was used in the ACC/AHA/ESC 2006 guidelines to tailor therapy for stroke prevention.⁶¹ Each of the letters in this acronym represents a risk factor—congestive HF, hypertension, age, diabetes, and stroke. Previous stroke or transient ischemic attack is the strongest predictor of stroke and therefore carries 2 points, whereas the other risk factors carry 1 point each. The adjusted stroke rate per 100 patient-years increases from 1.9 with a score of 1 to 18.2 with a score of 6 (see Table 83–2). Although CHADS₂ provides a simple tool for predicting individual risk of stroke related to AF, it accounts for only part of the risk (c-statistic = 0.570).⁶² Not all patients with a CHADS₂ score of 0 are at low risk and other risk factors have been identified that are not encompassed by this tool.^63,64

The 2012 ESC guidelines and 2014 ACC/AHA/HRS guidelines recommended use of a more nuanced risk stratification schema (CHA₂DS₂-VASc), summarized in Table 83–3.³ The CHA₂DS₂-VASc schema recognizes that stroke risk in patients with AF is related to age as a continuous variable, acknowledges the higher, albeit unequal, risk of stroke faced by women, and incorporates the less validated risk associated with vascular disease, prior myocardial infarction, complex aortic plaque, and peripheral arterial disease, although these may contribute unequally. Because of its greater sensitivity, the CHA₂DS₂-VASc better excludes lowest-risk patients who may not benefit as much from anticoagulation, but it still fails to account for a considerable proportion of risk (c = 0.578). Oral anticoagulants are recommended for patients with a prior stroke, transient ischemic attack, or CHA₂DS₂-VASc score of 2 or more; either oral anticoagulants, aspirin, or no antithrombotic therapy can be considered for CHA₂DS₂-VASc of 1; and antithrombotic therapy may be omitted for CHA₂DS₂-VASc score of 0.³

There is widespread consensus that all patients with rheumatic valvular heart disease or prosthetic heart valves and AF require anticoagulation unless there is an absolute contraindication. There is no difference in the indications for antithrombotic therapy between paroxysmal, persistent, or permanent AF. The pathogenic mechanisms linking AF with ischemic stroke are incompletely understood. Clinical risk assessment instruments like the CHA₂DS₂-VASC score do not fully account for thromboembolic risk, and stroke can occur after sinus rhythm is restored by electrical or pharmacological cardioversion. Atrial fibrosis correlates with both the persistence and burden of AF, and gadolinium-enhanced magnetic resonance imaging is gaining utility for detection and quantification of the fibrotic substrate, but methodological challenges limit its use. There is increasing evidence that the fibrotic atrial cardiomyopathy associated with AF is thrombogenic and that AF is a marker of stroke risk regardless of whether or not the arrhythmia is sustained. Antithrombotic therapy should, therefore, be guided by a comprehensive assessment of intrinsic risk rather than the presence or absence of AF at a particular time.

Antithrombotic Therapy

Warfarin is remarkably effective at reducing stroke risk in patients with AF (Fig. 83–7). This was demonstrated by a meta-analysis of five randomized, controlled clinical trials comparing warfarin versus placebo or no therapy. When analyzed according to intention-to-treat, there was a 68% risk reduction in stroke for patients taking warfarin compared with patients in the control groups who were not anticoagulated (P < .001).⁶⁵ Moreover, on-treatment analysis demonstrated an 83% risk reduction in stroke when patients were taking warfarin compared with placebo.⁶⁶ Warfarin should be administered to achieve an international normalized ratio (INR) between 2 and 3 for optimal efficacy and safety (Fig. 83–8).

Meta-analysis of studies comparing aspirin with placebo suggests a relative risk reduction of approximately 22% with aspirin. Comparisons of warfarin versus aspirin show superiority of warfarin (Fig. 83–9). Additional concerns using aspirin for stroke prevention in lieu of warfarin relate to severity of stroke.^68,69 Thus, warfarin with an INR ≥ 2 not only reduces the frequency of ischemic stroke, it also reduces the severity and risk of death from stroke compared with aspirin.

Several trials compared the safety and efficacy of alternative oral anticoagulants to reduce risk of stroke in patients with AF.^{70,71,72,73,74} In a trial involving patients with AF at increased risk of stroke who were deemed unsuitable for warfarin, the combination of aspirin plus clopidogrel compared with aspirin alone had a small, but significant, reduction in the risk of major vascular events, especially stroke, but increased the risk of major hemorrhage.⁷⁰ Several target-specific novel oral anticoagulants (NOACs) act by direct inhibition of thrombin (dabigatran) or activated factor X (rivaroxaban, apixaban, and edoxaban). Unlike vitamin K antagonists, these anticoagulants do not require routine INR monitoring and possess favorable pharmacological properties. They act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Trials comparing these agents to warfarin for stroke prevention in patients with nonvalvular AF demonstrated that they are at least as efficacious and safe as warfarin.⁷⁵ Clinical practice guidelines have incorporated these anticoagulants for stroke prevention in nonvalvular AF, but safe and effective use requires understanding of their distinct pharmacological properties.

Dabigatran, a direct competitive inhibitor of thrombin (coagulation factor IIa), and rivaroxaban, apixaban, and edoxaban, which inhibit coagulation factor Xa, have shown noninferior or superior efficacy against all stroke (ischemic plus hemorrhagic) and systemic embolism with rates of major bleeding comparable to, or lower than, warfarin. The doses of each are modified according to renal function. Considered collectively, the NOACs have been associated with significantly lower risks of intracerebral hemorrhage than even well-adjusted warfarin in the trials leading to their approval for clinical use, generally better outcomes, even in cases when major bleeding occurred, and lower rates of all-cause mortality when used for thromboembolism prevention in patients with nonvalvular AF. These agents have not been proven safe or effective in patients with AF associated with rheumatic mitral stenosis or mechanical heart valves, and experience in patients with AF who have undergone bioprosthetic heart valve replacement or valve repair is limited.

Despite several advantages, when introduced there were no readily available coagulation assays to measure anticoagulation effect of the NOACs, making it difficult to titrate dosage and identify causes of therapeutic failure and creating challenges in emergent situations including trauma, hemorrhage, or need for invasive procedures. There were initially no evidence-based strategies for rapid reversal of the anticoagulant effects of these agents for situations in which the relatively short half-lives were not sufficient. By contrast, anticoagulation induced by warfarin can be attenuated by administration of vitamin K and more rapidly reversed by fresh frozen plasma or four-factor prothrombin complex concentrate (PCC).⁷⁶ However, there is lack of evidence proving that the consequences of CNS hemorrhage occurring on warfarin can be favorably influenced by available reversal strategies, including four-factor PCC. A humanized antibody against dabigatran (idarucizumab) was introduced for clinical use in 2015,⁷⁷ and a decoy-based approach to reversal of anticoagulation induced by the factor Xa inhibitors is under accelerated clinical development.⁷⁸

Although several risk stratification schemes have been proposed to assess the risk of bleeding during anticoagulant therapy, notably the HEMORR2HAGES,⁷⁹ HAS-BLED,⁸⁰ and ATRIA⁸¹ scores, they are relatively limited, having been derived from historical cohorts anticoagulated with warfarin, and have not been validated for use in patients treated with NOACs. They are intended to predict major bleeding, but not specifically intracranial or fatal bleeding, and have been incorporated in the European (ESC) practice guidelines but not the American (ACC/AHA/HRS) guidelines, which do not advise formal use of bleeding risk scores. It is important to bear in mind that a stroke prevention benefit of anticoagulation is preserved even in patients at increased risk of bleeding, and that in the process of clinical decision making, risk should generally be stratified first on the basis of stroke risk, with the risk of bleeding considered as a modifying factor.

A percutaneous closure device introduced into the left atrial appendage may be an alternative for patients in whom long-term anticoagulation with warfarin is not considered optimum for stroke prevention.⁸² The left atrial appendage occlusion strategy has not been compared with anticoagulation using the NOACs for stroke prevention in patients with nonvalvular AF, and clear indications for the device-based approach are in evolution.

Rate Control Versus Rhythm Control Strategies

Whenever possible, potential reversible causes of AF should be identified and treated, even if they may only ameliorate AF.^2,3 Hyperthyroidism is a very uncommon cause of AF, but therapy of it often leads to disappearance of AF. Treatment of obstructive sleep apnea and significant weight loss in obese patients can reduce AF episodes.^83,84,85

Many factors should be considered when choosing a primary treatment strategy of rate or rhythm control. A rate control strategy assumes maintenance of sinus rhythm is not needed, but it is important to consider whether sinus rhythm may be needed in the future, for persistence of AF for years often results in the inability to restore and maintain sinus rhythm. An example is a patient with ventricular hypertrophy that may worsen over time, in whom sinus rhythm may then be important. Age is another factor to consider, for although several prospective, randomized trials have been published comparing the strategies of rate control and rhythm control in patients with AF, most patients have been over 65 years old.^86,87,88

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial enrolled 4060 patients aged older than 65 years (mean age 69.7 years) or with risk factors for stroke, randomizing them to rate versus rhythm control.⁸⁶ Over a mean follow-up period of 3.5 years, there was no significant difference in overall mortality between the two groups. Hypertension was present in 70.8% of patients and coronary artery disease in 38.2%. More than two-thirds of the patients in the rhythm control group received either sotalol or amiodarone.

The Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) trial⁸⁷ randomly assigned 522 patients with persistent AF after electrical cardioversion to either a rate-control or a rhythm-control treatment. The mean age was 68 years, and follow-up was a mean of 2.3 years. Hypertension was present in 55% and 43% of the rhythm and rate control groups, respectively (P = .007). There was no difference in the primary end point of the study (a composite of cardiovascular death, HF, thromboemboli, bleeding, need for pacemaker, or serious drug side effects) between the two strategies.

There was no difference in any clinical outcomes in a recent meta-analysis of 10 studies that compared rhythm (drugs) versus rate control strategies.⁸⁹ An observation of an exploratory subanalysis showed that patients younger than 65 years had an advantage with rhythm control in the prevention of all-cause death. Although interesting, this observation requires confirmation in prospective studies.

Follow-up in AFFIRM and RACE was less than 4 years. Caution should be exercised extending the results to longer follow-up periods and to younger patients. In a large population-based database of patients with AF, no difference in mortality was noted in those treated with either rhythm or rate control drugs during the first 4 years, but for those who survived more than 5 years, a lower mortality was noted in the rhythm control group.⁹⁰

Although stroke has been studied in detail in rate versus rhythm control trials, other neurologic consequences have not. Future studies should address the potential consequences of AF on cognitive impairment, silent cerebral infarcts, memory impairment, and Alzheimer disease, which have been reported with AF.^91,92 In summary, the choice of a rhythm or rate control strategy should be individualized for each patient, and the physician should be flexible and be willing to modify the strategy if the clinical situation changes.² If rate control is chosen and symptoms persist, rhythm control should be tried. In reality, many patients who have rhythm control using antiarrhythmic drugs will require AV node blockers to slow the ventricular rate if AF recurs. Selection of various drugs is shown in Fig. 83–6. Anticoagulation is needed in patients at high risk for stroke regardless of whether a rate-or rhythm-control strategy is chosen.

Rate Control

Medical Therapy

Control of the ventricular rate involves both acute and chronic phases. In the acute phase, intravenous metoprolol, esmolol, diltiazem, or verapamil have all been demonstrated to provide slowing of AV nodal conduction; these drugs are indicated for patients with severe symptoms related to a rapid ventricular rate.^2,3 Intravenous digoxin requires a longer duration to achieve rate control and is less useful. Intravenous amiodarone, usually employed for acute AF conversion, has the ability to slow the ventricular response via its β-blocking and calcium channel blocking effects. Heart rate slowing may be seen within minutes of its acute administration.⁹³

For patients with only mild or moderate symptoms, oral medications that slow AV nodal conduction should be prescribed. After control of the resting ventricular rate has been achieved, attention is paid to the ambulatory heart rate. There is no overall agreement on what constitutes optimum rate control.⁹⁴ One set of criteria is 60 to 80 bpm at rest and between 90 and 115 bpm during moderate exercise.³ In a small randomized study, lenient rate control (less than 110 bpm) was not found to be inferior to more stringent rate control (less than 80 bpm).⁹⁵

It is also uncertain which method is best to evaluate rate control, which has been done using a resting 12-lead ECG, 24-hour Holter monitor, exercise testing, and combinations of methods.⁹⁴ In essence, achievement of rate control for each patient during their usual daily activities seems reasonable, so titrating AV nodal blockers on an outpatient basis following the daily 24-hour heart rate plot as a guide appears useful.⁹⁴

Digoxin may provide effective control of the resting heart rate but is often ineffective during exertion, making it less than ideal in young active patients. β-Adrenergic blockers or calcium channel blockers achieve much better control of the ventricular rate during exercise and should be considered for most patients. Digoxin is most useful in the setting of impaired systolic function, and also can be used in combination with β-blockers or calcium antagonists if these agents do not provide adequate rate control. Recent conflicting data have been developed regarding digoxin's effect on cardiovascular and total mortality. The prevailing opinion is that digoxin can be used safely at lower doses and with careful monitoring of renal function.⁹⁶

Control of the ventricular rate can be especially challenging for patients with the tachycardia-bradycardia syndrome, who experience rapid ventricular rates during AF and sinus bradycardia or sinus pauses when AF terminates. Ablation of AF or AV node ablation and permanent pacemaker implantation is indicated for many of these patients.

Atrioventricular Node Ablation

Some patients may continue to experience significant symptoms from a rapid or irregular ventricular rhythm despite drug therapy. Catheter ablation of the AV conduction system and permanent pacemaker implantation is a highly effective means of establishing permanent control of the ventricular rate during AF in selected patients.^97,98,99 Despite the many favorable effects of this procedure, there are several limitations. First, AV nodal ablation does not change the long-term need for anticoagulation. Second, although an adequate junctional escape rhythm may be present after ablation, some patients may become pacemaker dependent as a result of an inadequate escape rhythm. Third, right ventricular pacing produces an abnormal LV contraction sequence, and acute worsening of hemodynamics has been observed in some patients. The development of a right-ventricular pacing-induced cardiomyopathy can occur.² In the Post AV Node Ablation Evaluation (PAVE) trial, patients who received biventricular versus right ventricular apical pacing, especially those with abnormal LV ejection fractions before ablation, had longer 6-minute walking distances and higher LV ejection fractions after ablation.¹⁰⁰

Rhythm Control

When a rhythm control strategy is chosen for patients with paroxysmal or persistent AF, prophylactic treatment with antiarrhythmic drugs is usually needed to maintain sinus rhythm. Although the ideal of pharmacologic therapy would be to prevent all recurrences of AF, this is unrealistic for many patients. Rather, marked reduction of the frequency, duration, and symptoms of AF may be a very acceptable clinical goal. In addition, the use of pharmacologic agents resulting in an apparent clinical resolution of AF does not change the indication for anticoagulation.

Some patients can be managed with intermittent antiarrhythmic drug therapy, the so-called pill-in-the-pocket approach (see "Pharmacologic Cardioversion" later in the chapter). This approach must be reserved for patients who have highly intermittent and terminable episodes of AF who are also motivated to keep drug supplies available over long intervals. A corollary is the "booster" approach in which patients are given permission to use supplemental doses of a safe and effective chronic therapy upon AF recurrence. Again, patient selection is the key to employing these strategies successfully.³

The choice of pharmacologic agent is largely determined by the potential side effects of a given drug in an individual patient, rather than comparative efficacy. The first drug chosen is usually associated with a lowest risk of serious side effects for that patient. For most patients, a specific etiologic factor for the initiation of AF cannot be identified. Conversely, if such an inciting factor is uncovered, therapeutic efforts should be targeted to eliminating it. Examples include β-blockers for exercise-induced AF and avoidance of alcohol in particularly sensitive individuals.

Many agents have effectiveness to maintain sinus rhythm in patients with AF.³ Because class IC drugs may suppress AF but promote atrial flutter, they are combined with a β-blocker or calcium channel blocker to decrease the risk of atrial flutter with 1:1 ventricular response, a potentially life-threatening situation. Monitoring the QRS duration and PR interval is important during class IC therapy. Sotalol, dofetilide, and amiodarone prolong ventricular refractoriness and the QT interval. Monitoring the QT interval during initiation of therapy is important. If possible, avoid corrected QT intervals of > 500 to 520 ms with sotalol and dofetilide, but longer QT intervals may occur without a risk of proarrhythmia in patients receiving amiodarone. Periodic ECGs should be obtained on an outpatient basis in patients receiving antiarrhythmic drugs, and efforts to avoid hypokalemia and hypomagnesemia are important.

Amiodarone is the most effective drug for the treatment of AF despite the fact that it has not gained regulatory approval for this indication in the United States. It is a complex drug pharmacologically with protean toxicity that mandates careful clinical supervision. Its most feared and dangerous side effect is pulmonary fibrosis, which can be lethal if not diagnosed promptly.¹⁰¹

Dronedarone is the most recent oral antiarrhythmic drug approved for the treatment of patients with AF and atrial flutter.¹⁰² It is a noniodinated benzofuran derivative of amiodarone.¹⁰³ Like amiodarone, it blocks multiple channels, including sodium, potassium, and calcium, and has noncompetitive antiadrenergic effects. Compared with placebo in two randomized controlled trials, dronedarone prolonged the median times to recurrence of arrhythmia.¹⁰⁴ In a multicenter randomized controlled trial of more than 4600 patients, dronedarone reduced the incidence of hospitalization from cardiovascular events or death in patients who had AF.¹⁰⁵ A follow-up study, PALLAS, failed to demonstrate a benefit on a similar end point when dronedarone was administered to patients with heart disease and permanent AF. Based on this study and ANDROMEDA, which enrolled recently hospitalized patients with HF,¹⁰⁶ dronedarone is contraindicated in patients with permanent AF, those with class II to IV HF, and those with recent decompensation requiring hospitalization or referral to a specialized HF clinic.

Recent data have emerged regarding the safety and efficacy of combining lower doses of dronedarone with ranolazine, a late sodium channel blocker that has been shown to be moderately effective in suppressing AF.¹⁰¹ In a late phase II trial, the combination was superior to both placebo and to individual components in reducing AF burden in patients with devices, with an excellent safety profile.¹⁰⁷ We await phase III studies of this interesting formulation.

There are few studies of the safety of initiating drugs in the outpatient setting, but some general rules are useful. Flecainide and propafenone can be initiated in patients without heart disease who are in sinus rhythm, and safety is maximized if AV nodal blockers are given first. Amiodarone can be used in patients with or without sinus rhythm, but frequent ECG monitoring, for example, by using event recorders, is recommended to identify any potential bradycardia or tachycardia proarrhythmia. Sotalol may be administered to patients in sinus rhythm with minimal or no heart disease and normal QT interval and electrolyte status; the lowest dose should be used and an ECG should be obtained within days of starting sotalol to determine the QT interval. The same process should occur for any dose increase. Dofetilide must be started in hospital, and dronedarone is typically started out of hospital.

Antiarrhythmic Drug Selection

As stated, antiarrhythmic drugs are selected on a safety-first basis (see Fig. 83–6). The ACC/AHA/HRS guidelines³ suggest that patients with no structural heart disease start with dofetilide, dronedarone, flecainide, propafenone, or sotalol, agents with minimal noncardiac toxicity. Second-line therapy is either amiodarone or catheter ablation. Patients with hypertension who do not have substantial LV hypertrophy have a similar treatment algorithm, but those with substantial LV hypertrophy are considered at increased proarrhythmic risk with most drugs other than amiodarone, which becomes first-line therapy in this circumstance. Catheter ablation is second-line treatment in most clinical situations, but may be considered first-line in some patients (discussed later). Safety of drugs in coronary artery disease has been demonstrated for dofetilide, dronedarone, and sotalol (first line) and amiodarone (second line), and catheter ablation is also a second-line treatment. For patients with HF, first-line treatment can be either amiodarone or dofetilide, but the authors prefer amiodarone in most circumstances, and ablation as second-line therapy. Class IA agents quinidine, procainamide, and disopyramide are rarely used in clinical practice, although quinidine, by virtue of its effect on Ito, and other nonsodium channels, may be useful for rare patients with inherited channelopathies such as Brugada syndrome and the short QT syndrome.¹⁰⁸ Dronedarone appears to be a safe drug to use as first-line therapy in patients with normal or nearly normal hearts.

Nontraditional Antiarrhythmic Agents

Several drugs used to treat other medical conditions have shown promise as adjuvant therapy in patients with AF including anti-inflammatory drugs. Drugs that modulate the renin-angiotensin-aldosterone system—for example, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers—may decrease the incidence of AF when examined retrospectively in trials of other purpose.³ These drugs can reduce atrial fibrosis and promote more favorable hemodynamics, but it is not clear if these actions are important to reduce AF. Prospective randomized trials have not proven benefit. Preliminary data also support the beneficial effect of statins to reduce AF without clear efficacy in controlled trials.³

Fish oils have also been touted as having a treatment effect in AF, although the largest and best controlled studies of these agents have failed to show benefit. At this time these is no evidence to support the routine use of nonmembrane-active antiarrhythmic drugs for the prevention or termination of AF.¹⁰⁹

Cardioversion

Cardioversion can be accomplished using either antiarrhythmic drugs or the direct-current approach. In situations in which urgent cardioversion is needed, such as marked hypotension, the direct-current approach is preferred. The need for anticoagulation before cardioversion must be considered. There is general consensus that AF that has been present for < 48 hours can be cardioverted without prior anticoagulation, but there are no randomized trial data to support this, and systemic emboli can potentially occur even in this situation.¹¹⁰ Because it is often impossible to time accurately the onset of AF, if cardioversion is needed soon, transesophageal echocardiography and anticoagulation therapy are recommended for AF of uncertain duration.

There are two basic anticoagulation strategies before cardioversion: (1) oral warfarin with a therapeutic INR (2-3) for 3 to 4 weeks before cardioversion followed by continued warfarin therapy for a minimum of 4 weeks, or (2) transesophageal echocardiography (TEE) and intravenous heparin immediately before cardioversion followed by oral warfarin thereafter.¹¹¹ The recent AHA/ACC/HRS guidelines suggest use of a NOAC for 3 weeks before cardioversion is reasonable,³ but there are few prospective data supporting this. The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study randomized 1222 patients with AF undergoing direct-current cardioversion between these strategies and found no difference in the rate of embolic events (0.5% TEE vs 0.8% conventional), but a lower risk of bleeding complications (2.9% vs 5.5%) and a shorter interval to cardioversion (3.0 vs 31 days) in the TEE-guided group.¹¹² The left atrial mechanical function may be significantly impaired for up to several weeks after cardioversion from AF to sinus rhythm. This stunning effect on the atria may occur after either electrical or pharmacologic cardioversion,^113,114,115 and is more marked with longer duration of AF. In patients without high-risk factors for stroke, anticoagulation can be discontinued approximately 4 weeks after cardioversion. If the patient has a standard indication for warfarin before cardioversion, anticoagulation should be continued indefinitely after cardioversion unless a clear reversible cause of AF has been corrected.

Direct Current Cardioversion

Successful electrical cardioversion requires attention to details. Always be sure the patient is adequately anticoagulated. Rather than use handheld paddles, adhesive gel electrodes can be placed anteriorly over the sternum (with the upper edge at the sternal angle) and posteriorly (just to the left of the spine).¹¹⁶ If cardioversion is not successful with this electrode position, a different electrode placement such as anterior-lateral configuration can be attempted. The shock must be synchronized to the QRS complex, and it is important to select an ECG lead that has a prominent R wave with no sensing of the T wave. Cardioversion shocks are painful and the patient requires adequate anesthesia. Biphasic waveforms clearly improve defibrillation efficacy at all energy settings as compared with monophasic shocks.^117,118 An initial shock energy of 200 J or more is recommended for both monophasic and biphasic waveforms.¹¹⁹ However, in patients with smaller body habitus who have not had AF of long duration, we typically start with approximately 120 J using biphasic waveform shocks. Another theoretical reason for using higher initial shock energies is to avoid initiating ventricular fibrillation if by accident the shock falls on the T wave. A high-energy shock has a better chance of being above the lower limit of vulnerability to induce ventricular fibrillation. Consideration should be given to selected patients, for example, those with AF duration > 3 months, to receive an antiarrhythmic drug before cardioversion to avoid immediate or early recurrence of AF.

Pharmacologic Cardioversion

The duration of AF is a major factor for cardioversion success using antiarrhythmic drugs, and AF lasting < 1 week has a substantial chance of cardioversion using oral flecainide, propafenone, dofetilide, and intravenous ibutilide.³ For longer duration AF, only dofetilide seems to have a reasonable chance of success, but amiodarone and ibutilide may be useful.³ A single oral dose of propafenone (eg, 600 mg) or flecainide (eg, 300 mg) can be useful to convert recent-onset AF to sinus rhythm.^{120,121,122,123} A recent study demonstrated the safety of the pill-in-the-pocket approach to outpatient conversion of AF in some patients.¹²⁴ Select patients were observed in hospital while being given a single oral loading dose of either propafenone or flecainide to convert AF. Those with success were allowed to self-administer the drug if they had a recurrence of AF, and few complications occurred during follow-up. Because a type 1C drug may convert AF to atrial flutter with 1:1 conduction to the ventricle, an AV nodal blocking agent should be administered concomitantly, although the actual occurrence is very low.

Dofetilide is useful to convert AF of both short and long duration, although it is not commonly used expressly for this purpose.^125,126 Intravenous ibutilide has also been demonstrated to provide effective cardioversion of recent-onset AF or flutter, and is one of the very few drugs that has gained regulatory approval for this indication.¹²⁷ The risk of nonsustained or sustained torsades de pointes ventricular tachycardia was 3.6% across studies. Thus, although effective, intravenous ibutilide requires continuous electrocardiographic monitoring for at least 4 hours after administration. Ibutilide is far more effective than intravenous procainamide (51% vs 21%) for the acute termination of AF.¹²⁸ Intravenous amiodarone has some efficacy, but onset of action is frequently delayed for several hours, which makes the drug less useful in clinical practice.¹²⁹

Vernakalant is a multichannel blocker that was studied extensively in an intravenous formulation for this indication and was found to have a placebo-subtracted efficacy of > 40% in most studies. The drug is available in a few countries primarily in Europe, but not in the United States, where concern was registered regarding cases of hypotension and bradycardia following conversion to sinus rhythm.¹³⁰

Nonpharmacologic Options of Rhythm Control

Catheter Ablation

The observation that rapidly firing atrial impulses from the pulmonary veins could initiate AF led to the catheter ablation approach of pulmonary vein isolation (PVI) to cure AF¹³ (see Fig. 83–3). Although the site of initiation of AF may be noted during the study (Fig. 83–10), the goal is usually to isolate all the pulmonary veins. PVI has had reasonably good success to cure patients with paroxysmal AF, but has shown limited efficacy in patients who have persistent or long-standing persistent AF.² Triggers can also originate in the right atrium, left atrial appendage, left atrial posterior wall, superior vena cava, crista terminalis, vein of Marshall, and coronary sinus.^3,131

Atrial substrate is likely important to the maintenance of AF, especially in persistent AF. Various approaches have been tried to modify atrial tissue including linear atrial ablation lines and ablation of complex fractionated atrial electrograms, but with limited success.² More recently, rotors (spiral waves) have been shown to sustain AF and these can be located in various sites in the right and left atria.^27,28,132 Ablation of these rotors (see Fig. 83–4) can yield improved outcomes even in patients with persistent AF.¹³² Using a noninvasive mapping technique, the concept of AF maintenance by focal drivers was validated during ablation of AF.¹³³ Radiofrequency energy is the most common energy source used for PVI, but cryoablation¹³⁴ is also effective to achieve PVI. In a recent multicenter randomized trial of patients with paroxysmal AF, efficacy was similar using cryoballoon ablation compared with radiofrequency ablation.¹³⁵ Using meta-analysis, the long-term success of AF ablation after a single procedure was 54.1% and 41.8% for paroxysmal and persistent AF, respectively.^2,136 The success improved to 79.8% with multiple procedures.¹³⁶ Further, data from multiple randomized clinical trials that compared medical therapy with catheter ablation showed the superiority of ablation to eliminate clinical AF symptoms and episodes.^{134,137,138,139,140,141,142,143,144} Current guidelines state that catheter ablation in experienced centers may be performed as first-line therapy in symptomatic patients who have paroxysmal AF (see Fig. 83–6).^3,131 In a worldwide survey of 85 institutions, major complications occurred in 4.5 % of ablations, including stroke and cardiac tamponade, and rarely death or atrial-esophageal fistula.¹⁴⁵

Surgical Options

Based on the pioneering research of Cox and coworkers, several surgical treatments for the prevention of AF have been developed.¹⁴⁶ Success rates have ranged from 70% to 95%.^147,148 For patients with AF who are undergoing cardiac surgery, consideration should be given to concomitant AF surgery. Gillinov and colleagues randomized patients with persistent or long-standing persistent AF undergoing mitral-valve surgery to additional surgical ablation for AF or not.¹⁴⁹ Freedom from AF at 6 and 12 months was significantly better for those with surgical AF ablation (63.2% vs 29.4%, P < .001). However, permanent pacemaker use was significantly higher in the patients who had AF ablation. Otherwise, its role is typically for patients who require sinus rhythm for symptom relief and have failed to respond to antiarrhythmic drugs and catheter ablation.

Management of Special Clinical Scenarios

Postoperative Atrial Fibrillation

AF may occur in approximately one-third of patients after open-heart surgery regardless of the technique used.¹⁵⁰ It is an important risk factor for postoperative stroke, and anticoagulation should be considered despite the increased bleeding risk inherent in this setting.^150,151,152 Several clinical trials have demonstrated a modest benefit of β-blockers for AF prevention, and they are used routinely for patients undergoing cardiac surgery of all types.¹⁵³ Amiodarone likewise has efficacy, but its toxicity profile has caused most to consider its use in patients at high risk for postoperative AF, such as the elderly and those with heart failure.^3,154 A recent trial comparing rate control versus rhythm control for postoperative AF showed no difference in absence of AF at 60 days,¹⁵⁵ which confirms previous observations suggesting most patients without preoperative AF who develop AF after cardiovascular surgery will not need long-term antiarrhythmic drug therapy.

Atrial Fibrillation and Wolff-Parkinson-White Syndrome

Wolff-Parkinson-White syndrome presents two specific clinical problems with AF. First, an accessory pathway–mediated AV reentrant tachycardia can degenerate into AF. Second, in some patients who have accessory pathways capable of rapid conduction to the ventricles (see Fig. 83–6), the AF may degenerate into ventricular fibrillation and cause sudden death.¹⁵⁶ Electrical cardioversion is necessary if patients are hemodynamically unstable. In stable patients, intravenous procainamide, ibutilide, or amiodarone can be used to block conduction over the accessory pathway. Intravenous β-blockers and calcium channel blockers could result in hypotension and accelerated conduction over the accessory pathway, and are contraindicated in this setting. Digoxin also is contraindicated in this setting because of concerns of accelerated conduction over the accessory pathway and paradoxic effect of increased ventricular rates from AV node blockade.³ Definitive therapy is radiofrequency ablation of the accessory pathway.

The term atrial flutter is generally used to describe atrial arrhythmias with large reentrant circuits. The surface ECG is characterized by regular repetitive flutter waves with an undulating baseline. The undulation of the baseline occurs because of continuous electrical activation of the atria from the reentrant circuit. The atrial rate is usually 240 to 340 bpm.

Classification and Mechanisms

Typical atrial flutter, also called counterclockwise atrial flutter, is characterized by negative sawtooth flutter waves (Fig. 83–11); and reverse typical atrial flutter, also called clockwise atrial flutter, is characterized by positive flutter waves in ECG leads II, III, and aVF.¹⁵⁷ These two atrial flutter types share the same right atrial reentrant circuit. In typical atrial flutter, the reentrant wavefront travels up the interatrial septum and down the right atrial free wall anterior to the crista terminalis and traverses the cavotricuspid isthmus to complete the circuit in a counterclockwise direction in the right atrium. The same circuit is completed in clockwise direction in reverse typical atrial flutter. Both types use the sub-Eustachian or cavotricuspid isthmus (ie, the isthmus between the tricuspid annulus on one side and the inferior vena cava–Eustachian ridge–coronary sinus on the other) as a critical part of the reentrant circuit.

Left atrial flutter, double wave reentry atrial flutter (two reentrant wave fronts simultaneously circulating in the same reentrant circuit),¹⁵⁸ lower loop and upper loop reentry right atrial flutter,¹⁵⁹ and atrial flutter caused by reentry around a surgical incision¹⁶⁰ have also been described. Left atrial flutter (Fig. 83–12) may be caused by reentry around the mitral valve annulus, the pulmonary veins, or a region of scar.¹⁶¹ Reentry around a surgical lesion is common in patients after repair of congenital heart defects,¹⁶⁰ although most (approximately two-thirds) atrial flutter in patients after surgical repair of congenital heart defects uses the classic cavotricuspid isthmus-dependent reentrant circuit.¹⁶²

Etiology

Atrial flutter often is initiated by AF. It is not surprising that it is also associated with chronic obstructive pulmonary disease, mitral or tricuspid valve disease, thyrotoxicosis, and postsurgical repair of certain congenital cardiac lesions (eg, atrial septal defect, the Mustard procedure, the Senning procedure, or the Fontan procedure),¹⁶³ as well as enlargement of the atria for any reason, especially the right atrium.^3,163 Atrial flutter occurs commonly in association with AF.

Diagnosis

Atrial flutter usually can be diagnosed from the ECG (see Figs. 83–11 and 83–12) by the presence of atrial complexes of constant morphology and cycle length with an undulating baseline. Although these ECG features are essential to clinical diagnosis, atrial flutter can present with discrete P waves, especially in atria that have extensive scar. On occasion, the identification of atrial flutter complexes in the ECG may be difficult because of their temporal superimposition on other ECG deflections or because of their low amplitude. Use of vagal maneuvers or the intravenous administration of adenosine to transiently prolong AV conduction may reveal the atrial flutter complexes.

Management

Although the choice between rate and rhythm control is similar to that in AF, there is bias toward rhythm control in atrial flutter as a result of the relative ease and high success rate of catheter ablation, but also to the difficulty in many patients to achieve good rate control. The regular and slower atrial rate seen in atrial flutter compared with AF yields less concealed conduction in the AV node and often shows a 2:1 AV conduction pattern. Consistent adequate slowing of the ventricular response is harder to achieve in this situation. Selection of rate-control agents and antiarrhythmic drugs to treat atrial flutter mirrors that to treat AF³ (see Fig. 83–6).

Initial management of atrial flutter is similar to treatment of AF. Urgent conversion to sinus rhythm or rapid control of the ventricular response rate may be needed, depending on the patient's hemodynamic status. Options for cardioversion include transthoracic direct current (DC) cardioversion or chemical cardioversion using antiarrhythmic medications.^3,127 Rapid atrial pacing in patients with permanent or temporary pacemakers can also be used to restore sinus rhythm.¹⁶⁴ Drug therapy with β-blockers, calcium channel blockers, and digitalis may be used to slow the ventricular response rate. It is often difficult to achieve sufficient AV nodal block to slow adequately the ventricular response during atrial flutter, and 2:1 AV conduction frequently recurs. When using a class IC antiarrhythmic agent to treat atrial flutter, care must be taken to provide adequate AV block. These agents slow intraatrial conduction time by blocking sodium channels and slow the rate of atrial flutter. Slower atrial flutter may result in a 1:1 AV conduction of the flutter waves, resulting in very fast ventricular rates. This can degenerate into fatal ventricular tachycardia or ventricular fibrillation. It is important to remember that atrial flutter is often initiated by AF, which may become manifest after atrial flutter reverts to sinus rhythm.

Anticoagulant therapy

In patients with atrial flutter, anticoagulation using daily warfarin therapy to achieve an INR between 2 and 3, or use of one of the direct oral anticoagulants (NOACs), is recommended using the same criteria as for AF.³ In addition, several studies indicate that the incidence of stroke associated with atrial flutter approaches that of AF.^165,166,167

Catheter Ablation Therapy

Catheter ablation is highly successful, typically 90% or greater, to eliminate the typical atrial flutter.³ This coupled with the recognized difficulty in achieving adequate long-term suppression with antiarrhythmic drug therapy make catheter ablation a first-line treatment option for many patients.¹⁶⁸ Because classical atrial flutter is usually preceded by a variable period of AF, successful ablation of the atrial flutter reentrant circuit per se does not prevent recurrence of AF. In fact, in our experience, the longer the follow-up after successful ablation of atrial flutter, the greater is the chance that AF will manifest, especially in more elderly patients.

We thank Dr. Benzy Padanilam and Dr. Albert Waldo, who contributed to the previous version of this chapter in the 13th edition. We also thank Mrs. Diana Carey for her expert assistance in the preparation of this chapter.