John Rickard and Mohamed Kanj
Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. There are estimated to be more than 2 million patients with AF in the United States. The prevalence and incidence of AF increase with advancing age. The mainstay of therapy includes pharmacologic rate control and antiarrhythmic therapy, cardioversion, and antithromboembolic management. Non-pharmacologic therapies, including ablation, device, and surgical approaches, are also becoming increasingly utilized.
EPIDEMIOLOGY
Prevalence
0.4% general population
0.2% in population 25 to 34 years old
2% to 5% in population >60 years old
18% in population >85 years old
8% to 14% in hospitalized patients
Incidence
The incidence of AF increases from <0.1% per year (>160,000 new US cases year) in those under 40 years of age to 1.5% per year in females and 2% per year in males over the age of 80 (Kannel et al. 1983).
20% to 40% after cardiac surgery
FACTORS PREDISPOSING TO ATRIAL FIBRILLATION
The most common cardiovascular (CV) diseases associated with AF are hypertension and ischemic heart disease. Other predisposing conditions include:
Advancing age
Rheumatic heart disease (especially mitral valve disease)
Nonrheumatic valvular disease
Cardiomyopathies
Congestive heart failure (CHF)
Congenital heart disease
Sick sinus syndrome/degenerative conduction system disease
Wolff–Parkinson–White syndrome
Pericarditis
Pulmonary embolism
Thyrotoxicosis
Chronic lung disease
Neoplastic disease
Postoperative states
Diabetes
Normal hearts affected by high adrenergic states, alcohol, stress, drugs (especially sympathomimetics), excessive caffeine, hypoxia, hypokalemia, hypoglycemia, or systemic infection
MORBIDITY AND MORTALITY
Survival
The presence of AF leads to a 1.5- to 2-fold increase in total and CV mortality (Emelia et al., 1998). Factors that may increase mortality include:
Age
Mitral stenosis
Aortic valve disease
Coronary artery disease (CAD)
Hypertension
CHF
Patients with myocardial infarction (MI) or CHF have higher mortality if AF is present.
Stroke/Thromboembolism
AF predisposes to stroke and thromboembolism.
Five- to sixfold increased risk of stroke (17-fold with rheumatic heart disease [RHD])
3% to 5% per year rate of stroke in nonvalvular AF
Single major cause (50%) of cardiogenic stroke
75,000 strokes per year
Silent cerebral infarction risk
Risk increases with age, concomitant CV disease, and stroke risk factors
Tachycardia-Induced Cardiomyopathy
Persistent rapid ventricular rates can lead to tachycardia-mediated cardiomyopathy and left ventricular (LV) systolic dysfunction. These are, however, reversible with ventricular rate control and regularization. Control can be achieved with medical rate control, atrioventricular (AV) node ablation, or achievement of sinus rhythm (SR). An atrial cardiomyopathy may develop leading to structural remodeling with an increase in atrial size.
Symptoms and Hemodynamics
Rapid ventricular rates
Irregularity of ventricular rhythm
Loss of AV synchrony
Symptoms: limitation in functional capacity, palpitations, fatigue, dyspnea, angina, CHF
PATHOGENESIS
While the pathophysiology of AF remains incompletely understood, it has been shown that AF requires a trigger and a substrate to sustain reentry. The triggering mechanism in most patients comes from ectopic firing within the pulmonary veins into which sleeves of atrial myocardium extend. Once AF has been sustained for a period of time, electrical and structural changes take place within the atria that can convert transient AF to persistent AF. Electrical changes, such as shortening of the atrial refractory period, occur shortly after AF onset and are reversible with conversion back to SR. Structural changes may take longer to develop, however, and are less amenable to reversal. In patients with CHF, the pathophysiology of AF is somewhat different. In this patient population, areas of interstitial fibrosis are found within the atria that lead to heterogeneous electrical conduction. These areas of slowed electrical conduction predispose to the development of AF.
Electrical activation: rapid, multiple waves of depolarization with continuously changing, wandering pathways
Intracardiac electrograms: irregular, rapid depolarizations, often >300 to 400 beats/min (bpm)
Mechanical effects:
Loss of coordinated atrial contraction
Irregular electrical inputs to the AV node and His–Purkinje system leading to irregular ventricular contraction
Surface electrocardiogram:
No discrete P waves
Irregular fibrillatory waves
Irregularly, irregular ventricular response
Atrial Flutter Reentrant Mechanism
Cavotricuspid Isthmus-Dependent Atrial Flutter
Cavotricuspid isthmus (CTI)-dependent flutters refers to circuits, which involve the isthmus of tissue in the right atrium between the tricuspid annulus and inferior vena cava (IVC) (Fig. 28.1).
The circuit can propagate around the isthmus in a clockwise or counterclockwise direction.
Counterclockwise atrial flutter is characterized by dominant negative flutter waves in the inferior leads and positive flutter deflection in lead V1.
Clockwise atrial flutter is characterized by positive flutter waves in inferior leads and negative flutter waves in lead V1.
In contrast to coarse AF, the flutter waves on an ECG will usually have the same morphology, amplitude, and cycle length.
Ablation of the CTI is curative.
FIGURE 28.1 Type I counterclockwise right atrial flutter.
Noncavotricuspid Isthmus-Dependent Atrial Flutter
Noncavotricuspid isthmus (NCTI)-dependent flutters do not use the CTI. NCTI flutters are often related to atrial scar which creates a conduction block and a central obstacle that allows for reentry.
NCTI can be found in patients with prior cardiac surgery involving the atrium, such as repair of congenital heart disease, mitral valve surgery, or maze procedure as well as in patients post pulmonary vein isolation procedures.
NCTI-dependent flutters are less common than CTI flutters.
Treatment
Atrial flutter may be difficult to treat medically (it is notoriously difficult to rate control) and may develop with organization of AF reentrant flutter circuits during treatment with antiarrhythmic therapy.
Successful ablation is dependent on identifying a critical portion of the reentry circuit where it can be interrupted with catheter ablation.
ATRIAL FIBRILLATION DEFINITIONS
Lone: Patients under the age of 60 years with absence of cardiopulmonary or other conditions predisposing to AF
New Onset: First episode of AF
Recurrent: Has two or more paroxysmal or persistent episodes
Paroxysmal: Self-terminating within 7 days, generally lasting 24 hours
Persistent: Is not self-terminating within 7 days or is terminated with treatment
Permanent: Persistent despite cardioversion
EVALUATION
History
Precipitating factors and conditions
Alcohol, caffeine, sympathomimetics, herbal supplements, or other drug use
Duration and frequency of episodes
Degree of associated symptoms
Manner of AF initiation
Prior therapies for AF (past antiarrhythmic drugs that may have failed or past ablation attempts)
Documentation of Atrial
Fibrillation and Initiation
ECGs, rhythm strips
Transtelephonic (remote) event monitoring
Evaluation for precipitating bradycardia, paroxysmal supraventricular tachycardia (PSVT), atrial flutter, atrial ectopy, atrial tachycardia
Diagnostic Testing
Lab studies—thyroid function, renal, and hepatic tests
Echocardiogram—evaluate LV function, valves, atrial size
Functional stress testing or cardiac catheterization—evaluate for CAD in patients with risk factors and evaluate candidacy for 1C agents
MANAGEMENT OF ATRIAL FIBRILLATION
Treatment Strategies
Ventricular rate control
AV nodal–blocking drugs
Atrioventricular node (AVN) modification/ablation and pacing
Achievement and maintenance of SR
Antiarrhythmic drugs
Cardioversions
Nonpharmacologic therapies
– Ablation
– Surgery—Maze procedure
Anticoagulation
Atrial Fibrillation Follow-Up Investigation of Rhythm Management
The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study (Wyse et al., 2002) was a multicenter trial of rate versus rhythm control strategies (Table 28.1). It tested the hypothesis that in patients with AF, total mortality with primary therapy intended to maintain SR is equal to that with primary therapy intended to control heart rate. The study randomized 4,060 patients (>65 years old or with risk factors for stroke), with a primary endpoint of total mortality. No significant difference in total mortality was found among strategies, although there was a strong trend toward better survival in the rate-control arm. The study also showed that continued anticoagulation is important even in the rhythm-control arm, so this may be the best strategy in relatively asymptomatic older patients with good rate control.
TABLE
28.1 Rate Control versus Rhythm Control
Control of Ventricular Rate
Rapid ventricular rates can cause symptoms and/or ventricular dysfunction. The goal of treatment, a heart rate of 70 to 100 bpm at rest, can be achieved pharmacologically with agents that slow AV nodal conduction, such as digoxin, beta-adrenergic blockers, and calcium channel blockers (Table 28.2). These agents, however, should not be used in patients with ventricular preexcitiation due to the risk of very rapid antidromic conduction during AF over the pathway. In patients who are hemodynamically stable with evidence of pre-excited AF, amiodarone, ibutilide, procainamide, or disopyramide are acceptable choices.
TABLE
28.2 Pharmacologic Rate Control for Atrial Arrhythmias
The RACE II trial compared strict rate control (resting heart rate <80 bpm) to lenient rate control (resting heart rate<110 bpm) in patients with permanent AF. Lenient rate control was comparable to strict rate control in terms of reaching the components of the primary endpoint. In addition, lenient rate control was much easier to achieve compared to strict rate control.
Digoxin
Digoxin has direct and indirect effects on the AV node, with a primary vagotonic effect. Advantages include:
It is inexpensive.
It can be given intravenously
It can be used safely in patients with heart failure.
It is effective in controlling resting ventricular rates in chronic, persistent AF.
Disadvantages are that:
Peak onset of heart rate-lowering effect is delayed by 1 to 4 hours.
The therapeutic window is narrow.
It is less effective in rate control of paroxysmal AF and should never be used as the sole agent for rate control in these patients.
It is less effective for rapid rates during hyperadrenergic states, when vagal tone is low, for example, during exercise or in acute MI and ICU settings, because of increased sympathetic tone.
Digoxin should be used with caution in elderly patients and in patients with decreased renal function.
Beta-Adrenergic Blockers
Advantages of beta-adrenergic blockers are that they:
Are very effective for heart rate control, even with exercise
Can be given intravenously
Have rapid onset of action
Have long-term benefits in patients with LV dysfunction
Disadvantages of beta-adrenergic blockers are that they:
May provoke bronchospasm
Are negatively inotropic and may exacerbate CHF
May reduce exercise tolerance as a result of their negative inotropy and chronotropy
Calcium Channel Blockers
The advantages of calcium channel blockers such as verapamil and diltiazem include:
Intravenous availability
Rapid onset of action
Can be used safely in chronic obstructive pulmonary disease (COPD) and diabetes mellitus
Disadvantages include:
Negative inotropic effects
Can cause hypotension
Long-term safety questioned
Class I or III Antiarrhythmic Drugs
Sotalol, dronedarone, amiodarone, propafenone, and flecainide can contribute to ventricular rate control.
NONPHARMACOLOGIC RATE CONTROL
Complete AV Junction Ablation
Radiofrequency catheter ablation of the AV node is usually technically easy to accomplish. It is best used in cases of atrial arrhythmias refractory to standard therapies in highly symptomatic patients.
Advantages
Effectively controls rapid ventricular rates
Significant symptomatic relief and improvement in quality of life demonstrated
Can reverse tachycardia-mediated cardiomyopathy
Disadvantages
Requires a permanent, rate-responsive pacemaker
The patient is pacemaker dependent.
Pacing RV alone may significantly worsen ventricular function. Biventricular pacing may be considered in patients with impaired LV systolic function.
RESTORATION OF SINUS RHYTHM
Electrical Cardioversion
Electrical cardioversion is the most effective method of restoring SR. In this technique, a shock is synchronized to the R wave. The optimal patch positioning is anterior–posterior (e.g., right parasternal to left paraspinal). For standard monophasic external cardioversion, usual initial energies are 200 J for AF and 50 to 100 J for atrial flutter. Energies can be increased up to 300 J if initial efforts are unsuccessful. Biphasic external conversion, however, requires less energy as a rule. All electrical cardioversion requires sedation with a short-acting anesthetic such as etomidate or methohexital, which is one limitation, compared to pharmacologic cardioversion.
Cardioversion is urgently indicated for patients with clinical instability (e.g., hypotension, ischemia, CHF). It is electively indicated for patients who remain in symptomatic AF after a trial of pharmacologic therapy. Electrical cardioversion is contraindicated in patients with AF and digoxin toxicity or hypokalemia.
Pharmacologic Conversion
A small, randomized, controlled study showed no effect of digoxin on conversion rate. However, quinidine, procainamide, flecainide, propafenone, sotalol, amiodarone, dofetilide, and ibutilide have shown success rates of 31% to 90%. Procainamide, ibutilide, and amiodarone are available for intravenous administration.
Procainamide is usually administered at a dose of 10 to 15 mg/kg IV at ≤50 mg/min, then at 1 to 2 mg/min. It is necessary to monitor blood pressure, as hypotension may require slowing the infusion rate; hemodynamic effects may limit dosing in severe LV dysfunction. It is also necessary to monitor for proarrhythmia—QT prolongation and torsades de pointes. Note that the active metabolite, N-acetyl procainamide (NAPA), may accumulate to toxic levels and cause renal failure.
Ibutilide is a class III potassium channel–blocking agent. In one study, it was shown to be more efficacious than procainamide in converting short-term AF/flutter to SR. Usual dosing is 1 mg IV over 10 minutes, which can be repeated after another 10 minutes. One should monitor for QT prolongation and torsades de pointes.
Amiodarone in its IV form is useful for patients who cannot take oral medications, though it is more expensive. It may be helpful for hemodynamically unstable patients with recurrent AF despite cardioversion or other antiarrhythmic drugs, for whom rate control is refractory to conventional
AV nodal–blocking drugs, or who are intolerant of standard antiarrhythmic or rate-controlling drugs as a result of negative inotropy. Rapid oral loading of amiodarone can usually also be achieved in patients with intact gastrointestinal function (Table 28.3).
TABLE
28.3 Pharmacologic Conversion Regimens
Maintenance of Sinus Rhythm
Maintenance of SR often requires an antiarrhythmic agent, particularly in patients with frequent or persistent AF, underlying CV disease, enlarged atria, or other continuing disease factors that predispose to AF. Common antiarrhythmic agents available that can be effective in maintaining SR include class IA (procainamide, disopyramide), IC (flecainide, propafenone), and III (sotalol, dronedarone, amiodarone, dofetilide). A substudy of the AFFIRM trial demonstrated that amiodarone is more effective at 1 year for the maintenance of SR than sotalol or other class I agents (Table 28.4).
TABLE
28.4 Drugs for Maintenance of SR
TdP, torsades de pointes; BP, blood pressure; CHF, congestive heart failure; CAD, coronary artery disease; LV, left ventricular.
CLASS IA ANTIARRHYTHMIC DRUGS
Class IA antiarrhythmic drugs:
Delay fast sodium channel–mediated conduction with a depression of phase 0
Prolong repolarization
Are associated with an incidence of torsade de pointes
Can enhance AV nodal conduction, potentially increasing ventricular rates during AF
Usually require concomitant use of AV nodal–blocking agents.
These drugs are usually not used chronically because of their potential proarrhythmic effects.
Quinidine
The use of quinidine is limited by proarrhythmia concerns and is thus rarely used. There is a higher risk in patients on diuretics and those with electrolyte depletion. From a meta-analysis by Coplen et al. (1990), the proportion of patients remaining in SR on quinidine at 1 year was 50% (control, 25%), but total mortality was 2.9% (control, 0.8%). Only 7 of 12 patients in the quinidine group, however, died of cardiac causes. Note that in-hospital initiation or systematic QT interval assessment may not have been followed for many of the studies in this analysis. The SPAF trial 1991 showed increased mortality on antiarrhythmic therapy, which usually consisted of quinidine, with risk seen in patients with a history of CHF. Because of the potential for proarrhythmia, including torsades de pointes, in-hospital initiation is recommended, with continuous ECG monitoring and assessment of QT interval. Quinidine increases serum digoxin levels, so concomitant digoxin dosage usually should be decreased. Other adverse effects of quinidine include gastrointestinal symptoms, particularly diarrhea.
Procainamide
Procainamide, given intravenously, is often a first-line antiarrhythmic agent for AF after cardiac surgery. Its long-term use is usually limited by a high incidence of drug-induced lupus; however, long-term controlled trials are not available.
Disopyramide
Disopyramide has been shown to be effective for maintenance of SR in approximately 50% of patients over a follow-up of 6 to 12 months. Its use is limited, however, because of its anticholinergic side effects and, in older males, urinary retention. Disopyramide is also negatively inotropic and thus has a niche use as a second-line option in patients with AF and hypertrophic cardiomyopathy with dynamic LVOT obstruction.
CLASS IC ANTIARRHYTHMIC DRUGS
The class IC antiarrhythmic drugs markedly slow sodium channel–mediated conduction, with a marked depression of phase 0, but only a slight effect on repolarization.
Flecainide and propafenone have been shown to be equivalent in efficacy in comparative studies. Proarrhythmia, however, in the form of a wide-complex tachycardia due to ventricular tachycardia or slow atrial flutter with 1:1 AV conduction can occur with these agents. They are usually avoided in patients with CAD or impaired ventricular function.
Patients with underlying heart disease may be at higher risk for proarrhythmia with class IC drugs. The Cardiac Arrhythmia Suppression Trial (CAST) reported increased mortality in patients treated with flecainide and encainide for ventricular arrhythmias after MI.
Flecainide
Flecainide has been shown to be effective in the treatment of AF and is usually well tolerated. Noncardiac effects include visual disturbances, dizziness, and paresthesias.
Propafenone
Propafenone has weak beta-blocking activity and is effective in the treatment of AF. It is available in a slow-release form that can be taken twice daily.
CLASS III ANTIARRHYTHMIC DRUGS
Class III antiarrhythmic drugs are potassium channel blockers that prolong repolarization.
Amiodarone
Amiodarone affects multiple ion channels. Its sodium and potassium channel effects include increased refractoriness in the atria, AV node, and ventricles. It also has noncompetitive beta-blocking and calcium channel–blocking activity. The drug inhibits phospholipase and antagonizes thyroid hormone but is effective against AF and has been reported to be superior to sotalol and quinidine, as well as to flecainide, in a meta-analysis.
Amiodarone has a long half-life, requiring weeks to months to achieve steady state. When used long-term, however, it has a potential for organ toxicity. It can cause significant bradycardia, but proarrhythmia is uncommon. The risk for pulmonary toxicity appears to be dose related. Other potential side effects include hypothyroidism or hyperthyroidism, liver function test elevation or toxicity, skin changes and photosensitivity, peripheral neuropathy, and, very rarely, optic neuritis. While amiodarone is known to prolong the QTc interval, Torsades de Pointes is rare. The usual maintenance dose of amiodarone for atrial arrhythmias is 100 to 200 mg daily. Of note, preoperative administration of amiodarone reduces the incidence of AF in patients undergoing cardiac surgery. As such prophylactic administration of amiodarone for patients at high risk of postoperative AF is reasonable.
Sotalol
Sotalol is a nonselective beta-blocker with class III activity that is effective in AF. It has significant beta-blocking activity with potential for bradycardia and negative inotropic effects that can lead to exacerbation of heart failure. Monitoring for QT interval prolongation and torsade de pointes is recommended. The d-isomer of sotalol (D-sotalol) studied in the Survival with Oral D-Sotalol Trial (SWORD) increased mortality in patients after MI and was withdrawn from development.
Dofetilide
Dofetilide is a potent inhibitor of Ikr, the rapid component of the delayed rectifier. In the DIAMOND trials of patients after MI or with CHF, it did not increase mortality and was found to be beneficial in maintaining SR. In-hospital initiation is mandated, and dosage should be adjusted in the presence of renal insufficiency. Common practice is to check an ECG 2 hours after the first five or six doses to monitor for significant QTc prolongation. Patients must be vigilant not to combine dofetilide (as well as any other QTc prolonging antiarrythmic) with other QTc prolonging drugs (e.g., certain antibiotics, antipsychotics) as the incidence of Torsades de Pointes can rise substantially with these combinations.
Dronedarone
Dronedarone is a deiodinated derivative of amiodarone that was recently approved for use in patients with AF. In development of the drug, the hope was that by doing away with the iodinated portion of the compound, the side effect profile would be improved compared to amiodarone without losing efficacy. In multiple clinical trials, the endocrinologic, neurologic, and pulmonary toxicity of amiodarone were not present with dronedarone. Compared to amiodarone, however, dronedarone was shown to be substantially less efficacious at preventing recurrences of AF.
Dronedarone is metabolized by the P-450 system in the liver primarily by (CYP) 3A4 and is highly bound to plasma proteins; therefore, the steady-state terminal elimination is approximately 30 hours compared to 58 days for amiodarone. In pooled data from the DAFNE, EURIDIS, ADONIS, and ATHENA trials, dronedarone was shown to delay recurrence of AF modestly compared to placebo. The DIONYSOS trial compared the efficacy and safety of dronedarone compared to amiodarone for at least 6 months for the maintenance of SR in patients with AF. This study showed that dronedarone was less efficacious in limiting recurrences of AF compared to amiodarone but had fewer discontinuations due to drug intolerance. ATHENA and ANDROMEDA were large randomized trials which evaluated the safety of dronedarone. The ANDROMEDA trial enrolled patients with recently symptomatic decompensated heart failure who may or may not have had AF. This study was stopped early due to excess mortality in patients on dronedarone. Caution is warranted with the use of dronedarone in patients with heart failure in general, and the use of the drug in patients with NYHA class IV heart failure or class II or III heart failure with recent decompensation is contraindicated (black box warning by the FDA).
ANTIARRHYTHMIC DRUG SELECTION
The decision to use an antiarrhythmic drug should include consideration of frequency and duration of the arrhythmia symptoms, reversibility of the arrhythmia, and the presence of structural heart disease. In addition, the risk of side effects, including organ toxicity and proarrhythmia, should be weighed against the benefits and efficacy rates of the drugs.
Approach to Antiarrhythmic Drug Selection
Consider:
Frequency and duration of AF
Symptoms
Reversibility
Structural heart disease
Risk of side effects
Proarrhythmia
Organ toxicity
Age and activity level
Assessment of risk versus benefits
Efficacy
Frequency, Duration, and Symptoms
First Episode After a first episode, the future pattern of recurrence cannot be predicted. The success rate and rate of recurrence are more favorable on an antiarrhythmic drug, but antiarrhythmic drug therapy may not be necessary after a first occurrence, unless factors such as structural heart disease, large atria, or advanced age suggest a high risk of recurrence.
A first episode can be converted either pharmacologically or electrically. If there are early recurrences of AF after cardioversion, then consider prescribing an antiarrhythmic drug. One may also consider stopping the antiarrhythmic drug after a few weeks or months.
Recurring, Paroxysmal Atrial Fibrillation For recurring, paroxysmal AF, assess the frequency and associated symptoms. If the patient is asymptomatic, consider a rate control strategy. If the patient is symptomatic, consider further rate control or addition of an antiarrhythmic drug.
For infrequent episodes in a patient with a normal heart, consider intermittent drug therapy also known as the “pill in a pocket approach” with the use of class IC agents (single oral dose of 300 mg of flecainide or 600 mg of propafenone) during an attack. The first time such a strategy is to be used however should be in a monitored setting (the patient comes to the ER or to clinic to administer the dose while monitored). For frequent symptomatic episodes, consider a rhythm control strategy with a daily administered antiarrhythmic drug.
Chronic, Persistent Atrial Fibrillation For persistent AF, assess the duration of the AF, atrial size, symptoms, and anticoagulation status. Based on this assessment, one may want to consider cardioversion. Antiarrhythmic therapy may also be required for successful conversion and maintenance of SR at least short term, if not chronically.
Structural Heart Disease
Patients with CAD and/or ventricular dysfunction are at higher risk of proarrhythmia. For these patients:
Avoid class IC drugs (based on the CAST trial).
In patients with hypertension and substantial left ventricular hypertrophy (LVH), the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend amiodarone as first-line therapy. Dronedarone is also an option.
In patients with CAD, sotalol or dofetilide are first-line options. Amiodarone is a second-line agent given its side effect profile.
In patients with heart failure, amiodarone and dofetilide are the agents of choice. Dronedarone can be used, but cautiously, in any patient with a history of heart failure. In patients with class IV heart failure or in those with a recent heart failure exacerbation, dronedarone is strictly contraindicated.
Sotalol can be used in patients with LV dysfunction so long as they can tolerate the negative inotropic effects of its beta-blocking activity.
Other Drug Considerations—Efficacy, Organ Toxicity, and Proarrhythmia
Efficacy Class IA and class IC drugs have efficacy rates of approximately 50% in maintaining SR at 6 months. The class III drugs have slightly higher efficacy rates (50% to 70%).
Side Effects Side effects are common with the use of antiarrhythmic agents. The side effect profile and risk for organ toxicity often limits continuation, although not necessarily, initiation of a particular drug.
Amiodarone has significant potential for organ toxicity. The risk is dose and duration related, and side effects often limit its use, particularly in younger patients.
Sotalol has negative inotropy, negative chronotropy, and bronchospastic side effects.
Procainamide has a high frequency of drug-induced lupus, which seriously limits its long-term use. There is also a small risk of agranulocytosis.
Quinidine has a small risk of agranulocytosis, thrombocytopenia, and/or lupus.
Proarrhythmic Risk Patients with normal hearts and non–life-threatening AF are at low risk for proarrhythmia. They may be treated with drugs with the lowest risk of proarrhythmia or organ toxicity. For these seasons, class IC drugs are often used as the first line of treatment. Class IA drugs and sotalol (class III) are lower-tier choices. Patients with CAD or ventricular dysfunction are at higher risk for proarrhythmia from class IC drugs, so one should consider dofetilide, sotalol, or amiodarone for these patients. Risk factors for proarrhythmia include structural heart disease, LV dysfunction, CHF, prior MI or CAD, LVH, female gender, prior torsades de pointes or CHF (amiodarone), and older age.
INPATIENT VERSUS OUTPATIENT INITIATION OF ANTIARRHYTHMIC DRUGS
The choice between initiating antiarrhythmic drug therapy on an inpatient or outpatient basis remains controversial, but inpatient initiation is usually recommended for:
Patients with LV dysfunction
Patients with persistent AF
Patients at risk for proarrhythmia (see above risk factors)
Class IA and III antiarrhythmic agents other than amiodarone: dofetilide (mandated in-hospital initiation), sotalol, quinidine, procainamide, or disopyramide
CHF patients with a history of torsades de pointes starting amiodarone
Prior history of proarrhythmia
Prolonged QT interval at baseline when initiating class IA and class III drugs
Propensity to bradycardia
History of ventricular arrhythmias in a patient with significant LV dysfunction and no ICD
ANTITHRMOBOTIC DRUG SELECTION
Chronic Anticoagulation and Antithrombotic Therapy
AF is associated with thromboembolic events and stroke. It is one of the most potent risk factors for stroke in the elderly and is the most common cause of cardiogenic stroke. The risk of stroke in nonvalvular AF varies with age and the presence of concomitant CV disease and other risk factors. In general, patients with nonvalvular AF have about a sixfold increased risk of stroke.
In patients younger than age 65 years and without hypertension or CV disease, the risk of stroke is low. A meta-analysis of five of the major primary prevention trials for stroke in AF indicated that the risk of stroke is approximately 1% per year for patients under age 65 without risk factors of hypertension, diabetes, or prior stroke or transient ischemic attack (TIA). For patients who are older or who have risk factors for stroke or concomitant CV disease, the risk of stroke is approximately 3% to 5% per year. Older patients (>75 years old) with risk factors for stroke are at higher risk (8% per year).
Most strokes associated with AF appear to result from cardiac emboli, presumably from thrombi formed most commonly in the left atrial appendage, a small, finger-like outpouching of the left atrium adjacent to the mitral valve. Patients with paroxysmal AF have a stroke rate of 3.7% per year with events clustered at the onset of the arrhythmia. The incidence of embolism is 6.8% in the first month and decreases to 2% per year over the subsequent 5 years. Patients with paroxysmal AF appear to be at similar risk as patients with chronic, persistent AF and generally are treated similarly with regard to anticoagulation. Patients with a single AF event, with no other risk factors or structural heart disease and <65 years old have a low stroke event rate of 1% per year. The incidence of stroke in patients with AF taking placebo versus aspirin alone and in patients taking aspirin versus coumadin are shown in Tables 28.5 and 28.6, respectively.
TABLE
28.5 Stroke/Thromboembolism Reduction in AF: Aspirin versus Control
RRR%, relative risk ratio (percent).
AFASAKI, atrial fibrillation, aspirin, anticoagulation study; SPAFI, stroke prevention in atrial fibrillation; EAFT, European atrial fibrillation trial; AFI, atrial fibrillation investigators; ESPS2, European stroke prevention study 2.
TABLE
28.6 Stroke/Thromboembolism Reduction in AF Warfarin versus Aspirin
RRR%, relative risk ratio (percent); AFASAKI, atrial fibrillation, aspirin, anticoagulation study; SPAF2, stroke prevention in atrial fibrillation phase 2; EAFT, European atrial fibrillation trial; AFASAK2, atrial fibrillation, aspirin, anticoagulation study phase 2.
Several large clinical trials have identified multiple risk factors for stroke when AF is present:
TIA or previous stroke
Diabetes Mellitus
Hypertension
Age >75 years
LV dysfunction
Increased left atrial size
Rheumatic mitral valve disease
Prosthetic valves
Mitral annular calcification
Increased wall thickness
Thyrotoxicosis
Peripheral vascular disease
CHADS II SCORE
The CHADS II score is a well-known, commonly used index used to gauge stroke risk in patients with nonrheumatic AF. CHADS stands for: Congestive heart failure (active within the last 100 days or evidence of LV dysfunction), Hypertension (blood pressure consistently above 140/90 mm Hg or treated hypertension on medication), Age (≥75 years), Diabetes Mellitus, and a history of Stroke (prior stroke or TIA). In the score the first 4 variables are counted as 1 point and a history of stroke or TIA 2 points. In patients with a CHADS II score of 0, the stroke risk is very low and daily aspirin is indicated. For a score of 1, either aspirin or Coumadin is appropriate. In patients with scores ≥ 2 daily coumadin is indicated for an international normalizing ratio (INR) between 2 and 3 (Table 28.7). For the boards, it is important not just to know the CHADS II scoring system, but the nuances as well:
TABLE
28.7 CHADS II Score Annual Risk of Stroke
RRR%, relative risk ratio (percent).
It is not applicable to patients with rheumatic heart disease and mitral stenosis (they should receive anticoagulation with Coumadin despite a low CHADS II score).
Patients with AF and thyrotoxicosis are thought to be at a high stroke risk; therefore, full anticoagulation with coumadin is indicated even with a low CHADS score. Of note, once the thyrotoxic state has been treated the CHADS II score is applicable.
Patients with hypertrophic cardiomyopathy are at higher risk of stroke with AF and require therapeutic Coumadin (INR 2.0 to 3.0) even in the absence of other risk factors.
Knowing how hypertension, CHF, and age are defined is important (e.g., a patient with treated hypertension counts).
If aspirin is deemed to be appropriate, a dose of 81 to 325 mg is acceptable per ACC guidelines.
Recommendations for Anticoagulation in Patients Undergoing Cardioversion
1. The risk of emboli after cardioversion is 0.6% to 5.6% without and 0.8% to 1% with anticoagulation.
2. Per the anticoagulation recommendations of the ACC/AHA/Heart Rhythm Society (HRS):
For AF >48 hours in duration, anticoagulate with warfarin (target INR 2.5, range 2.0 to 3.0) for 3 weeks before elective cardioversion.
Continue warfarin until SR has been maintained for 4 weeks (allows time for mechanical atrial transport to resume and for possible recurrence of AF).
A transesophageal echocardiography (TEE) protocol may be substituted for conventional therapy; however, intravenous heparin is required post cardioversion until the INR has risen to ≥2.0. Warfarin should be continued until SR has been maintained for at least 4 weeks.
3. Consideration should be given to managing anticoagulation for atrial flutter similar to that for AF.
4. Long-term anticoagulation beyond 4 weeks after cardioversion may be considered depending on patient risk factors for stroke.
5. Heparin anticoagulation followed by oral anticoagulation for 4 weeks is indicated for patients requiring emergency cardioversion for hemodynamic instability.
6. For AF of <48 hours duration, the risk of embolism after cardioversion appears to be low, but pericardioversion anticoagulation is recommended (from Albers et al., 2001).
7. In patients with AF who do not have a mechanical valve, it is reasonable to interrupt anticoagulation for up to 1 week without substituting heparin for surgical or diagnostic procedures that carry a risk of bleeding.
ROLE OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY
The ACUTE trial compared conventional anticoagulation versus a TEE-guided approach before cardioversion. It randomized 1,222 patients to conventional anticoagulation with therapeutic warfarin for 3 weeks prior to cardioversion or to a TEE-guided approach. There was no significant difference in thromboembolic complications occurring after cardioversion between the two arms.
Oral X A Inhibitors
On October 19, 2010, the U.S. Food and Drug administration approved the oral factor X A inhibitor, dabigatran, for use in nonvalvular AF. Dabigatran etexilate is a low-molecular prodrug that is converted to its active form, dabigatran, which is a competitive and reversible direct inhibitor of the active site of thrombin, the final effector in the coagulation cascade. The drug is 80% cleared by the kidneys and prolongs the activated partial thromboplastin (aPTT) with little effect on the prothrombin time and INR. One of the major advantages of dabigatran over Coumadin is that it does not require blood testing for monitoring. The RE-LY trial randomized 18,113 patients with nonvalvular AF and at least 1 additional risk factor for stroke to warfarin, dabigatran (150 mg twice daily), or dabigatran (110 mg twice daily). Compared to warfarin, dabigatran at a dose of 150 mg twice daily was more effective at preventing stroke or embolic events than warfarin with similar bleeding profiles. Of note, the rate of MI was higher in both dabigatran doses compared to warfarin, an effect that will need to be monitored in the future. Dose reduction is needed in patients with renal impairment. It is useful as an alternative to warfarin for the prevention of systemic thromboembolism in patients with risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance <15 mL/min), or advanced liver disease (impaired baseline clotting function).
NONPHARMACOLOGIC MANAGEMENT OF ATRIAL FIBRILLATION AND FLUTTER
Electrical cardioversion is the most effective method of conversion to SR and is the method of choice for hemodynamically
compromising AF. It is necessary, however, to evaluate the need for anticoagulation before cardioversion.
For elective direct-current cardioversion:
Fast for at least 6 to 8 hours.
Correct electrolyte imbalances.
Exclude toxic drug levels.
Generally, hold digoxin the morning of the procedure.
Electrode positioning should assure an appropriate vector for atrial defibrillation:
Anterior–posterior
R subclavicular/parasternal–L posterior patch position
Sedation could be achieved with a short-acting anesthetic (e.g., etomidate, methohexital, or propofol). Vital signs, ECG, respiratory status, and pulse oximetry must be closely monitored. In performing the procedure, synchronize to the QRS complex to minimize risk of inducing ventricular fibrillation. Atrial flutter may require less energy for successful cardioversion (e.g. 50 to 100 J monophasic) than atrial fibrillation (e.g. 200 J monophasic). If atrial pacing electrodes are present, atrial overdrive pacing may be attempted to terminate atrial flutter. Internal cardioversion may be used for AF that is refractory to standard external cardioversion. In this case, high-energy (200 to 360 J) transcatheter direct-current shocks are used. Lower energies (2 to 10 J) have been successful using catheters placed in the right atrium and coronary sinus.
Recently, biphasic external defibrillation has largely supplanted the use of monophasic defibrillation. Biphasic defibrillators deliver current in two directions. In the first phase, the current moves from one paddle to the other similar to that of monophasic defibrillation. During the second phase, the current reverses direction. While the underlying physiologic mechanism is not fully understood, it is clear that biphasic waveforms lower the electrical threshold for successful defibrillation. Typical starting energies for electrical cardioversion of AF using biphasic wave forms are between 100 and 200 J.
AV NODE ABLATION
Complete AV nodal (or His bundle) ablation with implantation of a permanent rate-responsive pacemaker was initially achieved with direct-current ablation. Now it is performed primarily using radiofrequency catheter ablation methods. The procedure is successful in up to 100% of patients, and most experience significant symptomatic improvement. Complete ablation is most appropriate and successful for patients whose symptoms are secondary to difficult-to-control rapid ventricular rates. AF patients who have undergone AV node junctional ablation and have a severely depressed ejection fraction should have a biventricular pacemaker implanted (PAVE study).
Advantages of complete AV node ablation include:
High rate of procedural success, nearing 100%
Only a low rate of recurrent rapid ventricular conduction (0% to 14%)
Improvement in symptoms and quality of life reported in 84% to 100% of patients
Ventricular dysfunction also shown to improve
Disadvantages of complete AV node ablation are
Dependence on a permanent pacemaker
Lack of effects on AV synchrony
No reduction in risk of thromboembolism
A possible small risk of late sudden death, primarily reported after direct-current ablation, has been reported, although the deaths may have been related to significant underlying structural heart disease. Increased cardiac output has been reported with regularization of ventricular rates, which would be achieved by complete AV junction ablation, but might not be attained after successful modification alone.
CATHETER ABLATION OF ATRIAL ARRHYTHMIAS
Radiofrequency catheter ablation may be used for the ablation of supraventricular tachycardias (SVTs) that may degenerate to AF. Ablation of atrial flutter consists of application of radiofrequency energy along a line from the tricuspid annulus to the IVC and/or from the coronary sinus os to the IVC and can effectively prevent the occurrence of typical, isthmus-dependent atrial flutter in approximately 90% of patients. It has been used successfully in patients with concomitant AF that can be controlled with antiarrhythmic medication but whose recurrences on medication may be in the form of atrial flutter, often occurring at a slow atrial rate that may facilitate 1:1 AV conduction. Atypical atrial flutter or tachycardias arising from the right or left atria have also been successfully ablated, particularly those associated with atrial scars or incisions.
ABLATION OF ATRIAL FIBRILLATION
Pulmonary Vein Isolation
The large majority of triggers for AF arise from pulmonary vein ostial regions. PVI seeks to electrically isolate the pulmonary veins via circumferential ablation around the respective antra therefore preventing triggers arising in the veins to initiate AF. This procedure typically involves one or more transseptal punctures in the interatrial septum through which a circular lasso catheter and an ablation catheter are placed. While the procedure varies significantly according to operator, many electrophysiologists use intracardiac echocardiography (ICE) to identify the pulmonary vein ostia. Additionally, electroanatomic mapping systems are often used to supplement the ICE images. The highest success rates tend to be in paroxysmal lone AF and may be substantially lower in AF associated with other cardiac disease, especially in patients with marked atrial scarring. Often, more than one PVI is needed to achieve long-term success since recovery of conduction out of the pulmonary veins is common.
While the incidence of complications from PVI at experienced centers is low, the risk of symptomatic pulmonary vein stenosis (PVS) is approximately 1% to 2%. The diagnosis of PVS requires a high level of suspicion as symptoms are often nonspecific. New onset shortness of breath, cough, or hemoptysis in a patient having undergone a PVI in the past should raise consideration of the diagnosis. A CT scan of the chest with contrast is useful for diagnosis. According to the 2011 AHA, ACC, HRS guidelines for AF, PVI is indicated in selected patients with significantly symptomatic, paroxysmal AF who have failed treatment with an antiarrhythmic drug and have normal or mildly dilated left atria, normal or mildly reduced LV function, and no severe pulmonary disease. In patients with heart failure and drug refractory AF, PVI was found to be superior to AV node ablation with biventricular pacing in terms of symptoms, exercise tolerance, and ejection fraction improvement.
Maze Procedure
The maze procedure is a surgical technique that divides the atria into “mazelike” corridors and blind alleys that limit the development of reentry by limiting available path length. Part of its success may be due to the PVI that is part of the operation. In some cases, atrial transport function may be preserved but reduced. A high degree of curative success (>80% to 90%) has been reported, but the procedure has had limited use and has been reserved primarily for patients with symptomatic refractory AF or performed in conjunction with mitral valve surgery. Surgical and minisurgical approaches to isolating the PV ostia are being developed that may accomplish the same results as catheter-based approaches.
Pacemaker Therapy
Permanent pacing may become necessary for sick sinus syndrome, tachy-brady syndromes, bradyarrhythmias occurring as a result of drug therapy, or after AV junction ablation. Mode-switching algorithms can change operation from dual-chamber pacing to single-chamber (VVI or VVIR) or DDIR pacing at the onset of atrial arrhythmias. Today’s pacemakers also provide atrial overdrive pacing algorithms.
Studies suggest that dual-chamber or atrial pacing that maintains AV synchrony may reduce the incidence of AF when compared to single-chamber ventricular pacing. These studies have consisted largely of patients with sick sinus syndrome who require permanent pacing. A prospective randomized trial of atrial versus ventricular pacing in 225 patients with sick sinus syndrome reported the frequency of AF and the thromboembolic event rate to be higher in the ventricular-paced group. However, another randomized study showed no difference in outcome.
Although most studies have been nonrandomized, comparisons of patients with physiologic dual-chamber, atrial synchronous (DDD, DDI, or AAI) pacing versus ventricular paced (VVI) modes suggest a decreased incidence in the development of AF in the physiologically paced groups. AF that occurs via vagally mediated mechanisms has also been successfully controlled by atrial overdrive pacing.
SUGGESTED READINGS
Current Practice Guidelines
Albers GW, Dalen JE, Laupacis A, et al. Antithrombotic therapy in atrial fibrillation. Chest. 2001;119(suppl):194S–206S.
Benjamin EJ, Wolf PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of death The Framingham Heart Study. Circulation. 1998;98:946–952.
Fuster V, Rydén LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol. 2011;15:101–198.
Kannel WB, Abbott RD, Savage DD, et al. Coronary heart disease and atrial fibrillation: the Framingham Study. Am Heart J. 1983;106:389–396.
Pharmacologic Management
Coplen SE, Antman EM, Berlin JA, et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: a meta-analysis of randomized control trials. Circulation. 1990;82:2248–2250.
Farshi R, Kistner D, Sarma JS, et al. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. J Am Coll Cardiol. 1999;33:304–310.
Jung F, DiMarco JP. Treatment strategies for atrial fibrillation. Am J Med. 1998;104:272–286.
Kassotis J. Costeas C, Blitzer M, Reiffel JA. Rhythm management in atrial fibrillation—with a primary emphasis on pharmacologic therapy: part 3. Pacing Clin Electrophysiol. 1998;21:1133–1145.
Masoudi FA, Goldschlager N. The medical management of atrial fibrillation. Cardiol Clin. 1997;15:689–719.
Olgin JE, Viskin S. Management of intermittent atrial fibrillation: drugs to maintain sinus rhythm. J Cardiovasc Electrophysiol. 1999;10:433–441.
Reiffel JA. Selecting an antiarrhythmic agent for atrial fibrillation should be a patient-specific, data-driven decision. Am J Cardiol. 1998;82:72N–81N.
Sigh D, Cingolani E, Diamond GA, et al. Dronedarone for atrial fibrillation. Have we expanded the antiarrythmic armamentarium? J Am Coll Cardiol. 2001;55:1560–1576.
Singh BN. Current antiarrhythmic drugs; an overview of mechanisms of action and potential clinical utility. J Cardiovasc Electrophysiol. 1999;10:283–301.
Torp-Pedersen C, Moller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med. 1999;341:857–865.
Van Gelder IC, Groenveld HF, Crijns HJGM, et al.; for the RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010; 362:1363–1373.
Wyse DG, Waldo AL, DiMarco JP, et al.; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825–1833.
Pathogenesis
Daoud EG, Knight BP, Weiss R, et al. Effect of verapamil and procainamide on atrial fibrillation-induced electrical remodeling in humans. Circulation. 1997;96:1542–1550.
Friedman HS, Rodney E, Sinha B, et al. Verapamil prolongs atrial fibrillation by evoking an intense sympathetic neurohumoral effect. J Investig Med. 1999;47:293–303.
Goette A, Honeycutt C, Langberg JJ. Electrical remodeling in atrial fibrillation. Time course and mechanisms. Circulation. 1996;94:2968–2974.
Lesh MD, Guerra P, Roithinger FX, et al. Novel catheter technology for ablative cure of atrial fibrillation. J Interv Card Electrophysiol. 2000;4(suppl 1):127–139.
Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart J 1964;67:200–220.
Tieleman RG, De Langen C, Van Gelder IC, et al. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation. 1997;95:1945–1953.
Tieleman RG, Van Gelder IC, Crijns HJ, et al. Early recurrences of atrial fibrillation after electrial cardioversion: a result of fibrillation-induced electrical remodeling of the atria? J Am Coll Cardiol. 1998;31:167–173.
Yu WC, Chen SA, Lee SH, et al. Tachycardia-induced change of atrial refractory period in humans: rate dependency and effects of antiarrhythmic drugs. Circulation. 1998;97:2331–2337.
Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92(7):1954–1968.
Stroke Incidence and Anticoagulation
Albers GW, Dalen JE, Laupacis A, et al. Antithrombotic therapy in atrial fibrillation. Chest. 2001;119(suppl):194S–206S.
Atrial Fibrillation Investigators. Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Arch Intern Med. 1998;158:1316–1320.
Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994;154:1449–1457.
Connolly SJ, Ezekowitz MD,Yusuf S, et al., and the RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361:1139–1151.
Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol. 1991;18:349–355.
EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in nonrheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet. 1993;342:1255–1262.
Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med. 1992;327:1406–1412.
Gullov AL, Koefoed BG, Petersen P, et al. Fixed minidose warfarin and aspirin alone and in combination vs. adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch Intern Med.1998;158:1513–1521.
Hankey GJ, Eikelboom JW. Dabigitan etexilate: A new oral thrombin inhibitor. Circulation; 2011; 123:1436–1450.
Laupacis A, Albers G, Dalen J, et al. Antithrombotic therapy in atrial fibrillation. Chest. 1998;114:579S–589S.
Petersen P, Boysen G, Godtfredsen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet. 1989;1:175–179.
Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet. 1994;343:687–691.
The Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk. Ann Intern Med. 1992;116:1–5.
The Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation: II. Echocardiography: features of at risk. Ann Intern Med. 1992;116:6–12.
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Takahashi N, Seki A, Imataka K, et al. Clinical features of paroxysmal atrial fibrillation: an observation of 94 patients. Jpn Heart J. 1981;22:143–149.
The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med. 1990;323:1505–1511.
The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. JAMA. 1998;279:1273–1277.
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Ablation for Atrial Flutter/Fibrillation
Chen SA, Tai CT, Tsai CF, et al. Radiofrequency catheter ablation of atrial fibrillation initiated by pulmonary vein ectopic beats. J Cardiovasc Electrophysiol. 2000;11:218–227.
Feld GK, Fleck RP, Chen PS, et al. Radiofrequency catheter ablation for the treatment of human type 1 atrial flutter. Identification of a critical zone in the reentrant circuit by endocardial mapping techniques. Circulation. 1992;86:1233–1240.
Haissaguerre M, Gencel L, Fischer B, et al. Successful catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 1994:5:1045–1052.
Haissaguerre M, Jais P, Shah DC, et al. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996;7:1132–1144.
Haissaguerre M, Jais 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.
Marrouche NF, Dresing T, Cole C, et al. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol. 2002;40(3):464–474.
Marrouche NF, Schweikert R, Saliba W, et al. Use of different catheter ablation technologies for treatment of typical atrial flutter: acute results and long-term follow-up. Pacing Clin Electro-physiol. 2003;26(3):743–746.
Khan MN, Jaïs P, Cummings J, et al.; PABA-CHF Investigators. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med. 2008;17:1778–85.
QUESTIONS AND ANSWERS
Questions
1. Which of the following antiarrhythmic medications are appropriate for use in patients with significant left ventricular (LV) hypertrophy due to hypertension?
a. Flecainide
b. Sotalol
c. Propafenone
d. Amiodarone
e. Quinidine
2. Which of the following is true of electrical cardioversion of atrial fibrillation (AF)?
a. 360 J is an appropriate starting energy level for biphasic defibrillation.
b. Biphasic defibrillation has been shown to lower the electrical threshold for successful defibrillation.
c. It is safe in patients with digoxin toxicity.
d. External defibrillation is not safe in patients with coexisting internal cardiac defibrillators; rather, defibrillation from the device is preferable.
e. Defibrillation should be unsynchronized.
3. A 77-year-old female has paroxysmal AF, treated hypertension on medications, COPD, and treated hyperthyroidism (she is currently euthyroid).
a. An appropriate anticoagulation strategy would be:
b. None
c. Aspirin 81 mg
d. Aspirin 325 mg
e. Coumadin for an INR of 2.5 to 3.5
f. Coumadin for an INR of 2.0 to 3.0
4. All of the following medications are appropriate therapies for patients with hemodynamically stable pre-excited AF except:
a. Amiodarone
b. Ibutilide
c. Procainamide
d. Disopyramide
e. Digoxin
5. A 50-year-old woman with a history of breast cancer, Menier disease, and poorly treated hyperthyroidism presents with paroxysmal AF with rapid ventricular rates. She has no history of valvular heart disease and her CHADS II score is 0. Appropriate pharmacologic therapies include:
a. Aspirin alone
b. Aspirin plus a beta blocker
c. Coumadin for an INR of 2.0 to 3.0 alone
d. Coumadin for an INR of 2.0 to 3.0 with a beta blocker
e. Coumadin for an INR of 2.5 to 3.5 with a beta blocker
Answers
1. Answer D: Per current ACC/AHA/HRS guidelines, amiodarone is the only acceptable pharmacologic option for the treatment of atrial fibrillation in patients with hypertension and significant left ventricular hypertrophy.
2. Answer B: Biphasic defibrillation has been shown to lower defibrillation thresholds in patients with a trial fibrillation. Cardioversion should be performed in a synchronized mode and is safe in patients with intracardiac devices. Cardioversion should not be performed in digoxin toxicity due to the risk of provoking ventricular arrhythmias.
3. Answer E: This patients CHADS II score is two by age and the presence of hypertension. The patient’s annual risk of stroke risk is approximately 4.0%. The patient should receive oral anticoagulation with the goal INR between 2 and 3.
4. Answer E: Digoxin should not be used in patients with pre-excited atrial fibrillation as it can cause slowing in the AV node which could lead to increased conduction down the accessory pathway leading to very fast ventricular rates and possible ventricular fibrillation.
5. Answer D: Despite the patient’s CHADS II score, the patient has untreated hyperthyroidism which increases the risk of stroke substantially. The patient should receive anticoagulation for an IRN between 2 and 3.