#90824: Clinical Management of Atrial Fibrillation

When an electrical impulse stimulates a cardiac cell, a series of events is initiated that causes the cell to depolarize and repolarize. This generates an action potential that allows the electrical impulse to propagate, ultimately resulting in the contraction of the cells of the myocardium. The basic events that occur during the formation of the action potential are as follows:

After the myocardial cell has depolarized, there is a period of time during which the cell cannot generate an action potential in response to another electrical impulse; this is referred to as the "absolute refractory period." As the cell continues to repolarize, an "effective refractory period" occurs in which the cell can transiently depolarize in response to an electrical impulse but generally will not develop enough of an action potential to propagate the impulse to surrounding cells. As repolarization nears completion, the cell is said to be in a "relative refractory period." In this period, a strong electrical stimulus can trigger the cell to depolarize and create another action potential [12,13,14].

When changes occur in the normal cardiac cycle, the normal ECG waveform is altered to reflect them. For example, prolonged repolarization is reflected in a prolonged QT interval. A slowing of conduction from the SA node through the AV node may be reflected in a prolonged PR interval. Abnormal conduction of the electrical impulse through the ventricles results in a QRS interval that is wider than usual or bizarre in shape. Careful analysis of the changes in a patient's ECG can provide valuable information in the diagnosis and treatment of the arrhythmia [6,15].

Antiarrhythmic medications interrupt or prevent arrhythmias by altering electrical conduction in the heart. Some antiarrhythmic medications have a single mechanism of action, but many have multiple mechanisms. In general, antiarrhythmic medications may act by:

Because antiarrhythmic medications impact specific events in cardiac conduction, they run the risk of creating new arrhythmias or worsening existing arrhythmias. Arrhythmias caused by the administration of an antiarrhythmic medication are referred to as proarrhythmias. Proarrhythmias can range from mild to severe. Serious proarrhythmias include ventricular tachycardia, torsades de pointes, and ventricular fibrillation. We will look at the actions and properties of specific antiarrhythmic agents in more detail in later sections.

Atrial fibrillation is an arrhythmia characterized by rapid, disorganized electrical activity in the atria. Instead of the SA node depolarizing to initiate a heartbeat, ectopic (or abnormal) areas in the atria depolarize rapidly and irregularly, resulting in chaotic atrial activity. Because of the chaotic electrical activity, normal atrial depolarization does not occur. Patchy areas of the atria may attempt to contract, giving the atria a "quivering" appearance, but the unified contraction of both the right and left atria (needed to complete active filling of the ventricles) cannot occur. One theory suggests that the mechanism underlying atrial fibrillation is the development of multiple impulses or "wavelets" in the atria. These impulses wander around and through the atria, getting caught in a cycle that continuously circulates in the atria, triggering small, erratic areas of depolarization. In atrial fibrillation, atrial impulses may be generated at a rate as high as 300 impulses per minute. Atrial impulses bombard the AV node. However, because of its inherent characteristics, the AV node tends to limit ventricular response to the atrial stimulation. Because the AV node is less excitable than the nearby atrial or ventricular cells, it conducts impulses more slowly, and its refractory period (when it cannot respond to another electrical stimulus) is relatively prolonged. Recently, there has been a re-assessment of the multiple wavelet hypothesis, demonstrating that the substrates of atrial fibrillation at the clinical level are focal trigger sites of action potentials rather than multiple micro re-entry sites [16].

Conduction in the AV node is also "decremental." This means that, as the impulse is conducted through the AV node, the action potentials that are generated have less and less ability to stimulate new action potentials. In atrial fibrillation, some atrial impulses are "blocked" or lost in the AV node because the action potentials that are generated are insufficient to stimulate further electrical activity.

Finally, the AV node has the property of concealed conduction. An atrial impulse may enter the AV node, stimulate depolarization of initial cells in the node, and be blocked from further conduction. Although the impulse is not sufficient to generate ventricular depolarization, it depolarizes enough cells in the AV node to create a refractory period. Subsequent impulses entering the AV node immediately following that impulse will be blocked. The AV node will be unable to accept or respond to them until repolarization has occurred. Due to the combination of slowed, decremental, and concealed conduction, the AV node can limit ventricular rate in atrial fibrillation to less than 200 beats per minute (bpm). It is important to note that these properties of the AV node create a relationship between atrial and ventricular rates in atrial fibrillation: when the atrial rate increases, the ventricular rate decreases. However, when the atrial rate slows, the ventricular rate may actually increase. At a slower rate, more atrial impulses are likely to stimulate the AV node at a time when the impulse can be conducted through the AV node to the ventricles [17,18,19].

Clinicians who work with patients who have atrial fibrillation are aware that the longer atrial fibrillation persists, the harder it becomes to terminate the arrhythmia and maintain normal sinus rhythm. Research suggests that atrial fibrillation triggers a process known as "atrial remodeling." In atrial remodeling, electrical, histologic, anatomic, and autonomic nervous system changes occur in the atria that facilitate the continuation of atrial fibrillation and impair the heart's ability to return to normal sinus rhythm [20,21,22]. Changes that have been hypothesized include:

Additional factors have emerged to complement the arrhythmogenic substrate that shed light on the perpetuation of arrhythmia. These include inflammation, fibrosis, altered gap junctions, and genetic predisposition, which are yet to be fully characterized across the different stages of atrial fibrillation [23,24,25,26,27].

The two key defining characteristics of atrial fibrillation are (Figure 2) [5,17,19]:

RHYTHM STRIP OF ATRIAL FIBRILLATION

Figure 2

Source: Created by Author

Additional characteristics associated with atrial fibrillation include:

The types of atrial fibrillation may be described in terms of onset or duration of rate. Descriptions based on rate include the following [17]:

Descriptions based on onset and duration have not been standardized throughout medical literature. Terms such as acute onset, chronic, and others have been used. In its published practice guidelines, the American College of Cardiology, the American Heart Association, and the European Society for Cardiology (ACC/AHA/ESC) Task Force recommends the following simplified terminology for episodes of atrial fibrillation that last more than 30 seconds and are not caused by another, reversible medical cause [28]:

Atrial fibrillation is one of several arrhythmias in which the electrical impulse is initiated at or above the AV node. These arrhythmias are usually referred to using the umbrella term, supraventricular tachycardias (SVT). Other common SVTs include atrial flutter and AV nodal re-entrant tachycardia.

In atrial flutter, the heartbeat originates in the atria somewhere outside the SA node. More organized than fib waves, atrial flutter (F) waves have a characteristic sawtooth appearance. Early studies designated atrial flutter with rates between 240 and 340 bpm as "type I flutter," and this term has commonly been applied to typical atrial flutter. An electrocardiographic appearance of atrial flutter with a rate faster than 340 bpm was designated as "type II flutter;" the mechanisms for type II flutter remain undefined [28]. The atrial rate is typically 240 to 300 bpm, but conduction delays in the atrial circuit due to scars from prior ablation, surgery, or antiarrhythmic drugs can slow the rate to less than 150 bpm in some patients [28]. One or more flutter waves may be present before each QRS interval. Conduction through the AV node is often regular (i.e., every second or third or fourth flutter wave is conducted). The most common pattern is 2:1 conduction, which results in a ventricular rate of 150 bpm. Flutter waves do not result in organized contraction of the atria, but they may increase atrial oxygen demands by triggering "near contractions." Atrial flutter is generally differentiated from atrial fibrillation by the presence of flutter waves that are more defined than fib waves and occur at regular intervals and regular ventricular rhythm [29]. The relationship between atrial fibrillation and atrial flutter may explain why 80% of patients who undergo radiofrequency catheter ablation of typical atrial flutter will have atrial fibrillation within the following five years [28].

In AV nodal re-entrant tachycardia, the ventricular rate falls between 150 and 250 bpm. Because of the abrupt onset and termination of the re-entrant SVT, the nonspecific term paroxysmal supraventricular tachycardia has been used to refer to these tachyarrhythmias. With improved knowledge of the electrophysiology of re-entrant SVT, greater specificity in nomenclature, based on the mechanisms of re-entry, has been possible [30]. With AV nodal re-entrant tachycardia, no evidence of atrial activity is present. The ventricular rhythm is regular. The arrhythmia has an abrupt onset and termination, with episodes lasting from seconds or minutes to days, and may occur in persons with no history of heart disease as well as in elderly persons with chronic heart disease. The arrhythmia may be differentiated from sinus tachycardia by rate; sinus tachycardia rarely exceeds a rate of 150 to 160 bpm in an adult at rest. It may also be differentiated from atrial fibrillation because the rhythm is regular. It may be differentiated from atrial flutter by rate; the usual rates associated with AV nodal re-entrant tachycardia are too slow for 1:1 (atrial to ventricular) conduction in atrial flutter and too fast for 2:1 conduction [17,30].

Differential diagnosis of atrial fibrillation is based on ECG analysis combined with patient history, description of symptoms, current medications, and past medical history [31]. At a controlled rate, atrial fibrillation is usually readily recognizable because of the absence of sinus P waves and the irregularly irregular rhythm. However, at higher rates, identification of these key characteristics may become more difficult. The physician may choose to facilitate diagnosis through the use of intravenous adenosine. Adenosine is a medication that may be administered intravenously to aid in the differential diagnosis of a narrow complex SVT [32]. Adenosine should not be administered in the presence of a wide QRS complex tachyarrhythmia, nor should it be administered if the arrhythmia's underlying mechanism has already been identified [31]. Adenosine has an immediate onset of action and an extremely short half-life (i.e., <10 seconds) [33]. Care should be taken to administer the medication rapidly enough to ensure that the medication reaches the systemic circulation before its half-life expires. Due to its extremely short half-life, adenosine is not effective for pharmacologic cardioversion; as soon as the effects wear off, the original arrhythmia resumes. Adenosine acts by interrupting re-entry pathways and slowing conduction through the AV node; it slows the ventricular rate to permit analysis and identification of the exact arrhythmia. Side effects include bradycardia, a brief period of asystole that does not exceed 15 seconds, and a sense of flushing and lightheadedness. It is a potent vasodilator and may cause hypotension. The side effects may be uncomfortable for the patient but are usually short and self-limiting [12,14,19,34]. In 2013, the U.S. Food and Drug Administration (FDA) issued a warning of a rare but serious risk of myocardial infarction and death with the use of adenosine [35]. Adenosine should be avoided in patients with unstable angina or cardiovascular instability. When administering adenosine, follow these tips [12,14,19,33,36]:

Atrial fibrillation causes a drop in cardiac output. Atrial contraction does not occur, thereby reducing ventricular filling during mechanical diastole. Loss of atrial contraction (or "atrial kick") may reduce cardiac output from 5% to 40%. Symptoms of decreased cardiac output may develop; how severe these symptoms are depends on multiple factors, including the person's age, overall health, and presence of structural heart disease. If atrial fibrillation occurs at a rapid ventricular rate, cardiac output is reduced further. Any tachycardia reduces ventricular filling time. When ventricular filling is already reduced due to the loss of atrial kick, further reduction in filling time from a rapid heart rate may greatly exacerbate signs of reduced cardiac output. Over time, atrial fibrillation with a rapid ventricular response may cause a tachycardia-induced cardiomyopathy. This cardiomyopathy may be reversible when the heart rate is controlled [17,19]. Loss of atrial contraction also causes stasis of blood in the atria. Stasis of blood increases the risk of thrombus formation and can lead to the development of thromboembolic complications such as CVAs [17,29].

The causes of atrial fibrillation may be grouped into three major categories [5,37]:

Historically, atrial fibrillation, as a primary arrhythmia, was thought to develop in isolation, with no known precipitating cause. Called "lone atrial fibrillation," this type of atrial fibrillation was defined as occurring in the presence of documented normal left ventricular function, typically in people 60 years of age or younger. It was characterized by a paroxysmal onset and termination and frequent recurrence. However, a Working Group of the American College of Cardiology suggests that the category of lone (idiopathic) atrial fibrillation is no longer mechanistically or clinically useful [2]. The Working Group posits several reasons for avoiding use of the term "lone atrial fibrillation," including [2]:

Instead, the term "paroxysmal atrial fibrillation" should be used.

As a secondary arrhythmia, atrial fibrillation may be caused by cardiac and noncardiac causes. Common cardiac causes include [37,38,39]:

The persons at highest risk to develop atrial fibrillation are those with long-standing hypertension, valvular heart disease, left ventricular hypertrophy, depressed left ventricular function, and coronary artery disease. Atrial fibrillation associated with cardiovascular disease may initially have a paroxysmal onset; however, the arrhythmia can continue to progress to persistent or chronic atrial fibrillation. Noncardiac, systemic diseases may also cause atrial fibrillation. Diabetes mellitus is a major risk factor for the development of atrial fibrillation. Other noncardiac causes include [2,37,38,39]:

Emerging risk factors for atrial fibrillation include [2]:

Atrial fibrillation caused by noncardiac causes is frequently reversible once the underlying condition is resolved. In some instances, the atrial fibrillation may spontaneously convert to normal sinus rhythm. In other cases, the arrhythmia responds well to pharmacologic or electrical cardioversion to restore normal sinus rhythm [37].

Patients in atrial fibrillation can present with symptoms that range from asymptomatic to severely incapacitating. Consider these patient examples:

As the simulated patient examples show, symptoms of atrial fibrillation may include one or more of the following [37,38,39]:

Because of the unpredictable pattern of paroxysmal atrial fibrillation, patients with this type of atrial fibrillation may feel frightened and out of control. They may choose to curtail their usual level of activity in an attempt to prevent the arrhythmia from occurring. Depression and a sense of helplessness may occur.

Atrial high-rate episodes may be detected by a cardiac implantable electronic device. These cases should result in further evaluation to establish the diagnosis and guide treatment decisions [40].

Physical assessment findings in atrial fibrillation may include the following [28,37]:

Assessment of the patient with atrial fibrillation should include laboratory and diagnostic tests to identify any factors that may be contributing to the development of the arrhythmia as well as to rule out any noncardiac causes of the arrhythmia. Appropriate laboratory and diagnostic tests may include the following [10,28,37,38,39]:

When a patient does not speak the same language as the clinician, a professional interpreter should be consulted to ensure accurate communication. A systematic review of the literature has shown that the use of professional interpreters provides better clinical care than the use of "ad hoc" interpreters, with the former improving the quality of care for patients with limited English language skills to a level equal to that for patients with no language barriers [41,42]. Use of professional interpreters has been associated with improvements in communication (errors and comprehension), utilization, clinical outcomes, and satisfaction with care [41,42]. Individuals with limited English language skills have indicated a preference for professional interpreters rather than family members [43].

Adequate patient assessment should focus on the patient's symptoms, past medical history, any concurrent illnesses, and psychosocial issues. When assessing the patient, consider the following [46]:

Based on a thorough evaluation of the patient's status and other factors, one or more medical goals should be identified. The initial goal for a patient who is hemodynamically unstable is the immediate restoration of normal sinus rhythm through electrical cardioversion. The initial goal for patients who present with atrial fibrillation with a rapid ventricular response is rate control. Once the patient's status has stabilized, long-term goals may be developed. When developing long-term goals, consider the following points [17,28,40,45,46,47,48,49]:

To assist the clinician in selecting and prioritizing appropriate medical goals, the ACC/AHA/ESC Task Force established recommendations for the management of various types of atrial fibrillation. These recommendations are summarized in Table 1.

Antiarrhythmic medications are the mainstay of treatment for atrial fibrillation. They may be used for acute and chronic rate control. They also may be used for pharmacologic cardioversion of atrial fibrillation to normal sinus rhythm and maintenance of normal sinus rhythm following successful conversion; however, their use for achieving rhythm control has decreased due to evidence of greater safety and lower costs for hospitalization obtained from the use of rate-control strategies [28,50]. The AHA/ACC/HRS recommends treating the precipitating or reversible causes of atrial fibrillation prior to initiating antiarrhythmic drug therapy [28]. Whatever the goal of treatment, selection of specific antiarrhythmic medications should be guided by the following [28,50]:

With the increasing emphasis on reduction of healthcare costs, there has been an increase in the use of generic (as opposed to proprietary) medications. Almost every state has passed regulations encouraging the substitution of less expensive drug products for more expensive proprietary products. State regulations may approve substitutions only for medications on an approved list, or the regulations may permit the substitution of any medication, except those specifically listed on a list of exclusions. On the national level, the FDA provides a specific list of approved drugs. This list is updated on a monthly basis [51].

When a pharmaceutical company develops a new drug, the company may apply for one or more patents for (1) the drug itself; (2) the manufacturing process; (3) how the drug is delivered to the bloodstream; or (4) how the medication is to be used. Although the patent gives the company exclusive rights to the new drug for 17 years, this period often involves at least 10 years of development. In reality, the company may have only seven years to exclusively sell the drug. A newly developed drug is given several names. The generic name, which is the medication's official name (derived from the drug's chemical name, structure, and/or formula), must be unique. Generic names are frequently difficult to pronounce, remember, and spell. The new drug is also given a trade name or proprietary name that signifies that the drug is the exclusive property of its company. Trade names are simpler, easier to remember, and often emphasize an attribute of the medication. Trade names must also be unique. After the patent on a specific drug has expired, other companies may manufacture and sell that drug under its generic name. Generics are frequently sold at a lower price than trade/proprietary drugs. Generic versions of a drug must meet FDA approval, specifically the following three points [51,52]:

Proprietary and generic versions of a medication may vary in several respects [33,52]:

Practically speaking, the use of a generic substitution means that the patient could experience different effectiveness with different preparations. Random switching from proprietary to generic or from one generic to another could increase side effects, decrease rate control, and cause more frequent relapse from normal sinus rhythm to atrial fibrillation. For that reason, any generic substitution of antiarrhythmic medications should be done very carefully. With many antiarrhythmic medications, very small variations in the serum blood level may influence the effectiveness of the medication in controlling the arrhythmia and significantly increase the risk of proarrhythmias and serious side effects. Physician groups have made the following recommendations regarding the use of generic antiarrhythmic medications [46]:

A classification system for antiarrhythmic drugs was developed in the early 1970s. An antiarrhythmic medication was classified according to its specific effect on the normal cardiac cycle. When the classification system was developed, it was believed that each antiarrhythmic medication had only one action. Electrophysiologic research has shown that the mechanisms involved in the generation and spread of an electrical impulse throughout the heart are complex, and that antiarrhythmic medications may impact more than one of these mechanisms. Although the classification system does not reflect the advances in the understanding of electrophysiology, it is still in common use today. Table 2 summarizes the classification system [53,54].

When selecting and initiating (or changing) antiarrhythmic therapy, the site of care should be considered. Sites of care may include the patient's home, a physician's office, an outpatient clinic, or an inpatient setting. Some antiarrhythmics, such as dofetilide, can only be initiated in an inpatient setting. For others, inpatient initiation is strongly recommended if risk of proarrhythmia is high. Proarrhythmic risk is increased in persons with structural heart disease, congestive heart failure, and those who already have a prolonged QT interval. Persons who have no structural heart disease and whose QT interval is normal are considered to be at low risk for development of proarrhythmias. In these cases, antiarrhythmic therapy may be initiated in outpatient settings. If antiarrhythmic therapy is initiated outside the hospital setting, transtelephone monitoring may be used to intermittently assess the patient's heart rate and rhythm for any undesired changes [55].

When selecting antiarrhythmic agents, potential drug interactions should be considered. Serious interactions may occur between two antiarrhythmic medications, between an antiarrhythmic and other cardiovascular medications, and between antiarrhythmics and noncardiac medications. Interactions that may occur include the following [12,14,19,33,52]:

Table 3 lists some common drug to drug interactions.

When a person presents with uncontrolled atrial fibrillation, his/her ventricular rate may reach 160 bpm. The immediate goal of medical therapy is to control the heart rate to decrease acute symptoms, relieve hypotension, reduce signs of ischemia, and reduce or prevent signs of congestive heart failure from developing. No single agent has been found to be more effective than others in controlling rapid rates. For acute rate control, the administration route of choice is intravenous. Antiarrhythmic drugs commonly prescribed for acute rate control include diltiazem, verapamil, esmolol, metoprolol, and digoxin [49].

If the long-term goal of clinical management is rate control, there are a number of oral preparations to choose from. Clinical decision making includes selecting the category, specific agent, effective dose, and preparation (e.g., short-acting, extended-release). As with acute rate control, no consensus exists on the best medication(s) for every patient. Specific antiarrhythmic agents should be selected on the basis of patient assessment. Again, factors to consider include the cost and complexity of the prescribed regimen, the risk of proarrhythmic effects, concurrent cardiovascular disease, and the risk of other troublesome or serious side effects. When choosing long-term therapy, the patient's lifestyle should be considered as well. Some medications provide effective rate control when the patient is at rest but do not provide adequate rate control during activity or exercise. A heart rate is considered "controlled" if it falls between 60 to 80 bpm at rest and 90 to 115 bpm with moderate exercise [20]. Adequate rate control may be achieved by a single antiarrhythmic drug, or it may require a combination of drugs. Antiarrhythmic drugs commonly used for long-term rate control include calcium channel blockers, beta blockers, and digoxin [49].

See Table 5 for a summary of antiarrhythmic medications that may be used for long-term rate control in atrial fibrillation.

Ibutilide is a drug approved by the FDA for the acute termination of atrial fibrillation and atrial flutter. A Class III antiarrhythmic, ibutilide acts by prolonging the duration of the action potential, the atrial refractory period, and the ventricular refractory period. It also slightly slows the sinus rate and conduction through the AV node. Ibutilide's exact mechanism of action is unknown [33]. On a cellular level, it has been reported to exert its effects by both blocking repolarizing potassium currents and initiating an inward depolarizing sodium current [56]. Ibutilide does not appear to have a direct impact on cardiac output, but monitoring for conduction disturbances and heart block is recommended [33].

Proarrhythmic Effects

Because ibutilide prolongs the ventricular refractory period (reflected by a prolonged QT interval), the risk of torsades de pointes is significant. Torsades de pointes is a rapid, polymorphic form of ventricular tachycardia. See Figure 3 for more information about torsades de pointes. With ibutilide administration, the risk of torsades de pointes is dependent on the dose of ibutilide administered; the higher the dose, the greater the risk.

TORSADES DE POINTES

Figure 3

Source: [13,28,33,37,71,72]

Dofetilide is a Class III antiarrhythmic approved for use in patients with atrial fibrillation and atrial flutter. Major clinical trials on dofetilide, including the European and Australian Multicenter Evaluation Research on Atrial Fibrillation Dofetilide (EMERALD) and Symptomatic Atrial Fibrillation Investigation and Randomized Evaluation of Dofetilide (SAFIRE) studies, have shown that dofetilide is effective in conversion of atrial fibrillation or atrial flutter to sinus rhythm, although it appears to be more effective in conversion of atrial flutter than atrial fibrillation [69]. On the cellular level, dofetilide blocks a specific potassium current, thus prolonging the duration of the cardiac action potential and effective refractory period. Prolonging the action potential and effective refractory period increases the likelihood that the entry atrial impulses will encounter a refractory period when the cardiac cells are unable to accept another electrical impulse, and the arrhythmia will break. Because dofetilide does not slow conduction velocity, the PR and QRS intervals remain normal. It also does not cause hypotension or bradycardia. The major proarrhythmia associated with dofetilide administration is torsades de pointes due to prolongation of the QT interval. The degree of risk is related to the dosage and serum concentration of dofetilide. The higher the dose (or the higher serum concentration), the higher the risk that proarrhythmias will develop. Other proarrhythmias seen with dofetilide administration include premature ventricular contractions, broad complex ventricular tachycardia, nonsustained ventricular tachycardia, and PSVT. Following oral administration, dofetilide is almost completely absorbed; it is primarily excreted by the kidneys [33].

The administration of dofetilide is very heavily regulated by the FDA. Only approved centers and physicians who have completed required educational programming on the initiation of dofetilide may prescribe dofetilide. Physicians and centers initiating dofetilide therapy are also required to provide the patient with specific educational information [33]. This includes information on the action of the medication, its side effects, and how to obtain and take the medication. An educational kit containing a videotape, written information, and prescribing information for the patient to give to other physicians is provided to the patient. Because of the restrictions on dofetilide, only selected pharmacies may dispense the medication. The patient may be unable to obtain dofetilide from his/her usual outpatient pharmacy. At the time of discharge, the patient will be provided with a small amount of dofetilide at the prescribed dose. He/she will then receive a larger quantity of dofetilide in the mail from an approved pharmacy [74]. Dofetilide must be initiated in the hospital setting where continuous ECG monitoring and emergency resuscitation equipment is available [28,74]. Prior to administration, the patient's baseline QTc and creatinine clearance must be assessed. If the patient's baseline QTc exceeds 440 msec (or 500 msec if ventricular conduction abnormalities), dofetilide is contraindicated. The initial dose is determined by the patient's initial creatinine clearance [33]. A detailed algorithm is provided in the dispensing information to assist the physician and pharmacologist in determining the appropriate dosage. If the patient's renal function is severely impaired, dofetilide is again contraindicated.

Amiodarone has received increasing attention for its ability to convert atrial fibrillation to normal sinus rhythm and to prevent atrial fibrillation in patients undergoing CABG surgery [54,57,75]. Categorized as a Class III antiarrhythmic, amiodarone has properties of all four classes. It inhibits conduction through the AV node, prolongs the action potential and refractory period, and inhibits adrenergic stimulation. It may be safely used for patients with congestive heart failure, coronary artery disease, and persons with accessory pathway conduction. The proarrhythmic effects associated with amiodarone include bradycardia, heart block, ventricular fibrillation, and ventricular tachycardias including torsades de pointes. Hypotension may occur with IV administration. Amiodarone is associated with multiple severe side effects and toxic effects. These include pulmonary fibrosis, impaired vision from corneal deposits, photosensitive skin, thyroid dysfunction, and liver dysfunction [33,76]. Prior to beginning amiodarone therapy, the physician should obtain baseline data. Appropriate data includes a chest x-ray, pulmonary function tests, thyroid function tests, liver function tests, and renal studies. Patients receiving amiodarone therapy should be monitored for development of toxic effects. Serious toxicity, including death due to bradycardia ending in cardiac arrest, has been reported [33]. If symptoms develop, amiodarone should be discontinued. Use of the lowest effective maintenance dose is highly recommended due to the multitude and severity of side effects associated with amiodarone therapy. The FDA has issued a warning regarding concurrent use of amiodarone and simvastatin [77]. In patients who are taking both simvastatin and amiodarone, the dose of simvastatin should not exceed 20 mg/day [33,73].

The usual initial dose of amiodarone is 150 mg over 10 minutes, then 1 mg/minute for six hours, then 0.5 mg/minute for 18 hours or 600–800 mg/day oral in divided doses up to 10 g/day [33]. When a cumulative dose of 10 g is reached, a maintenance dosage of 200–400 mg/day is begun. For elderly patients, dosing should be initiated at the lower end of the adult dosage range, and the maintenance dose is usually 100 mg/day. Elderly persons clear amiodarone more slowly [33,54,57].

Propafenone, a Class Ic antiarrhythmic, slows conduction by changing normal ion transportation across cardiac cell membranes. Studies show it may also have Class II antiarrhythmic effects [78]. It may be used for the conversion of paroxysmal atrial fibrillation to sinus rhythm. For an adult weighing 70 kg or more, an initial dose of 600 mg orally is given, followed by a maintenance oral dose of 150–300 mg every eight hours [33]. Propafenone has less risk of torsades de pointes than other antiarrhythmic agents because it does not prolong the QT interval; however, it is still associated with the development of bradycardia, heart block, and signs of congestive heart failure. For this reason, it should not be prescribed for patients immediately following acute myocardial infarction. Other common side effects include nausea, anorexia, constipation, and headache [33]. One case of a severe drug-drug interaction with mirtazapine leading to propafenone toxicity has been reported [79].

Procainamide, a Class Ia antiarrhythmic, has been used for management of atrial arrhythmias for many years, although it may be less useful than some other agents [28]. It increases both atrial and ventricular refractory periods. It can convert atrial fibrillation to normal sinus rhythm and maintain normal sinus rhythm following conversion. Depending on a patient's status, a loading dose may be administered intravenously or orally. Extended-release forms of oral therapy should not be used for initiation of therapy. Procainamide can have proarrhythmic effects including bradycardia, a prolonged QT interval, and heart block. Worsening or refractory tachyarrhythmias can develop in the presence of procainamide toxicity. Serum levels should be carefully monitored. The therapeutic serum level of procainamide is 4–10 mcg/mL. Toxicity may develop at serum levels of more than 10 mcg/mL. For some patients, especially those with impaired renal function, the combined procainamide/N-acetylprocainamide (NAPA) level should be monitored. NAPA is an active metabolite of procainamide that has antiarrhythmic properties. The combined procainamide/NAPA serum level should not exceed 30 mcg/mL [33].

Quinidine, another Class Ia antiarrhythmic, prolongs the effective refractory period and increases conduction time. It is effective in converting atrial fibrillation to normal sinus rhythm and in maintaining sinus rhythm following conversion. Because quinidine also decreases vagal tone, thereby facilitating conduction across the AV node, it does not slow ventricular rate. It is indicated for use in patients with controlled atrial fibrillation, usually after digoxin or verapamil has been given. Patients who are in uncontrolled atrial fibrillation should receive other antiarrhythmic agents prior to starting quinidine. Although quinidine comes in an IV form, IV administration is associated with a significant risk of severe hypotension, and use of IV quinidine is discouraged [33].

Flecainide is a Class Ic antiarrhythmic that acts by blocking sodium channels so that conduction through cardiac cells is slowed. Flecainide is only administered orally. Flecainide should not be prescribed for patients in the immediate post-myocardial infarction period. It should be used cautiously in patients with congestive heart failure, conduction defects, and impaired renal function [33]. It is a drug of choice for persons with paroxysmal atrial fibrillation [5,12,13,14,19,20,37,46,68].

Electrical cardioversion has been found to be an effective and safe method for restoring normal sinus rhythm in a number of patients. It is the treatment of choice for persons with hemodynamically unstable atrial fibrillation [28]. Electrical cardioversion is also indicated for [28,40]:

Persons who have severe dyspnea or chest pain with atrial fibrillation or who have pre-excited atrial fibrillation should undergo urgent cardioversion [37].

It is not indicated for prevention of subsequent episodes [80]. Cardioversion of atrial fibrillation and subsequent maintenance of sinus rhythm are more likely to be successful when the duration of atrial fibrillation is less than six months [28]. Because electrical cardioversion carries the risk of thromboembolic complications, it generally should be performed when the patient is adequately anticoagulated. Results of observational studies suggest that thromboembolic risk after cardioversion is highest in the first 72 hours and that the majority of events occur within 10 days [28]. Cardioversion may be performed without first anticoagulating the patient only when he/she is hemodynamically unstable and requires immediate intervention, when the patient has been in atrial fibrillation less than 48 hours, or when the absence of an atrial thrombus has been confirmed by TEE [5,20,28,47,80,81].

For patients with atrial fibrillation of greater than 48 hours or unknown duration undergoing elective electrical or pharmacologic cardioversion, the American College of Chest Physicians recommends therapeutic anticoagulation for at least four weeks after successful cardioversion to sinus rhythm rather than no anticoagulation, regardless of the baseline risk of stroke.

(https://journal.chestnet.org/article/S0012-3692(18)32244-X/fulltext Last Accessed: October 10, 2023)

Strength of Recommendation/Level of Evidence: Strong recommendation, moderate-quality evidence

Appropriate anticoagulation management around the time of cardioversion is essential for reducing thromboembolic risk. Results of observational studies suggest that thromboembolic risk after cardioversion is highest in the first 72 hours and that the majority of events occur within 10 days [82]. As indicated, anticoagulation before cardioversion is required for most patients. Warfarin should be initiated, and the dose adjusted to reach and maintain a target goal of an international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0). After the patient has been maintained for three weeks at that therapeutic goal, cardioversion may be performed. Following cardioversion, anticoagulation should be maintained for four weeks [28,40].

TEE guidance is an alternative to three weeks of anticoagulation before cardioversion. Therapeutic anticoagulation is achieved and followed by TEE. If no thrombus is seen, cardioversion is performed and anticoagulation is continued for four or more weeks. The absence of left arterial thrombus on TEE does not preclude the need for anticoagulation during and after cardioversion [28,37]. Alternative strategies for achieving rapid anticoagulation include administration of low-molecular-weight heparin or a new oral anticoagulant. If a thrombus is identified on TEE, cardioversion should be postponed, followed by three to four weeks of anticoagulation. Repeat TEE to ensure thrombus resolution is an option before attempting another cardioversion. If a thrombus remains on repeat TEE, an alternative strategy (e.g., rate control plus appropriate anticoagulation) may be considered [28]. TEE is a good predictor of acute risk. If no thrombus is seen in the cardiac chambers, particularly the left atrial appendage, and dense spontaneous echo contrast is not seen, cardioversion has low acute risk of stroke. Effective anticoagulation in patients with atrial fibrillation reduces the risk of stroke three-fold after four to six weeks [37]. Data on cardioversion risks for atrial flutter are limited. However, because atrial flutter can be associated with thrombi and episodes of atrial fibrillation, it is recommended that the anticoagulation management strategy for cardioversion of atrial flutter be the same as that for atrial fibrillation [28].

Prior to the procedure, the patient should be carefully assessed. Serum electrolytes and serum drug levels of medications such as digoxin should be checked. Electrolyte imbalances should be corrected. The administration of IV electrolytes has been found to increase the success rate of cardioversion in patients with persistent atrial fibrillation [83]. Testing for elevated C-reactive protein levels may predict the recurrence of atrial fibrillation following cardioversion [84,85,86,87]. Cardioversion should not be performed if the patient has digitalis toxicity. A baseline 12-lead ECG should be obtained. Oral antiarrhythmic medications, such as oral amiodarone or sotalol, may be started prior to the cardioversion. In some patients, this will facilitate conversion to normal sinus rhythm and maintenance of sinus rhythm following the procedure. The patient should be adequately sedated with a short-acting agent (e.g., midazolam, propofol), and an opioid analgesic, such as fentanyl, is commonly used. Reversal agents (e.g., flumazenil, naloxone) should be available [81]. The risks of the procedure should be explained to the patient and family. Common risks include the problems associated with moderate sedation, skin burns, and the development of proarrhythmias [37,81]. The procedure should be explained briefly to patients. Consider including these points:

Potentially life-threatening postprocedure events may occur, including the induction of ventricular tachycardia/fibrillation, asystole, and transient depression of myocardial function. Techniques to handle these situations should be readily available to prevent complications [80,81].

A variety of commercially available external cardioverters are available for external electrical cardioversion. The physician in charge of the procedure should be thoroughly familiar with the chosen device [66,80]. ECG leads are placed on the patient. The cardioverter delivers a programmed shock in synchronization with the patient's own QRS. Synchronization decreases the risk that the patient will go into ventricular fibrillation from the electrical shock. The initial shock may be a low voltage. If unsuccessful, the voltage will be increased. Following completion of the procedure, the patient will be monitored until he/she is recovered from the anesthesia/sedation. As noted, follow-up care includes oral antiarrhythmic therapy and oral anticoagulation with warfarin sodium [80]. In patients for whom external cardioversion is unsuccessful, an internal shock with electrode catheters has been shown to be successful [80,88,89].

For patients in atrial fibrillation, restoration of normal sinus rhythm may occur spontaneously or through electrical or pharmacologic cardioversion. Regardless of the mechanism of conversion, antiarrhythmic therapy is usually indicated to maintain sinus rhythm (Table 8). Some reversion to atrial fibrillation is likely to occur despite optimal antiarrhythmic therapy. However, some patients may benefit from therapy that restores sinus rhythm for prolonged periods [28]. The effectiveness of antiarrhythmic therapy in maintaining normal sinus rhythm should be based on an evaluation of the severity and duration of episodes and not on their occurrence. The following are general principles for initiating drug therapy for maintenance of normal sinus rhythm [28,54,83]:

Oral antiarrhythmic medications found to be effective in maintaining normal sinus rhythm include quinidine, disopyramide, flecainide, propafenone, sotalol, amiodarone, dofetilide, and dronedarone. However, pharmacologic therapy should be abandoned if symptomatic improvement is not achieved or if the patient experiences any adverse effects [49,90,91]. In addition to possible adverse effects, some antiarrhythmic medications (i.e., disopyramide, quinidine, and sotalol) may increase mortality. Possible benefits on clinically relevant outcomes (e.g., stroke, embolism, heart failure) remain to be established [75].

The ACC/AHA/ESC Task Force for management of patients with atrial fibrillation has suggested that outpatient maintenance of sinus rhythm, the "pill-in-the-pocket" approach, shows promise. This approach allows for intermittent (rather than daily) administration of oral antiarrhythmic medication as an acceptable treatment option for patients with sporadic episodes of atrial fibrillation. It is not recommended for patients with daily episodes [28]. Self-administration of oral antiarrhythmic drugs improves the patient's quality of life, decreases overall hospital admissions, and reduces treatment costs. Class Ic drugs, such as propafenone and flecainide, are recommended for their efficacy, rapid action, and safety (i.e., no organ toxicity and low incidence of proarrhythmia). They are not recommended for patients with underlying structural heart disease [6,28,91].

Warfarin is recommended for patients at high risk to develop thromboembolic events. It acts by inhibiting the synthesis of clotting factors II, VII, IX, and X that are dependent on vitamin K. Once warfarin therapy is initiated, it can take four to five days to achieve a therapeutic level. Effectiveness of warfarin therapy is evaluated by monitoring the patient's prothrombin time (PT) with the INR. The usual target level for the INR is 2.0–3.0 (target of 2.5) [20,49]. Some clinicians recommend using the lower end of that range for elderly patients. The risk of serious bleeding complications is greater in persons older than 75 years of age. Initially the PT/INR should be monitored at least weekly. Once the therapeutic goal is achieved, the monitoring may be reduced to monthly [40]. Drug-drug and food-drug interactions may play a significant role in maintaining a stable INR level for persons taking warfarin. Drugs that may impact warfarin effectiveness and INR levels include many anti-infectives and amiodarone. Food interactions include vitamin K containing foods that can antagonize the action of warfarin. Herbal products and nutritional supplements may contain components that can increase or decrease the effectiveness of warfarin [12,14,124,125].

For patients to take warfarin safely and correctly, they should receive appropriate patient education when the medication is initiated. See Table 12 for a summary of content to include.

In some cases, warfarin may be considered unsuitable due to patient preference or the physician's assessment of the patient's ability to safely sustain anticoagulation. In these patients, the addition of clopidogrel to aspirin to reduce the risk of major vascular events, including stroke, might be considered in patients with atrial fibrillation [49]. Aspirin as monotherapy for stroke prevention is not recommended [28,40].

Several DOAC alternatives to warfarin have emerged, including the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. The DOACs represent an advance in therapeutic safety and reduced intracranial bleeding as compared with warfarin, including no need for regular monitoring, faster onset of action, and potentially fewer adverse interactions [40,127]. As an alternative to warfarin, the 2019 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation recommends oral anticoagulation with one of these newer agents over warfarin for patients with nonvalvular atrial fibrillation or atrial flutter with prior stroke, transient ischemic attack, or significant stroke risk [40].

The AHA/ACC/HRS recommend catheter ablation may be reasonable in selected patients with symptomatic atrial fibrillation and heart failure with reduced left ventricular ejection fraction to potentially lower the mortality rate and reduce hospitalization.

(https://www.ahajournals.org/doi/10.1161/CIR.0000000000000665 Last Accessed: October 10, 2023)

Strength of Recommendation/Level of Evidence: IIbB-R (A weak recommendation based on moderate-quality evidence)

Radiofrequency ablation of the AV node is an interventional therapy commonly used in the management of atrial fibrillation. The relative safety of radiofrequency energy has contributed to the widespread adoption of this technique as a therapeutic modality for atrial fibrillation [136,137]. Radiofrequency ablation has been found to be effective for persons who have significant symptoms with atrial fibrillation and/or poorly controlled ventricular rate who also [19,40,49,58,138,139]:

It is indicated for atrial fibrillation with lifestyle-impairing symptoms and inefficacy or intolerance of at least one antiarrhythmic agent [28,140]. Radiofrequency ablation is performed in the electrophysiology lab. See Table 13 for additional details about electrophysiology procedures. To ablate the AV node, radiofrequency waves are sent through catheters positioned at the AV node. Radiofrequency energy is electrical energy produced by a high frequency alternating current. As this current passes through cardiac tissue, it produces heat and creates a lesion in the AV node. The atria remain in atrial fibrillation, but no atrial impulses are conducted through the AV node to the ventricles. With AV node ablation, the patient's only effective ventricular rhythm is a junctional or ventricular escape rhythm. Because this rhythm is insufficient to meet the body's needs for cardiac output, a permanent pacemaker is inserted [19,137].

Radiofrequency ablation of the AV junction is the simplest procedure performed in patients with atrial fibrillation. AV nodal modification is less effective and is not frequently performed, except in an attempt to avoid pacemaker implantation. Both approaches are used to achieve good rate control, but unlike ablation techniques in atrial tissue, neither restores normal sinus rhythm. Few absolute contraindications to radiofrequency ablation exist. Left atrial ablation and ablation for persistent atrial flutter should not be performed in the presence of known atrial thrombus [137].

Catheter-based cryoablation was developed after radiofrequency ablation. Cryoablation utilizes tissue cooling to cause tissue necrosis. Low-intensity cooling (-10° C) allows assessment of lesion efficacy and safety, prior to delivering the deeper cooling (-70° C) that causes irreversible tissue necrosis. Cryoablation is not as versatile nor as widely used as radiofrequency ablation, but it is safer for ablation near the AV node [137].

No consensus exists on the optimal ablation technique, nor is there a consensus on what constitutes a clinically successful procedure. Data reveal that it is difficult to eliminate every episode of atrial fibrillation with catheter ablation. However, catheter ablation renders 90% of patients free from symptomatic atrial fibrillation and reduces its burden by more than 99% at one year of follow-up [141]. Single-procedure ablation is successful in 60% to 80% of optimal candidates, but many patients require repeat ablation [141]. The results of a study that compared radiofrequency ablation and two regimens of cryoballoon ablation resulted in no difference in one-year efficacy (53% by time to first recurrence) but greater than 98% burden reduction, as assessed by continuous cardiac rhythm monitoring [142]. A meaningful discussion about ablation success rates must include a definition of success that includes how intensively patient rhythms are monitored [141]. Despite the lack of consensus, ablation for atrial fibrillation is generally more effective than antiarrhythmic drug therapy, especially for those patients in whom pharmacotherapy has failed [139,143].

Prior to radiofrequency ablation of the AV node, the patient should receive information about radiofrequency ablation and permanent pacemaker insertion. Informed consent is obtained. Preprocedure evaluation should include a thorough history, physical examination, and a review ECG (12-lead if available). Laboratory studies should minimally include a complete blood cell count and an assessment of the patient's renal function and electrolyte levels. Other tests that may be indicated include exercise testing with or without cardiac imaging and cardiac catheterization [137]. The patient should be kept NPO for at least six hours prior to the procedure. Cardiac medications with electrophysiologic effects (e.g., beta-blockers, calcium channel blockers, digoxin) and Class I and III antiarrhythmic drugs should be tapered and/or discontinued. Warfarin is usually discontinued for at least a few doses preprocedure [137]. IV access should be established.

In the electrophysiology lab, the patient will be sedated, and continuous monitoring of blood pressure, heart rate and rhythm, and oxygen saturation initiated. Following the procedure, the patient's vital signs and oxygen saturation levels will be monitored closely. The patient's ECG will be monitored to evaluate proper pacemaker functioning. The sites used for insertion of the ablating catheters (usually the right and left femoral veins) will be monitored for signs of bleeding or hematoma formation. Depending on the size of catheters used, the patient may be on bed rest for four to six hours. During this time, the patient will need to keep his/her legs straight to decrease the risk of the bleeding from the catheter insertion sites. The pacemaker insertion pocket (often in the subclavian area) is monitored for signs of bleeding or excessive swelling. The head of the patient's bed is often elevated 30 degrees for 24 hours to maintain stable placement of the pacemaker leads.

Patients who have received pacemakers frequently have many questions and concerns. Careful discharge teaching and provision of written information can help to alleviate anxiety. General measures to cover in discharge teaching include [53,137]:

Patients and their family members often have many questions about operating home, office, or industrial equipment. Pacemaker manufacturers provide detailed information in written booklets that should be given to the patient at the time the pacemaker is implanted.

Because the ectopic beats of atrial fibrillation can occur in various portions of the atrium, electrophysiology studies have been performed on many patients to determine the site or sites of the abnormal foci. The most common area of abnormal activity has been found to be in the vicinity of the pulmonary veins in the left atrium. This discovery led to the use of radiofrequency ablation of the pulmonary vein region as a cure for atrial fibrillation. It has even been suggested that the procedure could be used as a first-line approach to cure atrial fibrillation, because there is no need for long-term antiarrhythmic drug use. However, there is not yet a consensus on this approach as curative [137,144,145,146].

Pulmonary vein isolation is achieved in the electrophysiology lab, and a dose of radiofrequency energy is delivered to ablate the desired region. New energy sources such as laser, ultrasound, and cryothermia have also been used [147,148]. Multidimensional computed tomography (CT) and magnetic resonance angiography help visualize the anatomic landmarks necessary for ablation procedures and may also help prevent procedure-related complications [144,147,149]. Increasing evidence suggests that comprehensive evaluation of the left atrium using cardiac magnetic resonance imaging or CT has significant prognostic value for long-term outcomes [149,150]. Complications include fistulas, pseudoaneurysms, TIA, and cardiac tamponade. Pulmonary vein stenosis and stroke are rare, but serious, complications [80,144]. As with other ablation techniques, anticoagulation is initiated at the time of the procedure and continued for at least three months.

This procedure is suggested only for patients who have not responded to pharmacologic therapy with multiple antiarrhythmic medications, patients with paroxysmal atrial fibrillation, and patients with ECG evidence of an underlying electrophysiologic disorder (e.g., WPW syndrome) [70,151]. In 2013, the recommendations for catheter ablation were expanded to include patients with symptomatic persistent atrial fibrillation and symptomatic paroxysmal atrial fibrillation in patients with significant left atrial dilation or with significant left ventricular dysfunction [49].

A common complication of CABG surgery is atrial fibrillation. Although reported rates vary, it is estimated that 15% to 50% of persons undergoing CABG surgery will develop atrial fibrillation postoperatively [152,153]. If a patient undergoes CABG surgery combined with valve repair, the likelihood of developing atrial fibrillation increases markedly. This represents a serious problem, as it increases the length of a patient's stay and cost of care, increases the risk of CVA and of hemodynamic compromise in the postoperative patient, and causes discomfort for the patient from palpitations, dyspnea, and other signs and symptoms. Postoperative atrial fibrillation has also been found to be an independent predictor of poor long-term prognosis and long-term mortality [153,154]. Atrial fibrillation generally occurs within five days following surgery and is most likely to occur within two to three days [155]. However, it can develop as late as three weeks postoperatively [154]. Risk factors associated with development of atrial fibrillation include [46,47,80,153,156,157]:

For prevention of postoperative atrial fibrillation following CABG, many sources recommend that beta-blocker therapy be initiated (or resumed) as soon as reasonably possible following surgery [156,158]. Use of a beta blocker for development of atrial fibrillation following cardiac surgery is a class I recommendation in AHA/ACC/HRS guidelines [28]. Prophylactic use of other antiarrhythmic agents has not been recommended. Use of digoxin has been found to have little effect and is not recommended [28]. Preoperative administration of statins may reduce postoperative atrial fibrillation and shorten the patient's stay on the ICU and in the hospital [28,159]. Studies have found that the postoperative prophylactic use of amiodarone reduces the risk of atrial fibrillation and decreases the total cost of care [158,160,161]. However, the use of amiodarone and other antiarrhythmic medications, such as calcium channel blockers and procainamide has been linked to the unacceptable side effects of bradycardia and hypotension [75]. Early intervention for patients who develop increasingly frequent premature atrial contractions (PACs) has been recommended by some clinicians. However, there is no consensus regarding the best treatment. Immediate intervention is indicated for persons who develop atrial fibrillation in the postoperative period. Based on an assessment of the patient's symptoms and hemodynamic status, medical treatment may involve intravenous medications for rate control, pharmacologic cardioversion, or electrical cardioversion along with identification and correction of factors that may contribute to the development of arrhythmias such as hypokalemia and hypomagnesemia. If atrial fibrillation persists despite appropriate therapy, anticoagulation therapy should be started as soon as the surgeon decides it is feasible. Four to six weeks following surgery, the patient's status should be re-evaluated [162,163]. In some persons, postoperative atrial fibrillation is a relatively transient arrhythmia that may spontaneously resolve. However, for others, the arrhythmia may persist and require medical management as previously described for persons with coronary artery disease [28,40].

During early fetal development, a number of bundles of fibers exist that connect the atria and ventricles. As fetal development progresses, these connections disappear until the AV node is left as the only functional electrical connection between atria and ventricles. In persons with WPW, one or more of these fibrous connecting bundles has persisted into adulthood. The connecting bundle, called an accessory pathway, provides an alternative route for the conduction of an electrical impulse through the heart. Depending on a number of factors, an electrical impulse may travel only through the normal conducting pathway, through both the normal and the accessory pathways, or only through the accessory pathway. When the impulse travels through the accessory pathway, it bypasses the normal delay in the AV node and reaches the ventricles early. It initiates ventricular depolarization before the impulse traveling down the normal conduction pathway can reach the ventricles. The ventricles depolarize abnormally. The abnormal conduction through the accessory pathway alters the normal ECG waveform. The changes include [164]:

These ECG characteristics are often very subtle and may be confused with ECG changes associated with other conditions, such as acute myocardial infarction, bundle branch block, and left ventricular hypertrophy. The early depolarization of ventricles through accessory pathway conduction is called pre-excitation. The degree of pre-excitation (i.e., the extent to which the ventricles depolarize from accessory pathway conduction) can vary. Factors that increase conduction across the AV node decrease conduction through the accessory pathway. These factors include exertion, intense emotion that increases adrenergic stimulation, and certain medications, such as procainamide, beta agonists (e.g., epinephrine, albuterol, metaproterenol, terbutaline), and atropine. Factors that inhibit or slow conduction across the AV node increase the extent of pre-excitation. These factors may include a normal increase in vagal tone associated with sleep, and medications such as digoxin, adenosine, beta blockers, and calcium channel blockers. Medications known to slow conduction through the AV node should be not used for persons with WPW [165,166].

The presence of multiple conduction pathways (normal and one or more abnormal) often leads to development of tachyarrhythmias, including atrial fibrillation. Patients with WPW who develop atrial flutter or atrial fibrillation are at increased risk of dangerous ventricular arrhythmias due to the extremely fast conduction across the bypass tract [164]. Atrial fibrillation develops in approximately one-third of persons with WPW. Approximately 80% of patients with WPW syndrome will develop atrial fibrillation and 5% will have atrial flutter [164]. Atrial fibrillation seen in WPW is characterized by [17,19,164,165,166]:

WPW should be suspected in any person who shows the following signs and symptoms:

Definitive diagnosis can be done through electrophysiology testing [164].

When a patient with WPW presents with atrial fibrillation with rapid ventricular response, the patient's hemodynamic status should be immediately assessed. If there are signs of hemodynamic instability, such as hypotension, signs of congestive heart failure, or ischemic chest pain, the patient should be immediately cardioverted [28,164]. If the patient is not hemodynamically unstable, rate control is the high priority. Appropriate medication selection is critical. Use of medications such as verapamil and digoxin that slow or block conduction through the AV node will aggravate atrial fibrillation in WPW and run the risk of accelerating the ventricular rate to the point that ventricular fibrillation can occur [33,164]. The treatment of choice for hemodynamically stable patients with atrial fibrillation and WPW is IV procainamide or ibutilide [28]. Verapamil, diltiazem, adenosine, digoxin (oral or intravenous), and intravenous amiodarone can precipitate ventricular fibrillation and should not be used [28].