In the normal heart, the heartbeat is initiated by the sinoatrial (SA) node. From the SA node, the electrical impulse travels through both the right and left atria, causing depolarization of the atria. Atrial depolarization is followed by atrial contraction and atrial repolarization. The electrical impulse travels from the atria to the atrioventricular (AV) node located in the inferior wall of the right atrium. The speed of conduction slows in the AV node to allow time for the atria to depolarize, contract, and complete ventricular filling. From the AV node, the electrical impulse travels through the bundle of His located in the septum of the heart. The bundle of His divides into the right and left bundle branches. These branches divide further into the smaller fibers of the Purkinje system. Electrical conduction through the His-Purkinje system is rapid, causing rapid depolarization of both the right and left ventricles. Depolarization of the ventricular cells spreads from the apex of each ventricle to the base and moves from the endocardium to the epicardium. Ventricular depolarization is followed by ventricular contraction and ventricular repolarization [9,10,11].

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].

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

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].

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]:

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

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]:

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]:

Diltiazem acts by blocking calcium transport into the myocardial and vascular smooth muscle cells. As a result, conduction through the SA and AV nodes is slowed, and the refractory period of the AV node is prolonged. Ventricular rate is slowed, but the underlying atrial arrhythmia is not corrected. Diltiazem should be administered initially as an IV bolus. The usual dose is a 0.25 mg/kg bolus administered over a two-minute period. Diltiazem has a rapid onset of action. If effective, it should slow the patient's heart rate within three to seven minutes of administration. If the initial dose is ineffective in slowing the patient's heart rate, the bolus may be repeated at a higher dose of 0.35 mg/kg over two minutes. The patient's heart rate and rhythm and blood pressure should be monitored during administration. Bradycardia, bradyarrhythmias such as heart block, and hypotension may occur. To achieve or maintain rate control, a continuous infusion may be started following bolus administration. The infusion may be started at 10 mg/hour and increased in increments of 5 mg/hour to achieve rate control if no undesirable side effects occur. Diltiazem should be used with caution in patients with congestive heart failure, known pre-existing conduction defects, and significant hypotension [33,60].

Esmolol is a short-acting beta-adrenergic blocker that slows ventricular rate in atrial fibrillation by slowing conduction through the AV node. Initial administration is an IV bolus dose/loading dose of 0.5 mg/kg administered over one minute [28]. The bolus should be followed with an infusion of 0.05 mg/kg/min for four minutes. If the desired rate control is achieved, the infusion should be continued at that rate. If adequate rate control is not achieved at that dose, the bolus should be repeated followed by an infusion of 0.1 mg/min for four minutes. The total dose should not exceed 200 mcg/kg/min [33]. This procedure may be repeated until rate control is achieved or undesirable side effects occur. The patient's heart rate, ECG rhythm, and blood pressure should be monitored during the administration. Hypotension may occur. Once rate control is achieved, the infusion should be reduced to 0.025 mg/kg/min. Because esmolol has a short half-life, the therapeutic effects and side effects usually reverse within 10 to 20 minutes after the infusion is stopped. Because the therapeutic effects wear off quickly, care should be taken when switching the patient to an oral preparation to prevent relapse/loss of rate control. To transition the patient to oral medication, the first dose of the oral medication should be administered while the patient is still receiving esmolol. Thirty minutes after the first oral dose is given, the esmolol infusion should be reduced by one-half. The second dose of the oral agent should be administered at its scheduled time. One hour after the scheduled administration of the second oral dose, assess the patient's heart rate, ECG rhythm, and blood pressure. If rate control is maintained, the esmolol infusion may be discontinued. Note: Esmolol has no oral preparation; long-term control by oral agent requires a different agent [33].

Oral diltiazem preparations provide chronic rate control in atrial fibrillation and are a drug of choice for persons who have a physically active lifestyle; however, their use for rate control is unlabeled [33]. Diltiazem comes in immediate- and extended-release forms. Immediate-release doses must be taken three to four times per day; extended-release forms require only daily dosing. In addition to bradycardia, hypotension, and heart block, other side effects of oral diltiazem include flushing, angina, insomnia, headache, nausea, syncope, and signs of congestive heart failure. Care should be taken when diltiazem is combined with negative inotropic drugs, other calcium channel blockers, and digoxin. Combination therapy increases the risk of bradycardia, conduction abnormalities, hypotension, and signs of congestive heart failure [33,60].

Oral digoxin may be the first drug of choice for patients with atrial fibrillation and congestive heart failure caused by systolic dysfunction [67]. Digoxin does not provide adequate rate control during exercise or activity. The usual oral maintenance dose of digoxin is 0.125–0.25 mg daily. Serum digoxin levels should be monitored periodically. The patient should be monitored for signs of digitalis toxicity. The patient and/or family should be taught to recognize key signs of toxicity. These include nausea and vomiting, headache, unexplained weakness, malaise, and visual disturbances as well as slow heart rate. ECG changes that may occur with digitalis toxicity include sinus bradycardia, heart block, and multiple tachyarrhythmias. Digitalis toxicity is more likely to occur in elderly persons. Electrolyte imbalances such as hypokalemia, renal failure, or combined therapy with other antiarrhythmic agents may potentiate the effects of digoxin and increase the risk of digitalis toxicity. Severe digitalis toxicity may be treated with digoxin immune Fab [33].

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].

For persons with normal renal function, studies have shown that an oral dose of 500 mcg twice daily is effective in restoring normal sinus rhythm. In the presence of impaired renal function, the dose should be reduced. The dose may be as low as 125 mcg twice daily. The usual range for the maintenance dose (normal renal function) is 125–500 mcg twice daily. The administration protocol is as follows [33]:

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].

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]:

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].

Disopyramide may be administered in a short- or sustained-release form. Because it prolongs the QT interval, it is not indicated as a first drug of choice for persons who also have hypertension. The combination of left ventricular hypertrophy caused by long-standing hypertension and a prolonged QT interval greatly increases the risk of proarrhythmias such as torsades de pointes [33].

Flecainide is the drug of choice for the treatment of atrial fibrillation that has no identifiable cause. It is recommended for use only in the absence of structural heart disease and should not be prescribed for patients who have had a recent myocardial infarction or have abnormal left ventricular function [33].

Two medications used commonly in prevention of thromboembolic events are aspirin and warfarin. They may be used singly or in combination to prevent thromboembolic events, but the efficacy of combination therapy has not been established [119,120,121,122]. Warfarin in comparison to aspirin leads to a 39% relative risk reduction in stroke [123]. Rather than adding aspirin, the AHA/ACC/HRS Task Force recommends increasing the intensity of the anticoagulant to a maximum target INR of 2.0–3.0 [28]. Aspirin acts by decreasing platelet aggregation. Because it offers only modest protection against stroke for patients with atrial fibrillation, its use may be considered for low-risk patients [28,49]. As noted, low-risk patients include those who are younger than 65 years of age and have no underlying cardiac disease. It may also be recommended for use in patients, particularly elderly persons, who cannot safely take warfarin. The usual adult dose of aspirin is 81–325 mg oral per day [49].

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]:

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]:

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].

Patient D is a man, 68 years of age, who presents to the emergency department late one evening complaining of increasing shortness of breath, dizziness, and the sensation of his "heart racing." On admission, his heart rate is 160 bpm, blood pressure 100/50 mm Hg, respirations 26 breaths per minute, and oxygen saturation 88% on room air. Patient D says that his symptoms started abruptly earlier that day and have steadily become worse. He reports a history of long-standing hypertension, coronary artery disease, and a recent percutaneous transluminal angioplasty with placement of two stents.

Comments and rationale: Symptoms such as those Patient D presents are common indications of acute onset atrial fibrillation with rapid ventricular response. His past medical history is positive for risk factors for the development of atrial fibrillation. These include a positive cardiac history, with hypertension and coronary artery disease, as well as increasing age.

Laboratory tests are ordered, including a complete blood count, serum electrolytes, renal and hepatic function tests, chest x-ray, urinalysis, and PT/INR. A peripheral IV access is established. Continuous telemetry monitoring is maintained, and Patient W's vital signs are monitored every four hours. Her heart rate remains between 48 and 52 bpm. Patient W's oral antiarrhythmic medication is discontinued. Analysis of Patient W's ECG shows that her QTc is 580 msec. The therapeutic options of electrical cardioversion, radiofrequency ablation, and continued oral antiarrhythmic therapy with insertion of a demand pacemaker are discussed with the patient. The patient expresses reluctance to undergo pacemaker insertion at this time. With the patient's agreement, she is scheduled for electrical cardioversion. Patient W expresses the understanding that pacemaker insertion or ablation with pacemaker insertion might still be required if cardioversion is unsuccessful or if she becomes symptomatic on therapy to maintain sinus rhythm following successful cardioversion.