Pathophysiology | Etiology | Diagnosis | Symptoms | Treatment | Special Situations
Atrial fibrillation is the most common chronic arrhythmia, characterized by erratic atrial electrical activity with atrial rates of 400 to 600 beats per minute. The P wave is absent on the surface electrocardiogram and can, at times, be replaced with “fibrillatory waves.”
Atrial flutter is similar to atrial fibrillation in regards to symptoms and thromboembolic risk, including stroke. However, the pathophysiology and management differ.
The symptoms of atrial fibrillation are related to the loss of atrial mechanical activity (atrial contraction) and rapid ventricular heart rates, both of which can reduce cardiac output and lead to congestive heart failure. Thromboembolism frequently causes stroke in patients with atrial fibrillation.
Atrial fibrillation is classified into paroxysmal, persistent or permanent — the three Ps.
Paroxysmal atrial fibrillation is self-limiting, and sinus rhythm restores spontaneously. Paroxysmal atrial fibrillation lasts for less than 7 days and does not require intervention such as electrical or chemical cardioversion to convert to a normal rhythm.
Persistent atrial fibrillation lasts for greater than 7 days. The term persistent is used when there is a plan to use a rhythm control strategy and return the patient to sinus rhythm.
Permanent atrial fibrillation is present when atrial fibrillation is present 100% of the time for greater than 7 days, and there are no interventions planned to restore sinus rhythm.
The term “chronic atrial fibrillation” and the abbreviation “PAF” are no longer recommended for use. The term “lone atrial fibrillation” is used when structural heart disease is not present. Atrial fibrillation has also been classified as valvular vs. nonvalvular in etiology. Atrial fibrillation is termed “recurrent” when there have been two or more episodes.
Pathophysiology – Atrial Fibrillation
Atrial fibrillation occurs when irritable foci cause rapid action potentials that result in an atrial heart rate between 400 and 600 bpm. The foci are commonly located in the superior pulmonary veins; this is important in regards to the approach to atrial fibrillation ablation — also known as pulmonary vein isolation. Less commonly, the foci of atrial fibrillation can be within the right atrium; rarely, they are in the superior vena cava or coronary sinus.
Atrial tissue in patients with atrial fibrillation is well known to remodel, showing pathologic changes of fibrosis and inflammation ― the exact mechanism of which remains unclear. Any cardiac condition that results in left atrial enlargement will increase the risk for atrial fibrillation because the above-mentioned remodeling is more prominent in this setting. The left atrium will enlarge whenever the left atrial pressure is increased, as in congestive heart failure, chronic hypertension and valvular heart disease. The larger the left atrium, the higher the risk for atrial fibrillation. Likewise, the larger the left atrium, the less likely that maintaining sinus rhythm after cardioversion will be successful, especially without antiarrhythmic drugs.
Fortunately, not all 400 to 600 atrial action potentials during atrial fibrillation conduct to the ventricles in normal individuals due to the actions of the atrioventricular node. The AV nodal refractoriness inhibits more than half of these action potentials from reaching the ventricles; thus, the typical ventricular heart rate in patients with atrial fibrillation — in the absence of AV blocking medications — is about 100 to 170 bpm.
In patients with Wolff-Parkinson-White syndrome who develop atrial fibrillation, an “accessory pathway” is present, electrically connecting the atrium to the ventricles (separate from the AV node) and allowing many more action potentials to reach the ventricles — resulting in ventricular rates greater than 200 bpm. Blocking the AV node with medications such as beta-blockers or calcium channel blockers paradoxically increases the ventricular heart rate because more atrial action potentials can conduct through the accessory pathway, which commonly has a short refractory period (can conduct quite fast). This paradoxical increase in ventricular heart rates can lead to ventricular fibrillation (ventricular rates of 400-600 bpm) and death. Procainamide or electrical cardioversion is recommended in patients with WPW with AF for this reason.
The development of thrombi in the left atrial appendage can result in embolus, causing stroke in susceptible individuals. When AF is present, flow velocities are significantly decreased in the atrium including the left atrial appendage. This allows coagulation and thrombus formation. Certain predictors can be used to identify those at higher risk for thromboembolism; see the CHADS2 Score Topic Review, the CHA2DS2-VASc Score Topic Review and the American College of Cardiology/American Heart Association guidelines.
Etiology – Atrial Fibrillation
Identifying the cause of atrial fibrillation must not be under emphasized as the treatment of the cause is frequently necessary to eliminate atrial fibrillation. The classic mnemonic “PIRATES” encompasses a vast majority of the causes of atrial fibrillation:
Pulmonary embolus, pulmonary disease, post-operative, pericarditis
Ischemic heart disease, idiopathic (“lone atrial fibrillation”), intravenous central line (in right atrium)
Rheumatic valvular disease (specifically mitral stenosis or mitral regurgitation)
Anemia, alcohol (“holiday heart”), advanced age, autonomic tone (vagally mediated atrial fibrillation)
Thyroid disease (hyperthyroidism)
Elevated blood pressure (hypertension), electrocution
Sleep apnea, sepsis, surgery
Historically, hypertension was thought to be the most common cause of atrial fibrillation, however obstructive sleep apnea is present in about 40% of patients with atrial fibrillation, and it is well known that obstructive sleep apnea causes hypertension. The exact proportion of atrial fibrillation resulting directly from obstructive sleep apnea remains unclear.
Diagnosis – Atrial Fibrillation
Diagnosing atrial fibrillation (AF) is done predominantly on the surface ECG. Sinus P waves are absent and sometimes no atrial activity can be identified. Frequently, coarse “fibrillatory waves” can be seen representing the erratic atrial activity that occurs in the setting of atrial fibrillation.
The QRS complexes are “irregularly irregular” as there is no pattern to their frequency. This is commonly described as varying R-R intervals.
Note that there are three rhythms originating from the atrium that can be irregularly irregular: Atrial fibrillation, atrial flutter with variable conduction and multifocal atrial tachycardia.
The ventricular rate is frequently elevated; when significantly so (> 150 beats per minute), it is often difficult to distinguish atrial fibrillation from atrial flutter, atrial tachycardia, or atrioventricular nodal reentrant tachycardia (AVNRT). In this situation, giving adenosine will transiently slow the ventricular rate in patients with atrial fibrillation, allowing a more definitive diagnosis to be made. This should not be done in patients with Wolff-Parkinson-White syndrome (as described above) because this paradoxically increases the ventricular rate in this setting, leading to ventricular fibrillation, which can be fatal.
Below are multiple full 12-lead ECG examples of atrial fibrillation:
On physical examination, the heart rhythm will be “irregularly irregular” and frequently tachycardic. Findings of heart failure may be present depending on the ventricular rate, duration of atrial fibrillation and other factors. There will never be an S4 heart sound present during atrial fibrillation, as this heart sound is produced when atrial contraction forces blood into a noncompliant left ventricle. Normal atrial contraction is lost during atrial fibrillation.
The diagnosis of a left atrial appendage (LAA) thrombus, if suspected, must be done using transesophageal echocardiography (TEE) or cardiac CT — the latter less commonly used). It is important to note that transthoracic echocardiography does not detect left atrial appendage thrombi in the vast majority of patients. TEE findings of a left atrial appendage thrombus includes direct visualization of a mobile echodensity within the appendage. The echodensity should move independent of the walls of the atrium; this helps to distinguish artifact or trabeculae from thrombus. Pulse wave Doppler can be used in the left atrial appendage to determine the flow velocity; a velocity of less than 0.4 m/s indicates a higher risk for thromboembolism in general.
Symptoms – Atrial Fibrillation
The symptoms of atrial fibrillation relate either to the irregularly irregular heartbeat causing palpitations or decreased overall cardiac output from loss of atrial contraction and fast ventricular rates resulting in congestive heart failure. If hypotension is present from a significantly reduced cardiac output, dizziness and even syncope (loss of consciousness) can occur.
Treatment – Atrial Fibrillation
The approach to the management of patients with atrial fibrillation requires the consideration of two distinct areas — alleviating symptoms of atrial fibrillation and preventing thromboembolism. A summary image is below.
There are two main approaches which can be utilized to alleviate symptoms of atrial fibrillation — a “rate control” strategy or a “rhythm control” strategy.
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial evaluated the use of a rate control strategy vs. a rhythm control strategy. There was no difference in mortality between these approaches; thus, an individualized approach is recommended based on the degree of symptoms and the patient’s personal preference.
Commonly, controlling the ventricular rate in patients with atrial fibrillation can completely resolve symptoms, and no further therapy is needed. This is done using AV blocking medications — administered either intravenously in the acute setting or orally for long-term therapy.
Selecting the appropriate AV blocking agent requires the knowledge of other indications and contraindications for these drugs; knowledge of the left ventricular systolic function is particularly important. AV blocking agents used in AF include beta-blockers, nondihydropyridine calcium channel blockers and digoxin.
Beta-blockers (atenolol, metoprolol, carvedilol) antagonize beta-receptors, resulting in decreased conduction through the AV node, which reduces the heart rate in patients with atrial fibrillation. Caution is advised in patients with asthma, as antagonizing beta-2 receptors can cause bronchospasm. In severe left ventricular systolic dysfunction (reduced ejection fraction), beta-blockers can acutely decrease cardiac output leading to severe hypotension, acute heart failure and even cardiogenic shock. Despite this, beta-blockers are considered safe when used cautiously in this setting.
Nondihydropyridine calcium channel blockers (diltiazem, verapamil) reduce AV conduction by antagonizing voltage gated calcium channels, decreasing intracellular calcium. Because these drugs reduce left ventricular inotropy (contractility) via the same mechanism, they are generally not recommended for use in the setting of left ventricular systolic dysfunction (reduced ejection fraction).
Digoxin blocks the sodium/potassium ATPase pump. The mechanism by which this decreases AV conduction is not clear, but is perhaps due to increased vagal tone. Intracellular calcium within the cardiac myocytes is increased by digoxin, resulting in increased inotropy (contractility); thus, digoxin is frequently used when atrial fibrillation and left ventricular systolic dysfunction coexist. Digoxin is effective to reduce ventricular rates at rest but not effective during physical activity. Therefore, it is recommended to use digoxin in combination with a beta-blocker or nondihydropyridine calcium channel blocker.
Rarely, the above medications are not able to adequately reduce the ventricular rate, and AV nodal ablation with permanent pacemaker implantation is needed.
A rhythm control strategy is employed when rate control is not successful in completely eliminating symptoms from atrial fibrillation or if the ventricular rate is refractory to the previously mentioned AV blocking medications. This can be done using cardioversion, antiarrhythmic drug therapy or ablation.
The term “cardioversion” is used to describe an action taken to restore sinus rhythm. This can be done either electrically by delivering a shock (direct current cardioversion, or DCCV) or chemically with certain drugs (class IA, class IC or class III antiarrhythmic drugs).
Once sinus rhythm is restored, antiarrhythmic drug therapy can be utilized to maintain sinus rhythm, especially if the risk of recurrence is high such as in severe left atrial enlargement, severe valvular heart disease or uncontrolled sleep apnea.
There are numerous antiarrhymic medications used to treat atrial fibrillation. They are listed below, by class.
Class IA (quinidine, procainamide, disopyramide): Although class IA drugs are effective to treat atrial fibrillation, they are not commonly utilized for this purpose due to side-effects and significant proarrhythmia, except in special situations (atrial fibrillation with Wolff-Parkinson-White or vagally-mediated atrial fibrillation). These agents block cardiac sodium channels and depress phase 0 of the action potential. Procainamide can cause drug-induced lupus erythematosus, detected by measuring anti-histone antibodies. Quinidine can cause cinchonism.
Class IB (lidocaine, mexiletine): These agents are not effective to treat atrial fibrillation and are used for ventricular arrhythmias.
Class IC (flecainide, propafenone, moricizine): These drugs are commonly used to maintain sinus rhythm in patients with AF. Significant coronary artery disease is a contraindication to their use, as this increases the risk for proarrhythmia and sudden cardiac death. These agents must be used in combination with an AV blocking agent in order to prevent rapid AF or atrial flutter conduction (1:1 conduction) through the AV node resulting in very fast ventricular rates if a breakthrough episode occurs because they also act to increase AV nodal conduction. These drugs may be proarrhythmic in the setting of left ventricular hypertrophy (wall thickness > 1.4 cm). Flecainide can be used with a “pill-in-the-pocket” approach. If documented to be successful and safe while hospitalized, flecainide can be used on an as-needed basis in the outpatient setting. Note that propafenone is hepatically cleared (not recommended with liver disease), whereas flecainide is renally cleared.
Class III (amiodarone, sotalol, bretylium, dofetilide, dronedarone, ibutilide): These drugs are also commonly used in atrial fibrillation and act by blocking potassium channels. Amiodarone is very effective but toxicity is a concern. The half-life of amiodarone is 42 days. Sotalol is proarrhythmic in the setting of LVH. Amiodarone and dofetilide are preferred in patients with left ventricular systolic dysfunction (reduced ejection fraction). Dronedarone is not safe with systolic heart failure or in the setting of permanent atrial fibrillation. Bretylium is rarely used.
Atrial fibrillation ablation
A majority of cases of atrial fibrillation originate within the pulmonary veins. Ablation of atrial fibrillation — also known as “pulmonary vein isolation,” or PVI — electrically disconnects the erratic electrical activity in the pulmonary veins (which are creating action potentials at a rate of 400-600 beats per minute) from the rest of the heart, effectively eliminating the atrial fibrillation. Ablation for atrial fibrillation is complex, requires multiple catheters and is performed via venous access, then puncturing the interatrial septum to obtain entry to the left atrium where the pulmonary veins empty.
The highest success rates for atrial fibrillation ablation occur in patients where the arrhythmia is paroxysmal and not persistent or permanent. Those with smaller left atrial volumes and with shorter duration of atrial fibrillation also have higher success rates.
The indication for atrial fibrillation ablation is symptoms from atrial fibrillation and failure of at least one antiarrhythmic drug. An attempt at a second antiarrhythmic drug would also be reasonable.
Stroke related to thromboembolism occurs due to decreased flow in the left atrial appendage when atrial contraction is lost during atrial fibrillation. This results in stagnation of blood allowing thrombus formation which can embolize not only to the brain causing stroke, but to other organs as well.
Determining which patients should be fully anticoagulated and which are safe to take no anticoagulation for stroke prophylaxis involves many factors.
The method most commonly utilized is the CHA2DS2-VASc score. CHA2DS2 stands for Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke/Transient Ischemic Attack, or TIA. VASc stands for Vascular disease (peripheral arterial disease, previous MI, aortic atheroma), Age ≥ 65 years, Sex category (female). Each risk factor receives 1 point, with the exceptions of age greater than 75 years and Stroke/TIA, which receive 2 points each. If 2 or more points are present, full anticoagulation should be utilized. Patients with 1 point can be treated with either no anticoagulation or full anticoagulation, based on the specific individual. The more points on the CHA2DS2-VASc score, the higher the annual stroke risk in general; this is excellent information for clinicians to discuss with their patients. The CHADS2 score is also sometimes used.
As a general rule, regardless of the above scoring system, if a patient’s atrial fibrillation is caused by valvular heart disease (severe mitral regurgitation or mitral stenosis), anticoagulation should be utilized.
The choice of anticoagulation should be individualized. For example, some individuals are not good candidates for coumadin therapy, which requires dietary alteration and frequent monitoring of the protime (PT or INR) to prevent over- or under-anticoagulation. Dabigatran (Pradaxa), rivaroxaban (Xarelto) and apixaban (Eliquis) are relatively new anticoagulants approved by the FDA for thromboembolism prophylaxis in patients with atrial fibrillation. The drugs do not require frequent monitoring and have a more predictable dosing and fewer drug/dietary interactions — making them much more convenient for patients to use.
Left atrial appendage occlusion devices have more recently been utilized to prevent thromboembolism. Percutaneously or surgically employed, these devices essentially exclude the left atrial appendage, thereby reducing the risk for thrombus formation. They are indicated only for individuals who have a high risk for thromboembolism and are unable to tolerate anticoagulation due to bleeding (usually gastrointestinal bleeding). Options include the Watchman device and the Lariat procedure.
Special Situations – Atrial Fibrillation
Atrioventricular Nodal (AVN) Ablation and Permanent Pacing
When high doses of AV blocking drugs are not successful to lower ventricular rates in the setting of atrial fibrillation, AV nodal ablation can be utilized. Remember that all atrial action potentials must pass through the AV node to reach the ventricle. AV node ablation destroys this connection stopping any atrial activity from reaching the ventricle. This results in the intrinsic pacemaker of the heart shifting from the atria to the ventricles. Unfortunately, the His-Purkinje system in the ventricles is only able to generate action potentials at a rate of 30 to 40 beats per minute resulting in severe bradycardia after the AV node is ablated. Thus, a permanent pacemaker must be implanted to prevent symptoms of bradycardia.
Vagally-mediated Atrial Fibrillation
Atrial fibrillation triggered by situations of vagal stimulation has been well described (nausea, vomiting, abdominal pain, severe coughing, young healthy athletes with high vagal tone etc...). In this scenario, the antiarrhythmic drug disopyramide has historically proven successful. This agent has significant anticholinergic activity, making it more effective in this situation.
Sudden use of large amounts of alcohol (binge drinking) as frequently occurs during holidays is well known to trigger atrial fibrillation, even with a structurally normal heart. This has been termed “Holiday Heart.”
Atrial Fibrillation in Hypertrophic Obstructive Cardiomyopathy (HOCM)
Loss of atrial contraction and fast ventricular rates are not hemodynamically tolerated well in patients with hypertrophic obstructive cardiomyopathy. Due to the significant diastolic ventricular dysfunction in this disease, the atrial contraction is heavily relied upon to fill the ventricles, resulting in a significant decrease in cardiac output if atrial fibrillation develops. Also, because the ventricles fill during diastole — the duration of which is significantly shortened in the setting of tachycardia — less time is present to fill the ventricles, resulting in even further decline in cardiac output. Similar hemodynamics occur when atrial fibrillation develops in patients with severe left ventricular hypertrophy from hypertensive heart disease or aortic valve stenosis.
The treatment is frequently disopyramide, as this drug is used in patients with HOCM regardless of the presence of atrial fibrillation due to its significant negative inotropic effects, which are desirable to relieve the left ventricular outflow tract obstruction in these individuals.
Atrial fibrillation in Wolff-Parkinson-White (WPW)
The combination of atrial fibrillation and Wolff-Parkinson-White syndrome can be fatal due to rapid conduction of the atrial activity through the accessory pathway, resulting in rapid ventricular rates causing ventricular fibrillation. AV nodal blocking agents should be avoided in this setting; these drugs paradoxically increase ventricular rates, as more atrial activity will pass through the fast-conducting accessory pathway and less through the AV node itself. This results in ventricular fibrillation, which is universally fatal.
For this reason, recognizing atrial fibrillation with Wolff-Parkinson-White on ECG is crucial. Below is an ECG of a patient with atrial fibrillation and WPW syndrome. Note the wide-complex, irregularly irregular rhythm with “delta waves.” This ECG can be mistaken for polymorphic ventricular tachycardia (Tosades de Pointes), however the QRS axis remains stable in the setting of atrial fibrillation with WPW.
Procainamide is the recommended therapy; electrical cardioversion is recommended if hemodynamic instability is present.
When atrial fibrillation is seen in a patient with Wolff-Parkinson-White, ablation of the accessory pathway is recommended to prevent future rapid conduction to the ventricles.
1. ACC/AHA Guidelines for Atrial Fibrillation
2. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine
3. Hurst’s the Heart, 13th Edition
4. Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation. Circulation. 2006;doi:10.1161/CIRCULATIONAHA.106.177292.
5. Sherman DG, et al.; Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. Arch Intern Med. 2005;doi:10.1001/archinte.165.10.1185