Atrial Fibrillation

Introduction
Background

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by disorganized atrial electrical activity and progressive deterioration of atrial electromechanical function. Electrocardiographic manifestations of atrial fibrillation include absence of P waves; rapid oscillations (or fibrillatory [f] waves) that vary in amplitude, frequency, and shape; and an irregular ventricular response.

Atrial fibrillation is the most common arrhythmia encountered in clinical practice (see Media file 1) and is a significant public health problem in the United States. Atrial fibrillation affects more than 2.2 million Americans and almost 5% of the population older than 69 years. The prevalence of atrial fibrillation increases dramatically with age. Atrial fibrillation is associated with known cardiovascular risk factors such as hypertension, coronary artery and valvular heart disease, heart failure (HF) and diabetes mellitus.1

Data from the Framingham heart study show that atrial fibrillation is associated with a 1.5- to 1.9-fold higher risk of death, which is in part due to the strong association between atrial fibrillation and thromboembolic events.2 While patients can be asymptomatic, many experience a wide variety of symptoms, including palpitations, dyspnea, fatigue, dizziness, angina, and decompensated heart failure. In addition, atrial fibrillation can be associated with hemodynamic dysfunction, tachycardia-induced cardiomyopathy, and systemic thromboembolism.

Overall, approximately 15-25% of all strokes in the United States (75,000/y) can be attributed to atrial fibrillation. Known risk factors for stroke in patients with atrial fibrillation include male sex, valvular heart disease (rheumatic valvular disease), heart failure, hypertension, and diabetes. Additional risk factors, such as advanced age and prior history of stroke, diabetes, and hypertension, place patients with preexisting atrial fibrillation at even higher risk for further comorbidities such as stroke(see Table 1)

Table 1. Risk Factors for Stroke in Patients with Nonvalvular Atrial Fibrillation
Risk Factors Relative Risk
Prior stroke or TIA 2.5
History of hypertension 1.6
Heart failure and/or reduced left ventricular function 1.4
Advanced age 1.4
Diabetes 1.7
Coronary artery disease 1.5

Patients with rheumatic heart disease and atrial fibrillation have an even higher risk for stroke (17-fold). At least 4 large clinical trials have clearly demonstrated that anticoagulation with warfarin decreases the risk of stroke by 50-80%.

Unlike most cardiovascular diseases, the prevalence of atrial fibrillation is increasing in the United States and worldwide. Atrial fibrillation is frequently encountered in both the inpatient and outpatient settings. Primary therapeutic goals include rate control, maintenance of sinus rhythm, and prevention of thromboembolism.

Pathophysiology

While the precise mechanisms that cause atrial fibrillation are incompletely understood, atrial fibrillation appears to require both an initiating event and a permissive atrial substrate. Significant discoveries in the last decade have highlighted the importance of focal pulmonary vein triggers, but alternative and nonmutually exclusive mechanisms have also been evaluated. These include multiple wavelets, mother waves, fixed or moving rotors, and macro-reentrant circuits. In a given patient, multiple mechanisms may be present at any given time. The automatic focus theory and the multiple wavelet hypothesis appear to have the best supportive data.

A focal origin of atrial fibrillation is supported by several experimental models showing that atrial fibrillation persists only in isolated regions of atrial myocardium. This theory has garnered considerable attention recently as studies have demonstrated that a focal source of atrial fibrillation can be identified in humans and that isolation of this source can eliminate atrial fibrillation.

The pulmonary veins appear to be the most frequent source of these automatic foci, but other foci have been demonstrated in several areas throughout the atria. Cardiac muscle in the pulmonary veins appears to have active electrical properties similar, but not identical, to those of atrial myocytes. Heterogeneity of electrical conduction around the pulmonary veins is theorized to promote reentry and sustained atrial fibrillation. Thus, pulmonary vein automatic triggers may provide the initiating event and heterogeneity of conduction may provide the sustaining event in many patients with atrial fibrillation.

The multiple wavelet hypothesis proposes that fractionation of wavefronts propagating through the atria results in self-perpetuating “daughter wavelets.” In this model, the number of wavelets is determined by the refractory period, conduction velocity, and mass of atrial tissue. In this model, increased atrial mass, shortened atrial refractory period, and delayed intra-atrial conduction increase the number of wavelets and promote sustained atrial fibrillation. This model is supported by data from patients with paroxysmal atrial fibrillation demonstrating that widespread distribution of abnormal atrial electrograms predicts progression to persistent atrial fibrillation.4 Intra-atrial conduction prolongation has also been shown to predict recurrence of atrial fibrillation.5 Together, these data highlight the importance of atrial structural and electrical remodeling in the maintenance of atrial fibrillation.

Atrial fibrillation shares strong epidemiologic associations with other cardiovascular diseases such as heart failure, coronary artery disease, valvular heart disease, diabetes mellitus and hypertension.1 These factors have been termed upstream risk factors, but the relationship between comorbid cardiovascular disease and atrial fibrillation is incompletely understood and more complex than this terminology implies. The exact mechanisms via which cardiovascular risk factors predispose to atrial fibrillation are not fully understood but are under intense investigation. Catecholamine excess, hemodynamic stress, atrial ischemia, atrial inflammation, metabolic stress, and neurohumoral cascade activation are all purported to promote atrial fibrillation.

Frequency
United States

Atrial fibrillation affects more than 2.2 million Americans. One in 4 individuals 40 years of age and older will develop atrial fibrillation during their lifetime.6 Atrial fibrillation can occur in the absence of comorbidities, as it does in 10-15% of cases of atrial fibrillation (lone atrial fibrillation). However, atrial fibrillation is often associated with other cardiovascular diseases, including hypertension; heart failure; diabetes; ischemic heart disease; and valvular, dilated, hypertrophic, restrictive, and congenital cardiomyopathies.6

Atrial fibrillation can be triggered after cardiac surgery and is associated with pulmonary disease, thyrotoxicosis, acute ethanol intoxication, and electrolyte imbalance. Given the almost epidemic proportions of patients with atrial fibrillation, clinicians should be aware of the multiple mechanisms and triggers for atrial fibrillation. Correcting the underlying disorder is often necessary to successfully treat atrial fibrillation.

Mortality/Morbidity

Atrial fibrillation is associated with increased morbidity and mortality, in part due to the risk of thromboembolic disease in atrial fibrillation and in part due to its associated risk factors. Disruption of normal atrial electromechanical function in atrial fibrillation leads to blood stasis. This, in turn, can lead to development of thrombus, most commonly in the left atrial appendage. Dislodgement of a clot can lead to embolic phenomena, including stroke.

One of the major management decisions in atrial fibrillation (and atrial flutter) is determining the risk of stroke and appropriate anticoagulation regimen for low-, intermediate-, and high-risk patients. For each anticoagulant, the benefit in terms of stroke reduction must be weighed against the risk of serious bleeding.

Most clinicians agree that the risk-benefit ratio of warfarin therapy in low-risk patients with atrial fibrillation is not advantageous. Warfarin therapy has, however, been shown to be beneficial in higher-risk patients with atrial fibrillation. A target international normalized ratio (INR) of 2-3 is traditionally used in this cohort as this limits the risk of hemorrhage while providing protection against thrombus formation.

The appropriate treatment regimen for patients with atrial fibrillation at intermediate risk is controversial. In this population, the clinician should assess risk factors for thromboembolic disease, patient preference, risk of bleeding, risk of falls or trauma, and likelihood of medication adherence. Warfarin is also superior to clopidogrel or a combination of clopidogrel and aspirin in the prevention of embolic events in higher-risk patients. A new class of oral direct thrombin inhibitors are in the late stages of clinical trial or pending approval and may be as effective and as safe as warfarin in higher-risk nonvalvular atrial fibrillation.

Several risk factor assessment algorithms have been developed to aid the clinician in decision-making regarding anticoagulation in atrial fibrillation. The CHADS2 index7 (Cardiac failure, Diabetes, Stroke [or S2 = TIA]) is the most widely used of these algorithms. The CHADS2 index uses a point system to determine yearly thromboembolic risk. Two points are assigned for a history of stroke or TIA, and one point is given for age over 75 or a history of hypertension, diabetes, or heart failure. The predictive value of this scoring system was evaluated in 1733 elderly patients with nonvalvular atrial fibrillation aged 65-95 who were not given warfarin at hospital discharge. Although high scores were associated with an increased rate of stroke, few patients had a score greater than 5 or a score of 0 (see Table 2).

Table 2. Adjusted Stroke Rate in Patients with Nonvalvular Atrial Fibrillation not Treated with Anticoagulation


Open table in new windowCHADS2 Score Adjusted Stroke Rate (%/y)
0 1.9
1 2.8
2 4.0
3 5.9
4 8.5
5 12.5
6 18.2



Recommendations for anticoagulation for patients with nonvalvular atrial fibrillation are based on 2006 ACC/AHA/ESC task force guidelines on the management of patients with atrial fibrillation8 (see Table 3).

Table 3. Recommendations for Antithrombotic Therapy in Patients with Nonvalvular Atrial Fibrillation

Open table in new windowRisk Category Recommended Therapy
No risk factors Aspirin 81-325 mg daily
One moderate-risk factor Aspirin 81-325 mg daily or warfarin (INR 2-3)
Any high-risk factor or more than 1 moderate-risk factor Warfarin (INR 2-3)



High-risk factors include prior stroke, TIA, and systemic thromboembolism.

Moderate-risk factors include age older than 75 years, hypertension, heart failure, left ventricular function <35%, and diabetes mellitus.

Risk factors of unknown significance include female gender, age 65-74 years, coronary artery disease, and thyrotoxicosis.
Age

Atrial fibrillation is strongly age-dependent, affecting 4% of individuals older than 60 years and 8% of persons older than 80 years. The rate of ischemic stroke among elderly patients not treated with warfarin averages approximately 5% per year.

Clinical
History

Initial evaluation of the patient with new-onset atrial fibrillation should focus on the patient's hemodynamic stability. An effort should also be made to evaluate for potential comorbid diseases that contribute to initiation or maintenance of atrial fibrillation. Immediate electrical cardioversion should be considered for patients with hemodynamic collapse or evidence of cardiac ischemia.

Initial history
Clinical type of atrial fibrillation should be documented (paroxysmal, persistent, or permanent)
Type, duration, and frequency of symptoms should be assessed
Precipitating factors should be assessed (ie, exertion, sleep, caffeine, alcohol use)
Modes of termination should be assessed (ie, vagal maneuvers)
Prior antiarrhythmics and rate-controlling agents used should be documented
Presence of underlying heart disease should be assessed
Any previous surgical or percutaneous atrial fibrillation ablation procedures should be documented

Physical

The physical examination is helpful in determining underlying causes and sequelae of atrial fibrillation. An initial examination of the patient with new-onset atrial fibrillation should attend particularly to their hemodynamic stability.

Vital signs: Heart rate, blood pressure, respiratory rate, and oxygen saturation are particularly important in evaluating hemodynamic stability and adequacy of rate control in atrial fibrillation.
Head and neck: May reveal exophthalmos, thyromegaly, elevated jugular venous pressures, or cyanosis. Carotid artery bruits suggest peripheral arterial disease and increase the likelihood of comorbid CAD.
Pulmonary: May reveal evidence of heart failure (ie, rales or pleural effusion). Wheezes or diminished breath sounds are suggestive of underlying pulmonary disease (ie, chronic obstructive pulmonary disease or asthma).
Cardiac: The cardiac examination is central to the physical examination of the patient with atrial fibrillation. A displaced point of maximal impulse or S3 suggest ventricular enlargement and elevated left ventricular pressure. A prominent P2 points to the presence of pulmonary hypertension. Thorough palpation and auscultation are necessary to evaluate for valvular heart disease or cardiomyopathy.
Abdomen: Ascites, hepatomegaly or hepatic capsular tenderness suggest right ventricular failure or intrinsic liver disease.
Lower extremities: Examination of the lower extremities may reveal cyanosis, clubbing or edema. Assessment of peripheral pulses may lead to the diagnosis of peripheral arterial disease or diminished cardiac output.
Neurologic: Evidence of prior stroke and increased reflexes is suggestive of hyperthyroidism.
Causes

Atrial fibrillation is strongly associated with established cardiovascular risk factors and advancing age. Hypertension, diabetes, and coronary artery disease promote atrial fibrillation. Structural heart disease, including valvular and congenital heart disease, is also associated with atrial fibrillation. Acute pulmonary processes, acute or chronic alcohol use (ie, holiday or Saturday night heart, also known as alcohol-related cardiomyopathy), illicit drug use (ie, stimulants, methamphetamines, cocaine) and hyperthyroidism also increase the risk of atrial fibrillation. Patients undergoing cardiothoracic or esophageal surgery are another population at risk for atrial fibrillation. In all, 20-40% of these patients experience postoperative atrial fibrillation. Certain poorly defined genetic factors may also contribute to an individual's propensity to develop atrial fibrillation.

Hemodynamic stress: Increased intra-atrial pressure results in atrial electrical and structural remodeling and predisposes to atrial fibrillation. Mitral or tricuspid valve disease and left ventricular dysfunction are the most common causes of increased atrial pressure. Systemic or pulmonary hypertension also commonly predispose to atrial pressure overload. Intracardiac tumors or thrombi are rare causes of increased atrial pressure.
Atrial ischemia: Coronary artery disease can infrequently lead directly to atrial ischemia and atrial fibrillation. More commonly, severe ventricular ischemia leads to increased intra-atrial pressure and atrial fibrillation.
Inflammation: Myocarditis and pericarditis may be idiopathic or may occur in association with the following:
Collagen vascular diseases
Viral or bacterial infections
Cardiac, esophageal, or thoracic surgery
Drug use: Stimulants, alcohol, and cocaine can trigger atrial fibrillation.
Endocrine disorders: Hyperthyroidism and pheochromocytoma have been associated with atrial fibrillation.
Neurologic: Intracranial processes such as subarachnoid hemorrhage or stroke can also precipitate atrial fibrillation.
Familial atrial fibrillation: History of parental atrial fibrillation appears to confer increased likelihood of atrial fibrillation (and occasional family pedigrees of atrial fibrillation are associated with defined ion channel abnormalities, especially sodium channels).9

http://emedicine.medscape.com/article/151066-overview