Atrial Fibrillation, Part I: Classification, Presentation, and Diagnostic Evaluation
Part I: Classification, Presentation, and Diagnostic Evaluation
Author: Donald A. Moffa, Jr., MD, Associate Staff, Emergency Medicine, Cleveland Clinic Foundation, Cleveland, OH.
Peer Reviewers: Corey M. Slovis, MD, FACP, FACEP, Professor of Emergency Medicine and Medicine; Chairman, Department of Emergency Medicine, Vanderbilt University School of Medicine; Medical Director, Nashville Fire Department EMS, Nashville, TN; Stephen W. Smith, MD, Faculty Emergency Physician, Hennepin County Medical Center, Minneapolis, MN.
Atrial fibrillation (AF) is the most common sustained dysrhythmia in the United States, affecting an estimated 2.2 million adults.1 AF is also the most common dysrhythmia in emergency medicine.2 With rare exception, AF is non-lethal.3 However, it is a progressive disease, with 30% of paroxysmal AF eventually becoming chronic.4 AF rarely occurs in the first two decades of life, but it has been reported in the fetus and neonate, in whom it almost always is associated with an accessory atrioventricular (AV) pathway.5 In adolescents, AF has been reported in association with hyperthyroidism, dilated and hypertrophic cardiomyopathy, and accessory pathway conduction.6,7 AF is common in the elderly and in patients with organic heart disease.8 Cardiogenic thromboembolism from AF accounts for two-thirds of stroke in patients older than age 60.9
Duration of AF and frequency of its recurrence differentiate the various forms of the dysrhythmia. Paroxysmal AF lasts fewer that seven days and is separated by prolonged periods of normal sinus rhythm (NSR). Paroxysmal AF recurs approximately 30% of the time, and its prevalence often is underestimated because it may be asymptomatic.10 Chronic AF, on the other hand, lasts longer than seven days, usually without interceding NSR.11 The first episode of persistent AF, or the first time that AF is discovered, is called "recent-onset atrial fibrillation." Chronic AF is approximately twice as common as paroxysmal AF or recent-onset AF.10
The prevalence of AF varies with age and patient population. In general, AF affects 3-5% of the population older than age 60 and is associated with organic heart disease in 70-80% of those affected. "Idiopathic" or "lone" AF occurs in 3-31% of all cases and is named because of the absence of any detectable causes, including hyperthyroidism, sinus node dysfunction, or ventricular preexcitation.4,5,12
According to the 1985 report from Framingham, the relative risk for developing stroke in persons with AF is 4.1%, and stroke is the most important outcome affecting morbidity and mortality associated with the dysrhythmia.5,8
When presented with a patient in AF, the emergency physician (EP) quickly must evaluate, stabilize, and treat the patient according to his or her underlying disease state to minimize morbidity and mortality. Accordingly, the goals of therapy include: 1) control of ventricular rate; 2) restoration of normal sinus rhythm; 3) maintenance of normal sinus rhythm; and 4) prevention of thromboembolism.5,13 (See Table 1.)
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The following article will provide the EP with an understanding of the classification of AF, its pathophysiology, treatment strategy, medications used in its treatment, and considerations for treating AF associated with other medical conditions.—The Editor
Classification
AF may not represent a single entity and may be understood and studied better when assigned to a classification system. Consistent nomenclature should be used when describing AF. Consistency in the literature, however, is lacking. Bellet’s classification divides AF into three types (See Table 2): paroxysmal, chronic, and recent-onset. Paroxysmal AF is recurrent episodes of AF lasting more than two minutes but fewer than seven days.8 Chronic AF lasts more than one month.14 Recent-onset AF is persistent AF lasting seven or more days but less than one month.14 Some studies call the dysrhythmia "persistent" if it lasts seven or more days but less than one month, while others, implying similar causation, lump AF of different durations into the same study population.8
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Differences in the type of AF have treatment implications, and classification of the dysrhythmia based on the emergency patient population may be more appropriate. A proposed classification of AF based on emergency department (ED) population, duration of the arrhythmia, and response to treatment has been suggested as follows: 1) AF lasting fewer than 72 hours; 2) persistent AF lasting 72 hours or more; and 3) permanent AF. A recent study recognized that AF lasting fewer than 72 hours may convert spontaneously to NSR or may be converted using pharmacological or electrical means without grave consequences. Untreated AF lasting more than 72 hours became persistent and was more resistant to cardioversion.2 This implies that some forms of AF that fail to terminate early may be differentiated from those that do, which has implications for further patient testing and treatment.
Prevalence, Epidemiology, and Outcome
Prevalence. AF is more common than ventricular dysrhythmias.13 The overall prevalence of AF in the general population is between 0.4% and 0.9%.5 The relative prevalences are one-quarter paroxysmal, one-half chronic, and one-quarter recent-onset.10 (See Table 2.)
Prevalence varies with age group and patient population. Atrial fibrillation affects 2.3% of persons older than age 40, 3-6% older than age 60, and 8.8% older than age 80.13,15,16 (See Table 3.) Seventy percent of patients are between ages 65 and 85.16 The median age for AF is 75.13 On average, men get AF at a younger age than women do. The mean age for AF in men is 66.5 years, compared with 71.4 in women.16 The male to female ratio for AF decreases after age 50; after age 75, most of the patients with AF (approximately 60%) are women.16
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Conditions Associated with AF. Half of the patients with paroxysmal AF have underlying heart disease.10 Among all patients with AF, 70-80% have cardiovascular diseases,8 the most common being hypertension, coronary artery disease (CAD), and myocardial diseases.10 (See Table 4.) Risk factors for AF include rheumatic heart disease, hypertension, diabetes (in women), left ventricular hypertrophy, CAD (mainly in the elderly and patients with left ventricular dysfunction),8 and mitral valve prolapse.13 As many as 40% of patients with overt congestive heart failure (CHF) will develop AF.4 Underlying heart disease is significantly more common in women who have AF than in men with AF.10 Rheumatic valvular disease is present in one-quarter of women with AF but in only 8% of men with AF.10 Other conditions associated with AF include hypertrophic cardiomyopathy, dilated cardiomyopathy, pericarditis, left atrial myxoma, congenital heart disease (such as atrial septal defect), mitral stenosis, AV valvular disease, acute myocardial infarction, cardiac and non-cardiac surgery, diuretic use, advancing age, higher levels of systolic blood pressure, increased height, elevated blood glucose, enlarged left atrial size, hyperthyroidism, cholinergic drug use, and pulmonary conditions that cause hypoxemia, such as chronic obstructive pulmonary disease (COPD).5,8 On the other hand, high serum cholesterol, beta-blocker use, and high forced expiratory volume in one second (FEV1) reduce the risk of AF.17 There has been a shift away from valvular etiologies toward nonrheumatic causes of AF in recent decades.10
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Outcome. A spectrum of symptoms, from palpitations to dyspnea, that affect quality of life; hemodynamic consequences, such as pulmonary edema and hypotension; side effects of drugs used to control ventricular rate or maintain sinus rhythm; and thromboembolic complications make AF a potentially devastating condition.13 AF increases mortality 100% compared with patients without the dysrhythmia. The Framingham study showed that AF increases mortality and that this association persists regardless of age, history of hypertension, diabetes, smoking, left ventricular hypertrophy on electrocardiogram (ECG), myocardial infarction, CHF, valvular heart disease, or cerebrovascular disease.18 AF may be independent of cardiovascular disease in as many as 31% of patients and is called lone AF.4
Stroke Outcome for AF. Patients with rheumatic valvular heart disease, prior thromboembolism, CHF, hypertrophic cardiomyopathy, hypertension, diabetes, hyperthyroidism, and women older than age 75 are at high risk for thromboembolism.19 Patients without hypertension, CAD, or CHF who also develop AF are five times more likely to have a stroke than those without AF.20 CAD alone increases a patient’s risk of stroke by two times, and CHF increases it by four times.20 AF compounds the risk of stroke in patients with CAD and CHF, doubling the already increased risk of stroke in men and tripling it in women.20 According to age, attributed risk of stroke from AF is 1.5% for patients in their 50s and rises to 30% for those in their 80s.15,20 For patients in their 80s in the Framingham study, AF was the sole cardiac condition related to the incidence of stroke, suggesting that the elderly with AF particularly are vulnerable to stroke.20 More than one-third, approximately 38%, of patients with AF due to non-rheumatic, non-valvular heart disease who suffer a stroke will die from that event.21 For surviving patients who are not anticoagulated, the risk of a recurrent cerebrovascular event is approximately 20% per year.21
From 1987 to 1989, United States medical centers participated in the Stroke Prevention in Atrial Fibrillation (SPAF) study, which followed patients with AF for an average of 1.3 years.15 CHF (within three months of AF onset), a history of hypertension, and prior thromboembolism each, independently, was associated with a greater than 7% per year risk for subsequent thromboembolism.22 For patients without these risk factors, the risk was only 2.5% per year (1.4% per year in non-diabetics).22 AF patients with two or three risk factors had a 17.6% per year risk of thromboembolism. AF, especially in the setting of other coexistent diseases, must be managed to prevent stroke and death.22
Etiology and Pathophysiology
Electrophysiologic Mechanisms of AF. There appear to be at least two distinct causes of AF. First, Moe proposed the "multiple wavelet hypothesis" that describes multiple, small, reentrant, electrical circuits in AF that constantly arise in the atria, collide, extinguish, and arise again. Approximately six electrical wavelets per second and a critical mass of atrial tissue are required to sustain AF.12,23 The average number of wavelets, however, is fewer when the fibrillatory wavelength (the product of conduction velocity and refractory period) is longer, as occurs in coarse AF; there are more wavelets when shorter wavelengths are present, as in fine AF.23 Anything that lengthens the wavelet wavelength tends to prevent or terminate AF, whereas anything that shortens the wavelet wavelength tends to induce or sustain it. Antiarrhythmic drugs can lengthen the wavelet wavelength, thus terminating AF.23 Increased parasympathetic tone,24 rapid atrial pacing, or intra-atrial conduction abnormalities can shorten the wavelength and perpetuate AF.23
Second, a rapidly firing automatic focus or foci located at sites near the sinus node, the coronary sinus in the right atrium, or the pulmonary veins in the left atrium can initiate AF.12,25 AF caused by such foci may be amenable to radiofrequency catheter ablation, and patients may be identified for this curative procedure.25 Patients who are likely to have a focal source are relatively young, of either sex, without structural heart disease, and have frequent episodes of paroxysmal AF, monomorphic premature atrial systoles, or both.25 Both the right and left atria can be sources of atrial premature complexes that promulgate spontaneous AF.26 It also is possible that separate mechanisms in the same patient cause AF.5
Atrial fibrillation may be present in patients who have other forms of supraventricular tachycardias, especially atrioventricular nodal reentry tachycardia (AVNRT) and atrioventricular reentry tachycardia (AVRT).25 Elimination of the AVNRT or AVRT by radiofrequency catheter ablation also eliminates the AF in most of these patients.25 It is, therefore, a logical conclusion that the supraventricular tachycardia in some way initiates the AF and is an example of a tachycardia-induced tachycardia.25
Atrial Remodeling. AF causes progressive electrophysiological and structural changes of the atria that incite and promote AF.4 AF associated with structural heart disease commonly leads to atrial dilatation and patchy fibrosis ranging from scattered areas of scarring to diffuse involvement that may include destruction of the sinoatrial node.5 Atrial scarring and fibrosis may, indeed, predispose the patient to the very dysrhythmia that caused the structural changes by increasing atrial susceptibility to autonomic stimuli or local myocarditis.12 AF results in electrical changes, including inhomogeneity, greater dispersion, and shortening of atrial refractory periods, that may lead to persistence or recurrence of the dysrhythmia.4,26 In addition, chronic effects of AF are characterized by decreased atrial contractility, shortened action potential duration, and attenuated action potential rate adaptation.11 These effects have been demonstrated by intermittent rapid atrial pacing in goats.4 This pacing technique causes shortening of atrial refractoriness with loss of rate adaptation and leads to an increase in the rate, inducibility, and sustainability of AF.4 After 1-3 weeks of artificially maintained paroxysms of AF, the duration of the paroxysms becomes progressively longer, and the dysrhythmia becomes sustained.4 It is said, "Atrial fibrillation begets atrial fibrillation."25
Electrophysiological Changes in the AV Node. Electrophysiology of the AV node is complex. Many antiarrhythmic medications work at the AV node to slow conduction, terminate reentrant rhythms, and control ventricular rate response to the fibrillating atria. The refractory period of the AV node is prolonged relative to that of the surrounding myocardium.5 As an electrical impulse travels through the AV node, it encounters decremental conduction (a progressive decrease in the ability of the AV nodal cells to induce new action potentials along its course), and the impulse may encounter a conduction block.5 A blocked impulse may impair AV conduction of subsequent atrial impulses. Conduction through the AV node can be modulated by autonomic influences or medications. An increase in sympathetic stimulation (as during exercise) or withdrawal of vagal inhibition facilitates conduction through the AV node.5 Accessory AV pathways, such as those found in Wolff-Parkinson-White syndrome (WPW), do not share these electrophysiological properties with the normal AV node and, hence, do not respond to antiarrhythmic drugs the same way that the AV node does.5
The Possible Role of Calcium. Calcium in the electrolyte milieu at the cardiac myosite membrane may be an important factor in initiating and sustaining AF. Experimental animal models show a reduction (which may represent a down-regulation) in the L-type Ca2+ current (ICa) density in fibrillating myocytes.11 ICa density also is found to be reduced significantly in myocytes of patients with chronic AF.11 The reduction in myocyte ICa density in patients with chronic AF may be an adaptive response to arrhythmia-induced calcium overload.11 Calcium’s role in initiating or perpetuating AF is not fully understood nor is it understood how measurable serum calcium relates to this concept.
Natriuretic Peptides in AF. The association of AF with activation of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) is uncertain but may be important for the future diagnostic uses for natriuretic peptides. Compared with patients in sinus rhythm, patients with AF show higher N-ANP levels but similar BNP levels.27 Multivariate analysis shows that a higher N-ANP level is associated with higher likelihood of AF, symptom class, and endothelin-1 level independent of left atrial volume and left ventricular ejection fraction. BNP level shows no such association.27
Hemodynamic Effects of AF. Loss of AV synchrony and irregular RR intervals cause hemodynamic changes during AF. This effect is more pronounced in patients with diastolic dysfunction than in those with impaired systolic function. Myocardial contractility changes from beat to beat in AF because of the influence of the force-interval relationships between end-systolic volume and the preceding RR interval.28 The irregular ventricular response to the fibrillating atria may cause a marked decrease in cardiac output, especially in those patients with impaired diastolic ventricular filling, mitral stenosis, restrictive or hypertrophic cardiomyopathy, or pericardial diseases.5 For example, in dog hearts that are paced irregularly, cardiac output declines 15% compared with dog hearts that are paced regularly at the same average pacing rate.5 Patients with rapid ventricular rates (usually greater than 130 beats per minute) sustained for several months are at risk for developing a tachycardia-induced cardiomyopathy, which often is reversible once sinus rhythm is restored.5 Persistent tachycardia may lead to ventricular dysfunction.12
Left Atrial Appendage Flow and Hemostatic Markers. One study found that left atrial appendage flow is significantly slower in patients with AF than in those with sinus rhythm (mean velocity 33 ± 22 cm/second vs 61 ± 35 cm/second) and that a peak left atrial appendage antegrade flow velocity less than 20 cm/second is associated with the dense spontaneous echocardiographic contrast (SEC).29 Slow left atrial appendage flow and the presence of left atrial SEC or thrombus found by transesophageal echocardiography (TEE) suggest an elevated thrombogenic state in the patient who has nonvalvular AF.30 The maximum left atrial diameter is significantly greater and the left atrial expansion fraction significantly smaller in patients with slow left atrial appendage flow.30 Plasma levels of hemostatic markers in peripheral blood (thrombin-antithrombin III complex, fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4) are elevated significantly in patients with slow left atrial appendage flow.30 These patients are at risk for increased intravascular coagulation-fibrinolysis activity and platelet activation, and these abnormalities may be related closely to the thrombogenic state in patients with AF.30
Hemodynamic Changes after Cardioversion. After cardioversion of chronic AF, cardiac output declines in more than one-third of patients.31 The cardiac depressant effects of anesthetics (used during cardioversion) or heart disease itself may contribute to reduced cardiac function.31 In the majority of patients, however, cardioversion of chronic AF gradually increases cardiac output by approximately one-half during the month following restoration of sinus rhythm as left atrial mechanical strength increases and as the atrial myopathy subsides.31
Clinical Presentation
Presenting Symptoms in General. AF may occur: 1) as a primary dysrhythmia in the absence of structural heart disease; 2) as a secondary dysrhythmia in the absence of structural heart disease but in the presence of a systemic abnormality that predisposes the individual to the dysrhythmia; or 3) as a secondary dysrhythmia associated with cardiac disease affecting the atria.5 Thus, when faced with recent-onset AF, it is important to search for an underlying cause, such as ischemic heart disease, hyperthyroidism, or electrolyte abnormalities.
Symptoms are present in almost 90% of patients with AF and are significantly more frequent in females than in males.10 Patients with paroxysmal AF are younger and more likely to experience palpitations than patients with chronic AF, who are older and usually less symptomatic.10 Some patients have minimal symptoms or none at all, whereas others may have severe symptoms, particularly at arrhythmia onset.12 Factors affecting symptoms include ventricular rate, overall cardiac function, underlying medical conditions, and patient perception.5 Asymptomatic patients usually present with a relatively controlled ventricular rate less than 100 beats per minute, whereas patients who are tachycardic may present with chest discomfort, cardiac ischemia, or overt pulmonary edema.5 Symptoms range from occasional palpitations to severe dyspnea, but fatigue, dizziness, near syncope, and dyspnea are common.5,12 Dyspnea, in fact, is the most common presenting symptom in chronic AF and recent-onset AF.12,32
In paroxysmal AF, asymptomatic episodes occur more frequently than do symptomatic ones, and palpitations are the most common complaint.10,12 Paroxysmal AF does not occur randomly.33 Instead, it exhibits a circadian rhythm with a double peak, one occurring in the morning and the other in the evening.33 Moreover, there are substantially fewer episodes of paroxysmal AF on Saturdays; they are more frequent during the last months of the year.33
Prior thromboembolism may have occurred in 10% of patients with chronic AF.10 Therefore, one must be sensitive to any subtle neurological changes found on examination or reported by the patient or historian. Neurological symptoms and the patient’s underlying illnesses may help the EP decide whether a new stroke is due to AF. The sudden onset of neurological symptoms and a history of valvular heart disease predict a cardioembolic stroke. (See Table 5.) A subacute onset of symptoms and a history of COPD, hypertension, hypercholesterolemia, transient ischemic attack, ischemic heart disease, or diabetes predict an atherothrombotic stroke.34 In addition, chronic AF may impair cognitive function of elderly patients as compared with that of age-matched controls in sinus rhythm.12 It is unclear whether this impairment is due to recurrent cerebral embolism, cerebral hypoperfusion, or both.12
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Diagnostic Studies
ECG. AF causes irregular multiform f waves (the irregular undulation of the baseline that is depicted in Figure 1) and an irregularly irregular ventricular response on ECG or cardiac rhythm strip.35 (See Table 6.) The mean resting ventricular rate in a patient with new-onset AF is usually between 110 and 130 beats per minute,12 but rates as high as 200 beats per minute may develop in the absence of rate-controlling medications.35 The ventricular rate may be less than 100 beats per minute in patients who already are on antiarrhythmic medications. The EP should consider the possibility of digitalis toxicity when AF is accompanied by a regular ventricular rate.35 An ECG showing AF is correctly identified by 31-91% of physicians, which suggests a large margin for improving ECG interpretation.36
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Some medications used to slow AV conduction may enhance conduction down an accessory AV pathway, speeding ventricular response. A slow QRS upstroke may indicate the delta wave of ventricular preexcitation.35 Wide QRS beats during AF are more likely to be due to aberration than to a coincidental ventricular premature beat or to ventricular tachycardia (if wide QRS beats occur in series).35
Echocardiography. Transthoracic echocardiography (TTE) has little value in treating the ED patient with AF.37 TTE, however, may be useful to the cardiologist looking for high-risk features for AF, such as rheumatic valvular disease, hypertrophic cardiomyopathy, and left ventricular dysfunction.19,38 Left atrial size, left ventricular wall thickness, and left ventricular function are independent risk factors for developing AF.19 Left atrial size may have predictive value in determining the success of cardioversion and maintaining sinus rhythm, as well.19 According to SPAF, left ventricular dysfunction by echocardiogram and enlarged left atrial size are the strongest independent predictors of subsequent thromboembolism.39
Echocardiography also is useful to the cardiologist for assessing cardiac structure and function and the presence of thrombus or dense SEC "smoke" in the left atrium or left atrial appendage.37 In a multicenter trial, one study randomized 1222 patients with AF for more than two days to either treatment guided by TEE or conventional treatment, with three weeks of anticoagulation before cardioversion followed by four weeks of warfarin therapy after cardioversion.40 There was no significant difference between the two groups in the rate of embolic events, but hemorrhagic events were significantly fewer in the TEE group, which also had a shorter time to cardioversion and a greater rate of successful restoration of sinus rhythm.40 TEE, if readily available to the EP, shows promise in treating emergency patients with AF.
TEE is not readily available to the EP for assessing the hemodynamically unstable patient and mostly is used under controlled conditions in the electrophysiology lab by an echocardiographer who may use it to risk-stratify patients with AF or to identify patients who need prolonged anticoagulation.37 Therefore, its use in AF is appreciated most easily in elective cardioversion of the hemodynamically stable patient. For patients with chronic AF, it is recommended that cardioversion be attempted in patients who have AF for less than one year and who have been anticoagulated for at least four weeks.41 Alternatively, TEE may be used to screen the left atrium for thrombus in lieu of prior anticoagulation with heparin or warfarin.41 Low molecular weight heparin may be used as a "bridge" to full anticoagulation with warfarin in stable patients undergoing elective TEE-guided cardioversion, and low molecular weight heparin may be self-administered on an outpatient basis.42 For patients with a thrombus seen with the initial TEE, follow-up TEE to document thrombus resolution after 3-4 weeks of anticoagulation is recommended before cardioversion.43 Likewise, TEE also may prove useful in identifying patients with a low clinical risk profile who may be treated with aspirin alone.37
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