REVIEW

The Patient with Atrial Fibrillation

Julia Heisler Indik, MD, PhD, Joseph S. Alpert, MD
Sarver Heart Center, College of Medicine, University of Arizona, Tucson.

ABSTRACT Atrial brillation is a frequently encountered arrhythmia, particularly affecting the elderly. Patients at signicant risk for stroke should be considered for anticoagulation with warfarin. Management of atrial brillation revolves around either controlling the ventricular rate response or trying to maintain sinus rhythm with either pharmacologic or nonpharmacologic therapies. There are many treatment options to consider, based upon the patients expectations, symptoms, and comorbid conditions. Therefore, the treatment of atrial brillation must be individualized. 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 415-418 KEYWORDS: Ablation; Antiarrhythmic medication; Anticoagulation; Atrial brillation; Stroke

Atrial brillation is the most common sustained arrhythmia in North America and Europe. In the United States, atrial brillation affects approximately 2.2 million adults whose median age is 75 years, and nearly 10% of individuals over the age of 80 years, with a clear increase in incidence and prevalence with age.1,2 During the late 20th century, the Framingham Heart Study population demonstrated a 7.8% prevalence of atrial brillation in men aged 65-74 years, with a corresponding prevalence in men aged 75-84 years of 11.7%. As the population of older individuals has increased, the prevalence of atrial brillation also has grown.1-3 However, even age-adjusted prevalence of atrial brillation has increased in recent years, suggesting that age alone does not account for all aspects of the increased frequency of encountering this arrhythmia.3 Atrial brillation occurs approximately 1.5 times more frequently in men than in women. In the Framingham Heart Study, the prevalence of atrial brillation in men without a prior myocardial infarction was 8.7%. A similar cohort of women had a prevalence of atrial brillation of only 5.2%. Despite the sex difference in prevalence, the overall number of female patients with atrial brillation exceeds the number
Funding: There are no funding sources for this manuscript. Conicts of Interest: There is no conict of interest to disclose from Dr. Indik or Dr. Alpert. Authorship: Both authors had access to the data and content of this manuscript and had a role in the writing of the manuscript. Requests for reprints should be addressed to Julia Heisler Indik, MD, University of Arizona, Sarver Heart Center, 1501 N. Campbell Ave., Tucson, AZ 85724. E-mail address: jindik@email.arizona.edu

of men with this condition because of greater longevity in women. Thus, the most common hospitalized patient with atrial brillation in US hospitals is an elderly woman. The majority of patients with atrial brillation have some form of cardiovascular disease. Common cardiovascular conditions predisposing to atrial brillation include hypertension, valvular heart disease (especially mitral valve disease), arteriosclerotic heart disease with and without a prior myocardial infarction, pericardial disease, and heart failure. Noncardiovascular diseases that predispose to atrial brillation include diabetes mellitus, hyperthyroidism, acute and chronic alcohol abuse, and a variety of pulmonary diseases such as chronic obstructive lung disease, pneumonia, and pulmonary embolism. Finally, iatrogenic causes of atrial brillation include cardiac and noncardiac surgery as well as therapy with bronchodilating beta agonists, nonprescription cold remedies, antihistamines, and local anesthetics.4 Recent investigation has revealed that inammation in the atria might play an important role in the initiation, maintenance, and perpetuation of atrial brillation.5 Unfortunately, the underlying etiology of atrial brillation is often not well understood in individual patients, although there is increasing evidence for a genetic predisposition.6 Families with autosomal dominant inheritance of atrial brillation have been reported.7 In familial forms of atrial brillation, mutations have been described affecting both potassium and sodium channels, with associations with other inherited rhythm disorders such as Brugada syndrome, short QT syndrome, and, most recently, in a form of long QT syndrome.8 Idiopathic or lone atrial brillation is not as benign an entity as once thought. Jouven et al observed a 4-fold

0002-9343/$ -see front matter 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2008.12.012

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increase in cardiovascular mortality and a 2-fold increase in itant was exercise, present in nearly 19% of patients, folall-cause mortality for middle-aged French men with lone lowed by eating in 8%. Caffeine-containing beverages atrial brillation.9 A recent community-based study from precipitated atrial brillation in only 2.4% of patients. Omstead County in Minnesota and the EuroHeart Failure The diagnosis of atrial brillation is usually straightforSurvey demonstrated that patients with newly diagnosed ward, depending on the recognition of a randomly irregular atrial brillation with or without heart rhythm on physical examiheart failure had a high mortality nation or electrocardiogram. Atrial brillation is further characterized risk as well as prolonged hospitalCLINICAL SIGNIFICANCE by whether it terminates spontaneization, especially within the rst ously, paroxysmal atrial brilla4 months following diagnosis.10,11 Atrial brillation is the most common tion, or requires cardioversion to Of further concern are recent rearrhythmia in this country, with a prevrestore sinus rhythm, persistent ports that atrial brillation in paalence that has been increasing. atrial brillation. There are 2 potients without any evidence of Patients with atrial brillation need to be tential strategies to manage atrial stroke are associated with memory considered for the need for anticoagulabrillation: control of the ventricimpairment, dementia, and hiption, based upon their risk for stroke. ular heart rate, or restoration of pocampal atrophy.12,13 In patients sinus rhythm. In patients over the with paroxysmal atrial brillation, Atrial brillation can be managed with age of 65 years with at least one a precipitating event, for example, either rate or rhythm control strategies, risk factor for stroke, the Atrial binge drinking, heavy exertion, or which are based upon both pharmacoFibrillation Follow-up Investigaemotional upset, can be identied logic and nonpharmacologic methods, tion of Rhythm Management in approximately 40% of individincluding catheter ablation. (AFFIRM) trial demonstrated that uals.14 The most common precip-

Figure 1 To employ a rate control strategy to manage atrial brillation, patients should rst be assessed for the risk for stroke to determine the need for anticoagulation. For patients with rapid ventricular rates in atrial brillation, AV nodal blocking medications are utilized, which include beta-blockers, calcium channel blockers, and digoxin. Pacemaker and AV node ablation is reserved for patients who cannot be successfully managed medically. To employ a rhythm control strategy to manage atrial brillation, patients also should rst be assessed for the need for anticoagulation. Antiarrhythmic drug (AAD) therapy and cardioversion are utilized as needed to maintain sinus rhythm, and catheter ablation is reserved for patients who have symptomatic atrial brillation not adequately controlled by pharmacologic therapy.

Indik and Alpert

Management of Atrial Fibrillation

417 group of patients, except for severe systolic heart failure, where there has been concern for an increase in mortality seen in the Antiarrhythmic Trial with Dronedarone in Moderate to Severe CHF Evaluating Morbidity Decrease (ANDROMEDA) trial.17 Patients who are not adequately controlled on an antiarrhythmic medication can be considered for catheter ablation for atrial brillation.18 Other patients hardly seem to notice when they are in atrial brillation, as long as their heart rate is controlled. Pharmacologic options to achieve rate control include digoxin, beta-blockers, and calcium channel blockers (Figure 1). If such medications are not tolerated or are ineffective, then pacemaker implantation with AV node ablation can be considered. Ablation of the AV node does not restore sinus rhythm, but controls the consequence of atrial brillation, a rapid ventricular heart rate. It should be noted that, for rate control patients, digoxin therapy slows resting but not exercise heart rate, and this agent does not prevent recurrent episodes of atrial brillation, although betablocker administration can accomplish this goal.19 Digoxin also should be used cautiously in the elderly and in patients with chronic kidney disease, as the drug is cleared by the kidneys. The presence of atrial brillation markedly increases the patients risk for developing arterial embolism and stroke, depending on the presence of other clinical conditions, such as hypertension and diabetes. Consequently, most patients with atrial brillation should receive antithrombotic therapy with warfarin. Even patients in whom rhythm control is established should continue on warfarin because silent episodes of atrial brillation may still be occurring, for example, at night during sleep. The Cardiac Failure, Hypertension, Age, Diabetes, Stroke (Doubled) (CHADS2) score was developed to identify patients who are at high enough risk

there is no difference in survival using either a rate control or rhythm control strategy.15 In the AFFIRM study, the rate control strategy predominantly relied upon the use of atrioventricular (AV) nodal blocking medications, while the rhythm control strategy predominantly relied upon cardioversion and the use of antiarrhythmic medications, most commonly amiodarone. Whether rate and rhythm control strategies are equivalent in younger patients (under the age of 65 years) is unknown. Of note, newer techniques to maintain sinus rhythm, including catheter ablation, were not studied in the AFFIRM trial. Randomized trials are underway to assess whether ablation for atrial brillation can favorably alter cardiovascular outcomes. Which therapy strategy is chosen depends upon the symptoms of the patient and comorbidities. In particular, patients with infrequent symptoms may not require any further treatment. However, many individuals have frequent episodes of symptomatic atrial brillation, including fatigue and dyspnea. Indeed, quality of life and exercise tolerance are decreased in patients with atrial brillation, and both of these variables improve when sinus rhythm is restored.16 For rhythm control, many patients will require antiarrhythmic drug therapy to maintain sinus rhythm (Figure 1). Antiarrhythmic drugs include the Vaughn-Williams Class IC agents, such as propafenone or ecainide, and Class III agents such as sotalol, dofetilide, or amiodarone. The choice of antiarrhythmic medication is dependent on whether there is any other heart disease such as signicant hypertrophy, systolic heart failure, or coronary artery disease (Figure 2). Dronedarone is a new antiarrhythmic drugawaiting Food and Drug Administration approvalthat is related to amiodarone but without iodine on its aromatic ring, which is responsible for the long-term toxicity of amiodarone. Dronedarone may be approved for management in a broad

Figure 2 Antiarrhythmic drug therapy is chosen according to whether the patient has heart disease, including systolic heart failure, coronary artery disease, and substantial left ventricular hypertrophy. Dronedarone, indicated in parentheses, may be approved as an appropriate choice for a broad range of patients, except in those with systolic heart failure.

418 for stroke to warrant anticoagulation with warfarin.20 Patients with 2 moderate risk factors (age over 75 years, hypertension, diabetes, or heart failure) or one high risk factor (prior stroke, prosthetic heart valve, or mitral stenosis) have an estimated risk of stroke of 3.1%-5.1% per year and should be anticoagulated with warfarin.20 If the risk of bleeding is markedly increased, then aspirin may be the therapy of choice because hemorrhage is less common with this agent than with warfarin. The presence of atrial brillation can contribute to patient morbidity. A rapid ventricular response can produce myocardial ischemia or even infarction in a patient with underlying coronary artery disease. Whether atrial brillation worsens prognosis in patients with acute myocardial infarction or new-onset heart failure has been the subject of considerable debate. Interestingly, some studies have reported that atrial brillation independently worsens prognosis in patients with heart failure or myocardial infarction, whereas other observers have found no effect of associated atrial brillation on outcomes.20-25 Despite the generally worsened prognosis for patients with atrial brillation, many patients do well for years and even decades. Therefore, the prognosis for the individual patient is variable. As noted earlier, excellent rate control with betablockers, nondihydroperidine calcium blockers (diltiazem and verapamil) and digoxin, along with anticoagulation and control of other cardiovascular risk factors, can stabilize patients with atrial brillation for years. In this regard, it is of interest that 2 studies have documented signicant improvement in prognosis for patients with atrial brillation treated during the 1990s as compared with individuals managed during the 1980s.26,27 In our own practice, we work hard with patients to assess their symptoms and expectations with regard to choosing a rate or rhythm control strategy.

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11. Rivero-Ayerza M, Scholte Op Reimer WS, Lenzen M, et al. Newonset atrial brillation is an independent predictor of in-hospital mortality in hospitalized heart failure patients: results of the EuroHeart Failure Survey. Eur Heart J. 2008;29:1618-1624. 12. Knecht S, Oelschlager C, Duning T, et al. Atrial brillation in strokefree patients is associated with memory impairment and hippocampal atrophy. Eur Heart J. 2008;29:2125-2132. 13. Miyasaka Y, Barnes ME, Petersen RC, et al. Risk of dementia in stroke-free patients diagnosed with atrial brillation: data from a community-based cohort. Eur Heart J. 2007;28:1962-1967. 14. Levy S, Maarek M, Coumel P, et al. Characterization of different subsets of atrial brillation in general practice in France. The ALFA Study. Circulation. 1999;99:3028-3035. 15. Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial brillation. N Engl J Med. 2002;347:1834-1840. 16. Singh SN, Tang XC, Singh BN, et al.; SAFE-T Investigators. Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial brillation: a Veterans Affairs Cooperative Studies Program Substudy. J Am Coll Cardiol. 2006;48:721-730. 17. Kober L, Torp-Pedersen C, McMurray JJV, et al. for the Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358:2678-2687. 18. European Heart Rhythm Association (EHRA); European Cardiac Arrhythmia Society (ECAS); American College of Cardiology (ACC); American Heart Association (AHA); Society of Thoracic Surgeons (STS); Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial brillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial brillation. Heart Rhythm. 2007;4:816-861. 19. Crenshaw BS, Ward SR, Granger CB, et al. Atrial brillation in the setting of acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol. 1997;30:406-413. 20. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial brillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European Society of Cardiology committee for practice guidelines (writing committee to revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol. 2006; 48:e149-e246. 21. Sakata K, Kurihara H, Iwamori K, et al. Clinical and prognostic signicance of atrial brillation in acute myocardial infarction. Am J Cardiol. 1997;80:1522-1527. 22. Goldberg RJ, Seeley D, Becker RC, et al. Impact of atrial brillation on the in-hospital and long-term survival of patients with acute myocardial infarction: a community-wide perspective. Am Heart J. 1990; 119:996-1001. 23. Behar S, Tanne D, Zion M, et al. Incidence and prognostic signicance of chronic atrial brillation among 5839 consecutive patients with acute myocardial infarction. Am J Cardiol. 1992;70:816-818. 24. Middlekauff HR, Stevenson WG, Stevenson LW. Prognostic signicance of atrial brillation in advanced heart failure: a study of 390 patients. Circulation. 1991;84:40-48. 25. Carson PE, Johnson GR, Dunkman WB, et al. The inuence of atrial brillation on prognosis in mild to moderate heart failure. The V-HeFT studies. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87(6 Suppl):VI102-VI110. 26. Stevenson WG, Stevenson LW, Middlekauff HR, et al. Improving survival for patients with atrial brillation and advanced heart failure. J Am Cardiol Coll. 1996;28:1458-1463. 27. Frost L, Engholm G, Moeller H, Husted S. Decrease in mortality in patients with a hospital diagnosis of atrial brillation in Denmark during the period 1980-1993. Eur Heart J. 1999;20:1592-1599.

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