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Acute Management of Atrial Fibrillation: Part I. Rate and Rhythm Control DANA E

Acute Management of Atrial Fibrillation: Part I. Rate and Rhythm Control DANA E

COVER ARTICLE PRACTICAL THERAPEUTICS

Acute Management of Atrial : Part I. Rate and Rhythm Control DANA E. KING, M.D., LORI M. DICKERSON, PHARM.D., and JONATHAN L. SACK, M.D. Medical University of South Carolina, Charleston, South Carolina

Atrial fibrillation is the most commonly encountered in family practice. Serious complications can include congestive failure, , and thromboembolism. Initial treatment is directed at controlling the ventricular rate, most often with a , a , or . Medical or electrical to restore is the next step in patients who remain in atrial fibrillation. should be administered to hospitalized patients undergoing med- ical or electrical cardioversion. Anticoagulation with should be used for three weeks before elective cardioversion and continued for four weeks after cardioversion. The recommendations provided in this two-part article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality. (Am Fam Physician 2002;66:249-56. Copyright© 2002 American Academy of Family Physicians.)

n recent years, management ness of breath, dizziness, or . strategies for atrial fibrillation The arrhythmia should also be suspected have expanded significantly, and in patients with acute fatigue or exacer- new drugs for ventricular rate bation of congestive .3 In control and rhythm conversion some patients, atrial fibrillation may be Ihave been introduced.1-3 Family physi- identified on the basis of an irregularly cians have the challenge of keeping cur- irregular or an electrocardiogram rent with recommendations on (ECG) obtained for the evaluation of control, antiarrhythmic drug therapy, car- another condition. dioversion, and antithrombotic therapy. Cardiac conditions commonly associ- Atrial fibrillation is the most common ated with the development of atrial fibril- sustained arrhythmia encountered in the lation include rheumatic dis- primary care setting. Approximately 4 per- ease, coronary disease, congestive Members of various cent of persons in the general U.S. popula- heart failure, and . Noncar- family practice depart- tion have permanent or intermittent atrial diac conditions that can predispose ments develop articles fibrillation, and the prevalence of the patients to develop atrial fibrillation for “Practical Therapeu- arrhythmia increases to 9 percent in per- include , , alco- tics.” This article is one 2 4 in a series coordinated sons older than 60 years. Atrial fibrillation hol intoxication, and surgery. by the Department of can result in serious complications, The ECG is the mainstay for diagnosis Family Medicine at the including congestive heart failure, myocar- of atrial fibrillation (Figure 1). An irregu- Medical University of dial infarction, and thromboembolism. larly irregular rhythm, inconsistent R-R South Carolina. Guest Recognition and acute management of interval, and absence of P waves are usu- editor of the series is William J. Hueston, M.D. atrial fibrillation in the physician’s office or ally noted on the cardiac monitor or emergency department are important in ECG. Atrial fibrillation waves (f waves), This is part I of a two- preventing adverse consequences. which are small, irregular waves seen as a part article on atrial rapid-cycle baseline fluctuation, indicate fibrillation. Part II, “Pre- Diagnosis rapid atrial activity (usually between 150 vention of Thrombo- embolic Complications,” The diagnosis of atrial fibrillation and 300 beats per minute) and are the appears in this issue should be considered in elderly patients hallmark of the arrhythmia. on pages 261-4. who present with complaints of short- When the fibrillation waves reach 300

JULY 15, 2002 / VOLUME 66, NUMBER 2 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 249 { {

FIGURE 1. Atrial fibrillation. The tracing demonstrates the absence of P waves (long arrow), as well as the presence of the fine f waves of atrial fibrillation (short arrows). Note the irregularity of the ventricular response, as seen from the variable R-R interval (brackets).

beats per minute, they may be difficult to see rate of approximately 150 beats per minute. In (fine versus coarse fibrillation).5 These waves this condition, the atrial rate is regular (unlike may be even harder to detect on a cardiac the irregular disorganized f waves of atrial fib- monitor in a busy emergency department rillation), but conduction to the ventricles is because of interference from other electrical not regular. The resultant irregularly irregular equipment. The f waves may be easier to iden- rhythm may be difficult to differentiate from tify on a printed rhythm strip. In addition, atrial fibrillation.3 when the ventricular response to atrial fibril- lation is very rapid (more than 200 beats per Initial Management minute), variability of the R-R interval can Recent advances in treatment and the intro- frequently be seen more easily using calipers duction of new drugs have not changed initial on a paper tracing. management goals in patients with atrial fibril- is included in the spectrum of lation. These goals are hemodynamic stabiliza- supraventricular arrhythmia. This rhythm tion, ventricular rate control, and prevention disturbance is usually distinguishable by its of embolic complications.4,6-8 When atrial fib- more prominent saw-tooth wave configura- rillation does not terminate spontaneously, the tion and slower atrial rates (Figure 2). Atrial ventricular rate should be treated to slow ven- fibrillation should also be distinguished from tricular response and, if appropriate, efforts atrial with variable atrioventricu- should be made to terminate atrial fibrillation lar block, which usually presents with an atrial and restore sinus rhythm4,7,9 (Figure 3).8

FIGURE 2. Atrial flutter. Note the saw-tooth wave configuration, or flutter waves (arrows).

250 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 66, NUMBER 2 / JULY 15, 2002 Atrial Fibrillation

Initial Management of Atrial Fibrillation

Patient with diagnosis of atrial fibrillation

Hemodynamically stable (no , no , etc.)?

Yes No

Control ventricular rate (goal = <100 beats per Electrical cardioversion: sedate, minute): administer (Cardizem), then (100 J, 200 J, 300 J, 15 mg IV over 2 minutes, then 5 to 15 mg per 360 J) until sinus rhythm returns. hour by continuous IV infusion or administer other rate-control drug (see Table 1).

Spontaneous conversion to sinus rhythm?

Yes No

Assess cause of atrial Contraindications to cardioversion? fibrillation; hospital discharge, follow-up Yes No

Consider long-term Consider cardioversion, if indicated (see text): anticoagulation. Start heparin IV; then choose— Atrial fibrillation < 48 hours: immediate medical or electrical cardioversion Atrial fibrillation > 48 hours or unknown duration: Later elective cardioversion (electrical cardioversion with or without medical cardioversion) after 3 weeks of warfarin (Coumadin) Early TEE–guided cardioversion (electrical cardioversion with or without medical cardioversion)

Atrial fibrillation persists?

Yes No

Consider long-term Assess cause of atrial fibrillation; anticoagulation. hospital discharge, follow-up

FIGURE 3. Initial approach to the patient with acute atrial fibrillation. (IV = intravenous; J = joule; TEE = transesophageal ) Information from Falk RH. Atrial fibrillation. N Engl J Med 2001;344:1067-78.

JULY 15, 2002 / VOLUME 66, NUMBER 2 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 251 Compared with beta blockers and calcium In patients with atrial fibrillation, the initial management channel blockers, digoxin is less effective for goals are hemodynamic stabilization, ventricular rate control, ventricular rate control, particularly during and prevention of embolic complications. exercise. Digoxin is most often used as adjunc- tive therapy because of its slower onset of action (usually 60 minutes or more) and its weak potency as an – VENTRICULAR RATE CONTROL blocking agent.3,13 It can be used when rate Ventricular rate control to achieve a rate of control during exercise is of less concern.4,7,12 less than 100 beats per minute is generally the Digoxin is a positive inotropic agent, which first step in managing atrial fibrillation. Beta makes it especially useful in patients with sys- blockers, calcium channel blockers, and tolic heart failure.7 digoxin (Lanoxin) are the drugs most com- The calcium channel blockers diltiazem monly used for rate control3,4,7 (Table 1).3 (Cardizem) and (Calan, Isoptin) These agents do not have proven efficacy in are effective for initial ventricular rate control converting atrial fibrillation to sinus rhythm in patients with atrial fibrillation. These agents and should not be used for that purpose.4,7,10,11 are given intravenously in bolus doses until Beta blockers and calcium channel blockers the ventricular rate becomes slower.7 Dihydro- are the drugs of choice because they provide pyridine calcium channel blockers (e.g., nifed- rapid rate control.4,7,12 These drugs are effec- ipine [Procardia], amlodipine [Norvasc], tive in reducing the heart rate at rest and dur- felodipine [Plendil], isradipine [DynaCirc], ing exercise in patients with atrial fibrilla- nisoldipine [Sular]), are not effective for ven- tion.4,7,12 Factors that should guide drug tricular rate control. selection include the patient’s medical condi- Physicians can use the “rule of 15” in tion, the presence of concomitant heart fail- administering diltiazem to patients weighing ure, the characteristics of the medication, and 70 kg (154 lb): first, give 15 mg intravenously the physician’s experience with specific drugs. over two minutes, repeat the dose in 15 min- utes if necessary, and then start an intravenous infusion of 15 mg per hour; titrate the dose to control the ventricular rate (5 to 15 mg per The Authors hour). Verapamil, in a dose of 5 to 10 mg DANA E. KING, M.D., is associate professor in the Department of Family Medicine at administered intravenously over two minutes the Medical University of South Carolina, Charleston. Dr. King graduated from the Uni- and repeated in 30 minutes if needed, can also versity of Kentucky College of Medicine, Lexington, and completed a family practice residency at the University of Maryland Hospital, Baltimore. He also completed an aca- be used for initial rate control. Although all demic faculty development fellowship at the University of North Carolina at Chapel Hill calcium channel blockers can cause hypoten- School of Medicine. sion, verapamil should be used with particular LORI M. DICKERSON, PHARM.D., is a board-certified pharmacotherapy specialist and caution because of the possibility of pro- associate professor in the Department of Family Medicine at the Medical University of longed hypotension as a result of the drug’s South Carolina. Dr. Dickerson completed a clinical pharmacy residency in family med- icine at the Medical University of South Carolina. relatively long duration of action. Beta blockers such as propranolol (Inderal) JONATHAN L. SACK, M.D., is assistant professor and medical director of University Fam- ily Medicine, the community site for the Department of Family Medicine at the Medical and esmolol (Brevibloc) may be preferable to University of South Carolina. He received his medical degree from the University of the calcium channel blockers in patients with Witwatersrand, Johannesburg, South Africa, where he also completed his internship myocardial infarction or angina, but they and residency training. In addition, Dr. Sack completed an academic faculty develop- ment fellowship at the University of North Carolina at Chapel Hill School of Medicine. should not be used in patients with asthma. As initial treatment, 1 mg of propranolol is given Address correspondence to Dana E. King, M.D., Family Medicine Research Section, Medical University of South Carolina, 295 Calhoun St., P.O. Box 250192, Charleston, intravenously over two minutes; this dose can SC 29425 (e-mail: [email protected]). Reprints are not available from the authors. be repeated every five minutes up to a maxi-

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mum of 5 mg. Maintenance dosing of propra- Limited data suggest that combination reg- nolol is 1 to 3 mg given intravenously every imens provide better rate control than any four hours. Esmolol has an extremely short agent alone.15 half-life and may be given as a continuous intravenous infusion to maintain rate control RESTORATION OF SINUS RHYTHM (Table 1).3 Medical (Pharmacologic) Cardioversion. Despite depressive effects on contractility After patients with atrial fibrillation have been (unless the ejection fraction is below 0.20), cal- stabilized and the ventricular rate has been cium channel blockers and beta blockers can be controlled, conversion to sinus rhythm is the used for initial ventricular rate control in next consideration. The decision to restore patients with heart failure. Oxygen delivery to sinus rhythm should be individualized. the heart is usually much improved once the The many reasons for not attempting phar- ventricular rate is controlled (less than 100 beats macologic cardioversion include duration of per minute). A slower ventricular response rate atrial fibrillation for more than 48 hours, also allows more filling time for the heart and, recurrence of atrial fibrillation despite mul- thus, improved .14 However, the tiple treatment attempts, poor tolerance of benefits of long-term treatment with calcium antiarrhythmic agents, advanced patient age channel blockers or beta blockers should be and concomitant structural disease, large size carefully weighed against the negative inotropic of left (greater than 6 cm), and the effects. Drugs for rate control can generally be presence of sick sinus syndrome.2 However, stopped once sinus rhythm is restored.3 continued atrial fibrillation is associated with

TABLE 1 Drugs Commonly Used to Control Ventricular Rate in Patients with Atrial Fibrillation

Drug Initial dosing Maintenance dosing Comments

Calcium channel blockers Diltiazem (Cardizem) 15 to 20 mg IV over 2 minutes; 5 to 15 mg per hour by Convenient; easy to titrate to heart may repeat in 15 minutes continuous IV infusion rate goal Verapamil (Calan, 5 to 10 mg IV over 2 minutes; Not standardized More myocardial depression and Isoptin) may repeat in 30 minutes hypotension than with diltiazem Beta blockers Esmolol (Brevibloc) Bolus of 500 mcg per kg IV 50 to 300 mcg per kg per Very short-acting; easy to over 1 minute; may repeat in minute by continuous titrate to heart rate goal 5 minutes IV infusion Propranolol (Inderal) 1 mg IV over 2 minutes; may 1 to 3 mg IV every 4 hours Short duration of action; hence, repeat every 5 minutes to need for repeat dosing maximum of 5 mg Digoxin (Lanoxin) 0.25 to 0.5 mg IV; then 0.25 mg 0.125 to 0.25 mg per day Adjunctive therapy; less effective IV every 4 to 6 hours to IV or orally for rate control than beta blockers maximum of 1 mg or calcium channel blockers

IV = intravenous. Adapted with permission from Li H, Easley A, Barrington W, Windle J. Evaluation and management of atrial fibrillation in the emergency department. Emerg Med Clin North Am 1998;16:389-403.

JULY 15, 2002 / VOLUME 66, NUMBER 2 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 253 long-term complications that can best be , disopyramide, , avoided by prompt return to sustained nor- and have been found to be effective in mal sinus rhythm and correction of underly- maintaining sinus rhythm. One study com- ing ischemic or structural abnormality. Early paring and disopyramide found successful cardioversion may also reduce the moderate evidence of efficacy for amiodarone incidence of recurrent atrial fibrillation.3 in the maintenance of sinus rhythm.17 Medical cardioversion may be appropriate Overall, antiarrhythmic drug selection in certain situations, especially when adequate should be individualized based on the patient’s facilities and support for electrical cardiover- renal and hepatic function, concomitant ill- sion are not available or when patients have nesses, use of interacting medications, and never been in atrial fibrillation before. Phar- underlying cardiovascular function. Because of macologic agents are effective in converting intravenous-formulation availability and effec- atrial fibrillation to sinus rhythm in about tiveness, one drug may be used for conversion 40 percent of treated patients.2,3 and another for maintenance therapy. Amio- Physicians should use medical cardiover- darone is the recommended agent in patients sion only after careful consideration of the with a low ejection fraction (below 0.35) or possibility of proarrhythmic complications, structural heart disease. Patients should be particularly in patients with structural heart monitored closely because quinidine, pro- disease or congestive heart failure.7 Because pafenone, and amiodarone may increase the cardioversion can lead to systemic emboli, International Normalized Ratio when they are heparin should be given before medical cardio- used with warfarin. These same drugs and ver- version is attempted7 (see part II for more apamil raise digoxin levels, which may necessi- information on this subject). Anticoagulation tate a decrease in the digoxin dosage.7 with warfarin (Coumadin) should be contin- The question of whether rate control or ued for four weeks after cardioversion. rhythm control should take precedence is cur- After anticoagulation is initiated, quinidine rently being investigated in a randomized trial sulfate (Quinidex), (Tambocor), or (Atrial Fibrillation Follow-up Investigation of propafenone (Rythmol) may be used to attempt Rhythm Management).18 A recent small pharmacologic conversion. The following intra- study19 examined rate control (using dilti- venously administered drugs may also be used: azem) versus rhythm control (using amio- (Tikosyn), (Corvert), pro- darone) plus anticoagulation. Overall, rate cainamide, or amiodarone (Cordarone).8,16 control was as good as rhythm control in A recent review4 and a meta-analysis17 con- reducing or eliminating symptoms and in cluded that flecainide, ibutilide, and dofetilide reducing hospitalization rates, but the com- were the most efficacious agents for medical parative effect on risk was not studied. conversion of atrial fibrillation, but that Electrical Cardioversion. When patients with propafenone and quinidine were also effec- atrial fibrillation are hemodynamically unstable tive. In the presence of Wolff-Parkinson- (e.g., angina, hypotension) and not responding White syndrome, is the drug of to resuscitative measures, emergency electrical choice for converting atrial fibrillation.7 Less cardioversion is indicated. In stable patients, evidence supports the use of disopyramide elective cardioversion is performed after three (Norpace) and amiodarone, and evidence weeks of warfarin therapy.7,8 To prevent throm- supports a negative effect for sotalol (Beta- bus formation, warfarin is continued for four pace).4,17 However, some investigators con- weeks after cardioversion. Although the success sider amiodarone to be the most effective rate for electrical cardioversion is high (90 per- agent for converting to sinus rhythm in cent), proper equipment and expertise are nec- patients who do not respond to other agents.7 essary for safe performance.3

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If there is time and patients are conscious, sedation should be achieved before cardiover- Although the success rate for electrical cardioversion is high sion is attempted. Synchronized external (90 percent), proper equipment and expertise are necessary direct-current cardioversion is performed with for safe performance. the pads placed anteriorly and posteriorly (over the sternum and between the scapulae) at 100 joules (J). If no response occurs, the cur- rent is applied again at 200 J; if there is still no ever, restoration of sinus rhythm is not always response, the current is increased to 300 J, and possible. In elderly patients with longstanding then to a maximum of 360 J. If patients cannot atrial fibrillation, repeated attempts at cardio- be moved, the pads can be applied over the version may be counterproductive. The right sternal border and left lateral chest wall.3 chances of reverting to and maintaining sinus Patients with atrial fibrillation at a ventricu- rhythm are lower with longer duration of atrial lar rate of less than 150 beats per minute who fibrillation and decrease to particularly low lev- are hemodynamically stable can be initially els when atrial fibrillation has been present for treated with drugs for ventricular rate control more than one year. When cardioversion is and intravenously administered heparin for inappropriate or unsuccessful, medication anticoagulation (see part II for more informa- should be used for ventricular rate control, and tion). Medical cardioversion or elective elec- anticoagulation therapy should be considered. trical cardioversion can then be considered as General recommendations for the initial appropriate. Patients are usually monitored in management of atrial fibrillation are summa- the hospital while cardioversion is being rized in Table 2.2,3,7,8,22 attempted. However, one study20 documented positive results for emergency-department The authors indicate that they do not have any con- performance of cardioversion followed by flicts of interest. Sources of funding: none reported. direct discharge of hemodynamically stable patients without congestive heart failure. TABLE 2 An alternative approach for achieving ear- General Recommendations for Initial Management lier return to sinus rhythm is early electrical of Atrial Fibrillation cardioversion and the use of transesophageal echocardiography according to American Acute control of the ventricular rate is best achieved with an intravenously 7 Heart Association guidelines. Transesophageal administered calcium channel blocker (e.g., diltiazem [Cardizem]) or beta echocardiography is used to detect thrombi in blocker (e.g., esmolol [Brevibloc]). the right atrium. If no thrombi are present, Immediate electrical cardioversion should be considered in hemodynamically electrical cardioversion can be performed unstable patients with atrial fibrillation. immediately; if thrombi are detected, cardio- Medical (pharmacologic) or electrical cardioversion following anticoagulation version can be delayed until patients have should be considered in hemodynamically stable patients with atrial fibrillation. undergone three weeks of oral anticoagulation Elective electrical cardioversion should be used in patients with persistent or using warfarin.21 One recent comparative recurrent atrial fibrillation. The success rate for electrical cardioversion is 90%. 22 study found no differences in thromboem- Medical cardioversion is a convenient and reasonable alternative in some bolic complications between conventional patients, but it does not always terminate atrial fibrillation. The success rate treatment and early cardioversion following for medical cardioversion is about 40%. transesophageal echocardiography. Early cardioversion after transesophageal echocardiography with intravenous Because of the risk of complications such as anticoagulation is an increasingly used alternative strategy. heart failure and embolic stroke, restoration of sinus rhythm is thought to be preferable to Information from references 2, 3, 7, 8, and 22. allowing atrial fibrillation to continue. How-

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REFERENCES man SN, Powe NR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam 1. Ellenbogen KA, Wood MA, Stambler BS. Intra- Pract 2000;49:47-59. venous therapy for atrial fibrillation: more choices, 13. Falk RH, Leavitt JI. Digoxin for atrial fibrillation: a more questions, more trials. Am Heart J 1999; drug whose time has gone? Ann Intern Med 1991; 137:992-5. 114:573-5. 2. Podrid PJ. Atrial fibrillation in the elderly. Cardiol 14. Rich MW. Heart failure. Cardiol Clin 1999;17:123- Clin 1999;17:173-88,ix-x. 35. 3. Li H, Easley A, Barrington W, Windle J. Evaluation 15. Farshi R, Kistner D, Sarma JS, Longmate JA, Singh and management of atrial fibrillation in the emer- BN. Ventricular rate control in chronic atrial fibrilla- gency department. Emerg Med Clin North Am tion during daily activity and programmed exercise: 1998;16:389-403. a crossover open-label study of five drug regimens. 4. Management of new onset atrial fibrillation. Evid J Am Coll Cardiol 1999;33:304-10. Rep Technol Assess (Summ) 2000;(12):1-7. 16. Masoudi FA, Goldschlager N. The medical man- 5. Wagner GS, Marriott HJ. Marriott’s Practical elec- agement of atrial fibrillation. Cardiol Clin 1997; trocardiography. 10th ed. Philadelphia: Lippincott 15:689-719. Williams & Wilkins, 2001:302-11. 17. Miller MR, McNamara RL, Segal JB, Kim N, Robinson 6. Pritchett EL. Management of atrial fibrillation. N KA, Goodman SN, et al. Efficacy of agents for phar- Engl J Med 1992;326:1264-71. macologic conversion of atrial fibrillation and subse- 7. Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay quent maintenance of sinus rhythm: a meta-analysis GN, Myerburg RJ, et al. Management of patients of clinical trials. J Fam Pract 2000;49:1033-46. with atrial fibrillation. A statement for healthcare 18. Wyse DG. The AFFIRM trial: main trial and sub- professionals. From the Subcommittee on Electro- studies—what can we expect? J Interv Card Elec- cardiography and , American Heart trophysiol 2000;4(suppl 1):171-6. Association. Circulation 1996;93:1262-77. 19. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate 8. Falk RH. Atrial fibrillation. N Engl J Med 2001; control in atrial fibrillation—Pharmacological Inter- 344:1067-78. vention in Atrial Fibrillation (PIAF): a randomised 9. Ergene U, Ergene O, Fowler J, Kinay O, Cete Y, trial. Lancet 2000;356:1789-94. Oktay C, et al. Must antidysrhythmic agents be 20. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Car- given to all patients with new-onset atrial fibrilla- dioversion of paroxysmal atrial fibrillation in the tion? Am J Emerg Med 1999;17:659-62. emergency department. Ann Emerg Med 1999;33: 10. Noc M, Stajer D, Horvat M. Intravenous amio- 379-87. darone versus verapamil for acute conversion of 21. Camm AJ. Atrial fibrillation: is there a role for low- paroxysmal atrial fibrillation to sinus rhythm. Am J molecular-weight heparin? Clin Cardiol 2001;24(3 Cardiol 1990;65:679-80. suppl):I15-9. 11. Schreck DM, Rivera AR, Tricarico VJ. Emergency 22. Klein AL, Grimm RA, Murray RD, Apperson-Hansen management of atrial fibrillation and flutter: intra- C, Asinger RW, Black IW, et al. Use of trans- venous diltiazem versus intravenous digoxin. Ann esophageal echocardiography to guide cardiover- Emerg Med 1997;29:135-40. sion in patients with atrial fibrillation. N Engl J Med 12. Segal JB, McNamara RL, Miller MR, Kim N, Good- 2001;344:1411-20.

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