Jce_90405.tex

Overview of the Management of Atrial Fibrillation: What is the
PETER R. KOWEY, M.D., GAN-XIN YAN, M.D., PH.D., TARA L. DIMINO, M.D., From the Cardiovascular Division, Lankenau Hospital and Medical Research Center, and the Main Line Health Heart Center, Wynnewood, Pennsylvania, USA; and the Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Management of Atrial Fibrillation. There are three fundamental approaches to the management of
atrial fibrillation (AF): rate control, rhythm control, and anticoagulation. Selecting a course of treatment
requires a thorough knowledge of these therapeutic alternatives. This article explores treatment options,
including the relative benefits of rate control versus rhythm control, which are complicated by the lack
of highly effective and safe antiarrhythmic drugs. Anticoagulation is also an important issue in AF man-
agement, and warfarin effectively reduces the incidence of thromboembolic events in AF patients. The
use of warfarin, however, presents its own complications. We conclude that individualization of therapy is
paramount when treating AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. S275-S280, December 2003, Suppl.)
sinus arrhythmia, antiarrhythmic drugs, anticoagulants, atrial fibrillation, left ventricular dysfunction Introduction
AV nodal conduction, some rate control medication is nec-essary. Which drug is used and how it is delivered depends Atrial fibrillation (AF) is a complicated disease state that on several factors, including the drug’s pharmacologic pro- requires a multifaceted management approach. It is not an file, the urgency of the clinical situation, the patient’s clinical exaggeration to say that this disease requires as much clin- stability, and concomitant drug therapy and medical condi- ical skill in management as any disorder that doctors treat.
tions.1,2 In general, rapidly acting calcium channel blockers On one hand, we have learned that AF need not be treated or beta-blockers are administered intravenously when a clin- aggressively in many patients, but we also know that AF fre- ical effect is needed quickly. It is important to note that only quently is complicated by disabling stroke, an outcome worse a minority of patients who develop AF have so much hemo- than death for most patients who experience this devastating dynamic compromise that intravenous administration of AV and avoidable complication of the disease. Thus, as in no nodal-blocking agents is necessary. In the majority, a short- other condition, individualization of therapy is paramount, acting oral beta-blocker or calcium channel blocker, with a while still adhering, as best we can, to basic treatment dic- short time to effect, may suffice, with longer-acting oral con- tums derived from well-designed and well-executed clinical geners reserved for long-term clinical use. Weaker AV nodal blockers, such as digitalis, are reserved as adjuvant therapy In this article, we consider the three major components for patients whose AV nodes are diseased, when single-drug of AF treatment: rate control, rhythm control, and antico- treatment does not suffice, or for management of heart fail- agulation. Because other articles in this issue of the Journal ure.3-6 The adequacy of rate control is difficult to define, but review specific therapies, we confine this discussion to the heart rates of <80 beats/min at rest with attainment of <90% broad categories, highlighting treatment options and the trial of the maximum predicted heart rate with maximal exercise evidence to support them. For most of this discussion, atrial would be considered acceptable. Alternatively, criteria have flutter will not be discussed separately unless there are spe- been applied based on control of rate during a range of activ- cific data pertaining to that arrhythmia that are not applicable ities of daily living. It is critical, however, that optimization of heart rate be judged with the patient at rest and then duringexertion, because the rate control effect of agents such as dig- Rate Control
italis may be overcome by catecholamines, rendering the pa-tient uncontrolled during a significant portion of her/his daily The first step in the treatment of AF generally is control of routine.6,7 In those rare cases where conventional AV nodal- the ventricular response rate. In elderly patients, especially blocking agents are ineffective, such as in very ill patients, those with conduction disease, rates may be well controlled amiodarone may be useful because the drug’s earliest effect, at the onset of AF, but for the majority of patients with intact when administered intravenously, is negative dromotropismvia its noncompetitive beta-adrenergic and calcium channel-blocking effects.6 Careful rate control is paramount no mat-ter which agent is used, because high heart rates over time Supported in part by the Rose and Adolph Levis Foundation, Haverford,Pennsylvania.
may cause severe symptoms as well as profound left ventric-ular dysfunction in some individuals.8,9 This is part of the Address for correspondence: Peter R. Kowey, M.D., Main Line Health Heart rationale for considering AV nodal ablation and permanent Center, Lankenau Medical Office Building, Suite 558, 100 Lancaster Av- pacemaker implantation in select patients who also may be enue, Wynnewood, PA 19096. E-mail: [email protected] suffering from severe symptoms caused by the rapidity and irregularity of their arrhythmia.8 The relative benefits of rate Journal of Cardiovascular Electrophysiology
Vol. 14, No. 12, Supplement, December 2003 Pharmacologic conversion, although less effective, has the potential of better patient acceptance and wider applicabil-ity. It is important to note that, in general, drugs are moreefficacious for converting AF of shorter than longer dura-tion. In fact, very few drugs have been systematically studiedand approved for this indication. Class IA and IC drugs havebeen used intravenously and orally with good reported suc-cess. The Class IC drugs appear to be effective and safe fortermination of AF of relatively recent onset in patients withnormal or nearly normal hearts, and they can be used eitherorally or parenterally.20-22 However, the drugs approved forthis indication are intravenous ibutilide and oral dofetilide,both Class III antiarrhythmic drugs. Ibutilide has no oral con-gener and thus is limited to acute therapy only. It appears towork better in patients with arrhythmias of relatively recentonset and has greater efficacy in atrial flutter.23,24 Its prin-cipal liability is torsades de pointes, which occurs in 2% to4% of patients and is more likely in women, the elderly, andpatients with left ventricular dysfunction.25-27 Dofetilide wasapproved for this indication based on its record of effective-ness in patients hospitalized for oral drug loading. Conversionto SR occurs in 30% of patients with persistent AF comparedwith a placebo conversion rate of about 1% to 3%.28 As with Figure 1. An approach to the management of “new” atrial fibrillation, as
ibutilide, dofetilide’s principal liability is torsades de pointes, previously published in the ACC/AHA/ESC guidelines.10 (Reproduced with which fortunately happens early in dosing while the patient permission from Fuster V, Ryden LE, Asinger RW, et al.; American College is under observation.25,27,29 of Cardiology/American Heart Association Task Force on Practice Guide- Other drugs have been used for acute conversion of AF lines; European Society of Cardiology Committee for Practice Guidelinesand Policy Conferences (Committee to Develop Guidelines for the Manage- without convincing demonstration of effectiveness. Amio- ment of Patients with Atrial Fibrillation); North American Society of Pac- darone has gained popularity for this indication. Although ing and Electrophysiology: ACC/AHA/ESC guidelines for the management many previous studies were unconvincing as to amiodarone’s of patients with atrial fibrillation: Executive summary. Circulation 2001; efficacy for this indication,30 more recent data have sug- gested that infusion of high doses for several hours mightbe useful.31 Spontaneous conversions in this populationoccur with such variable frequency that carefully done, control versus rhythm control will be considered in a subse- large, placebo-controlled trials are essential before any con- clusions can be reached about the efficacy and safety ofdrugs for this indication. Amiodarone’s peculiar pharmacoki- Rhythm Control
netic profile makes such studies difficult to execute and tointerpret.
The other broad strategy in AF management is mainte- Proper anticoagulation prior to and following cardiover- nance of sinus rhythm (SR) (Fig. 1).10 This approach has two sion is a key item in its safe implementation. Fortunately, parts: restoration of SR for patients whose AF is persistent, we now have good data on which to base firm recommenda- and chronic treatment to prevent AF recurrence. Conversion tions about the proper use of anticoagulant therapy to prevent of AF to SR can be accomplished electrically or pharma- stroke and other thromboembolic events.30 These recommen- cologically. Electrical conversion is well established, highly dations will be presented in the section on anticoagulation effective, and generally safe, especially when carried out electively. Emergent cardioversion is an uncommon event, Chronic maintenance of SR remains the major challenge because most patients can be rendered stable with acute rate in this realm. To date, we have not seen the development of control and measures to treat an underlying disease process.
any antiarrhythmic drug with sufficient efficacy and safety This is fortunate, because patients frequently are not pre- to allow us to administer it with confidence to a broad sam- pared properly for cardioversion, having recently eaten and ple of patients. It is important to remember that even with not being properly anticoagulated. In addition, emergent car- optimal therapy, drug treatment is rarely “curative.” In most dioversion is plagued with a very high relapse rate because cases, the most we should expect is a reduction in the fre- the conditions that led to the arrhythmia still are present.11,12 quency, duration, and severity of the events, which may be For elective cardioversion, with good technique including the adequate in some patients to improve their quality of life use of biphasic waveform devices and adequate anesthesia, and to allow them to pursue their usual activities.32 In addi- >95% of patients can be shocked into SR.13-15 Unfortunately, tion, antiarrhythmic drugs have the potential for toxicity. The early recurrence of AF and late relapses are not uncommon best we have been able to do is to describe safety and effi- and occur as a consequence of concomitant cardiac or elec- cacy in carefully defined patient populations to allow physi- trical disease and other factors, the most important of which cians to prescribe one or another agent depending on the may be the duration of the antecedent arrhythmia.16,17 Pre- individual patient profile. For example, it is important to dis- vention of early or late relapses usually requires predosing tinguish between paroxysmal and persistent AF, because the with antiarrhythmic drugs or beta-blockers.5,6,11,12,18,19 former frequently causes severe symptoms in young active Management of Atrial Fibrillation
disease in order to be able to provide physicians with the bestprescribing information.
Finally, it is important to note that nonantiarrhythmic drugs may play an important role in rhythm control. For manyof these agents, the magnitude of the treatment effect may bemodest, but if applied to a very large at-risk population, thedividends could be significant. For example, emerging datasuggest that drugs that interfere with the renin-angiotensinsystem may limit atrial fibrosis and at the same time reducethe frequency of AF when used in patients after myocardialinfarction. Widespread use of these agents, which also con-trol hypertension, the most common cause of AF, would beexpected to reduce the disease burden.36 Studies to confirmthis benefit are in progress.
Figure 2. A pharmacologic approach to maintenance of sinus rhythm, as
Rate Versus Rhythm Control
previously published in the ACC/AHA/ESC guidelines.10 (Reproduced withpermission from Fuster V, Ryden LE, Asinger RW, et al.; American College The lack of highly effective and safe antiarrhythmic drugs of Cardiology/American Heart Association Task Force on Practice Guide- prompted several investigators to ask the question whether lines; European Society of Cardiology Committee for Practice Guidelines maintenance of SR is actually preferable to allowing AF and Policy Conferences (Committee to Develop Guidelines for the Manage- to persist. Obviously, the question is valid only for patients ment of Patients with Atrial Fibrillation); North American Society of Pac- who have minimal or no symptoms while in rate-controlled ing and Electrophysiology: ACC/AHA/ESC guidelines for the management AF, because severe symptoms would prompt the physician of patients with atrial fibrillation: Executive summary. Circulation 2001; to recommend rhythm reversion. It should be clear that this is not a new idea. For decades, experienced clinicians al-lowed AF to persist, based on the premise that antiarrhythmicdrugs are not safe, particularly in the elderly, and could placethe patient in more danger than the arrhythmia itself.37,38 individuals whereas the latter may become less noticed and For example, all antiarrhythmic drugs depress the conduc- more amenable to a conservative strategy of rate control only.
tion system, including the sinoatrial node, and many patients The latest guidelines issued by our professional organizations with AF have concomitant conduction disease. Thus, insis- have grouped patients by type of heart disease and presented tence on maintenance of SR could mandate a pacemaker what might be considered first-line and alternative drug ther- implantation, which would be avoided if AF is allowed to apy based on that classification (Fig. 2).10 For example, in the realm of congestive heart failure, the drugs best studied Four randomized studies that have been completed and re- for efficacy and safety are clearly dofetilide and amiodarone, ported have examined this question.39-41 Although the studies which makes those two agents the preferred therapy for pa- are of varying size and used different methods and endpoints, tients with severe left ventricular dysfunction. It appears from the overwhelming message from all of them is that, aside from good trial data that neither drug is associated with deterio- symptom control, there does not appear to be an advantage ration of left ventricular function in these patients, nor does for rhythm control in terms of quality of life, mortality, hos- either agent predispose patients to lethal proarrhythmia once pitalization rates, or any other endpoint examined.41 In fact, they have been started carefully and as long as rigid dosing in many of the analyses, the advantage went to the more sim- guidelines are adhered to. Similarly, sotalol, dofetilide, and ple strategy of rate control. Although there are a number of amiodarone are featured for patients with ischemic heart dis- caveats in the interpretation of these data (including patient ease based on good data from randomized clinical trials that selection bias, inefficiencies in SR retention, and relatively the drugs were safe in such patients, and with effectiveness short follow-up periods), it is now axiomatic that letting el- not diminished in comparison to patients without coronary derly patients remain in SR for a few years is not inimical artery disease.33-35 Many more agents have been examined to their outcome and may be preferred to exposing those in- in patients with normal hearts, multiplying the therapeutic dividuals to the hazards of antiarrhythmic drug therapy and alternatives for those patients. Although highly useful for repeated cardioversions. Although some of these randomized clinical purposes, schema such as these point out the limi- trials permitted nonpharmacologic therapy for SR mainte- tations of the chemical agents currently on the market and nance, too few of those patients were so treated to allow any the need for better comparative information. It also is clear conclusions as to whether a nondrug approach would alter that we need better antiarrhythmic drugs with less attendant cardiac and organ toxicity. In fact, several new agents are un-der active investigation that have greater specificity for atrialelectrophysiology or have novel mechanisms of action to cir- Anticoagulation
cumvent the problems engendered by blocking standard ioncurrents. Whether these agents will make it to market and By far, the most important issue in AF management is an- what impact they will have on AF management remain to ticoagulation.10,42 It now is clear that avoidance of stroke ren- be seen.6 It is clear that new antiarrhythmic drugs will be ders AF treatment an exercise in symptom reduction rather held to a high standard of safety and will need to be studied than an attempt to preserve life and prevent major disabil- comprehensively in patients with a broad spectrum of cardiac ity. Fortunately, a number of large, well-done clinical trials Journal of Cardiovascular Electrophysiology
Vol. 14, No. 12, Supplement, December 2003 Anticoagulation Trials in Atrial Fibrillation Reference Year Published No. of Patients
Interventions
Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation I (AFASAK I) Copenhagen Atrial Fibrillation, Aspirin, Anticoagulation II (AFASAK II) Stroke Prevention in Atrial Fibrillation I (SPAF I) Stroke Prevention in Atrial Fibrillation II (SPAF II) Stroke Prevention in Atrial Fibrillation Ill (SPAF Ill) Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) Canadian Atrial Fibrillation Anticoagulation (CAFA) Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF) European Atrial Fibrillation Trial (EAFT) Studio ltaliano Fibrillazione Atriale (SIFA) Minidose Warfarin in Nonrheumatic Atrial Fibrillation Prevention of Arterial Thromboembolism in Atrial Fibrillation (PATAF) Low-dose Aspirin, Stroke, Atrial Fibrillation (LASAF) European Stroke Prevention Study II (ESPS II) French Aspirin Coumarin Collaborative Study Stroke Prevention using an Oral Thrombin Inhibitor in AF = atrial fibrillation; ASA = aspirin; LMW = low molecular weight; OA = oral anticoagulation; OA∗ = low-dose oral anticoagulation.
Adapted and reproduced with permission from Hart RG, Benavente O, McBride R, Pearce LA: Antithrombotic therapy to prevent stroke in patients withatrial fibrillation: A meta-analysis. Ann Intern Med 1999;131:492-501.
have proven that warfarin is effective in dramatically reduc- It is very clear that risk for stroke in AF can be quanti- ing the incidence of thromboembolic events in patients with fied based on a number of clinical characteristics, including valvular and nonvalvular AF (Table 1).10,42 Warfarin, how- age, sex, cardiac function, and associated clinical conditions ever, is a complex drug, and the incidence of major bleeding such as diabetes and hypertension (Table 1).10,47,48 For high- associated with its use is not inconsequential. Thus, physi- risk individuals, we now believe that warfarin anticoagulation cian and patient acceptance and its applicability to high-risk should never be discontinued once initiated. This recommen- populations have all been major issues limiting its general dation comes from several lines of evidence. We know that application. In addition, strict guidelines must be followed at many patients do not know when they are having AF. Asymp- each phase of the disease’s management in order to obtain tomatic relapses may predispose to stroke. In fact, the first the benefits that have been described in clinical trials. For presenting symptom of AF is stroke in a sizable percentage example, patients with recent-onset arrhythmia (<48 hours) of elderly patients.49 Recently, the randomized studies of rate must have a continuously therapeutic level of anticoagula- versus rhythm control reported a disturbingly high incidence tion (international normalized ratio [INR] >2.0) for 3 to 4 of strokes in patients in the rhythm control arm of the trials weeks prior to an elective drug or electrical conversion.10,43 whose anticoagulation either was stopped or was at an inad- Alternatively, such patients may undergo a transesophageal equate level.40 The reason for this is not clear but could have echocardiogram and simultaneous anticoagulation with hep- been due to AF recurrences during which symptoms were arin followed by warfarin and cardioversion if the study indi- masked by drugs that slow the ventricular response to AF cates the absence of left atrial clot.44,45 Although the studies if they do not suppress it, rendering stroke more likely. In supporting these recommendations were not necessarily well any case, guidelines that in the past advocated cessation of controlled or randomized, their results are well accepted and anticoagulation in patients maintaining SR for several weeks after conversion may have to be restricted to patients who Chronic anticoagulation is a more complex issue. First, it have AF without stroke risk factors.
is clear that aspirin, although effective, is grossly inferior to What also is clear is that warfarin alternatives are desper- warfarin for this indication and should be used only in patients ately needed. To date, evidence supporting the efficacy of who cannot take warfarin.10 Although routinely used in “low- alternative therapy has been lacking. Heparins, including re- risk” patients, the rationale for this practice is nil. Patients cently some low-molecular-weight heparins, have been found with atrial flutter require warfarin anticoagulation, as do AF useful in association with the transesophageal cardioversion patients based on their relative risks of atrial clot formation strategy discussed earlier, but they have not been well studied and stroke in large series.46 Although we try to differentiate otherwise.50,51 The need for parenteral administration greatly risk based on AF burden, there are no data concluding that diminishes their clinical applicability in any case. Recently, patients with paroxysmal AF are at less risk for stroke than we have seen encouraging results from trials in which di- patients with persistent AF. Whether relative frequency of rect thrombin inhibitors have been compared with warfarin AF within the paroxysmal category is a risk stratifier has not in patients with nonvalvular AF.52 These drugs have the po- tential advantage of a shorter half-life, permitting faster onset Management of Atrial Fibrillation
and offset, fewer drug interactions, and empiric dosing with- 11. Villani GQ, Piepoli MF, Terracciano C, Capucci A: Effects of dilti- out the need for monitoring coagulation status. Given the azem pretreatment on direct-current cardioversion in patients with per- dire nature of the clinical outcomes in these trials, placebo sistent atrial fibrillation: A single-blind, randomized, controlled study.
Am Heart J 2000;140:437-443.
controls are not possible. Positive controlled studies versus 12. Marcus GM, Sung RJ: Antiarrhythmic agents in facilitating electrical warfarin, even those with a noninferiority endpoint, mandate cardioversion of atrial fibrillation and promoting maintenance of sinus the inclusion of a very large number of at-risk patients, with double dummy and phantom INR-based dose adjustments 13. Page RL, Kerber RE, Russell JK, Trouton T, Waktare J, Gallik D, Olgin JE, Ricard P, Dalzell GW, Reddy R, Lazzara R, Lee K, Carl- and scrupulous safety monitoring. The ability to use sim- son M, Halperin B, Bardy GH; BiCard Investigators: Biphasic versus pler drugs for this indication would have far-reaching con- monophasic shock waveform for conversion of atrial fibrillation: The sequences and could revolutionize our approach to patients results of an international randomized, double-blind multicenter trial. J with low-to-intermediate risk of stroke, including those with compliance issues. The preliminary results have been very 14. Havranek E: Biphasic waveform shocks were effective and efficient for cardioversion of atrial fibrillation. ACP J Club 2003;138:8.
encouraging, and we anticipate that anticoagulation of pa- 15. Ermis C, Zhu AX, Sinha S, Iskos D, Sakaguchi S, Lurie KG, Benditt tients with AF soon will be simplified.
DG: Efficacy of biphasic waveform cardioversion for atrial fibrillationand atrial flutter compared with conventional monophasic waveforms.
Conclusion
16. Alt E, Ammer R, Lehmann G, Putter K, Ayers GM, Pasquantonio Management of AF is a highly complex task that requires a J, Schomig A: Patient characteristics and underlying heart disease thorough knowledge of several therapeutic alternatives, care- as predictors of recurrent atrial fibrillation after internal and exter- ful individualization of therapy, and patience on the part of the nal cardioversion in patients treated with oral sotalol. Am Heart J1997;134:419-425.
physician and patient. The search for better treatment alter- 17. Ortiz De Murua JA, del Carmen Avila M, Ochoa C, de La Fuente L, natives continues because of the burden of this arrhythmia in Morena De Vega JC, del Campo F, Villafranca JL: Independent predic- our population and the limitations of what is currently avail- tive factors of acute and first year success after electrical cardioversion able. Although many of these new treatments will come to in patients with chronic atrial fibrillation. Rev Esp Cardiol 2001;54:958-964.
fruition, AF will remain a challenge for clinicians for years to 18. Miller MR, McNamara RL, Segal JB, Kim N, Robinson KA, Goodman come. It deserves the attention it has received and will receive SN, Powe NR, Bass EB: Efficacy of agents for pharmacologic conver- from the scientific and clinical communities.
sion of atrial fibrillation and subsequent maintenance of sinus rhythm:A meta-analysis of clinical trials. J Fam Pract 2000;49:1033-1046.
19. Dayer M, Hardman SM: Special problems with antiarrhythmic drugs Acknowledgment: The authors thank Rose Marie Wells for her usual patient in the elderly: Safety, tolerability, and efficacy. Am J Geriatr Cardiol help in the preparation of the manuscript.
20. Wijffels MC, Dorland R, Allessie MA: Pharmacologic cardioversion References
of chronic atrial fibrillation in the goat by class IA, IC, and III drugs:A comparison between hydroquinidine, cibenzoline, flecainide, and d- 1. Yadav A, Scheinman M: Atrial fibrillation in the elderly. Am J Geriatr sotalol. J Cardiovasc Electrophysiol 1999;10:178-193.
21. Alp NJ, Bell JA, Shahi M: Randomised double blind trial of oral versus 2. Cain ME: Atrial fibrillation-rhythm or rate control. N Engl J Med intravenous flecainide for the cardioversion of acute atrial fibrillation.
3. Crijns HJ, Van den Berg MP, Van Gelder IC, Van Veldhuisen DJ: Man- 22. Khan IA: Oral loading single dose flecainide for pharmacological car- agement of atrial fibrillation in the setting of heart failure. Eur Heart J dioversion of recent-onset atrial fibrillation. Int J Cardiol 2003;87:121- 4. Matalka MS, Deedwania PC: Atrial fibrillation in patients with heart 23. Foster RH, Wilde MI, Markham A: Ibutilide: A review of its pharma- failure: Pharmacologic options. Congest Heart Fail 2001;7:22-29.
cological properties and clinical potential in the acute management of 5. Reiffel JA: Drug choices in the treatment of atrial fibrillation. Am J atrial flutter and fibrillation. Drugs 1997;54:312-330.
24. Eversole A, Hancock W, Johns T, Lopez LM, Conti CR: Ibutilide: Ef- 6. Nattel S, Khairy P, Roy D, Thibaut B, Guerra P, Talajic M, Dubuc M: ficacy and safety in atrial fibrillation and atrial flutter in a general car- New approaches to atrial fibrillation management: A critical review of diology practice. Clin Cardiol 2001;24:521-525.
a rapidly evolving field. Drugs 2002;62:2377-2397.
25. Kowey PR, VanderLugt JT, Luderer JR: Safety and risk/benefit analysis 7. Lamaison D, Laureille B: Antiarrhythmic treatments of permanent atrial of ibutilide for acute conversion of atrial fibrillation/flutter. Am J Cardiol fibrillation. Rev Prat 1993;43:1523-1531.
8. Tepper D: Frontiers in congestive heart failure: Tachycardia-related car- 26. Howard PA: Ibutilide: An antiarrhythmic agent for the treatment of atrial diomyopathy: A common cause of ventricular dysfunction in patients fibrillation or flutter. Ann Pharmacother 1999;33:38-47.
with atrial fibrillation referred for atrioventricular ablation. Congest 27. Gowda RM, Punukollu G, Khan IA, Patlola RR, Tejani FJ, Cosme- Thormann BF, Vasavada BC, Sacchi TJ: Ibutilide-induced long QT 9. Aslam MS, Brookfield L: Difficult cases in heart failure: Reversible car- syndrome and torsade de pointes. Am J Ther 2002;9:527-529.
diomyopathy due to atrial fibrillation in a 46-year-old patient. Congest 28. Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, Billing CB Jr: Efficacy and safety of oral dofetilide in converting to and main- 10. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, taining sinus rhythm in patients with chronic atrial fibrillation or atrial Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky flutter: The Symptomatic Atrial Fibrillation Investigative Research on EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon Dofetilide (SAFIRE-D) study. Circulation 2000;102:2385-2390.
DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, 29. Al-Dashti R, Sami M: Dofetilide: A new class III antiarrhythmic agent.
Smith SC Jr, Klein WW, Alonso-Garcia A, Blomstrom-Lundqvist C, de Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, 30. Kowey PR, Marinchak RA, Rials SJ, Filart RA: Acute treatment of atrial Torbicki A; American College of Cardiology/American Heart Associa- fibrillation. Am J Cardiol 1998;81:16C-22C.
tion Task Force on Practice Guidelines; European Society of Cardiology 31. Cybulski J, Danielewicz H, Kulakowski P, Budaj A, Maciejewicz J, Committee for Practice Guidelines and Policy Conferences (Commit- Kawka-Urbanek T, Ceremuzynski L: Intravenous amiodarone in con- tee to Develop Guidelines for the Management of Patients with Atrial version of new-onset atrial fibrillation. (Abstract) J Am Coll Cardiol Fibrillation); North American Society of Pacing and Electrophysiol- ogy: ACC/AHA/ESC Guidelines for the Management of Patients with 32. Dorian P, Paquette M, Newman D, Green M, Connolly SJ, Talajic M, Atrial Fibrillation: Executive Summary. Circulation 2001;104:2118- Roy D: Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Am Heart J 2002;143:984-990.
Journal of Cardiovascular Electrophysiology
Vol. 14, No. 12, Supplement, December 2003 33. Wong CK, White HD, Wilcox RG, Criger DA, Califf RM, Topol EJ, for stroke in type 2 diabetes mellitus: United Kingdom Prospective Ohman EM, GUSTO-III Investigators: Management and outcome of Diabetes Study (UKPDS) 29. Arch Intern Med 1999;159:1097-1103.
patients with atrial fibrillation during acute myocardial infarction: The 49. Wolf PA, Abbott RD, Kannel WB: Atrial fibrillation: A major contrib- GUSTO-III experience. Global Use of Strategies To Open Occluded utor to stroke in the elderly. The Framingham Study. Arch Intern Med Coronary Arteries. Heart 2002;88:357-362.
34. Dofetilide in patients with left ventricular dysfunction and either heart 50. Murray RD, Deitcher SR, Klein AL: Use of low-molecular-weight hep- failure or acute myocardial infarction: Rationale, design, and patient arin as bridge anticoagulation therapy in patients with atrial fibrillation characteristics of the DIAMOND studies. Danish Investigations of Ar- undergoing transoesophageal echocardiography guided cardioversion.
rhythmia and Mortality ON Dofetilide. Clin Cardiol 1997;20:704-710.
35. Pedersen OD, Bagger H, Keller N, Marchant B, Kober L, Torp-Pedersen 51. Wodlinger AM, Pieper JA: Low-molecular-weight heparin in trans- C: Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in esophageal echocardiography-guided cardioversion of atrial fibrillation.
patients with reduced left ventricular function: A Danish Investigation of Arrhythmia and Mortality on Dofetilide (DIAMOND) substudy. Cir- 52. SPORTIF III Investigators: Stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular atrial fib- 36. Goette A, Arndt M, Rocken C, Spiess A, Staack T, Geller JC, Huth rillation. Late breaking clinical trial session, American College of Car- C, Ansorge S, Klein HU, Lendeckel U: Regulation of angiotensin diology Meeting, Chicago, Illinois, April 2003.
II receptor subtypes during atrial fibrillation in humans. Circulation2000;101:2678-2681.
Discussion
37. Waldo AL: Long-term pharmacologic management of atrial fibrillation in the elderly. Am J Geriatr Cardiol 2002;11:233-244.
Dr. Prystowsky: What percent of people were not enrolled
38. Essebag V, Hadjis T, Platt RW, Pilote L: Amiodarone and the risk of bradyarrhythmia requiring permanent pacemaker in elderly patients in AFFIRM because the clinician felt they specifically needed with atrial fibrillation and prior myocardial infarction. J Am Coll Cardiol Dr. Waldo: We don’t know. There were about 3,300 pa-
39. Hohnloser SH, Kuck KH: Randomized trial of rhythm or rate control tients followed who opted not to be in AFFIRM, and two in atrial fibrillation: The Pharmacological Intervention in Atrial Fibril- thirds of those who opted not to participate made the deci- lation Trial (PIAF). Eur Heart J 2001;22:801-802.
40. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, sion on their own. The other third did not participate because Schron EB, Kellen JC, Green HL, Mickel MC, Dalquist JE, Corley SD, Atrial Fibrillation Follow-up Investigation of Rhythm Management Dr. Packer: There is a bit of a problem on the whole abla-
(AFFIRM) Investigators: A comparison of rate control and rhythm con- tion scene because people keep coming in and thinking that trol in patients with atrial fibrillation. N Engl J Med 2002;347:1825-1833.
after AFFIRM and RACE we shouldn’t be ablating anybody 41. Nattel S: Rhythm versus rate control for atrial fibrillation manage- because it doesn’t matter. These are totally different patients.
ment: What recent randomized clinical trials allow us to affirm. CMAJ Dr. Naccarelli: As an AFFIRM investigator, there may
have been some bias against randomizing the most symp- 42. Hart RG, Palacio S, Pearce LA: Atrial fibrillation, stroke, and acute tomatic patients. However, a number of the patients random- antithrombotic therapy: Analysis of randomized clinical trials. Stroke2002;33:2722-2727.
ized in our center were very symptomatic. Some of these 43. Gallagher MM, Hennessy BJ, Edvardsson N, Hart CM, Shannon MS, very symptomatic patients were randomized to rate control Obel OA, Al-Saady NM, Camm AJ: Embolic complications of direct and subjectively did well with complete abolition of their current cardioversion of atrial arrhythmias: Association with low inten- symptoms. However, rate control is probably not for every- sity of anticoagulation at the time of cardioversion. J Am Coll Cardiol2002;40:926-933.
body, and there is a large group of patients who probably 44. Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, are not candidates for rate control and may be for pharma- Black IW, Davidoff R, Erbel R, Halperin JL, Orsinelli DA, Porter TR, cologic suppression or even nonpharmacologic abolition of Stoddard MF, Assessment of Cardioversion Using Transesophageal Echocardiography Investigators: Use of transesophageal echocardio- Dr. Packer: I’m not even going as far as saying that they’re
graphy to guide cardioversion in patients with atrial fibrillation. N EnglJ Med 2001;344:1411-1420.
not a candidate for rate control. We don’t know about those 45. Manning WJ, Silverman DI, Seto TB, Weigner MJ: Value of precar- dioversion transesophageal echocardiography in managing cardiover- Dr. Prystowsky: My own approach is to control the heart
sion in atrial fibrillation. J Am Coll Cardiol 2002;40:1889-1890.
rate before making a decision on symptoms. But often pa- 46. Schmidt H, von der Recke G, Illien S, Lewalter T, Schimpf R, Wolpert Becher H, Luderitz B, Omran H: Prevalence of left atrial chamber and tients have their rate well controlled by the time they are appendage thrombi in patients with atrial flutter and its clinical signifi- referred to me, and they are still quite symptomatic and want cance. J Am Coll Cardiol 2001;38:778-784.
to be in sinus rhythm. The message of AFFIRM for me is if 47. Wehinger C, Stollberger C, Langer T, Schneider B, Finsterer J: Eval- a person is in an older age group, they can have an option uation of risk factors for stroke/embolism and of complications due of rate control. We shouldn’t forget that we have minimal to anticoagulant therapy in atrial fibrillation. Stroke 2001;32:2246-2252.
data on younger patients without a high stroke risk regarding 48. Davis TM, Millns H, Stratton IM, Holman RR, Turner RC: Risk factors

Source: http://arrhythmology.narod.ru/articles/JCE_Kowey_AFib.pdf