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Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation
Factors Determining Maintenance of Sinus Rhythm After Chronic Atrial Fibrillation with Left Atriai Dilatation Michael A. Brodsky, MD, Byron J. Allen, MD, Edmund V. Capparelli, PharmD, Cathy R. Luckett, RN, Rebecca Morton, BS, and Walter L. Henry, MD
Successful therapy of atrial fibrillation (AF) has been reportedly influenced by a variety of factors including patient age, type of underlying heart disease, duration of arrhythmia, lefl ventricular function and left atrial (LA) size. To determine which of these factors are associated with maintenance of sinus rhythm after conversion, 43 patients with symptomatic chronic AF in the setting of a dilated left atrium (145 mm, range 45 to 78) were followed for at least 6 months after the return of sinus rhythm. Class IA drugs, IC drugs or amiodacone were used for therapy. Life table analysis showed sinus rhythm to be maintained in 81% for 6 months, 79% for 12 months and 60% for 24 months. Factors positively associated with success were conversion with drug therapy alone, duration of chronic AF I1 year, absence of mitral valve disease and LA dimension 160 mm (all p <0.05). Patient age, left ventricular function and presence of coronary disease were not associated with outcome. Thus, patients with moderate LA dilatation (45 to 60 mm) and a short duration of chronic AF can often be maintained in sinus rhythm, especially if they convert with pharmacologic intervention alone. (Am1 Cardiol 1989;63:1065-1068)
From the Department of Medicine, Division of Cardiology, University of California at Irvine, Orange, California. Manuscript received November 28,1988; revised manuscript received and accepted February 2, 1989. Address for reprints: Michael A. Brodsky, MD, Division of Cardiology, University of California at Irvine Medical Center, 101 City Drive, Orange, California 92668.
P
revious studies suggest that the finding of an echocardiographicleft atria1 (LA) dimension 145 mm identifies patients who are unlikely to maintain sinus rhythm after conversion from chronic atria1 fibrillation (AF).lm3 Unfortunately, these patients are the ones most likely to benefit from being in sinus rhythm, as they often experiencea worsening of symptoms when in AF. The mainstay of therapy for preventing recurrent AF has been class IA antiarrhythmic drugs (quinidine, procainamide and disopyramide).4-13 Yet, AF recurs within the first year in 43 to 78% of patients thus treated.9J0J3 Recently available drugs such as amiodarone and class IC agents appear promising for AF.14J5Studies specifically correlating LA size with recurrence of AF antedate the availability of these newer drugs. The purpose of the current study was to reexamine the efficacy of antiarrhythmic therapy, including the newer drugs, with regard to whether a group of patients with LA dilatation could be maintained in sinus rhythm after conversion from chronic AF. METHODS Patients: We evaluated a total of 43 patients with
chronic AF meeting the following inclusion criteria: (1) the arrhythmia had to persist for at least 48 hours and be associatedwith either disabling palpitations, poor exercisetolerance or symptomatic congestiveheart failure; (2) the LA dimension had to be 145 mm as documented by M-mode echocardiography;and (3) patients had to be able to take oral anticoagulants and be willing to undergo electrical cardioversion. The 25 men and 18 women had a mean age of 58 f 10 years, with 27 (63%) being younger than 60 years of age. Atria1 fibrillation had beenpresent for a mean of 1,070days and 16 patients (37%) had arrhythmia for
1065
SINUS RHYTHM
TABLE
AFTER IdIAL
I Characteristics
FlBRlLLATlON
of 43 Patients
with Chronic
nus rhythm, that point (the last intervention) was considered the starting point for analysis of duration of sinus rhythm. All patients were followed for at least 6 months after the last intervention at intervals of 6 to 26 weeks.Cardiac rhythm was documented by electrocardiography (12-lead electrocardiogram or rhythm strip) or ambulatory electrocardiographic monitoring. Statistical analysis: Life-table analysis was carried out using the method of Kaplan and Meier, with comparisons between survival curves analyzed by the method of Mantel and COX.‘~,~O
Atrial
Fibrillation Clinical Variable
No. of Pts
Sex (M/F) (%) Underlying cardiac disease Valvular disease (%) Mitral stenosis (%) Mitral regurgitation (%) Mixed stenosis/regurgitation (%) Mitral valve replacement (%) Coronary artery disease (“9) Idiopathic dilated cardiomyopathy (%) Systemic hypertension (%) Miscellaneous (%) Duration of atrial fibrillation >l yr (“h)3 (%) Left ventricular function 228% fractional shortening (%) <28% fractional shortening (%) Left atrial dimension 45-60 mm (%) >60 mm (%)
25/18
TABLE
II Six-Month
lncfividual Total
Drug Class IA Quinidine Procaihamide Disopyramide Class IC (combined) Amiodarone Solitary Plus IA (combined)
(58/42)
15 (35)
8 (19) 3 (7) 4 (10) 7 (16) 8 (19) 7 (16) 5 (12) 8 (1% 27 16 14 4
RESULTS
(63) (37) (33) (9)
23 (53) 20 (47) 20 (56)
16(44) 32 (74) 11 (26)
Drug Efficacy Success
Percent Success
39 15 15 8
7 2 2 4
18 13 13 50
29 6
16 4
55 67
All patients were successfully converted to sinus rhythm either pharmacologically or with electrical cardioversion. After conversionthe patients maintained sinus rhythm for an averageof 598 f 502 days (range 1 to 1,602). Of 43 patients, 3.5 (81%) maintained sinus rhythm for 16 months. Pharmacologic therapy: The last intervention involved a class IA drug in 18 patients (quinidine 13, disopyramide 3, procainamide 2). Of these 18 patients, 6 (33%) had pharmacologic conversions (all with quinidine) and 12 (67%) required electrical cardioversion in addition to medication. Amiodarone was used as the last intervention in 15 patients, 6 (40%) of whom converted pharmacologically. Amiodarone plus a class IA drug was used in 6 patients (quinidine 4, disopyramide 1, procainamide l), all of whom required electrical cardioversion. A class IC drug was utilized as the last intervention in 4 patients. Flecainide was used in 2 patients, both of whom converted pharmacologically. Propafenone and encainide were given to 1 patient each (both required electrical cardioversion). Alterations in the medical regimen after conversion to sinus rhythm were required in 7 patients (16%). A compilation of overall drug responseusing the last intervention as well as all previous drug trials revealedclassIA agentsto be effective in 16%,class IC agents in 50%, amiodarone in 55% and amiodarone plus class IA agents in 67% (Table II).
Before conversion,patients were anticoagulated with warfarin for 12 weeks. During the phase of chronic AF, the ventricular responsewas controlled with digoxFactors related to maintenance of sinus rhythm: in (93% of patients), calcium antagonists (39%) or /3 The ability to maintain sinus rhythm in all patients is blockers (24%), given singly or in combination. Pharmacologic or electrical conversion was accomplished in all patients. Before conversion, a class IA 1 drug (quinidine; procainamide or disopyramide) was loaded orally in-hospital using previously describedregimens.7J2Out-of-hospital loading with either amiodarone or a class IC drug (flecainide, encainide or propafenone) was done over 1 to 3 months.14The doseof any antiarrhythmic agent was determined by the endpoints of QRS or QTc prolongation of 150% over control, development of intolerable side effects or blood levels in the toxic range of selectedagents.Patients were typically treated with IA agents as initial therapy and, failing 11 of these agents,were then treated with either a class IC drug or amiodarone. Many patients were referred -. 0 200 400 600 600 1000 1200 for therapy after failing all 3 approved class IA agents. DAYS After drug loading, 29 patients (67%) remained in -I AF and were then subjected to synchronized electrical cardioversion.18Once all patients were converted to si- FIGURE 1. Ability to maintain sinus rhythm in all 43 patients. 1066
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
63
shown in Figure 1. The 6-, 12- and 24-month likelihood of maintaining sinus rhythm after therapy with each patient’s last intervention was 81, 79 and 60%, respectively. The influence of a markedly dilated left atrium (>60 mm) on time to recurrence of AF after conversion is shown in Figure 2A. Patients with LA dimensions >60 mm had recurrent AF soonerthan patients who had LA dimensions of 45 to 60 mm. Other factors associated with the ability to maintain sinus rhythm were duration of AF I1 year, pharmacologic conversion to sinus rhythm and absenceof mitral valve disease(Figure 2B, C and D). Patient age, sex, presenceof coronary artery diseaseand left ventricular function were not related to outcome.
Conversion of atrial fibrillation: Conversion to sinus rhythm can usually be accomplishedpharmacologically or electrically. Digoxin reducesthe ventricular response to AF, but its efficacy in converting patients to sinus rhythm remains in doubt.23Quinidine has beenreported to convert between 11 and 84% of patients,7J3J5,26 whereas procainamide converts approximately 50% of them.5 Flecainide has been reported to convert 60% of patients, although most had AF 110 days.15The best results have been achievedwith amiodarone,which converted approximately 65% of patients.19y27*28 In the current study, 33% of the patients converted to sinus rhythm with drug therapy alone. In addition, when pharmacologic conversion did occur, it was associated with long-term maintenance of sinus rhythm. DISCUSSION Maintenance of sinus rhythm: Therapy with either AF is associated with a doubling of mortality re- quinidine or disopyramide allows maintenance of sinus gardless of the underlying cardiac condition.21The risk rhythm in 20 to 60% of patients during the first of stroke is up to 17.6 times greater in patients with AF year.g-13Amiodarone has been more effective, mainthan that of a control population.22AF is also associ- taining sinus rhythm in approximately 70% of paated with disabling palpitations or dyspnea that may tients.27-2gIn the current study, class IA drugs were efpersist despite medical therapy-as AF is significantly fective in only 16% of patients, although referral patless efficient hemodynamically than sinus rhythm even terns tended to create a bias against these drugs. with control of the ventricular rate.23v24 Conversion of Amiodarone had a successrate of 55% by itself and, AF to sinus rhythm often ameliorates symptoms and when combined with a class IA agent, allowed additionimproves hemodynamic parameters.25It is thus desir- al patients to be effectively treated. The successrate for able to maintain a patient in sinus rhythm whenever class IC drugs was 50%. but these drugs were used in practical. only a limited number of patients in our study.
46-60 8 0.4
mm
-
iiT
0.2 -
A
‘0
‘60mm
200
400
000 DAYS
800
loo0
1200
0’ 0
B
I 200
400
000
800
1000
1200
DAYS
PHARMACOLOGIC NO MITRAL DISEASE
0.0 0.4 -
0.2
I c Oo
I 200
400
600
DAYS
800
loo0
1200
MITRAL DISEASE D
O0
200
400
000
800
1000
1200
DAYS
FlGURE 2. A, inttuence of left atrial size on time to recwremz of atrial fibrillation (p <0.05). B, influence of duration of chronic atrial fibrillation before the last intervention on time to recurrence of atrial fiMllation (p
1067
SINUS RHYTHM
AFTER ATRIAL
Factors associated
FIBRILLATION
with maintaining
sinus rhythm:
3. Flugelman MY, Hasin Y, Katz&son
N, Kriwisky M, Shefer A, Gotsman MS.
Restoration and maintenance of sinus rhythm after mitral valve surgery for mitral Duration of AF, type of underlying heart disease,pa- stenosis. Am J Cardiol 1984;54:617-619. tient age, left ventricular function and LA size influence 4. Parkinson J, Campbell M. Quinidine treatment of auricular fibrillation. Q J the outcome of therapy of AF. Some investigators sug- Med 192%1929;22:281-303. 5. Miller G, Weinberg SL, Pick A. The effect of procainamide (Pronestyl) in gest that patients are unlikely to maintain sinus rhythm clinical auricular fibrillation and flutter. Circulation 1952,6:41-50. when AF persists 21 year.3j8J1,28 However, Vitolo et 6. Morris JJ, Peter RH, McIntosh HD. Electrical conversion of atria1 fibrillation. a127did not find duration of AF to be an important fac- Ann Intern Med 1966;65:216-231. Rossi M, Lawn B. The use of quinidine in cardioversion. Am J Cardiol tor in determining the responseto amiodarone therapy. 7.1967;19:234-238. Some investigators suggest that the type of heart dis- 8. Hall JI, Wood DR. Factors affecting cardioversion of atria1 arrhythmias with reference to quinidine. Br Heart J 1968;30:84-90. ease influences outcome.*,” Nevertheless, Gold et a128 special 9. ByrneQuinn E, Wing AJ. Maintenance of sinus rhythm after DC reversion of suggest that this is not a factor when amiodarone is atria1 fibrillation: a double blind controlled trial of long-acting quinidine bisulused. Patient age greater than 50 years has also been phate. Br Heart J 1970;32:370-376. 10. Szekely P, Sideris DA, Batson GA. Maintenance of sinus rhythm after atria1 suggestedto be important, l1 although others have dis- defibrillation. Br Heart J 1970;32:741-746. puted this, especially with amiodarone therapy.8,27,28 Il. Waris E, Kreus KE, Salokannel J. Factors influencing persistence of sinus Flugelman et al3 suggestedthat left ventricular dysfunc- rhythm after DC shock treatment of atria1 fibrillation. Acta Med Stand tion prevents successfultherapy of AF, but other inves- 1971:189:161-166. 12. Hartel G. Louhijo A, Konttinen A. Disopyramide in the prevention of recurtigators8 maintain that left ventricular dysfunction does rence of atria1 fibrillation after electrcconversion. Clin Pharmacol Ther 1974; not preclude maintenance of sinus rhythm. Previous re- 15:551-555. 13. Sodermark T, Jonsson B, Olsson A, Oro L, Wallin H, Edhag 0, Sjogren A, ports indicated that LA dimension 145 mm opposesthe Danielsson M, Rosenhamer G. Effect of quinidine on maintaining sinus rhythm successfulmaintenance of sinus rhythm.le3 When amio- after conversion of atria1 fibrillation or flutter: a multicenter study from StockBr Heart J 1975;37:486-492. darone therapy is used, the importance of LA dilatation holm. 14. Ward DE, Camm AJ, Spurrell RAJ. Clinical antiarrhythmic effects of in determining outcome has been disputed.27-29 A com- amiodarone in patients with resistant paroxysmal tachycardias. Br Heart J parative analysis of these factors is difficult becauseof a 1980;44:91-95. 15. Borgeat A, Goy JJ, Maendly R, Kaufman U, Grbic M, Sigwart U. Flecainide lack of uniformity in patient populations and therapies versus quinidine for conversion of atria1 fibrillation to sinus rhythm. Am J Cardiol used. Becauseassociationsregarding maintenance of si- 1986;58:496-498. 16. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding nus rhythm have been generally based on therapy with quantitation in M-mode echocardiography: results of a survey of echocardioclass IA drugs, these associationsmay no longer be val- graphic measurements. Circulation 1978;58:1072-1083. 17. Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in id with therapy with newer agents. subjects from infancy to old age. Circulation 1980,62:1054-1061. In the current study, duration of AF I1 year, ab- normal 18. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; senceof mitral valve diseaseand pharmacologic conver- 29:469-489. sion were associatedwith a good outcome. The results 19. Kaplan E, M&r P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481. of our study also suggestthat a patient with a moder- 20. Mantel N. Ranking procedures for arbitrarily restricted observations. Bioately dilated left atrium (45 to 60 mm) may be main- metrics 1967;23:65-78. Kannel WB, Abbott RI), Savage DD, McNamara PM. Epidemiologic featained in sinus rhythm. A patient with a markedly dilat- 21. tures of chronic atria1 fibrillation. The Framingham Study. N Engl J Med ed left atrium (>60 mm) is still unlikely to maintain 1982;306:1018-1022. 22. Wolf PA, Dawber TR, Thomas HET, Kannel WB. Epidemiologic assessment sinus rhythm despite therapy. chronic atria1 fibrillation and risk of stroke: the Framingham Study. Neurology Limitations of the current study: This study was of1978;28:973-977. limited in that it was a retrospective analysis. Multiple 23. Falk RH, Knowlton AA, Bernard SA, Gotlieb NE, Battinelli NJ. Digoxin for drug regimenswere used,which might tend to confound converting recent-onset atria1 fibrillation to sinus rhythm. Ann Intern Med 1987;106:503-506. the relation between other clinical factors and outcome. 24. David D, Segni ED, Klein HO, Kaplinski E. Inefficacy of digitalis in the We did not routinely monitor plasma drug levels for control of heart rate in patients with chronic atria1 fibrillation: beneficial effect of an added beta adrenergic blocking agent. Am J Cardiol 1979;44:1378-1382. analysis. Woosley30has pointed out the many problems 25. Morris JJ Jr, Entman M, North WC, Kong Y, McIntosh H. The changes in associatedwith plasma drug concentration monitoring, cardiac output with reversion of atria1 fibrillation to sinus rhythm. Circulation including a lack of correlation between drug levels and 1965;31:670-678. 26. Goldman M. Quinidine treatment of auricular fibrillation. Am J Med Sci response. 1951;222:382-391.
REFERENCES
1. Henry WL, Morganroth J, Pearlman AS, Clark CE, Redwood DR, Itscoitz SB, Epstein SE. Relation between echocardiographically determined left atria1 size and atria1 fibrillation. Circulation 1976;53:273-279. 2. Ewy G, Ulfers L, Hager WD, Rosenfeld AR, Roeske WR, Goldman S. Response of atria1 fibrillation to therapy: role of etiology and left atria1 diameter. J Electrocardiol 1980;13:119-124.
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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63
27. Vitolo E, Tronci M, Larovere MT, Rum010 R, Morabito A. Amiodarone versus quinidine in the prophylaxis of atria1 fibrillation. Acta Cardiol (Brux) 1981;36:431-444. 28. Gold RL, Haffajee CI, Charos K, Sloan K, Baker S, Alpert JS. Amiodarone for refractory atria1 fibrillation. Am J Cardiol 1986;57:124-127. 29. Brcdsky MA, Allen BJ, Walker CJ, Casey TP, Luckett CR, Henry WL. Amiodarone for maintenance of sinus rhythm after conversion of atria1 fibrillation in the setting of a dilated left atrium. Am J Cardiol 1987,60:572-575. 30. Woosley RL. Role of plasma concentration monitoring in the evaluation of response to +ntiarrhythmic drugs. Am J Cardiol 3988,62:9H-17H.
Successful therapy of atrial fibrillation (AF) has been reportedly influenced by a variety of factors including patient age, type of underlying heart disease, duration of arrhythmia, lefl ventricular function and left atrial (LA) size. To determine which of these factors are associated with maintenance of sinus rhythm after conversion, 43 patients with symptomatic chronic AF in the setting of a dilated left atrium (145 mm, range 45 to 78) were followed for at least 6 months after the return of sinus rhythm. Class IA drugs, IC drugs or amiodacone were used for therapy. Life table analysis showed sinus rhythm to be maintained in 81% for 6 months, 79% for 12 months and 60% for 24 months. Factors positively associated with success were conversion with drug therapy alone, duration of chronic AF I1 year, absence of mitral valve disease and LA dimension 160 mm (all p <0.05). Patient age, left ventricular function and presence of coronary disease were not associated with outcome. Thus, patients with moderate LA dilatation (45 to 60 mm) and a short duration of chronic AF can often be maintained in sinus rhythm, especially if they convert with pharmacologic intervention alone. (Am1 Cardiol 1989;63:1065-1068)
From the Department of Medicine, Division of Cardiology, University of California at Irvine, Orange, California. Manuscript received November 28,1988; revised manuscript received and accepted February 2, 1989. Address for reprints: Michael A. Brodsky, MD, Division of Cardiology, University of California at Irvine Medical Center, 101 City Drive, Orange, California 92668.
P
revious studies suggest that the finding of an echocardiographicleft atria1 (LA) dimension 145 mm identifies patients who are unlikely to maintain sinus rhythm after conversion from chronic atria1 fibrillation (AF).lm3 Unfortunately, these patients are the ones most likely to benefit from being in sinus rhythm, as they often experiencea worsening of symptoms when in AF. The mainstay of therapy for preventing recurrent AF has been class IA antiarrhythmic drugs (quinidine, procainamide and disopyramide).4-13 Yet, AF recurs within the first year in 43 to 78% of patients thus treated.9J0J3 Recently available drugs such as amiodarone and class IC agents appear promising for AF.14J5Studies specifically correlating LA size with recurrence of AF antedate the availability of these newer drugs. The purpose of the current study was to reexamine the efficacy of antiarrhythmic therapy, including the newer drugs, with regard to whether a group of patients with LA dilatation could be maintained in sinus rhythm after conversion from chronic AF. METHODS Patients: We evaluated a total of 43 patients with
chronic AF meeting the following inclusion criteria: (1) the arrhythmia had to persist for at least 48 hours and be associatedwith either disabling palpitations, poor exercisetolerance or symptomatic congestiveheart failure; (2) the LA dimension had to be 145 mm as documented by M-mode echocardiography;and (3) patients had to be able to take oral anticoagulants and be willing to undergo electrical cardioversion. The 25 men and 18 women had a mean age of 58 f 10 years, with 27 (63%) being younger than 60 years of age. Atria1 fibrillation had beenpresent for a mean of 1,070days and 16 patients (37%) had arrhythmia for
1065
SINUS RHYTHM
TABLE
AFTER IdIAL
I Characteristics
FlBRlLLATlON
of 43 Patients
with Chronic
nus rhythm, that point (the last intervention) was considered the starting point for analysis of duration of sinus rhythm. All patients were followed for at least 6 months after the last intervention at intervals of 6 to 26 weeks.Cardiac rhythm was documented by electrocardiography (12-lead electrocardiogram or rhythm strip) or ambulatory electrocardiographic monitoring. Statistical analysis: Life-table analysis was carried out using the method of Kaplan and Meier, with comparisons between survival curves analyzed by the method of Mantel and COX.‘~,~O
Atrial
Fibrillation Clinical Variable
No. of Pts
Sex (M/F) (%) Underlying cardiac disease Valvular disease (%) Mitral stenosis (%) Mitral regurgitation (%) Mixed stenosis/regurgitation (%) Mitral valve replacement (%) Coronary artery disease (“9) Idiopathic dilated cardiomyopathy (%) Systemic hypertension (%) Miscellaneous (%) Duration of atrial fibrillation >l yr (“h)
25/18
TABLE
II Six-Month
lncfividual Total
Drug Class IA Quinidine Procaihamide Disopyramide Class IC (combined) Amiodarone Solitary Plus IA (combined)
(58/42)
15 (35)
8 (19) 3 (7) 4 (10) 7 (16) 8 (19) 7 (16) 5 (12) 8 (1% 27 16 14 4
RESULTS
(63) (37) (33) (9)
23 (53) 20 (47) 20 (56)
16(44) 32 (74) 11 (26)
Drug Efficacy Success
Percent Success
39 15 15 8
7 2 2 4
18 13 13 50
29 6
16 4
55 67
All patients were successfully converted to sinus rhythm either pharmacologically or with electrical cardioversion. After conversionthe patients maintained sinus rhythm for an averageof 598 f 502 days (range 1 to 1,602). Of 43 patients, 3.5 (81%) maintained sinus rhythm for 16 months. Pharmacologic therapy: The last intervention involved a class IA drug in 18 patients (quinidine 13, disopyramide 3, procainamide 2). Of these 18 patients, 6 (33%) had pharmacologic conversions (all with quinidine) and 12 (67%) required electrical cardioversion in addition to medication. Amiodarone was used as the last intervention in 15 patients, 6 (40%) of whom converted pharmacologically. Amiodarone plus a class IA drug was used in 6 patients (quinidine 4, disopyramide 1, procainamide l), all of whom required electrical cardioversion. A class IC drug was utilized as the last intervention in 4 patients. Flecainide was used in 2 patients, both of whom converted pharmacologically. Propafenone and encainide were given to 1 patient each (both required electrical cardioversion). Alterations in the medical regimen after conversion to sinus rhythm were required in 7 patients (16%). A compilation of overall drug responseusing the last intervention as well as all previous drug trials revealedclassIA agentsto be effective in 16%,class IC agents in 50%, amiodarone in 55% and amiodarone plus class IA agents in 67% (Table II).
Before conversion,patients were anticoagulated with warfarin for 12 weeks. During the phase of chronic AF, the ventricular responsewas controlled with digoxFactors related to maintenance of sinus rhythm: in (93% of patients), calcium antagonists (39%) or /3 The ability to maintain sinus rhythm in all patients is blockers (24%), given singly or in combination. Pharmacologic or electrical conversion was accomplished in all patients. Before conversion, a class IA 1 drug (quinidine; procainamide or disopyramide) was loaded orally in-hospital using previously describedregimens.7J2Out-of-hospital loading with either amiodarone or a class IC drug (flecainide, encainide or propafenone) was done over 1 to 3 months.14The doseof any antiarrhythmic agent was determined by the endpoints of QRS or QTc prolongation of 150% over control, development of intolerable side effects or blood levels in the toxic range of selectedagents.Patients were typically treated with IA agents as initial therapy and, failing 11 of these agents,were then treated with either a class IC drug or amiodarone. Many patients were referred -. 0 200 400 600 600 1000 1200 for therapy after failing all 3 approved class IA agents. DAYS After drug loading, 29 patients (67%) remained in -I AF and were then subjected to synchronized electrical cardioversion.18Once all patients were converted to si- FIGURE 1. Ability to maintain sinus rhythm in all 43 patients. 1066
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
63
shown in Figure 1. The 6-, 12- and 24-month likelihood of maintaining sinus rhythm after therapy with each patient’s last intervention was 81, 79 and 60%, respectively. The influence of a markedly dilated left atrium (>60 mm) on time to recurrence of AF after conversion is shown in Figure 2A. Patients with LA dimensions >60 mm had recurrent AF soonerthan patients who had LA dimensions of 45 to 60 mm. Other factors associated with the ability to maintain sinus rhythm were duration of AF I1 year, pharmacologic conversion to sinus rhythm and absenceof mitral valve disease(Figure 2B, C and D). Patient age, sex, presenceof coronary artery diseaseand left ventricular function were not related to outcome.
Conversion of atrial fibrillation: Conversion to sinus rhythm can usually be accomplishedpharmacologically or electrically. Digoxin reducesthe ventricular response to AF, but its efficacy in converting patients to sinus rhythm remains in doubt.23Quinidine has beenreported to convert between 11 and 84% of patients,7J3J5,26 whereas procainamide converts approximately 50% of them.5 Flecainide has been reported to convert 60% of patients, although most had AF 110 days.15The best results have been achievedwith amiodarone,which converted approximately 65% of patients.19y27*28 In the current study, 33% of the patients converted to sinus rhythm with drug therapy alone. In addition, when pharmacologic conversion did occur, it was associated with long-term maintenance of sinus rhythm. DISCUSSION Maintenance of sinus rhythm: Therapy with either AF is associated with a doubling of mortality re- quinidine or disopyramide allows maintenance of sinus gardless of the underlying cardiac condition.21The risk rhythm in 20 to 60% of patients during the first of stroke is up to 17.6 times greater in patients with AF year.g-13Amiodarone has been more effective, mainthan that of a control population.22AF is also associ- taining sinus rhythm in approximately 70% of paated with disabling palpitations or dyspnea that may tients.27-2gIn the current study, class IA drugs were efpersist despite medical therapy-as AF is significantly fective in only 16% of patients, although referral patless efficient hemodynamically than sinus rhythm even terns tended to create a bias against these drugs. with control of the ventricular rate.23v24 Conversion of Amiodarone had a successrate of 55% by itself and, AF to sinus rhythm often ameliorates symptoms and when combined with a class IA agent, allowed additionimproves hemodynamic parameters.25It is thus desir- al patients to be effectively treated. The successrate for able to maintain a patient in sinus rhythm whenever class IC drugs was 50%. but these drugs were used in practical. only a limited number of patients in our study.
46-60 8 0.4
mm
-
iiT
0.2 -
A
‘0
‘60mm
200
400
000 DAYS
800
loo0
1200
0’ 0
B
I 200
400
000
800
1000
1200
DAYS
PHARMACOLOGIC NO MITRAL DISEASE
0.0 0.4 -
0.2
I c Oo
I 200
400
600
DAYS
800
loo0
1200
MITRAL DISEASE D
O0
200
400
000
800
1000
1200
DAYS
FlGURE 2. A, inttuence of left atrial size on time to recwremz of atrial fibrillation (p <0.05). B, influence of duration of chronic atrial fibrillation before the last intervention on time to recurrence of atrial fiMllation (p
1067
SINUS RHYTHM
AFTER ATRIAL
Factors associated
FIBRILLATION
with maintaining
sinus rhythm:
3. Flugelman MY, Hasin Y, Katz&son
N, Kriwisky M, Shefer A, Gotsman MS.
Restoration and maintenance of sinus rhythm after mitral valve surgery for mitral Duration of AF, type of underlying heart disease,pa- stenosis. Am J Cardiol 1984;54:617-619. tient age, left ventricular function and LA size influence 4. Parkinson J, Campbell M. Quinidine treatment of auricular fibrillation. Q J the outcome of therapy of AF. Some investigators sug- Med 192%1929;22:281-303. 5. Miller G, Weinberg SL, Pick A. The effect of procainamide (Pronestyl) in gest that patients are unlikely to maintain sinus rhythm clinical auricular fibrillation and flutter. Circulation 1952,6:41-50. when AF persists 21 year.3j8J1,28 However, Vitolo et 6. Morris JJ, Peter RH, McIntosh HD. Electrical conversion of atria1 fibrillation. a127did not find duration of AF to be an important fac- Ann Intern Med 1966;65:216-231. Rossi M, Lawn B. The use of quinidine in cardioversion. Am J Cardiol tor in determining the responseto amiodarone therapy. 7.1967;19:234-238. Some investigators suggest that the type of heart dis- 8. Hall JI, Wood DR. Factors affecting cardioversion of atria1 arrhythmias with reference to quinidine. Br Heart J 1968;30:84-90. ease influences outcome.*,” Nevertheless, Gold et a128 special 9. ByrneQuinn E, Wing AJ. Maintenance of sinus rhythm after DC reversion of suggest that this is not a factor when amiodarone is atria1 fibrillation: a double blind controlled trial of long-acting quinidine bisulused. Patient age greater than 50 years has also been phate. Br Heart J 1970;32:370-376. 10. Szekely P, Sideris DA, Batson GA. Maintenance of sinus rhythm after atria1 suggestedto be important, l1 although others have dis- defibrillation. Br Heart J 1970;32:741-746. puted this, especially with amiodarone therapy.8,27,28 Il. Waris E, Kreus KE, Salokannel J. Factors influencing persistence of sinus Flugelman et al3 suggestedthat left ventricular dysfunc- rhythm after DC shock treatment of atria1 fibrillation. Acta Med Stand tion prevents successfultherapy of AF, but other inves- 1971:189:161-166. 12. Hartel G. Louhijo A, Konttinen A. Disopyramide in the prevention of recurtigators8 maintain that left ventricular dysfunction does rence of atria1 fibrillation after electrcconversion. Clin Pharmacol Ther 1974; not preclude maintenance of sinus rhythm. Previous re- 15:551-555. 13. Sodermark T, Jonsson B, Olsson A, Oro L, Wallin H, Edhag 0, Sjogren A, ports indicated that LA dimension 145 mm opposesthe Danielsson M, Rosenhamer G. Effect of quinidine on maintaining sinus rhythm successfulmaintenance of sinus rhythm.le3 When amio- after conversion of atria1 fibrillation or flutter: a multicenter study from StockBr Heart J 1975;37:486-492. darone therapy is used, the importance of LA dilatation holm. 14. Ward DE, Camm AJ, Spurrell RAJ. Clinical antiarrhythmic effects of in determining outcome has been disputed.27-29 A com- amiodarone in patients with resistant paroxysmal tachycardias. Br Heart J parative analysis of these factors is difficult becauseof a 1980;44:91-95. 15. Borgeat A, Goy JJ, Maendly R, Kaufman U, Grbic M, Sigwart U. Flecainide lack of uniformity in patient populations and therapies versus quinidine for conversion of atria1 fibrillation to sinus rhythm. Am J Cardiol used. Becauseassociationsregarding maintenance of si- 1986;58:496-498. 16. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding nus rhythm have been generally based on therapy with quantitation in M-mode echocardiography: results of a survey of echocardioclass IA drugs, these associationsmay no longer be val- graphic measurements. Circulation 1978;58:1072-1083. 17. Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in id with therapy with newer agents. subjects from infancy to old age. Circulation 1980,62:1054-1061. In the current study, duration of AF I1 year, ab- normal 18. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; senceof mitral valve diseaseand pharmacologic conver- 29:469-489. sion were associatedwith a good outcome. The results 19. Kaplan E, M&r P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481. of our study also suggestthat a patient with a moder- 20. Mantel N. Ranking procedures for arbitrarily restricted observations. Bioately dilated left atrium (45 to 60 mm) may be main- metrics 1967;23:65-78. Kannel WB, Abbott RI), Savage DD, McNamara PM. Epidemiologic featained in sinus rhythm. A patient with a markedly dilat- 21. tures of chronic atria1 fibrillation. The Framingham Study. N Engl J Med ed left atrium (>60 mm) is still unlikely to maintain 1982;306:1018-1022. 22. Wolf PA, Dawber TR, Thomas HET, Kannel WB. Epidemiologic assessment sinus rhythm despite therapy. chronic atria1 fibrillation and risk of stroke: the Framingham Study. Neurology Limitations of the current study: This study was of1978;28:973-977. limited in that it was a retrospective analysis. Multiple 23. Falk RH, Knowlton AA, Bernard SA, Gotlieb NE, Battinelli NJ. Digoxin for drug regimenswere used,which might tend to confound converting recent-onset atria1 fibrillation to sinus rhythm. Ann Intern Med 1987;106:503-506. the relation between other clinical factors and outcome. 24. David D, Segni ED, Klein HO, Kaplinski E. Inefficacy of digitalis in the We did not routinely monitor plasma drug levels for control of heart rate in patients with chronic atria1 fibrillation: beneficial effect of an added beta adrenergic blocking agent. Am J Cardiol 1979;44:1378-1382. analysis. Woosley30has pointed out the many problems 25. Morris JJ Jr, Entman M, North WC, Kong Y, McIntosh H. The changes in associatedwith plasma drug concentration monitoring, cardiac output with reversion of atria1 fibrillation to sinus rhythm. Circulation including a lack of correlation between drug levels and 1965;31:670-678. 26. Goldman M. Quinidine treatment of auricular fibrillation. Am J Med Sci response. 1951;222:382-391.
REFERENCES
1. Henry WL, Morganroth J, Pearlman AS, Clark CE, Redwood DR, Itscoitz SB, Epstein SE. Relation between echocardiographically determined left atria1 size and atria1 fibrillation. Circulation 1976;53:273-279. 2. Ewy G, Ulfers L, Hager WD, Rosenfeld AR, Roeske WR, Goldman S. Response of atria1 fibrillation to therapy: role of etiology and left atria1 diameter. J Electrocardiol 1980;13:119-124.
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27. Vitolo E, Tronci M, Larovere MT, Rum010 R, Morabito A. Amiodarone versus quinidine in the prophylaxis of atria1 fibrillation. Acta Cardiol (Brux) 1981;36:431-444. 28. Gold RL, Haffajee CI, Charos K, Sloan K, Baker S, Alpert JS. Amiodarone for refractory atria1 fibrillation. Am J Cardiol 1986;57:124-127. 29. Brcdsky MA, Allen BJ, Walker CJ, Casey TP, Luckett CR, Henry WL. Amiodarone for maintenance of sinus rhythm after conversion of atria1 fibrillation in the setting of a dilated left atrium. Am J Cardiol 1987,60:572-575. 30. Woosley RL. Role of plasma concentration monitoring in the evaluation of response to +ntiarrhythmic drugs. Am J Cardiol 3988,62:9H-17H.