QuinidineTreatment of Chronic Lone Atrial Fibrillation c,E,
NWIJER. M . D . . C.
M.SPARLING.M.D.
DePfimentof Cardiology, LeyenburgHospital, The Hague, The Netherlands
Summary: Patients with chronic lone atrial fibrillation (LAF) were treated with quinidine according to a special to establish sinus rhythm and prevent recurrences. Twentyseven patients following this schedule were identified retrospectively. TOprevent relapses, quinidine had ken continued in 25 patients in doses 100 mg qid lower than those used for conversion. In 8 of the latter group, quinidine had to be discontinued or reduced. All patients converted to sinus rhythm. If well tolerated, quinidine pwented recurrence of LAF in 75% of those on longterm (mean follow-up 3.5 years) prophylaxis. After discontinuation of quinidine in 8 patients, LAF recurred in all but one patient. Side effects were observed in 22% of the patients and precluded continuation of the prophylaxis in 15%. No incidence of torsade de pointes was encountered.
Key words: lone atrial fibrillation, quinidine, conversion, prophylaxis
Introduction Among the large number of patients with persistent atrial fibrillation,a subgroup can be distinguished in which the cause of the rhythm disturbance cannot be found. This form of atrial fibrillation has been termed benign, idiopathic, and functional. Evans and Swan first used the qualification “lone” for this entity. I
1
Address for reprints:
c. de Nooijer kpanrnent of Cardiology kenburg Hospital b w e g 275 2g5CH The Hague, The Netherlands December 29, 1989 Accepted with revision: June 10. F)9o
Although lone atrial fibrillation (LAF) does not always produce symptoms, it leads to loss of presystolic filling of the ventricles.2 Furthermore, there is a risk of thromb o e m b o li~ m , and ~ - ~the pulse frequency may change inappropriately. Since the mid-I960s, one of us (CMS) had used quinidine to convert LAF to sinus rhythm. Spontaneous recurrence of LAF is to be expected if quinidine prophylaxis is not continued. The present retrospective study covered a series of patients with LAF treated in this way since 1973.
Methods Patients The medical records of all patients with atrial fibrillation or flutter, admitted between 1973 and July 1986 to the Cardiology Department of Leyenburg Hospital, The Hague, were reviewed. Prior to admission, a detailed medical history had been obtained. Physical examination and laboratory investigation, including T4 analysis, ECG, and chest x-ray had been performed in all patients. Echocardiography was performed in all but 8 patients before conversion, and in all 27 patients before the end of the study. For the present study, any patient with one of the following features was excluded: coronary artery disease, valvular heart disease, congestive heart failure, cardiomyopathy, pericardial disease, hypertension on at least two occasions, chronic pulmonary disease, age >75 years, alcoholism, any ECG abnormality other than atrial fibrillation or flutter, cardiomegaly, end-systolic left atrial dimension >45 mm or other echocardiographic abnormalities, hyperthyroidism and occurrence of paroxysmal atrial fibrillation either spontaneouslyor in association with trauma, surgery, or an acute illness such as pulmonary embolism. Twenty-seven patients (4 female, 23 male), who had suffered from LAF for a mean period of two months (range 10 days to 2.5 years) were located. The range was 30-72 years (mean 53.3 years). All were being treated with anticoagulants. Table I lists medications taken before quinidine conversion.
Clin. Cardiol. Vol. 13, October 1990
712
TABLE I Medication taken before the quinidine conversion (n=27) ~
:I
~
14 1
Digoxin Digoxin combined with beta blocker Digoxin combined with verapamil Beta blocker Verapamil Chinidine" Disopyramide
n=27
':lt
2 5
I 3 3
4
2
"Low dose, not according to schedule.
00000
8 828$ m
00000
a2$sz
Dose of quinidine (rng)
Conversion Schedule
FIG.I Quinidine dosage (A) at conversion and (B) after dixbrg(,
All patients were monitored by telemetry. Anticoagulants were continued, but digoxin was withdrawn at least 3 days before quinidine was started. A beta blocker was added when the ventricular rate exceeded 90/min (12 patients), and in one case verapamil was used for this purpose. If an oral dose of I00 mg quinidine sulfate was well tolerated, patients were given 200 mg quinidine qid. On each successive day the dose was increased by 100 mg qid until conversion to sinus rhythm occurred. After that, the dose was decreased one step, but was not decreased below 200 mg qid. Quinidine plasma levels were not measured. If sinus rhythm persisted for one month after conversion, anticoagulation was discontinued.
fate (durettes), 250 mg of which is considered equivalenl to 200 mg sulfate. No relation was found between the dose at conversion and the age of the patient, the duration of LAF, or the width of the left atrium on the echocardie gram (Fig. 2). In eight patients no preconversion eche cardiography findings were available. A later echocardiographic examination showed no cause of the atrid fibrillation. Patients who registered ventricular responses higher than 90/min and who had been receiving beta blockers additionally needed a higher dose of quinidine, which suggests that LAF with a lower spontaneous ventricular mponse is more easily convertible (Table 11). Unfortunately, we were unable to determine the ventricular rate just before conversion systematically.
Results Primary Conversion
Secondary Prophylaxis
Lone atrial fibrillation converted to sinus rhythm in all 27 patients after 1 to 5 (mean 2) days of treatment with quinidine (Fig. IA). Sulfate of quinidine was used in all but one patient, who was given quinidine hydrogen sul-
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Two of the 27 patients did not continue quinidine treatment after discharge. In one of them LAF recurred within 24 h; he was maintained on digoxin and phenpmou-
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C . de Nooijer and C. M. Sparling: Quinidine treatment of AF
713
(22%) and led to discontinuation or dose reduction in 4 (15%). Dose (mg)
With beta blocker
Without beta blocker
Discussion
0
0
tm
4 2
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T A e ~ 111 E Overview of the secondary prophylaxis with quinidine ( n = 2 3
-a, ~uinidinecontinued
persisting sinus rhythm Recurrence of lone atrial fibrillation b. Quinidine discontinued or dose reduced Persisting sinus rhythm Recurrence of lone atrial fibrillation
17
l3
4
76.5% SR
8 7
12.5% SR
marin. In the second patient, quinidine had to be discontinued because of severe diarrhea. Figure 1B shows the dose of quinidine at the time of discharge. Two patients wee given durettes bid 750 mg (second column in Fig.
IB). Of the 25 patients shown in Table 111, 17 took quinidine continuously and 13 (76.5%) of the latter maintained sinus rhythm. Of these 13 patients, 10 have been followed for 7 months to 7 years (mean 3.0 years); three others were well after 4,5, and 7 years and are no longer in our care. Four of the 17 patients reverted to LAF after 2 weeks, 2 months, 1 year, and 5 years, respectively. These four did not differ as to age, duration of LAF, or size of LA from the 13 in whom sinus rhythm persisted. In the other 8 of 25 patients, quinidine was decreased Orstopped, in three because of side effects and in five because sinus rhythm had persisted so long that secondary Prophylaxis was no longer deemed necessary. Only one of these eight (12.5%) did not revert to LAF; in this man rhythm has persisted for 5.5 years since quinidine was withdrawn. In 7 patients reversion to LAF occurred.
side Effects Four patients developed diarrhea, one nausea, and one ventn~ularbigeminy. Torsade de pointes did not complicate the quinidine schedule in any of our patients. In two quinidine was withdrawn, in two others the dose ’as lowered, and in one the symptoms disappeared after thePatient was switched to durettes in an equivalent dose. In one patient diarrhea did not persist on continued quinidine therapy. Side effects occurred in 6 of 27 patients
Patients suffering from atrial fibrillation with an adequately controlled ventricular rate seldom complain of palpitations. Furthermore, LAF usually does not limit the patient’s activities. So why convert LAF to sinus rhythm when consensus has not been reached about the risk of thromboembolism? According to the Framingham study, the risk of “stroke” is four times greater in patients with LAF than in a comparable group without LAF.3.7In that study, however, LAF was not strictly defined; for example, thyroid disease was not routinely excluded and echocardiography and chest radiography were not performed in all of the patients.8 Recently Frey and Jenzer studied 47 patients, 14 of whom had chronic LAF when first seen and 33 developed chronic LAF after a paroxysmal onset. In these 47 cases the annual embolism rate was 1% .6 In a recent survey of patients attending the Mayo Clinic a group of 97 with “lone” atrial fibrillation was selected, but more than half of these patients had paroxysmal atrial fibrillation and would not satisfy our criteria for LAF.S In the subgroup with chronic atrial fibrillation, the survival rate was 81 % at 10 and 15 years after diagnosis, which means a mortality rate 2 to 4 times higher than that of an age- and sex-matched population. Unfortunately this subgroup was not homogeneous, since those with electmardiographic abnormalities such as nonspecific ST-segment or T-wave changes, intraventricular conduction delay, and left axis deviation were not excluded, nor were some with decreased left ventricular function on echographic examination. According to these authors, the calculated risk of thromboembolism was 0.55 per 100 person-years for their 97 patients, which is lower than that for the subgroup with permanent LAF.S However, other authors emphasize the benign course of LAF.’.9 h b s t efal. suggest that atrial fibrillation itself can lead to atrial dilatation. lo.ll W e included patients with an atria1 diameter up to 45 mm on echocardiography in our LAF series. In more than half of them the atrial diameter was between 40 and 45 mm. Unlike others,’* we found no relation between the recurrence of LAF and atrial width. Many studies have shown that quinidine can prevent atrial fibrillation. I 3 - l 6 Long-acting preparations are superior to the short-acting sulfate of quinidine, because they give a more constant blood level and better patient compliance. I4-l6 LAF was not treated separately in any of these studies. Gastrointestinal side effects of quinidine are frequent.3.14,’6The occurrence of syncope, sudden death, and torsade de pointes has been reporteg in a small percentage of those treated with quinidine, 1 7 , 1 8 the majority of the cases in the first week and more often in ischemic heart
Clin. Cardiol. Vol. 13, October 1990
714
disease.'$ In our series, conversion followed by prophylaxis was carried out in hospital during a period of at least 5 days on telemetric surveillance without detectable cardiac abnormalities other than LAF. Based on the results of the present study, we conclude that quinidine is successful in converting LAF to sinus rhythm. Quinidine also seems to prevent relapses, however the question as to whether LAF should be treated with quinidine will be answered by a prospective mndomized study.
References I . Evans W, Swann P: Lone auricular fibrillation. Br Heart J 16, 189 ( 1954)
2. Khaja F, Parker JO: Hemodynamic effects of cardioversion in chronic atrial fibrillation. Arch Znfern Ued 129, 433 (1972) 3. Brand FN, Abbott RD, Kannel WB, Wolf PhA: Characteristics and prognosis of lone atrial fibrillation. J Am Med Assoc 254, 3449 (1985) 4. Flegel KM, Shipley MJ, Rose G: Risk of stroke in nonrheumatic atrial fibrillation. Lancer 1, 526 (1987) 5 . Kopecky SL, Gersh BJ, Phil D, Mc Goon MD, Whisnant JP. Holmes DR Jr, llstrup DM, Frye RL: The natural history of lone atrial fibrillation. N Engl J Med 317, 669 (1987) 6. Frey R, Jenzer HR: ldiopathisches Votttofflimmem: Verlauf bei paroxysmaler und chronischer Form. Schweiz Med Wschr 118, 198 (1988) 7. Anonymous: Is lone atrial fibrillation really benign? (editorial). Lancet I , 305 (1986)
8. Evans DW. Bailey SM: 1s lone atrial fibrillation e a l l ~kn (letter). Lancer I . 499 (1986) 9. Close B, Evans DW, Bailey SM: Persistent lone fibrillation-its prognosis after clinical diagnosis,J R Coll Prac 29, 547 (1979) 10. Probst P, Glodschlager N, Selzer A: Left atrial size and fibrillation in mitral stenosis. Circulation 38, 1282 ( 1 1 1 . Selzer A: Atrial fibrillation revisited. N E n g / J M e d J M , ( 1982) 12. Hoglund C. Rosenhamer G : Ehoardiographic leftatrial d,l sion as a predictor of maintaining sinus rhythm after coI sion of atrial fibrillation. Acra Med Scand 217, 411 ( I $ 13. Sijdermark T. Jonsson B, Olsson A. Or0 L, Wallin H, 0,Sjogren A, Danielsson M, Rosenhamer G: Effectofq, dine on maintaining sinus rhythm after conversion ofatrialf lation or flutter. Br Hean J 37. 486 (1975) 14. hissel JP, Wolf E, Gillet J, Soubmne A, Cavallam A, M~ G , Delhaye JP: Controhd trial Of a longacting guinidin maintenance of sinus rhythm after conversion of sustained ; fibrillation. Eur Heart J 2, 49 (1981) 15. Normand JP. Legendre M.Kahn JC, Bourdarias JP. Mall A: Comparative efficacy of shortacting and longacting dine for maintenance of sinus rhythm after electrical COI sion of atrial fibrillation. Br Hean J 38, 381 (1976) 16. Cramer G: Early and late results of conversion of atrial f lation with quinidine. Acra Ued Scand 49O(suppl), 1 ( I 17. Koster RW. Wellens HJJ: Quinidine-induced ventricular ter and fibrillation without digitalis therapy. Am J Cordio 519 (1976) 18. Bauman JL, Bauemfeind RA, Hoff JV, Stmskg B, sv s, Rosen KM: Torsade de pointes due to quinidine: O h tions in 31 patients. Am Heart J 107, 425 (1984) '
;
~
NWIJER. M . D . . C.
M.SPARLING.M.D.
DePfimentof Cardiology, LeyenburgHospital, The Hague, The Netherlands
Summary: Patients with chronic lone atrial fibrillation (LAF) were treated with quinidine according to a special to establish sinus rhythm and prevent recurrences. Twentyseven patients following this schedule were identified retrospectively. TOprevent relapses, quinidine had ken continued in 25 patients in doses 100 mg qid lower than those used for conversion. In 8 of the latter group, quinidine had to be discontinued or reduced. All patients converted to sinus rhythm. If well tolerated, quinidine pwented recurrence of LAF in 75% of those on longterm (mean follow-up 3.5 years) prophylaxis. After discontinuation of quinidine in 8 patients, LAF recurred in all but one patient. Side effects were observed in 22% of the patients and precluded continuation of the prophylaxis in 15%. No incidence of torsade de pointes was encountered.
Key words: lone atrial fibrillation, quinidine, conversion, prophylaxis
Introduction Among the large number of patients with persistent atrial fibrillation,a subgroup can be distinguished in which the cause of the rhythm disturbance cannot be found. This form of atrial fibrillation has been termed benign, idiopathic, and functional. Evans and Swan first used the qualification “lone” for this entity. I
1
Address for reprints:
c. de Nooijer kpanrnent of Cardiology kenburg Hospital b w e g 275 2g5CH The Hague, The Netherlands December 29, 1989 Accepted with revision: June 10. F)9o
Although lone atrial fibrillation (LAF) does not always produce symptoms, it leads to loss of presystolic filling of the ventricles.2 Furthermore, there is a risk of thromb o e m b o li~ m , and ~ - ~the pulse frequency may change inappropriately. Since the mid-I960s, one of us (CMS) had used quinidine to convert LAF to sinus rhythm. Spontaneous recurrence of LAF is to be expected if quinidine prophylaxis is not continued. The present retrospective study covered a series of patients with LAF treated in this way since 1973.
Methods Patients The medical records of all patients with atrial fibrillation or flutter, admitted between 1973 and July 1986 to the Cardiology Department of Leyenburg Hospital, The Hague, were reviewed. Prior to admission, a detailed medical history had been obtained. Physical examination and laboratory investigation, including T4 analysis, ECG, and chest x-ray had been performed in all patients. Echocardiography was performed in all but 8 patients before conversion, and in all 27 patients before the end of the study. For the present study, any patient with one of the following features was excluded: coronary artery disease, valvular heart disease, congestive heart failure, cardiomyopathy, pericardial disease, hypertension on at least two occasions, chronic pulmonary disease, age >75 years, alcoholism, any ECG abnormality other than atrial fibrillation or flutter, cardiomegaly, end-systolic left atrial dimension >45 mm or other echocardiographic abnormalities, hyperthyroidism and occurrence of paroxysmal atrial fibrillation either spontaneouslyor in association with trauma, surgery, or an acute illness such as pulmonary embolism. Twenty-seven patients (4 female, 23 male), who had suffered from LAF for a mean period of two months (range 10 days to 2.5 years) were located. The range was 30-72 years (mean 53.3 years). All were being treated with anticoagulants. Table I lists medications taken before quinidine conversion.
Clin. Cardiol. Vol. 13, October 1990
712
TABLE I Medication taken before the quinidine conversion (n=27) ~
:I
~
14 1
Digoxin Digoxin combined with beta blocker Digoxin combined with verapamil Beta blocker Verapamil Chinidine" Disopyramide
n=27
':lt
2 5
I 3 3
4
2
"Low dose, not according to schedule.
00000
8 828$ m
00000
a2$sz
Dose of quinidine (rng)
Conversion Schedule
FIG.I Quinidine dosage (A) at conversion and (B) after dixbrg(,
All patients were monitored by telemetry. Anticoagulants were continued, but digoxin was withdrawn at least 3 days before quinidine was started. A beta blocker was added when the ventricular rate exceeded 90/min (12 patients), and in one case verapamil was used for this purpose. If an oral dose of I00 mg quinidine sulfate was well tolerated, patients were given 200 mg quinidine qid. On each successive day the dose was increased by 100 mg qid until conversion to sinus rhythm occurred. After that, the dose was decreased one step, but was not decreased below 200 mg qid. Quinidine plasma levels were not measured. If sinus rhythm persisted for one month after conversion, anticoagulation was discontinued.
fate (durettes), 250 mg of which is considered equivalenl to 200 mg sulfate. No relation was found between the dose at conversion and the age of the patient, the duration of LAF, or the width of the left atrium on the echocardie gram (Fig. 2). In eight patients no preconversion eche cardiography findings were available. A later echocardiographic examination showed no cause of the atrid fibrillation. Patients who registered ventricular responses higher than 90/min and who had been receiving beta blockers additionally needed a higher dose of quinidine, which suggests that LAF with a lower spontaneous ventricular mponse is more easily convertible (Table 11). Unfortunately, we were unable to determine the ventricular rate just before conversion systematically.
Results Primary Conversion
Secondary Prophylaxis
Lone atrial fibrillation converted to sinus rhythm in all 27 patients after 1 to 5 (mean 2) days of treatment with quinidine (Fig. IA). Sulfate of quinidine was used in all but one patient, who was given quinidine hydrogen sul-
(A)
2400-
-
2000 -
x ~1200800 I
.. 1
4"
I
2400
-
-
2000
-
1600
-
1600- * *
...
"
24002000
.. ..
z16OO-
1
Two of the 27 patients did not continue quinidine treatment after discharge. In one of them LAF recurred within 24 h; he was maintained on digoxin and phenpmou-
I . .
... I
1200-
800I
-
-
1
'
**
. .
@
.
1
-
1
.
1
.
1
.
1
.
1
1
1('
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1200-
800
..
I
"
.
'
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"
.
: '
'
I
a
'
I
C . de Nooijer and C. M. Sparling: Quinidine treatment of AF
713
(22%) and led to discontinuation or dose reduction in 4 (15%). Dose (mg)
With beta blocker
Without beta blocker
Discussion
0
0
tm
4 2
ltao 1600 2ooo
T A e ~ 111 E Overview of the secondary prophylaxis with quinidine ( n = 2 3
-a, ~uinidinecontinued
persisting sinus rhythm Recurrence of lone atrial fibrillation b. Quinidine discontinued or dose reduced Persisting sinus rhythm Recurrence of lone atrial fibrillation
17
l3
4
76.5% SR
8 7
12.5% SR
marin. In the second patient, quinidine had to be discontinued because of severe diarrhea. Figure 1B shows the dose of quinidine at the time of discharge. Two patients wee given durettes bid 750 mg (second column in Fig.
IB). Of the 25 patients shown in Table 111, 17 took quinidine continuously and 13 (76.5%) of the latter maintained sinus rhythm. Of these 13 patients, 10 have been followed for 7 months to 7 years (mean 3.0 years); three others were well after 4,5, and 7 years and are no longer in our care. Four of the 17 patients reverted to LAF after 2 weeks, 2 months, 1 year, and 5 years, respectively. These four did not differ as to age, duration of LAF, or size of LA from the 13 in whom sinus rhythm persisted. In the other 8 of 25 patients, quinidine was decreased Orstopped, in three because of side effects and in five because sinus rhythm had persisted so long that secondary Prophylaxis was no longer deemed necessary. Only one of these eight (12.5%) did not revert to LAF; in this man rhythm has persisted for 5.5 years since quinidine was withdrawn. In 7 patients reversion to LAF occurred.
side Effects Four patients developed diarrhea, one nausea, and one ventn~ularbigeminy. Torsade de pointes did not complicate the quinidine schedule in any of our patients. In two quinidine was withdrawn, in two others the dose ’as lowered, and in one the symptoms disappeared after thePatient was switched to durettes in an equivalent dose. In one patient diarrhea did not persist on continued quinidine therapy. Side effects occurred in 6 of 27 patients
Patients suffering from atrial fibrillation with an adequately controlled ventricular rate seldom complain of palpitations. Furthermore, LAF usually does not limit the patient’s activities. So why convert LAF to sinus rhythm when consensus has not been reached about the risk of thromboembolism? According to the Framingham study, the risk of “stroke” is four times greater in patients with LAF than in a comparable group without LAF.3.7In that study, however, LAF was not strictly defined; for example, thyroid disease was not routinely excluded and echocardiography and chest radiography were not performed in all of the patients.8 Recently Frey and Jenzer studied 47 patients, 14 of whom had chronic LAF when first seen and 33 developed chronic LAF after a paroxysmal onset. In these 47 cases the annual embolism rate was 1% .6 In a recent survey of patients attending the Mayo Clinic a group of 97 with “lone” atrial fibrillation was selected, but more than half of these patients had paroxysmal atrial fibrillation and would not satisfy our criteria for LAF.S In the subgroup with chronic atrial fibrillation, the survival rate was 81 % at 10 and 15 years after diagnosis, which means a mortality rate 2 to 4 times higher than that of an age- and sex-matched population. Unfortunately this subgroup was not homogeneous, since those with electmardiographic abnormalities such as nonspecific ST-segment or T-wave changes, intraventricular conduction delay, and left axis deviation were not excluded, nor were some with decreased left ventricular function on echographic examination. According to these authors, the calculated risk of thromboembolism was 0.55 per 100 person-years for their 97 patients, which is lower than that for the subgroup with permanent LAF.S However, other authors emphasize the benign course of LAF.’.9 h b s t efal. suggest that atrial fibrillation itself can lead to atrial dilatation. lo.ll W e included patients with an atria1 diameter up to 45 mm on echocardiography in our LAF series. In more than half of them the atrial diameter was between 40 and 45 mm. Unlike others,’* we found no relation between the recurrence of LAF and atrial width. Many studies have shown that quinidine can prevent atrial fibrillation. I 3 - l 6 Long-acting preparations are superior to the short-acting sulfate of quinidine, because they give a more constant blood level and better patient compliance. I4-l6 LAF was not treated separately in any of these studies. Gastrointestinal side effects of quinidine are frequent.3.14,’6The occurrence of syncope, sudden death, and torsade de pointes has been reporteg in a small percentage of those treated with quinidine, 1 7 , 1 8 the majority of the cases in the first week and more often in ischemic heart
Clin. Cardiol. Vol. 13, October 1990
714
disease.'$ In our series, conversion followed by prophylaxis was carried out in hospital during a period of at least 5 days on telemetric surveillance without detectable cardiac abnormalities other than LAF. Based on the results of the present study, we conclude that quinidine is successful in converting LAF to sinus rhythm. Quinidine also seems to prevent relapses, however the question as to whether LAF should be treated with quinidine will be answered by a prospective mndomized study.
References I . Evans W, Swann P: Lone auricular fibrillation. Br Heart J 16, 189 ( 1954)
2. Khaja F, Parker JO: Hemodynamic effects of cardioversion in chronic atrial fibrillation. Arch Znfern Ued 129, 433 (1972) 3. Brand FN, Abbott RD, Kannel WB, Wolf PhA: Characteristics and prognosis of lone atrial fibrillation. J Am Med Assoc 254, 3449 (1985) 4. Flegel KM, Shipley MJ, Rose G: Risk of stroke in nonrheumatic atrial fibrillation. Lancer 1, 526 (1987) 5 . Kopecky SL, Gersh BJ, Phil D, Mc Goon MD, Whisnant JP. Holmes DR Jr, llstrup DM, Frye RL: The natural history of lone atrial fibrillation. N Engl J Med 317, 669 (1987) 6. Frey R, Jenzer HR: ldiopathisches Votttofflimmem: Verlauf bei paroxysmaler und chronischer Form. Schweiz Med Wschr 118, 198 (1988) 7. Anonymous: Is lone atrial fibrillation really benign? (editorial). Lancet I , 305 (1986)
8. Evans DW. Bailey SM: 1s lone atrial fibrillation e a l l ~kn (letter). Lancer I . 499 (1986) 9. Close B, Evans DW, Bailey SM: Persistent lone fibrillation-its prognosis after clinical diagnosis,J R Coll Prac 29, 547 (1979) 10. Probst P, Glodschlager N, Selzer A: Left atrial size and fibrillation in mitral stenosis. Circulation 38, 1282 ( 1 1 1 . Selzer A: Atrial fibrillation revisited. N E n g / J M e d J M , ( 1982) 12. Hoglund C. Rosenhamer G : Ehoardiographic leftatrial d,l sion as a predictor of maintaining sinus rhythm after coI sion of atrial fibrillation. Acra Med Scand 217, 411 ( I $ 13. Sijdermark T. Jonsson B, Olsson A. Or0 L, Wallin H, 0,Sjogren A, Danielsson M, Rosenhamer G: Effectofq, dine on maintaining sinus rhythm after conversion ofatrialf lation or flutter. Br Hean J 37. 486 (1975) 14. hissel JP, Wolf E, Gillet J, Soubmne A, Cavallam A, M~ G , Delhaye JP: Controhd trial Of a longacting guinidin maintenance of sinus rhythm after conversion of sustained ; fibrillation. Eur Heart J 2, 49 (1981) 15. Normand JP. Legendre M.Kahn JC, Bourdarias JP. Mall A: Comparative efficacy of shortacting and longacting dine for maintenance of sinus rhythm after electrical COI sion of atrial fibrillation. Br Hean J 38, 381 (1976) 16. Cramer G: Early and late results of conversion of atrial f lation with quinidine. Acra Ued Scand 49O(suppl), 1 ( I 17. Koster RW. Wellens HJJ: Quinidine-induced ventricular ter and fibrillation without digitalis therapy. Am J Cordio 519 (1976) 18. Bauman JL, Bauemfeind RA, Hoff JV, Stmskg B, sv s, Rosen KM: Torsade de pointes due to quinidine: O h tions in 31 patients. Am Heart J 107, 425 (1984) '
;
~
