J Cardiol 2001 Dec; 38（6）: 351 – 354

Special Article
Safety and Effectiveness of Oral Quinidine in Cardioversion ofPersistent Atrial Fibrillation
Christos

KIRPIZIDIS, MD

AlexiaSTAVRATI, MD

Parashos

GELERIS, MD

Harisios BOUDOULAS, MD ＊Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────Objectives. The effectiveness of oral quinidine for conversion of atrial fibrillation to sinus rhythm wasevaluated in 49 patients with persistent atrial fibrillation on anticoagulation therapy. Atrial fibrillation wasconsidered as persistent when the duration was longer than 3 days but less than 6 months.
Methods. Patients received orally one to 7 doses of 150 mg hydroquinidine hydrochloride every one
hour until restoration of sinus rhythm, or to a maximum of 7 tablets. Patients who were not converted
underwent elective electrical cardioversion.
Results. Thirty-nine of 49 patients（79.6%）
were converted with quinidine and only one of the remaining
10 was converted with electrical cardioversion. Quinidine had no significant effect on blood pressure orunexpected changes on the QRS duration and the QT interval. Four patients developed gastrointestinal
symptoms（8.1%）.
Conclusions. Oral quinidine was safe and effective in the conversion of persistent atrial fibrillation tosinus rhythm.
─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2001 ; 38（6）: 351−354

Key Words
Atrial fibrillation

Antiarrhythmia agents quinidine

INTRODUCTION
Atrial fibrillation has emerged as the most common cardiac arrhythmia requiring therapy1）.
Many pharmacological agents have been used
for the conversion of persistent atrial fibrillation tosinus rhythm with variable rates of success2）. It
appears, however, that not a single pharmacologic
agent is clearly superior to any other for this purpose. Quinidine has been reported to have a wide
range of success rates from 30% to 90% in heterogenous populations3,4）.
The present study was undertaken to define theAnticoagulants

efficacy and safety of oral quinidine for the conversion of persistent atrial fibrillation to sinus rhythm.
For the purpose of this study persistent atrial fibrillation was defined when its duration was greaterthan 3 days but shorter than 6 months.
METHODS
Forty-nine consecutive patients（24 men and 25women）admitted in the Division of Cardiology ofthe Second Idrima Kinonikon Asfaliseon Hospital,
Thessaloniki, Greece, with persistent atrial fibrillation were studied prospectively（Table 1）. Onset ofatrial fibrillation was considered at the time when──────────────────────────────────────────────Division of Cardiology, The Second Idrima Kinonikon Aslaliseon Hospital, Thessaloniki, Greece ; ＊ Division of Cardiology, Heart andLung Research Institute, Ohio State University, Colombus, OH, USA
Address for correspondence: GELERIS P, MD, Division of Cardiology, The Second Idrima Kinonikon Asfaliseon Hospital, N. Plastira
22 N Krini, Thessaloniki, Greece
Received for publication September 20, 2001

351

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Kirpizidis, Stavrati, Geleris et al

Table 1 Clinical characteristics of patients studied
Mean age（yr）

63.42（range 45 to 78）

Mean duration of persistentatrial fibrillation（days）

69.94±58.25

Mean left atrial size（mm）

43.41±4.44

Mean systolic blood pressure（mmHg）

137.1±16.15

Values are mean ±SD .

patients became symptomatic and started to complain of palpitations. Atrial fibrillation was documented by 12-lead electrocardiogram on the day ofadmission in all patients. Patients with valvular
heart disease were excluded prior to entry into thestudy. Serum potassium, sodium, and thyroid function tests were within normal limits on the day ofadmission in all patients. Twenty-one of thepatients had a history of arterial hypertension, 7 hadcoronary artery disease, and 6 had diabetes mellitus. Patients did not receive any antiarrhythmic
therapy prior to admission in the hospital and all
were on chronic anticoagulation therapy（＞ 4weeks）
with an international normalized ratio（INR）
2.5−3 times above normal control.
Two-dimensional, M-mode echocardiography,and Doppler echocardiography were performed in
all patients with Acuson 128 XP echocardiographic
machine with a 2.5 MHz transducer using standard
techniques as recommended by the American
Society of Echocardiography5）. Five consecutive
cardiac cycles were used for analysis and the values
were averaged. Left atrial and ventricular diameters
were measured by two-dimensional directed Mmode echocardiography. None of the patients had
mitral stenosis, or significant mitral regurgitation（greater than ＋ 1）as defined by Doppler echocardiography.
Electrocardiographic monitoring was maintained
during the entire study. A 12-lead electrocardiogram was recorded every 30 min for the analysis of
QRS and QT intervals. The duration of QT intervalof 10 successive beats was measured and the results
were averaged. The QT interval was corrected as
described previously by Boudoulas et al.6） and theQT index（QTI）
was obtained. Brachial artery pressure was measured every 15 min by sphygmomanometry.
Hydroquinidine hydrochloride, 150 mg tablet,
was given orally every one hour until restoration ofsinus rhythm or to a maximum amount of 7 tablets（1,050 mg）. Patients who were not converted after

7 oral doses of quinidine underwent elective electrical cardioversion.
Patients who restored sinus rhythm received ondischarge 150 mg of propafenone three times a day
and continued anticoagulation therapy for a minimum of 4 weeks.
Statistical evaluation was performed using theStudent t-test and chi-square analysis.
RESULTS
Conversion to sinus rhythm was obtained in 39
patients（ 79.6%）. The mean conversion dose ofquinidine was 4.7 tablets（705 mg）
in 4.7 hours.
The 10 patients who remained in atrial fibrillation
after administration of 7 tablets of quinidinehydrochloride underwent synchronized electrical
cardioversion ; only one of them converted to sinus
rhythm.
The conversion to sinus rhythm was not related
to the duration of atrial fibrillation, left atrial size or
the coexisting cardiac diseases（Table 2）.
Quinidine had no significant effect on bloodpressure or unexpected effects on the QRS durationand the QT interval（Table 3）.
Four patients developed gastrointestinal symptoms（8.1%）; in only one of them was the treatment discontinued because of side effects.
DISCUSSION
This study demonstrated that a high rate of conversion to sinus rhythm occurred with quinidine ina group of patients with persistent atrial fibrillation.
Quinidine is a sodium channel blocking classⅠa
antiarrhythmic agent which has been used extensively in the treatment of atrial and ventriculararrhythmias, especially in patients with atrial fibrillation or atrial flutter, often in combination withverapamil or digoxin7−9）.
Other pharmacologic agents also have been usedfor conversion of atrial fibrillation with variable
rates of success. Amiodarone, a class Ⅲ drug, hasbeen reported to be effective in restoring sinus
rhythm in 48% to 81% of patients with atrial fibrillation10,11）. It was usually administered as a highoral dose and occasionally intravenously.
Amiodarone and quinidine plus verapamil had similar rates of success, 60% and 55% respectively, in
terminating persistent atrial fibrillation（4 weeks to12）
2 years duration）. Amiodarone was also effective
in restoring sinus rhythm in approximately 50% of
the patients with persistent atrial fibrillation refracJ Cardiol 2001 Dec; 38（6）: 351 – 354

Oral Quinidine for Persistent Atrial Fibrillation

353

Table 2 Characteristics of patients converted
Conversion to sinus rhythm（n＝39）

No conversion to sinus rhythm（n＝10）

p value

Mean duration of atrial
fibrillation（days）

68.75

73.6

NS

Mean left atrium size（mm）

43.45

43.25

NS

History of arterial hypertension（% patients）

4340

NS

History of coronary artery disease（% patients）

1320

NS

Table 3 Systolic blood pressure, QRS duration, and QT index in patients treated with quinidine
Systolic blood pressure（mmHg）

QRS duration（msec）QT index（msec）

Baseline values

137.1±16.5

72.6±6.65

388.5±24.74＊

Quinidine

129.2±12.5

73.2±6.62

402.1±25.15＊

Values are mean ±SD. ＊p＜0.001.

tory to therapy with quinidine13）.
Propafenone, a class Ⅰc pharmacologic agent has
been used in different doses orally or intravenously,
for conversion of atrial fibrillation to sinus rhythmwith success rates from 55% to 81%14,15）. There is
still no agreement about the optimal doses ofpropafenone for conversion of atrial fibrillation tosinus rhythm. One oral dose of 600 mg is considered to be effective for this purpose.
Studies also have shown that quinidine was more
effective than sotalol in conversion of paroxysmal
atrial fibrillation to sinus rhythm（ 86% vs52%）16,17）. Quinidine was also more effective thansotalol in conversion of persistent atrial fibrillation（mean duration of 45 days）to sinus rhythm with
rates of success 60% vs 20%18）.
We found that left atrial size and arrhythmia
duration did not influence the therapeutic responsein this selective population. In previous studies,
however, where propafenone or amiodarone wereused, the duration of atrial fibrillation was longer,
and the left atrial size was greater in those patientsin whom atrial fibrillation was not converted tosinus rhythm19−22）. In the present study, the durationof arrhythmia was less than 6 months and the atrial
size was not markedly large.
Minor side effects related to therapy with quinidine were seen, however, only in one patient discontinuation of therapy was necessary. It is imporJ Cardiol 2001 Dec; 38（6）: 351 – 354

tant to emphasize that patients who were refractory
to therapy with quinidine were also refractory toelectrical cardioversion.
CONCLUSIONS
Our study, although performed in a rather small
number of patients, suggests that oral quinidine canbe used for the conversion of persistent atrial fibrillation to sinus rhythm, because it is effective andsafe.
References
1）The National Heart, Lung, and Blood Institute Working
Group on Atrial Fibrillation : Atrial fibrillation : Current
understandings and research imperatives. J Am CollCardiol 1993 ; 22 : 1830−18342）Waldo AL, Prystowsky EN : Drug treatment of atrial fibrillation in the managed care era. Am J Cardiol 1998 ; 81（Suppl 5A）: C30−C343）Clark A, Cotter L : Cardioversion in atrial fibrillation. Br J
Hosp Med 1993 ; 49 : 256−2614）Hurst JW, Paulk EA, Proctor HD, Schlant RC :Management of patients with atrial fibrillation. Am J Med
1964 ; 37 : 728−7415）Sahn DJ, DeMaria S, Kisslo J, Weyman A : Recommendations regarding quantitation in M-mode echocardiography : Results of a survey of echocardiographic measurements. Circulation 1978 ; 58 : 1072−10836）Boudoulas H, Geleris P, Lewis RP, Rittgers SE : Linear
relationship between electrical systole, mechanical systoleand heart rate. Chest 1981 ; 80 : 613−617

354

Kirpizidis, Stavrati, Geleris et al7）Antman EM, Beamer AD, Cantillon C, McGowan N,
Friedman PL : Therapy of refractory symptomatic atrial fibrillation and atrial flutter : A staged care approach with newantiarrhythmic drugs. J Am Coll Cardiol 1990 ; 15 : 698−7078）Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers
TC : Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion : A meta-analysisof randomized controlled trials. Circulation 1990 ; 82 :1106−11169）Haines DE, DiMarco JP : Sustained intraatrial reentrant
tachycardia : Clinical, electrocardiographic and electrophysiologic characteristics and long-term follow-up. J Am
Coll Cardiol 1990 ; 15 : 1345−135410）Tieleman RG, Gosselink ATM, Crijns HJGM, van Gelder
IC, van den Berg MP, De Kam PJ, van Gilst WH, Lie KI :Efficacy, safety, and determinants of conversion of atrial
fibrillation and flutter with oral amiodarone. Am J Cardiol
1997 ; 79 : 53−5711）Levy S : Amiodarone as a first-line drug in the treatment ofatrial fibrillation : The protagonist viewpoint. Cardiovasc
Drugs Ther 1994 ; 8 : 769−771
12）Zehender MO, Hohnloser S, Muller B, Meinertz T, Just H :Effects of amiodarone versus quinidine and verapamil inpatients with chronic atrial fibrillation : Results of a comparative study and a 2-year follow-up. J Am Coll Cardiol
1992 ; 19 : 1054−105913）Horowitz LN, Spielman SR, Greenspan AM, Mintz GS,
Morganroth J, Brown R, Brady PM, Kay HR : Use of amiodarone in the treatment of persistent and paroxysmal atrial
fibrillation resistant to quinidine therapy. J Am Coll Cardiol
1985 ; 6 : 1402−140714）Boriani G, Capucci A, Lenzi T, Sanguinetti M, Magnani B :Propafenone for conversion of recent-onset atrial fibrillation : A controlled comparison between oral loading doseand intravenous administration. Chest 1995 ; 108 : 355−35815）Boriani G, Biffi M, Capucci A, Botto GL, Broffoni T,Rubino I, Della S, Sanguinetti M, Magnani B : Oral
propafenone to convert recent-onset atrial fibrillation inpatients with and without underlying heart disease : A randomized, controlled trial. Ann Intern Med 1997 ; 126 :621−62516）Bryson HM, Palmer KJ, Langtry HD, Fitton A :Propafenone : A reappraisal of its pharmacology, pharmacokinetics, and therapeutic use in cardiac arrhythmias.
Drugs 1993 ; 45 : 85−13017）Halinen MO, Huttunen M, Paakinen S, Tarssanen L :Comparison of sotalol with digoxin-quinidine for conversion of acute atrial fibrillation to sinus rhythm. Am JCardiol 1995 ; 76 : 495−49818）Hohnloser S, van de Loo A, Baedeker F : Efficacy andproarrhythmic hazards of pharmacologic cardioversion ofatrial fibrillation : Prospective comparison of sotalol versus
quinidine. J Am Coll Cardiol 1995 ; 26 : 852−85819）Pritchett ELC : Management of atrial fibrillation. N Engl J
Med 1992 ; 326 : 1264−127120）Brodsky MA, Allen BJ, Walker CJ Ⅲ, Casey TP, Luckett
CR, Henry WL : Amiodarone for maintenance of sinus
rhythm after conversion of atrial fibrillation in the setting ofa dilated left atrium. Am J Cardiol 1987 ; 60 : 572−57521）Bianconi L, Boccadamo R, Pappalardo A, Gentili C,
Pistolese M : Effectiveness of intravenous propafenone forconversion of atrial fibrillation and flutter of recent onset.
Am J Cardiol 1989 ; 64 : 335−33822）Suttorp MJ, Kingma JH, Jessurun ER, Lie-A-Huen L, vanHemel NM, Lie KI : The value of class IC antiarrhythmic
drugs for acute conversion of paroxysmal atrial fibrillation
or flutter to sinus rhythm. J Am Coll Cardiol 1990 ; 16 :1722−1727

J Cardiol 2001 Dec; 38（6）: 351 – 354