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The Safety and Efficacy of Quinidine Sulphate in Conversion of Atrial Fibrillation to Sinus Rhythm

Potpara, Tatjana; Grujic, Miodrag; Marinkovic,
Jelena; Radojkovic, Biljana; Vujisic Bosiljka.

Institute for Cardiovascular Diseases, Clinical Centre of Serbia, Belgrade, Yugoslavi

SUMMARY
Objectives: The present study investigates the efficacy and safety of quinidine sulphate in conversion of persistent atrial fibrillation (PAF) to sinus rhythm (SR).
Background: The first line therapy of PAF still is restoration and maintenance of SR mostly by antiarrhythmics. However, there is a reasonable concern about potential risk of proarrhythmia.
Materials and Methods: We examined the efficacy and safety of quinidine in restoration of SR in a cohort of 342 patients with PAF. While continuously monitored, each patient received 200mg of quinidine sulphate in 2 hours intervals up to 2400mg/24 hours. Quinidine was discontinued when SR was restored or if QT prolongation (QTc>500ms), PVCs or QRS complex widening were recorded as well as if patients complained of gastrointestinal disturbances.
Results: Sinus rhythm was achieved in 265 (77.5%) patients and complications occurred in 63 (18.4%) of them. Serious rhythm disorders in form of polymorphic ventricular tachycardia and/or ventricular fibrillation developed in 3 (0.88%) patients but there were no fatal events.
Discussion: Quinidine sulphate is the oldest known antiarrhythmic drug. It has been used since 1918, but when Coplen and others reported increased mortality of patients with AF treated with quinidine its use began to decline. The efficacy of quinidine in conversion of PAF is well known and we feel that short-term, in-hospital use of quinidine for conversion of PAF is unreasonably neglected.
Conclusions: We concluded that quinidine is efficacious and safe in conversion of atrial fibrillation to sinus rhythm

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OBJECTIVES
   The present study investigates the efficacy and safety of quinidine sulphate in conversion of persistent atrial fibrillation to sinus rhythm.

BACKGROUND
    Atrial fibrillation is the most common cardiac rhythm disorder and the most frequent cause of repeated admissions to hospital among cardiac arrhythmias. Rhythm control (i.e. restoration and maintenance of sinus rhythm) is considered to be the therapy of choice for patients with atrial fibrillation, offering symptom relief and successful prevention of the potential complications. Future results of some ongoing controlled prospective clinical trials are expected to provide scientific proof confirming this way of clinical thinking, actually based almost on the common sense. In current clinical practice rhythm control is most frequently achieved pharmacologically and class IA, IC and class III antiarrhythmics (i.e. sodium and potassium channel blockers) are the first line therapy for conversion of persistent atrial fibrillation to sinus rhythm with success rate ranging from 30% to 90%, depending on previous arrhythmia duration and other parameters. However, pharmacotherapy of atrial fibrillation is associated with a reasonable concern about potential risk of proarrhythmia, especially when class IA antiarrhythmics are administered. Meta-analysis of 6 studies about quinidine revealed that the risk of proarrhythmic death is 2.98 times greater in patients with atrial fibrillation treated with quinidine as compared to placebo, although some authors do not agree with these results.

MATERIAL AND METHODS
   We examined the efficacy and safety of quinidine in restoration of sinus rhythm in a cohort of 342 patients with persistent atrial fibrillation. Patients with acute causes of atrial fibrillation such as hyperthyroidism, patients with advanced valvular heart disease and/or significant left ventricular systolic dysfunction (left ventricular ejection fraction = 30%), patients with heart conduction system diseases and/or permanent artificial pacing devices, as well as patients with Wolff-Parkinson-White syndrome were excluded from the study.

   Besides detailed history, clinical examination, biochemistry and routine 12-lead electrocardiogram each patient underwent transthoracic echocardiography in M-mode, Two-dimensional and Continuous and Colour Doppler techniques. Upon admission to hospital, all patients received some medication for slowing atrioventricular conduction (digitalis, beta blockers or verapamil) orally or intravenously. While continuously monitored, each patient then received 200mg of quinidine sulphate per os in two hours intervals during 24 hours (up to 2400mg for 24 hours), with 12-lead electrocardiogram repeatedly recorded every two hours. Quinidine was discontinued when sinus rhythm was restored or if QT interval prolongation (QTc>500ms), premature ventricular complexes, nonsustained ventricular tachycardia and/or QRS complex widening for more than 40ms were recorded, as well as if patients complained of gastrointestinal or neurological disturbances. The restoration of sinus rhythm was documented electrocardiographically and conversion of atrial fibrillation was considered to be successful if sinus rhythm lasted at least 12 hours after last administered dose of quinidine.

RESULTS
   In a group of 342 patients aged 17 to 78 years (mean 56.2 ± 11.14 years), 237 patients (69.3%) were males and 105 (30.7%) were females. Lone atrial fibrillation was present in 137 (40.0%) patients, while the others had some cardiac underlying disease: systemic arterial hypertension (130 patients or 38.0%), coronary heart disease (23 patients or 6.7%), cardiomyopathies (36 patients or 10.5%), mild heart valvular diseases (20 patients or 5.8%) and prosthetic mechanical valves (15 patients or 4.4%), or noncardiac disorder: diabetes mellitus (21 patient or 6.1%), chronic obstructive lung disease (8 patients or 2.3%) or hiatus hernia (9 patients or 2.6%).

   Echocardiographic examination revealed dilated left atrium with left atrial anteroposterior diameter over 40mm in 177 patients (51.7%), left ventricular dilatation with end systolic diameter over 56mm and/or end systolic diameter over 40mm in 78 patients (22.8%), left ventricular ejection fraction lower then 55% in 63 patients (18.4%) and left ventricular hypertrophy with left ventricular wall diameter over 11mm in 21 patients (6.1%). Right heart cavities were enlarged in 17 patients (5.0%) and mild to moderate mitral regurgitation was found in 131 patients (38.3%).

   Atrial fibrillation persisted 48 hours to 9 years before attempted cardioversion (mean duration of atrial fibrillation was 8.6 ± 18.14 months). The average and the most frequently administered dose of quinidine sulphate was 1400 mg (range 200 to 2400mg). Sinus rhythm was achieved in 265 (77.5%) patients while 77 patients (22.5%) developed permanent atrial fibrillation.

   Overall, complications occurred in 63 (18.4%) of the patients and quinidine was discontinued in 50 of them (14.6%). Serious rhythm disorders in form of polymorphic ventricular tachycardia and/or ventricular fibrillation developed in 3 (0.88%) patients after 200 - 600mg of quinidine and sinus rhythm was restored by external DC shock. All the three patients had previously diagnosed dilated cardiomiopathy (one patient had coronary artery disease, too) with significantly reduced left ventricular ejection fraction (EF ~ 30%). Nonsustained ventricular tachycardias and frequent premature ventricular complexes were registered in 16 patients (4.6%), QT interval prolongation in 27 patients (7.9%) and QRS complex widening in 5 patients (1.5%). Transformation of atrial fibrillation to atrial flutter with 1:1-2 atrioventricular conduction and high ventricular rates occurred in 12 patients (3.5%) while 20 patients (5.8%) complained of gastrointestinal and/or neurological disturbances. There were no fatal events during the study.

DISCUSSION
   Most studies that evaluate the efficacy of different antiarrhythmics in conversion of atrial fibrillation to sinus rhythm include patients with so-called recent onset atrial fibrillation where the arrhythmia duration has been measured by hours, days or, rarely, weeks and where sinus rhythm may be successfully restored in over 90% of patients. Papers about conversion of long-lasting atrial fibrillation are not that numerous. Zehender et al. compared the efficacy of quinidine and amiodarone in conversion of atrial fibrillation lasting from 4 months to 2 years. Quinidine restored sinus rhythm in 55% of patients while amiodarone was successful in 60% of patients, without statistically significant difference. In other reports quinidine was successful in 40% to 80% of patients with atrial fibrillation, similarly to our results. In our study quinidine successfully restored sinus rhythm in 77.5% of patients with long-lasting atrial fibrillation (mean arrhythmia duration in our patients was 8.6 months).

   In general, the use of antiarrhythmic drugs is limited by their possible proarrhythmic actions, especially pronounced in patients with significantly reduced left ventricular systolic function and in patients with prolonged QT interval. Quinidine is the oldest known antiarrhythmic drug. It has been widely used since 1918, but when Coplen and others reported increased mortality of patients with AF treated with quinidine its use began to decline. According to literature, proarrhythmic action of quinidine in form of polymorphic ventricular tachycardias (i.e. torsades de pointes) previously known as "quinidine syncope" is expected in 1% to 2% patients treated with quinidine. The initiation of ventricular tachycardia usually does not correlate with administered dose of quinidine; it is rather a consequence of idiosyncratic reaction. Polymorphic ventricular tachycardia often degenerates to ventricular fibrillation resistant to electroshock and as many as half of these patients may die suddenly. Other less severe proarrhytmogenic effects of quinidine (QT and/or PR interval prolongation, frequent premature ventricular complexes) may be expected in 6% to 15% of patients.

   Proarrhythmic effects of procainamide are manifested in 9% of patients and those of dysopiramide in 6% of patients. This is why the use of class IA antiarrhythmic drugs for conversion of atrial fibrillation and for maintenance of sinus rhythm is not routinely recommended any more.

   On the other hand, serious ventricular arrhythmias occurred in less than 1% of patients treated with quinidine during our study and those were patients with significant left ventricular systolic dysfunction (left ventricular ejection fraction
~ 30%). Close, continuous monitoring of patients and proper discontinuation of quinidine therapy when indicated could explain low incidence of serious complications during quinidine administration in our study. Obviously, quinidine should not be administered to patients with significantly compromised left ventricular function and must be discontinued in patients who develop QT interval prolongation and/or frequent premature ventricular complexes during treatment.

   Finally, since the efficacy of quinidine in conversion of atrial fibrillation is well established we feel that short-term, in-hospital use of quinidine for conversion of atrial fibrillation is unreasonably neglected.

CONCLUSIONS
   According to presented results we concluded that quinidine is efficacious and safe in conversion of atrial fibrillation to sinus rhythm in patients with preserved or mildly compromised left ventricular systolic function.

 

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
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