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Communications to the Editor |

Quinidine as an Antiarrhythmic Quinidine as an Antiarrhythmic FREE TO VIEW

Basil M. RuDusky, MD, FCCP
Author and Funding Information

Affiliations: Wilkes-Barre, PA,  Mobile, AL

Correspondence to: Basil M. RuDusky, MD, FCCP, Bicentennial Building, 15 Public Square, Wilkes-Barre, PA 18701-1702



Chest. 2001;119(5):1617-1619. doi:10.1378/chest.119.5.1617
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The excellent clinical investigation concerning the use of amiodarone as a first-choice drug for converting atrial fibrillation to normal sinus rhythm (June 2000)1and the accompanying editorial2 by Dr. Martin Alpert on the medical conversion of atrial fibrillation serve to illustrate one of the many continued challenges facing the clinician.

Quinidine, once considered to be the quintessential antiarrhythmic drug, although dethroned from its previously unique and lofty position, is still the most frequently and most widely prescribed antiarrhythmic drug despite the concern over its proarrhythmic potential.

The resurgent interest in atrial fibrillation and its consequences in patients of all ages has led to renewed interest in its medical management. The questions that remain, and still need to be answered, are first, whether to treat or not to treat and second, which drug to utilize. This also assumes that following pharmacologic or direct current cardioversion in selected patients, maintenance drug therapy is usually necessary. In my opinion, conversion of atrial fibrillation is not as great a problem as the maintenance of sinus rhythm postconversion, which implies long-term drug therapy. In relegating the importance of the complications of atrial fibrillation, those most often discussed and feared are the embolic events: macrovascular peripheral and cerebral arterial occlusions; pulmonary arterial emboli; and microvascular coronary, cerebral, and peripheral arterial events. Those complications, which often are not discussed and are omitted by many authors entirely, include a decrease in cardiac output and aggravation or precipitation of heart failure and angina pectoris.

Despite all that has been said and written, it is important to remember that quinidine has withstood the test of time better than most of its competition, and, although not unblemished, in my opinion, the record of its use has been tainted only slightly up to the present day. Having used quinidine for > 3 decades has led me to believe that, considering the present state of our antiarrhythmic armamentarium, we should not yet displace quinidine from its proper place and use in medical therapy. It is as effective as most of its competition and is less dangerous than many other similar drugs, which is why it still continues to be widely utilized by the medical profession. The questions that continue to need to be addressed are the following: Who are we benefiting with antiarrhythmic therapy, and who are we harming? Which patients should be selected for therapy and which should we manage conservatively (ie, which should we ignore)? These questions have not yet been answered to a satisfactory degree, regardless of the studies published. The proarrhythmic potential exists in all antiarrhythmic drugs, even in digitalis. With each drug, one needs to address the time period during which the proarrhythmic potential is most likely to arise and the comorbid medical problems that contribute to the increased propensity toward the development of torsade de pointes, which is the most feared complication of all antiarrhythmic drugs and is the one that is cited most often in the quinidine-related literature. This, in turn, can result in quinidine-induced syncope resulting from the related hemodynamic instability caused by ventricular tachyarrhythmia, the latter reported in 1.5 to 8% per patient-year of treatment. Since relentless diarrhea, which is refractory to all previously known therapy, is a common side effect of quinidine therapy, hypokalemia and hypomagnesemia must be addressed. Electrolyte imbalance is a notorious potentiator in the development of torsade de pointes. This issue finally has been laid to rest, in my opinion, since effective therapy to prevent quinidine-induced diarrhea now exists.3

Since it has been estimated that from 2 to 8% of patients receiving quinidine will develop QT prolongation, the observation of this and other ECG criteria should diminish the frequency of the more serious complications, as should happen with all the antiarrhythmic agents. A more unusual problem exists with quinidine, however, for QT prolongation can occur with plasma concentrations well within the normal therapeutic range or even at subtherapeutic levels. It is likely that some patients have a genetically induced, inherent predisposition toward the development of enhanced inhomogeneity of ventricular repolarization (which is considered to be a prerequisite for the occurrence of polymorphic ventricular tachycardia). It appears likely that quinidine, because of its Na+ and K+ current (channel) blocking effects, has a greater propensity for selecting and affecting those individuals with obvious or forme fruste genetic abnormalities of these channels. Which effect has greater importance in this regard is uncertain, although it is accepted that Na+ channel blockade is a primary electrophysiologic effect of quinidine therapy. The K+ channel-blocking effect is less well-known to most cardiologists, but importantly, the normalization of acquired QT prolongation has been alleviated by the use of IV potassium therapy in order to increase the serum potassium level to a higher range of normality. This electrophysiologic situation produces increased QT dispersion as measured on the ECG in some patients (and sometimes only noted during exercise). Therefore, the determination of QT dispersion may help to predict arrhythmogenic propensity when using quinidine, or any antiarrhythmic drug for that matter.4 The association and importance of measuring myocardial afterpotentials prior to and following quinidine therapy is, as yet, totally unexplored. Of future interest is the present research involving the development of a computerized electrophysiologic analyzer utilizing data obtained from routine ECGs, which is said to be able to predict the subsequent development of atrial and ventricular tachyarrhythmias with a high degree of success. Although quinidine has been known to exacerbate heart failure or conduction system disease, these events appear to be rare. Most patients with heart failure tolerate quinidine quite well, perhaps because of its vasodilating effects secondary to α-adrenergic receptor blockade and vagal inhibition.

Limited prospective trials comparing quinidine to other antiarrhythmic drugs have yielded a paucity of conclusions regarding quinidine, some favorable, others equivocal. Di Benedetto,5in an interesting study, concluded that quinidine was more efficacious and at least as well tolerated as propafenone in the conversion of atrial fibrillation to sinus rhythm and that it continues to have an important role in the acute treatment of atrial fibrillation. Studies comparing quinidine to sotalol have yielded contradictory results. The study of de Paola and Veloso6 concluded that sotalol was more effective in recent-onset atrial fibrillation, whereas quinidine was more effective in chronic atrial fibrillation. Hohnloser et al4 concluded that quinidine, although more effective in terminating atrial fibrillation than sotalol, was associated with more side effects; 3 patients of the 25 patients in the quinidine group developed torsade de pointes shortly after conversion to normal sinus rhythm, a vulnerable phase when the heart rate is slow.

The meta-analyses combining various quinidine studies must be interpreted cautiously and viewed with a certain degree of scientific skepticism at present.

Pritchett7 concluded that increased numbers of deaths from cardiovascular causes and sudden deaths due to arrhythmias, as proposed in some quinidine meta-analyses, should be considered a hypothesis generated by the study, rather than a firm conclusion. He rightly pointed out a number of limitations in these studies and also concluded that quinidine remains a drug of first choice for maintaining sinus rhythm.

The excellent review by Grace and Camm8indicated that the patient selection, the concomitant therapy, and the low overall mortality rates exhibited in various meta-analyses preclude the direct application of these data to current practice and that many adverse conclusions regarding quinidine therapy have been based on retrospective studies. They further noted, on review of the limited prospective studies, that direct estimates of quinidine-associated cardiac risk were generally similar to those for other drugs. The effectiveness of combined quinidine and verapamil therapy in the successful treatment of paroxysmal atrial fibrillation was reported by Innes et al,9although the study was too small to be of substantial significance. More recently, La Pointe and Li,10 have reported the successful treatment of atrial fibrillation and atrial flutter with continuous IV quinidine infusion.

Long-term successful outcomes using electrophysiologic-guided quinidine therapy for patients with idiopathic ventricular fibrillation with or without the Brugada syndrome have been reported.11

Doubtlessly, the perfect antiarrhythmic agent is not yet in sight. One certainly can question whether the development of such an agent is possible when one realizes the complexly intertwined electrophysiology involved.

It is my present opinion that quinidine can still be effectively considered as a front-line antiarrhythmic agent, as I recall an old axiom: “Be not the first on whom the new are tried, nor the last to lay the old aside.”

Vardas, PE, Kochiadakis, GE, Igoumenidis, NE, et al (2000) Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized controlled study.Chest117,1538-1545. [CrossRef] [PubMed]
 
Alpert, MA Medical cardioversion of atrial fibrillation [editorial]Chest2000;117,1529-1531. [CrossRef] [PubMed]
 
RuDusky BM. Cholestyramine therapy for quinidine-induced diarrhea. Angiology 1997:173–176.
 
Hohnloser, SH, van de Loo, A, Baedeket, F Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine.J Am Coll Cardiol1955;26,852-858
 
Di Benedetto, S Quinine versus propafenone for conversion of atrial fibrillation to sinus rhythm.Am J Cardiol1997;80,518-519. [CrossRef] [PubMed]
 
de Paola, AA, Veloso, HH Efficacy and safety of sotalol versus quinidine for the maintenance of sinus rhythm after conversion of atrial fibrillation: SOCESP Investigators; The Cardiology Society of Sao Paulo.Am J Cardiol1999;84,1033-1037. [CrossRef] [PubMed]
 
Pritchett, EL Management of atrial fibrillation.N Engl J Med1992;326,1264-1271. [CrossRef] [PubMed]
 
Grace, AA, Camm, AJ QuinidineN Engl J Med1998;338,35-45. [CrossRef] [PubMed]
 
Innes, GD, Vertesi, L, Dillon, EC Effectiveness of verapamil-quinidine versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation.Ann Emerg Med1997;29,126-134. [CrossRef] [PubMed]
 
La Pointe, NM, Li, P Continuous intravenous quinidine infusion for the treatment of atrial fibrillation or flutter: a case series.Am Heart J2000;139,114-121. [PubMed]
 
Belhassen, B, Viskin, S, Fish, R, et al Effects of electrophysiologic-guided therapy with class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome.J Cardiovasc Electrophysiol1999;10,1301-1312. [CrossRef] [PubMed]
 
To the Editor:

The article by Vardas et al (June 2000)1and my accompanying editorial2focused on the issue of medical cardioversion of atrial fibrillation. The article itself dealt with the use of a regimen of IV and oral amiodarone used for this purpose. It described a high rate of medical cardioversion within 48 h when amiodarone was selected as the initial antiarrhythmic drug. I attempted to create a context for these findings by describing the previous clinical experience with amiodarone and other antiarrhythmic drugs. In his letter to the editor, Dr. RuDusky focuses primarily on quinidine and its role in the medical cardioversion of atrial fibrillation, but he also speaks to the issue of long-term therapy. He reminds us that we should not be so quick to abandon established therapies in favor of new ones. Indeed, in medical cardioversion of atrial fibrillation, comparative studies3 have shown the efficacy of quinidine to be comparable to some antiarrhythmic drugs and superior to others, but rarely inferior. Moreover, the most feared complication of medical cardioversion with quinidine (proarrhythmic ventricular tachyarrhythmias) occurs with most commercially available antiarrhythmic drugs, although not usually as early as with quinidine.3 Small studies suggest that the efficacy of quinidine and amiodarone in medical cardioversion of atrial fibrillation is comparable.3However, larger comparison studies in patients with similar characteristics are needed to confirm these observations. The administration of quinidine by IV infusion described by Dr. RuDusky and reported by LaPointe and Li4 is of particular interest, as it would increase the versatility of this drug in medical cardioversion, which is particularly important in hospitalized, critically ill patients. While accepting that quinidine remains an important part of the pharmacologic armamentarium for medical cardioversion of atrial fibrillation, I continue to be reticent about recommending its long-term use to prevent recurrences, particularly in patients with current or prior congestive heart failure. Data demonstrating increased mortality with quinidine in this clinical setting remain compelling and uncontested.5

References
Vardas, P, Kochiadokis, GE, Igoumentis, NE, et al Amiodarone as a first choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study.Chest2000;117,1538-1545. [CrossRef] [PubMed]
 
Alpert, MA Medical cardioversion of atrial fibrillation.Chest2000;117,1529-1531. [CrossRef] [PubMed]
 
Sra, J, Dhala, A, Blanch, Z, et al Atrial fibrillation: epidemiology, mechanisms and management.Curr Probl Cardiol2000;25,457-491
 
LaPointe, NM, Li, P Continuous intravenous quinidine infusion for the treatment of atrial fibrillation or flutter: a case series.Am Heart J2000;139,114-121. [PubMed]
 
Flaker, GC, Blackshear, JL, McBride, R, et al Anti-arrhythmic drug therapy and cardiac mortality in atrial fibrillation: the Stroke Prevention in Atrial Fibrillation Investigators.J Am Coll Cardiol1992;20,527-532. [CrossRef] [PubMed]
 

Figures

Tables

References

Vardas, PE, Kochiadakis, GE, Igoumenidis, NE, et al (2000) Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized controlled study.Chest117,1538-1545. [CrossRef] [PubMed]
 
Alpert, MA Medical cardioversion of atrial fibrillation [editorial]Chest2000;117,1529-1531. [CrossRef] [PubMed]
 
RuDusky BM. Cholestyramine therapy for quinidine-induced diarrhea. Angiology 1997:173–176.
 
Hohnloser, SH, van de Loo, A, Baedeket, F Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine.J Am Coll Cardiol1955;26,852-858
 
Di Benedetto, S Quinine versus propafenone for conversion of atrial fibrillation to sinus rhythm.Am J Cardiol1997;80,518-519. [CrossRef] [PubMed]
 
de Paola, AA, Veloso, HH Efficacy and safety of sotalol versus quinidine for the maintenance of sinus rhythm after conversion of atrial fibrillation: SOCESP Investigators; The Cardiology Society of Sao Paulo.Am J Cardiol1999;84,1033-1037. [CrossRef] [PubMed]
 
Pritchett, EL Management of atrial fibrillation.N Engl J Med1992;326,1264-1271. [CrossRef] [PubMed]
 
Grace, AA, Camm, AJ QuinidineN Engl J Med1998;338,35-45. [CrossRef] [PubMed]
 
Innes, GD, Vertesi, L, Dillon, EC Effectiveness of verapamil-quinidine versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation.Ann Emerg Med1997;29,126-134. [CrossRef] [PubMed]
 
La Pointe, NM, Li, P Continuous intravenous quinidine infusion for the treatment of atrial fibrillation or flutter: a case series.Am Heart J2000;139,114-121. [PubMed]
 
Belhassen, B, Viskin, S, Fish, R, et al Effects of electrophysiologic-guided therapy with class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome.J Cardiovasc Electrophysiol1999;10,1301-1312. [CrossRef] [PubMed]
 
Vardas, P, Kochiadokis, GE, Igoumentis, NE, et al Amiodarone as a first choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study.Chest2000;117,1538-1545. [CrossRef] [PubMed]
 
Alpert, MA Medical cardioversion of atrial fibrillation.Chest2000;117,1529-1531. [CrossRef] [PubMed]
 
Sra, J, Dhala, A, Blanch, Z, et al Atrial fibrillation: epidemiology, mechanisms and management.Curr Probl Cardiol2000;25,457-491
 
LaPointe, NM, Li, P Continuous intravenous quinidine infusion for the treatment of atrial fibrillation or flutter: a case series.Am Heart J2000;139,114-121. [PubMed]
 
Flaker, GC, Blackshear, JL, McBride, R, et al Anti-arrhythmic drug therapy and cardiac mortality in atrial fibrillation: the Stroke Prevention in Atrial Fibrillation Investigators.J Am Coll Cardiol1992;20,527-532. [CrossRef] [PubMed]
 
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