Renal function and digoxin clearance during quinidine therapy

Summary. To investigate further the handling of digoxin by the kidneys during quinidine therapy, clearances of digoxin, ⁵¹Cr-EDEA, PAH and endogenous creatinine were measured together with β₂-microglobulin in the urine before and during quinidine therapy in 10 patients on maintenance digoxin therapy. Renal clearance of digoxin (corrected for 30% plasma binding) decreased on the average by 55% (137 ± 73 to 73 ± 25 ml/min, mean ± SD). The steady state plasma concentration of digoxin increased more than twofold (1·0 ± 0·34 to 2·5 ± 0±79 nmol/l, mean ± SD). The clearances of ⁵¹Cr-EDTA and PAH were not altered during quinidine therapy, indicating that neither glomerular filtration nor total renal blood flow changed when quinidine was added. The ratio of the renal clearance of unbound digoxin to that of the glomerular filtration rate was above one for all 10 patients before quinidine, indicating the involvement of tubular secretion in the renal elimination of digoxin. After the administration of quinidine this ratio decreased in all patients (from 1·51 ± 0·30 to 0·83 ± 0·38, mean ± SD). Some patients had ratios well below one suggesting re-absorption of digoxin. β²-microglobulin excretion was unchanged during treatment with quinidine. It is concluded that a significant portion of the renal elimination of digoxin in man results from tubular secretion and that this excretory mechanism is inhibited by quinidine.     

Digoxin remains useful in the management of chronic heart failure

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure. 5. Serial assessment of serum digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the drug. There appears to be little relationship between serum digoxin concentration and the drug's therapeutic effects. 6. Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist. Likewise, the concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity. 7. For patients with heart failure and atrial fibrillation with a rapid ventricular response, the administration of high doses of digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker therapy or amiodarone (strength of evidence = C). If amiodarone is added, the dose of digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.     

Amiodarone Induced Torsades de Pointes with Excessive QT Dispersion Following Quinidine Induced Polymorphic Ventricular Tachycardia

We report a case of amiodarone induced torsades de pointes (TdP) associated with increase QT dispersion in a patient with a history of quinidine induced TdP. An increase in QT dispersion of > 100% was noted on the 12 lead surface ECG postamiodarone therapy. In summary, amiodarone has a potential to induce TdP in patients with a previous history of quinidine induced TdP. QT dispersion could be a potential marker of TdP in these patients.     

Different Effects of Amiodarone and Quinidine on the Homogeneity of Myocardial Refractoriness in Patients With Intraventricular Conduction Delay

BACKGROUND: Increases in QT and JT dispersion have been suggested as indicative of a proarrhythmic potential as a result of heterogeneity in myocardial refractoriness, the reduction of which by antiarrhythmic agents might be associated with a beneficial effect on the development of serious ventricular arrhythmias. METHODS: To test the hypothesis that amiodarone reduces the heter-ogeneity of ventricular refractoriness to a significantly greater extent than quinidine in patients with intraventricular conduction defects under treatment for ventricular arrhythmias, the corrected and uncorrected QT and JT intervals and dispersions from 12-lead surface electrocardiograms were determined in 120 patients with intraventricular conduction defects with cardiac arrhythmias before and during treatment with amiodarone (n = 60) and quinidine (n = 60). RESULTS: Amiodarone increased QT from 403 +/- 50 ms to 459 +/- 47 ms (P <.001), with a similar increase in the corrected QT interval (QTc) (P <.001). Amiodarone reduced QT dispersion by 40% (P <.001), whereas quinidine increased by 18% (P <.001). The net effects of both drugs were similar for OTc. Amiodarone, but not quinidine, reduced heart rate significantly; amiodarone had no effect on the QRS; but quinidine increased if (P <.001). Quinidine as well as amiodarone increased the JT and JTc intervals significantly, but the effect of quinidine was qualitatively less striking. Amiodarone decreased the JT dispersion by 33% (P <.001) and JTc dispersion by 37% (P <.001). On the other hand, quinidine increased the corresponding values for JT and JTc by 18% (P <.001) and 21% (P <.001), respectively. The overall data on QT and JT dispersion indicate an improvement in the homogeneity of myocardial refractoriness with amiodarone treatment and the converse with quinidine treatment; this observation is consistent with a lower proarrhythmic propensity and mortality with amiodarone than with quinidine. Quinidine increased the QRS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization. CONCLUSIONS: Amiodarone and quinidine both increased the corrected and uncorrected QT and JT intervals; amiodarone decreased and quinidine increased the dispersion of these intervals, and these results suggested an improvement in the homogeneity of myocardial refractoriness as a result of amiodarone treatment and the converse as a result of quinidine treatment. Quinidine increased the QTS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization.     

Digoxin-quinidine-spironolactone interaction

Digoxin kinetics are substantially altered by quinidine and by spironolactone. We evaluated the effect of the combination of quinidine and spironolactone on digoxin kinetics and compared it to the effect on digoxin of each drug alone. Six normal subjects each received a 1.0-mg intravenous dose of digoxin alone, digoxin with quinidine, digoxin with spironolactone, and digoxin with both quinidine and spironolactone. Spironolactone and quinidine, alone and in combination, reduced digoxin systemic, renal, and nonrenal clearances and prolonged digoxin elimination t 1/2. A greater alteration in digoxin kinetics was induced by quinidine than by spironolactone, and an even greater effect resulted from the combination. We did not assess clinical consequences of the interaction. We advise reduction in digoxin dose, careful clinical evaluation, and measurement of serum digoxin concentrations when digoxin is used in combination with quinidine and spironolactone.     

Reversibility of blue-gray cutaneous discoloration from amiodarone

A 45-year-old man had severe blue-gray cutaneous discoloration during amiodarone therapy for atrial fibrillation. Therefore, this drug regimen was discontinued, and long-term anticoagulation and digoxin therapy were used. The patient was advised to avoid exposure of his skin to sunlight, and a bleaching agent was prescribed. After 18 months of follow-up, the blue-gray hyperpigmentation had diminished. Although photosensitivity reactions from amiodarone occur in more than 50% of patients, blue-gray cutaneous discoloration occurs in less than 10% of patients on prolonged therapy with amiodarone. The presence of high concentrations of iodine, detected by electron probe analysis, suggests that the cutaneous deposits are amiodarone itself or a metabolite. The slow rate of elimination of amiodarone and a high uptake by fat-associated tissues may explain the delayed disappearance of cutaneous photosensitivity and late resolution of the blue-gray discoloration. Our current case supports the reversibility of these adverse effects on long-term follow-up.     

Amiodarone: guidelines for use and monitoring

Amiodarone is a potent antiarrhythmic agent that is used to treat ventricular arrhythmias and atrial fibrillation. The drug prevents the recurrence of life-threatening ventricular arrhythmias and produces a modest reduction of sudden deaths in high-risk patients. Amiodarone is more effective than sotalol or propafenone in preventing recurrent atrial fibrillation in patients for whom a rhythm-control strategy is chosen. When long-term amiodarone therapy is used, potential drug toxicity and interactions must be considered. The dosage of amiodarone should be kept at the lowest effective level. In patients who also are taking digoxin and warfarin, physicians must pay close attention to digoxin levels and prothrombin time, keeping in mind that the effects of interaction with amiodarone do not peak until seven weeks after the initiation of concomitant therapy. Laboratory studies to assess liver and thyroid function should be performed at least every six months.     

Effect of quinidine on the digoxin receptor in vitro.

To investigate the basis for a clinically important digitalis-quinidine interaction that is characterized by increases in serums digoxin concentrations when quinidine is administered to digoxin-treated patients, we have studied in vitro the interaction of quinidine with the digoxin receptor. Evidence has been obtained that quinidine is capable of decreasing the affinity for digoxin of cardiac glycoside receptor sites on purified Na,K-ATPase and on intact human erythrocyte membranes. As others have shown, quinidine is capable of inhibiting Na,K-ATPase activity, and evidence has been obtained in the current study that, while quinidine can reduce the affinity of the enzyme for digoxin, it is also capable of acting together with digoxin in inhibiting enzyme activity to a degree greater than the inhibitory effect of digoxin alone. The concentrations of digoxin and quinidine used in this study were considerably greater than their therapeutic serum concentrations. Nevertheless, these observations are consistent with the hypothesis that the increases in serum digoxin concentrations and the decreases in volumes of digoxin distribution observed clinically when quinidine is administered to digoxin-treated patients may reflect, at least in part, a decrease in the affinity of tissue receptors for digoxin. The possibility must also be considered that enhanced cardiac effects of digoxin may occur clinically as the result of an augmentation, by quinidine, of digoxin effects, which more than compensates for the modest reduction in digoxin binding.     

Quinidine reduces biliary clearance of digoxin in man

Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal-marker-perfusion technique. Quinidine caused an average 42% (range 21-65%, P less than 0.02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion.     

Antiadrenergic therapy in the control of atrial fibrillation

Atrial fibrillation (AF) in heart failure develops commonly in older individuals and its prevalence increases as heart failure severity progresses. Because of deteriorating hemodynamics, patients with heart failure are at increased risk for developing AF and, conversely, AF in heart failure patients is associated with adverse hemodynamic changes. AF is believed to increase the mortality risk in heart failure, which may be minimized by treatment that includes the control of ventricular rate, prevention of thrombotic events, and conversion to normal sinus rhythm. Clinical guidelines recommend amiodarone or dofetilide in heart failure patients, but these drugs have certain drawbacks, such as an increased risk for bradyarrhythmias with amiodarone and proarrhythmic reaction with dofetilide. Some but not all clinical trials have suggested that rate control should be the primary therapeutic goal in high-risk heart failure patients with AF and, if unsuccessful, followed by rhythm control. The former is effectively achieved with rate-lowering beta-blockers alone or in combination with digoxin. Recent studies evaluating the effects of combination carvedilol/digoxin therapy demonstrate synergistic effects between the two drugs. This combination therapy decreased heart failure symptoms, effectively reduced ventricular rate, and improved ventricular function to a greater extent compared with that produced by either drug alone. Although digoxin alone is an effective heart failure treatment, its use as a single rate-control therapy is often ineffective in heart failure patients with AF associated with rapid ventricular response. Carvedilol is effective, alone or in combination, with digoxin in such heart failure patients with AF, and has been shown to reduce mortality risk in patients with chronic heart failure during prolonged therapy.     

New antiarrhythmic drugs: tocainide, mexiletine, flecainide, encainide, and amiodarone

Tocainide, mexiletine, flecainide, encainide, and amiodarone are antiarrhythmic agents that have recently been approved by the Food and Drug Administration for general use in the treatment of ventricular arrhythmias. All five agents are effective in the treatment of patients with ventricular arrhythmias, whereas encainide, flecainide, and amiodarone are also useful in patients with supraventricular arrhythmias and the Wolff-Parkinson-White syndrome (although not yet approved for these indications). Tocainide and mexiletine are similar to lidocaine and are as effective as quinidine in patients with ventricular arrhythmias. Encainide and flecainide are superior to quinidine for the control of ventricular ectopic beats and as effective as quinidine for patients with ventricular tachycardia. Amiodarone is the most effective agent available for treating patients with ventricular tachycardia, but it is also the most toxic antiarrhythmic agent and should be used only when other antiarrhythmic drugs have not been effective or tolerated.     

Serial electrophysiological studies in a young patient with recurrent ventricular fibrillation

A 28-year-old male with recurrent episodes of ventricular fibrillation, which were initiated by very early ventricular premature depolarizations with a normal QT interval, was subjected to three consecutive electrophysiological studies. During the first study, which was carried out to test the efficacy of amiodarone treatment, no ventricular arrhythmias could be induced. While on amiodarone therapy, the patient experienced another syncopal episode and therefore a second electrophysiological study was done. In that study, ventricular fibrillation was induced by ventricular stimulation. During the third study, which was carried out in order to evaluate the effect of the addition of quinidine to the ongoing amiodarone therapy, no more than three repetitive ventricular responses could be induced. The patient has been asymptomatic since the third study (fifteen months) with combined therapy of amiodarone and quinidine. The significance of the ability to induce ventricular fibrillation during an electrophysiological study is discussed as well as the value of such studies in determining the long-term efficacy of antiarrhythmic drug therapy.     

Ex situ inhibition of hepatic uptake and efflux significantly changes metabolism: hepatic enzyme-transporter interplay

The disposition of digoxin and the influence of the organic anion transporting polypeptide (Oatp)2 inhibitor rifampicin and the P-glycoprotein (P-gp) inhibitor quinidine on its hepatic disposition were examined in the isolated perfused rat liver. Livers from groups of rats were perfused in a recirculatory manner after a bolus dose of digoxin (10 microg), a dual substrate for Oatp2 and P-gp as well as CYP3A. Perfusions of digoxin were also examined in groups of rats in the presence of the inhibitors: rifampicin (100 microM) or quinidine (10 microM). In all experiments, perfusate samples were collected for 60 min. Digoxin and its primary metabolite were determined in perfusate and liver by liquid chromatography/mass spectrometry. The area under the curve (AUC) from 0 to 60 min was determined. The AUC +/- S.D. of digoxin was increased from control (3880 +/- 210 nM x min) by rifampicin (5200 +/- 240 nM x min; p < 0.01) and decreased by quinidine (3220 +/- 340 nM x min; P < 0.05). It is concluded that rifampicin limits the hepatic entrance of digoxin and reduced the hepatic exposure of digoxin to CYP3A by inhibiting the basolateral Oatp2 uptake transport, whereas quinidine increased the hepatic exposure of digoxin to CYP3A by inhibiting the canalicular P-gp transport. These data emphasize the importance of uptake and efflux transporters on hepatic drug metabolism.     

Increase in serum digoxin concentration produced by quinidine does not increase the potential for digoxin-induced ventricular arrhythmias in dogs

Chronic treatment of dogs with digoxin alone, quinidine alone and digoxin in combination with quinidine was initiated in dogs to assess changes in arrhythmogenic potential associated with the quinidine-induced increase in serum digoxin concentration observed during combined digoxin and quinidine treatment. The arrhythmogenic potential of digoxin was evaluated through the use of the acetylstrophanthidin (AcS) tolerance test. AcS was infused at a rate of 5 micrograms/kg/min until ventricular arrhythmias occurred during a drug-free period and during chronic treatment with digoxin, quinidine and digoxin plus quinidine. The dose of AcS required to initiate ventricular arrhythmias is inversely related to the arrhythmogenic potential of digoxin present at the time of AcS infusion. Administration of quinidine alone in two different dosage regimens produced serum quinidine concentrations of 5.99 +/- 1.18 and 2.99 +/- 0.43 micrograms/ml and significantly increased AcS tolerance, whereas digoxin alone, over a wide range of serum digoxin concentrations, significantly decreased AcS tolerance. This decrease in AcS tolerance was linearly related to the serum digoxin concentration. The addition of quinidine treatment to animals receiving digoxin resulted in a significant elevation in the steady-state serum digoxin concentration. However, the AcS tolerance determined during the elevated serum digoxin concentration induced by quinidine was greater than that determined during treatment with the same dose of digoxin alone. Thus, quinidine administration to animals receiving digoxin resulted in a significant increase in the steady-state serum digoxin concentration but did not increase the arrhythmogenic potential of digoxin over that observed during treatment with the same dose of digoxin alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of pharmacodynamic interactions between quinidine and digoxin in isolated atrial muscle of guinea pig heart

Quinidine has been reported to have no effect on the positive inotropic action of digoxin observed in isolated cardiac muscle preparations. This is surprising because quinidine has been shown to reduce Na+ influx in cardiac muscle. The conditions which increase Na+ influx stimulate the glycoside binding to Na+- and K+-activated Mg++-dependent ATP phosphohydrolase (Na+,K+-ATPase), and therefore quinidine may be expected to have an opposite effect. Thus, the effects of quinidine on cardiac muscle and its possible interactions with digoxin were re-evaluated using electrically paced left atrial muscle preparations of guinea pig heart. Quinidine caused a frequency- and concentration-dependent decrease in maximal upstroke velocity and amplitude of the action potential without altering resting membrane potential. In addition, quinidine prolonged action potential duration markedly in a frequency-dependent manner. Despite action potential prolongation, the alkaloid reduced net Na+ influx as determined by a decrease in steady-state ouabain-sensitive 86Rb+ uptake. Under these conditions, however, quinidine failed to reduce the rate of onset or the maximal positive inotropic effect of digoxin; or did it reduce digoxin binding to Na+,K+- ATPase in beating atrial muscle preparations. Benzocaine, which reduced net Na+ influx without increasing the action potential duration, also failed to affect the peak inotropic effect of digoxin or the glycoside binding. Quinidine had no direct effects on glycoside binding to isolated cardiac Na+,K+-ATPase. Moreover, [3H]ouabain binding to isolated enzyme was relatively insensitive to changes in Na+ concentrations between 1 and 8 mM although binding was stimulated clearly by Na+ above 8 mM. These results indicate that quinidine, at therapeutic concentrations, does not interact pharmacodynamically with digoxin in isolated cardiac muscle.     

Drug interactions with calcium inhibitors in man

The most common interactions concern cardiovascular drugs. The combination of calcium antagonists (CA) and beta-blockers is more effective than single-agent therapy in stable effort angina and hypertension. But there is an increased risk of hemodynamic or electrophysiological side effects in patients with left ventricular or sinus dysfunction, or disturbances of conduction. Pharmacokinetic interactions have been observed in particular with verapamil (VE) which increases propranolol bioavailability. VE increases the T1/2 of elimination and plasma digoxin concentration following single or prolonged administration. The primary mechanism appears to be renal. These modifications increase the risk of digitalis intoxication. Diltiazem (DTZ) inconsistently increases steady state plasma digoxin levels. In healthy subjects, nifedipine (NF) increases plasma digoxin concentrations and decreases digoxin renal clearance. These findings have not been observed in patients with heart failure. NF therefore leads to less marked modifications in digitalis pharmacokinetics than do VE and DTZ. Nitrendipine and nicardipine interact only slightly with digoxin, and consequently there are no pharmacodynamic effects. In healthy subjects, VE increases quinidine t1/2 and markedly decreases its metabolic clearance. Conversely, quinidine increases plasma NF levels. The primary CA are extensively metabolized by liver microsome oxidases. These result in interactions with the drugs that are also metabolized by these enzymes, or able to modify their activity. VE and DTZ decrease antipyrine and carbamazepine clearance. VE, DTZ and nicardipine lead to a marked increase in plasma ciclosporin levels. Cimetidine, but not ranitidine, increases plasma NF levels. The effects on VE are controversial. Prolonged rifampicin treatment decreases plasma VE levels.     

Understanding digoxin use in the elderly patient

There are many disease states in the elderly that mandate the use of drugs with extremely narrow therapeutic indexes and potentially fatal toxicity. Digoxin is one example of such drugs. It is extensively used for the treatment of congestive heart failure of diverse origin and of cardiac arrhythmias of supraventricular origin. Aging can produce changes in essentially all organ systems, which as a whole render geriatric patients particularly vulnerable to the toxic effects of digoxin. Among all age-related pharmacokinetic and pharmacodynamic changes, declining renal function is perhaps the most important factor that must be considered. This often means a significantly less efficient renal digoxin clearance, which necessitates a reduction in dosage. The geriatric population tends to consume more drugs and are more at risk for undesirable multidrug interactions than their younger counterparts. To name a few, quinidine, verapamil, amiodarone, and non-K(+)-sparing diuretics are notorious for predisposing the patient to digoxin toxicity when administered concurrently with digoxin. Therefore, digoxin must be prescribed to elderly patients with great judiciousness, with careful interpretation of serum digoxin assay, and due consideration of its intrinsic limitations.     

Effects of quinidine on the renal tubular and biliary transport of digoxin: in vivo and in vitro studies in the dog

Quinidine is known to inhibit the renal clearance of digoxin without affecting glomerular filtration rate. The renal interaction between these drugs was investigated by a combination of in vivo and in vitro methods. The uptake of digoxin by brush border membrane vesicles was not affected by quinidine. Similarly, digoxin did not inhibit the uptake of the cation N-methylnicotinamide by these vesicles and did not alter the binding kinetics of digoxin to the Na+, K+-adenosine triphosphatase by the antiluminal membrane vesicles. By using the in vivo multiple indicator dilution technique transtubular transport of digoxin was documented; renal-artery infusion of quinidine did not affect the recovery of digoxin in the renal vein or urine. Clearance studies documented that the decrease in the renal clearance of digoxin is paralleled by a significant fall in renal blood flow evidenced by a decrease in p-aminohippuric acid clearance. It is concluded that quinidine inhibits the renal excretion of digoxin not by competition at the tubular cell membrane level, but rather by decreasing renal blood flow. A parallel decrease in biliary clearance of digoxin is documented and may suggest a similar mechanism.     

Excellent Long‐Term Reproducibility of the Electrophysiologic Efficacy of Quinidine in Patients with Idiopathic Ventricular Fibrillation and Brugada Syndrome

Background: Quinidine is very effective in preventing the reinduction of sustained ventricular fibrillation (VF) during electrophysiologic study (EPS) in patients with idiopathic VF and Brugada syndrome. However, there are no data on the long‐term reproducibility of this EP efficacy. Methods and Results: Nine patients (seven males and two females, aged 21–72 years), who suffered from aborted cardiac arrest (n = 8) or recurrent syncope (n = 1) due to Brugada syndrome (n = 5) or idiopathic VF (n = 4), comprised the study. All patients had inducible sustained VF at baseline that was prevented by quinidine therapy and underwent another EPS on medication after 1.7–23.6 (9.8 ± 6.8) years (>5 years in eight patients). Two patients underwent two late EPS on quinidine. The goal of repeat EPS on quinidine was to ensure persistent long‐term drug efficacy (n = 6) or to elucidate the reason of syncopal episodes during therapy (n = 3). The EPS protocol significantly evolved over the years as it became more aggressive (more pacing sites and/or more ventricular extrastimuli). All nine patients tolerated the medication well and had no recurrent documented arrhythmic events during long‐term follow‐up (mean 15 ± 7 years). No sustained ventricular tachyarrhythmias could be induced in any patient during repeat late EPS. In six patients, a more aggressive stimulation protocol could be tested at repeat EPS. Conclusion: The long‐term reproducibility of the EP efficacy of quinidine in patients with idiopathic VF and Brugada syndrome is excellent. EP‐guided quinidine therapy represents a valuable long‐term alternative to ICD therapy in these patients.     

Sudden Cardiac Death in a Southeast Asian Immigrant: Clinical, Electrophysiologic, and Biopsy Characteristics

The syndrome of sudden cardiac death in southeast Asians has only recently been given attention in the American medical literature. This case report describes a patient who presented with this rare syndrome. The physical examination, Holter monitor. 2-D echocardiogram, exercise treadmill test, radionuclide ventriculogram, coronary angiography, and endomyocardial biopsy were all normal. Programmed ventricular stimulation reproducibly induced sustained polymorphic ventricular tachycardia, Oral procainamide, oral quinidine and oral quinidine plus propranolol were not successful in suppressing inducible polymorphic ventricular tachycardia. The arrhythmia remained inducible after six weeks of oral amiodarone therapy. However, he has had no clinical recurrences while on amiodarone after one year of follow-up.