Long term efficacy of propafenone for prevention of atrial fibrillation.

OBJECTIVE: Propafenone, a class IC antiarrhythmic drug, has been successful in the treatment of ventricular and supraventricular arrhythmias. This study retrospectively evaluated the efficacy of propafenone in the prevention of recurrent atrial fibrillation. DESIGN: Propafenone was given to 81 patients (49 males and 32 females, mean age 61 +/- 16 years) with recurrent atrial fibrillation. The mean dose of propafenone was 701 +/- 235 mg. Patients were monitored for recurrent arrhythmias. MAIN RESULTS: Long term follow-up over 30 +/- 1.7 months showed 31 patients (38%) remained on propafenone with complete or partial control of atrial fibrillation. The drug was stopped in 35 due to inefficacy, in 12 due to adverse effects, and in three due to desire for ablation therapy. CONCLUSION: Propafenone may be effective in some patients for long term prevention of atrial fibrillation, although efficacy may decrease over time.     

Mechanism of Action of Antiarrhythmic Agents: Focus on Propafenone

Propafenone is a new antiarrhythmic compound that has an unusual spectrum of pharmacological actions. Its dominant action in cardiac muscle is to block the fast sodium channel with slow onset and offset kinetics. Thus it has a marked depressant effect on conduction with a modest effect in prolonging the effective refractory period in fibers that are fast-channel dependent. In addition, it has beta-blocking and calcium-channel blocking actions that are likely to affect its overall spectrum of activity. Propafenone should be effective in suppressing both ventricular as well as supraventricular arrhythmias.     

Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy

OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open-label, dose-finding phase followed by a randomized, double-blind, placebo-controlled, crossover phase, with each treatment period lasting up to 60 days. SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial fibrillation (n = 17) were enrolled. Their arrhythmias were documented by electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were randomized and the data obtained from these patients were used in the efficacy analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300 mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching placebo tablets were administered in a randomized sequence. MEASUREMENTS: Symptomatic arrhythmia was documented by telephone transmission of the electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for the overall group of 23 patients while they received propafenone (P = 0.004). The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo. CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal supraventricular arrhythmias.     

Electrophysiology of beta blockers in supraventricular arrhythmias

β-adrenergic blocking agents are efficacious in the treatment of patients with a variety of supraventricular tachycardias, based directly on their capacity to counter the effects of β-adrenergic stimulation on sinus and atrioventricular nodal tissue. Specifically, β blockers depress sinus node automaticity and inhibit atrioventricular nodal function by prolonging refractoriness and slowing conduction. Supraventricular arrhythmias that depend on these structures either for perpetuation or for conduction to the ventricles are predictably sensitive to β blockade. These arrhythmias include sinus tachycardia, sinoatrial reentrant, atrioventricular nodal reentrant (dual pathway) and atrioventricular reciprocating (concealed bypass tract) tachycardias, as well as atrial flutter and fibrillation, β blockers may also be used, in selected patients, to inhibit catecholamine-facilitated accessory pathway function by prolonging refractoriness. β blockers offer particular clinical advantages, including an acceptable side-effect profile, titratable effect, varied pharmacology and reasonable concordance between efficacy of parenteral and oral dosage forms. The key element in the most effective use of these drugs appears to be an accurate arrhythmia diagnosis that allows for the most appropriate application of a reliable treatment form.     

Control of refractory cardiac arrhythmias with amiodarone.

Amiodarone hydrochloride was used to treat 19 patients with symptomatic arrhythmias refractory to quinidine sulfate, procainamide hydrochloride, disopyramide phosphate, antazoline hydrochloride, lidocaine hydrochloride, bretylium tosylate, propranolol hydrochloride, phenytoin sodium, and practotol acetanilide given to the limit of tolerance. In 17 patients, attacks were completely controlled. Arrhythmias treated successfully included recurrent supraventricular tachycardias, recurrent supraventricular tachycardias with Wolff-Parkinson-White syndrome, and refractory ventricular arrhythmias including recurrent ventricular tachycardia and ventricular fibrillation complicating acute coronary heart disease. Control was confirmed by continuous ECG monitoring both in the hospital and when ambulatory and was maintained for up to four years. Attacks of supraventricular tachycardia were reduced from 7.9/mo to one attack every 53.5 months on amiodarone. Hospital admissions for arrhythmias were reduced from 34 the year before treatment to none the year after. Therefore, amiodarone is an excellent drug for control of many refractory arrhythmias, but two patients with recurrent atrial fibrillation were refractory to this treatment.     

Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias.

Oral amiodarone has been used to treat 21 patients with various supraventricular arrhythmias; 13 had Wolff-Parkinson-White syndrome, which was complicated by atrial fibrillation and re-entry atrioventricular tachycardia in four, and re-entry tachycardia alone in the other nine. The remaining eight patients had paroxysmal atrial fibrillation or flutter without pre-excitation. All were refractory to conventional treatment and had undergone intracardiac electrophysiological study. Fifteen have been controlled with amiodarone, this treatment proving most effective in atrial fibrillation or flutter with or without pre-excitation. Amiodarone was successful in only four of the nine patients with re-entry atrioventricular tachycardia. In two patients who responded well the drug had to be discontinued because of side effects.     

Supraventricular tachyarrhythmias: Drug therapy versus catheter ablation

Until recently, the only options available for treatment of supraventricular arrhythmias involved the use of drug therapy or cardiac surgery. However, over the past several years with the introduction of radiofrequency energy sources as well as steerable catheters, the clinician has a variety of additional nonpharmacologic options. This article reviews the use of pharmacologic therapy versus catheter ablation for the treatment of reentrant supraventricular arrhythmias, involving the atrioventricular junction and/or accessory atrioventricular connection, as well as arrhythmias emanating from the atria such as atrial fibrillation, atrial flutter, and atrial tachycardia.     

European experience with the antiarrhythmic efficacy of propafenone for supraventricular and ventricular arrhythmias

Seventy-one patients (mean age 53 years) were treated with oral propafenone, 900 mg/day, for a mean of 6.6 months. A large spectrum of arrhythmias was encountered, and particular attention was paid to their relation with the autonomic nervous system. Drug efficacy was graded from 1 (no effect) to 5 (complete control) according to the clinical result and Holter recording. This method permitted comparisons to be made between propafenone and 3 other antiarrhythmic agents: quinidine, beta-blockers and amiodarone. Among the 32 patients with supraventricular arrhythmias, 9 cases of vagally dependent atrial flutter and fibrillation were less sensitive to propafenone (mean effect 1.4) than to quinidine (mean effect 2.0) or amiodarone (mean effect 2.3). However, 8 cases of adrenergically dependent atrial tachycardia and fibrillation were more sensitive to propafenone (mean effect 4.1) than to beta blockers (3.0) or amiodarone (mean effect 3.5). In 12 cases of miscellaneous atrial arrhythmias the response to propafenone was intermediate. However, 3 patients with resistant junctional tachycardia were improved with propafenone. Among 42 ventricular arrhythmias, 5 patients with extrasystole who were responsive to quinidine (mean effect 3.8) were also improved with propafenone (mean effect 4.6). Propafenone (mean effect 4.1) was much more effective than quinidine (mean effect 2.4) in treating 8 cases of idiopathic benign ventricular tachycardia and even more successful in treating 13 cases of more severe arrhythmias in diseased hearts (propafenone's mean effect 4.1, quinidine's mean effect 1.9 and amiodarone's mean effect 1.9). Propafenone was less effective (mean effect 3.3) than amiodarone (mean effect 4.0) in 4 cases of severe, adrenergically dependent idiopathic ventricular tachycardia (VT).(ABSTRACT TRUNCATED AT 250 WORDS)     

Elective cardioversion in the presence of conduction disturbances

Elective cardioversion of supraventricular arrhythmias has been demonstrated to be an effective procedure which can be performed with minimal risk. The risks of cardioversion are increased in the presence of digoxin intoxication, failure of synchronization, conversion in the presence of high energies, long standing atrial fibrillation, atrial fibrillation with slow ventricular rates, and dysrhythmias in association with ischemic heart disease or cardiomyopathy. However, the risk of cardioversion of supraventricular arrhythmias in the presence of conduction disturbances, although thought to be increased, has never been carefully studied. This study was designed to examine the effects of conduction disturbances (CD) on the success and risk of elective cardioversion of supraventricular arrhythmias (atrial fibrillation and atrial flutter) and to define the role of temporary pacemakers prior to cardioversion in these patients.     

Arrhythmogenic implications of non-iatrogenic thyroid dysfunction

We studied all patients with hyperkinetic and hypokinetic arrhythmias, who were recovered in the Cardiology Department and Arrhythmologic Centre of S. Chiara Hospital in Trento between 1983 and 1987. From these we selected all the patients who, on admission, had clinical and biochemical symptoms of dysthyroidism. Of the 2465 patients with cardiac arrhythmias, 93 (3.8%) had an evident thyroid pathology which was due to chronic amiodarone treatment in 42 (44.6%) and was primary and non-iatrogenic in 51 (55.4%). In the latter the thyroid pathology consisted of hyperthyroidism in 43 cases (toxic nodular goitre or Graves' disease), and of hypothyroidism in 8. As regard the types of arrhythmias, hyperthyroidism is predominant in patients with atrial fibrillation (70%) and in those with paroxysmal supra-ventricular reciprocating tachycardia (11.5%), but it is also present in patients with hyperkinetic ventricular arrhythmias (14%). Hypothyroidism is found in patients with hyperkinetic ventricular arrhythmias (25%), atrial fibrillation (37.5%) and atrio-ventricular block (37.5%). The average age of the hyperthyroid population with atrial fibrillation is higher than that of patients with paroxysmal supraventricular reciprocating tachycardia. The control of the thyroid pattern, especially as regards atrial fibrillation and paroxysmal supraventricular reciprocating tachycardia results in absence of arrhythmic episodes even without treatment in 40% of cases, and in an easier drug control in the other cases. Our study indicates that it is necessary to carry out systematic research of a thyroid dysfunction in all patients with cardiac arrhythmias, especially as regards women, atrial fibrillation and paroxysmal supraventricular reciprocating tachycardia. It is also evident that in order to achieve long-term control over hyperkinetic arrhythmia it is very important to overcome hyperthyroidism.     

Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 5. Pindolol (LB-46) therapy for supraventricular arrhythmia: a viable alternative to propranolol in patients with bronchospasm.

Pindolol (LB-46) is a new beta-adrenoceptor blocking agent with intrinsic sympathomimetic activity. In order to evaluate the efficacy of pindolol in the treatment of patients with supraventricular arrhythmias and propranolol-induced bronchospasm, 18 patients with paroxysmal supraventricular tachycardia, atrial fibrillation, atrial flutter, multifocal atrial tachycardia or junctional tachycardia, were treated with placebo followed by pindolol in intravenous and then oral form. Following a no-response placebo period (in all patients), intravenous pindolol converted six out of seven patients with paroxysmal supraventricular tachycardia to normal sinus rhythm. In six patients with atrial fibrillation, three reverted to normal sinus rhythm, and three remained in atrial fibrillation but with a slower ventricular response (less than 100 beats/minute). Of two patients with atrial flutter, one converted to normal sinus rhythm, while the other patient failed to respond. Both patients with junctional tachycardia and one with multifocal atrial tachycardia converted to normal sinus rhythm. Long-term oral pindolol therapy sustained these responses in most patients, as documented by serial Holter ECG studies. There was no deterioration in indices of airway resistance ($\text{FEV}{}_{\mathrm{1·0}}\text{VC}$) in patients treated with pindolol (both intravenously and orally), in contrast to a marked deterioration in $\text{FEV}{}_{\mathrm{1·0}}\text{VC}$ in the same patients treated with propranolol. Pindolol appears to be a reasonable substitute for propranolol in patients with bronchospastic illness who require beta-blockade for control of supraventricular arrhythmias.     

Use of Propafenone in Patients With Supraventricular Tachycardia

Propafenone prolongs refractoriness and slows conduction of the atrium, atrioventricular node, and accessory atrioventricular pathway. By interfering with conduction in locations necessary to support supraventricular tachycardia, propafenone effectively treats several mechanisms of rhythm disturbance. Early experience shows that propafenone, when administered in the electrophysiology laboratory, effectively terminates or prevents reinduction of paroxysmal supraventricular reentrant tachycardia in 50% to 75% of patients. The most effective dose associated with the fewest side effects has been 2 mg/kg infused over 10 minutes. Long-term success with propafenone has been demonstrated in patients with paroxysmal atrial fibrillation, paroxysmal atrial flutter, atrioventricular node reentrant tachycardia, atrioventricular reentrant tachycardia using a concealed accessory pathway, and tachycardias associated with the Wolff-Parkinson-White syndrome, including paroxysmal atrial fibrillation and atrioventricular reentrant tachycardia. In 67% (range, 27% to 89%) of patients receiving long-term therapy with propafenone, episodes of supraventricular tachycardia have been either eliminated or significantly reduced in frequency and treatment has not had to be stopped because of side effects. The effective daily dose for longterm therapy has been 550 to 750 mg administered in three or four divided doses. Although the number of patients reported in the literature at this time is small, propafenone appears to be an effective agent for treating supraventricular tachycardia due to one of several mechanisms.     

Hepatic toxicity of propafenone: a case description

A case of acute liver injury associated with the use of the antiarrhythmic drug propafenone in a 62-year-old woman undergoing clinical observation for recurrent atrial fibrillation is reported. Propafenone hydrochloride, a class 1C antiarrhythmic drug widely used in the clinical practice for the treatment of supraventricular and ventricular arrhythmias, rarely (0.1-0.2% of incidence) causes liver injury characterized by a rise in hepatic cell enzymes or cholestatic enzymes or both. Within 2 months of the discontinuation of therapy the liver function tests return to normal, therefore there are no known fatalities secondary to propafenone liver injury including fulminant hepatitis and death. The close temporal relationship between the administration of the drug and the acute onset of signs of liver injury, the marked rise in liver function tests following the increase of the drug dosage and their gradual normalization after its withdrawal strongly suggest that propafenone is involved in the pathogenesis of this syndrome. Although rare, hepatotoxicity due to this widely used antiarrhythmic drug should be borne in mind in the differential diagnosis of sudden hepatocellular or cholestatic syndrome of obscure origin. It seems prudent to obtain baseline liver function before starting therapy with propafenone and then follow up laboratory tests some months later at least in patients with known liver disease.     

Effective treatment of supraventricular arrhythmias with acebutolol.

To evaluate the antiarrhythmic efficacy of the new beta adrenergic blocking agent acebutolol, 15 monitored patients with supraventricular arrhythmias received, in double-blind fashion, an intravenous infusion of either acebutolol or saline solution after a control period. Patients treated with saline solution demonstrated no change (P greater than 0.05) in heart rate or arterial blood pressure or conversion to sinus rhythm. After administration of acebutolol, significant (P less than 0.05) reductions in heart rate were noted at 5 minutes. Peak reduction occurred at 10 to 30 minutes and correlated with maximal acebutolol plasma concentrations, antiarrhythmic activity persisted for 24 hours. Mild reductions in systolic blood pressure were observed in the majority of patients. Two patients with atrial fibrillation and one with multifocal atrial tachycardia had conversion to sinus rhythm. Frequent premature atrial complexes noted in one patient were greatly suppressed after administration of the drug. In the nine patients with clinical evidence of chronic obstructive lung disease acebutolol was well tolerated. Adverse reactions were limited to transient dyspnea in one patient with prior heart failure and a decrease in systolic blood pressure to less than 90 mm Hg in three patients who remained asymptomatic. In the patients studied, acebutolol was an effective agent for the treatment of supraventricular arrhythmias and appeared to be of special value in those with chronic obstructive lung disease.     

Acute myocardial infarction promptly complicated by atrial fibrillation during Holter recording]

We observed, during Holter recording, a case of inferior acute myocardial infarction complicated by paroxystic hyperkinetic atrial fibrillation, which occurred 12 min after the onset of acute irreversible myocardial ischemia. The atrial fibrillation was preceded by a complex pattern of hyperkinetic supraventricular arrhythmias characterized by single premature supraventricular beats, paired premature supraventricular beats and many runs of paroxystic supraventricular tachycardia. The most plausible hypothesis is that atrial fibrillation and the preceding arrhythmic pattern have been due to an extension of ischemia from ventricular to atrial myocardium.     

Propafenone—Clinical Electrophysiology and Efficacy in Patients with Documented or Potentially Life-threatening Arrhythmias

Propafenone is a new antiarrhythmic agent that inhibits the fast sodium channel and decreases phase 0 of the cardiac action potential. Since it has relatively little effect on the action potential duration, it has been classified as a type IC agent. Propafenone prolongs electrocardiographic intervals including PR and QRS. In addition, atrial and ventricular refractory periods generally are lengthened. Initial reports suggest a favorable effect on suppressing conduction over accessory pathways. Propafenone has been shown to have effectiveness in suppressing life-threatening ventricular arrhythmias as well. Electrophysiological testing is useful, but data such as mode of induction and rate of induced tachycardia should be considered in addition to inducibility status.     

Aktueller Stellenwert von Amiodaron in der antiarrhythmischen Therapie

Decades after its registration, amiodarone is still regarded as the most effective antiarrhythmic drug available for the treatment of tachyarrhythmias. Amiodarone is classified as a class III antiarrhythmic drug. In addition to the prolongation of cardiac repolarization, its leading pharmacologic features are sodium and calcium channel block, nonselective β-adrenergic inhibition as well as high lipophilicity and a very long plasma half-life. In patients with paroxysmal atrial fibrillation, amiodarone is the most effective antiarrhythmic drug in maintaining sinus rhythm. Furthermore, it prevents ventricular arrhythmias, such as frequent ventricular extrasystoles or nonsustained runs of ventricular tachycardia, as well as sustained ventricular tachycardia and ventricular fibrillation. In patients with increased risk for sudden cardiac death, e.g., with severely depressed left ventricular function, amiodarone is a highly effective and safe antiarrhythmic drug. In addition, amiodarone has been shown to reduce the number of appropriate and inappropriate shocks in patients with an implantable cardioverter-defibrillator. During long-term amiodarone treatment, typical side effects including corneal microdeposits, blue-gray skin discoloration, photosensitivity, hypothyroidism, hyperthyroidism, peripheral neuropathy, optical neuritis and hepatotoxicity accrue. Upon cessation of medication, these are almost always reversible. Irreversible, severe adverse effects, such as pulmonary toxicity, are very rare under the currently used maintenance dose of 200 mg/day. With regard to its side effect profile, an adequate follow-up of patients including laboratory values, lung function tests, and visual acuity is necessary.     

Akuttherapie lebensbedrohlicher tachykarder Rhythmusstörungen

Life-threatening supraventricular tachyarrhythmias include atrial fibrillation, atrial flutter, AV-nodal reentrant tachycardia with rapid ventricular response and preexcitation syndromes combined with atrial fibrillation. Ventricular tachyarrhythmias still remain one of the leading causes of death; these arrhythmias include monomorphic and polymorphic ventricular tachycardia, torsade de pointes tachycardia, ventricular fibrillation and ventricular flutter. In all patients with tachycardias, an attempt should be made to differentiate between narrow (QRS duration < 0.12 s) or wide QRS complex (QRS duration ≥ 0.12 s) tachycardias. In the assessment of patients (pts) with supraventricular/ventricular tachyarrhythmias, attention should be given to identify whether the tachycardia is associated with worsening angina or low cardiac output. In pts with narrow QRS complex tachycardias or pts with atrial fibrillation and preexcitation syndromes immediate synchronized cardioversion should be performed if signs or symptoms of instability (hypotension, evidence of end-organ dysfunction, worsening angina) exist. In pts with a stable hemodynamic situation, vagal maneuvers, adenosine or calcium channel blockers can be used. Management of atrial flutter usually centers on cardioversion or rapid atrial pacing to normal sinus rhythm. In the treatment of patients with deemed unstable ventricular tachycardia (VT), electrical cardioversion is the treatment of choice. In more stable patients, ajmaline is the preferred agent after myocardial infarction and lidocaine if myocardial ischemia is present. In pts with torsade de pointes tachycardias aggressive steps must be taken to prevent degeneration of this rhythm to ventricular fibrillation (VF). Magnesium sulfate has recently been demonstrated efficacious and is currently considered first-line drug therapy. Transcutaneous overdrive pacing should be attempted if magnesium is unsuccessful. The pt with pulseless VT or VF demands early electrical countershock.     

Oral class III antiarrhythmics: what is new?

PURPOSE OF REVIEW: This review describes the latest developments in the clinical usage of class III antiarrhythmics. It also discusses some new studies providing insight into the mechanism of action of these drugs. RECENT FINDINGS: New data suggest that amiodarone is one of the most effective drugs for management of ventricular as well as supraventricular tachyarrhythmias. As over the years we have learned to deal with the toxic side effects of this drug, the risk of bradyarrhythmias requiring placement of a pacemaker is becoming more significant. Sotalol was approved for treatment of atrial fibrillation and atrial flutter (AF). It was also found to be effective in management of postoperative AF. Dofetilide has been approved for the conversion and maintenance of sinus rhythm in AF; its role in ventricular arrhythmias remains unclear. Data are emerging regarding clinical efficacy of azimilide and dronedarone. SUMMARY: Management of arrhythmias in patients with structural heart disease remains a challenge. Class III antiarrhythmics are the mainstay of treatment in this group of patients.     

The effect of magnesium versus verapamil on supraventricular arrhythmias

Magnesium has previously been used in the treatment of various arrhythmias, but few randomized and prospective studies are available. In a single-blind study, the efficacy and safety of intravenous magnesium sulfate (bolus doses of 5 + 5 mmol followed by infusion of 0.04 mmol/min) versus verapamil (5 + 5 mg followed by 0.1 mg/min) was evaluated in 57 patients with supraventricular arrhythmias (supraventricular tachycardia, atrial fibrillation, and atrial flutter) of recent onset (less than 1 week). Fifteen (58%) of the patients receiving magnesium (n = 26) converted to sinus rhythm within 4 h, and 16 (62%) within 24 h. Verapamil caused a lower ventricular rate, but only six (19%) of the patients (n = 31) converted to sinus rhythm within 4 h (p < 0.01) and 16 (52%) within 24 h (NS). No side effects were observed during magnesium infusion, whereas six patients receiving verapamil had to be withdrawn from further study medication due to symptomatic side effects (hypotension in three, cardiac failure in three). Magnesium appears to be an effective and safe drug for the treatment of supraventricular arrhythmias. The overall efficacy for conversion to sinus rhythm is at least as effective as with verapamil, and its action is more rapid.