Pharmacologic treatment of supraventricular tachycardia: the German experience.

Tachyarrhythmias that originate above the bifurcation of the bundle of His or in tissue proximal to it are classified as supraventricular tachyarrhythmias (SVTs). Primary treatment of SVT tries to influence the underlying disease. Symptomatic therapy is subdivided into drug therapy, electrotherapeutic tools (e.g., antitachycardia pacemakers, catheter ablation), and antiarrhythmic surgery. Antiarrhythmic agents that slow conduction and suppress premature beats are efficient for emergency and long-term treatment of SVTs. We evaluated some of the most relevant antiarrhythmic drugs in SVT, including propafenone, diprafenone, cibenzoline, sotalol, and diltiazem; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine, and flecainide are summarized. In 1990, the case load of supraventricular arrhythmias per physician in Germany was more than 30 patients seen per month. About 50% of them were treated with drug therapy; i.e., approximately 17 patients were treated with antiarrhythmic drugs per month per physician for supraventricular arrhythmias. The most important antiarrhythmic agents used in Germany are propafenone (40%), combination of quinidine and verapamil (23%), sotalol (12%), disopyramide (6%), flecainide (6%), and other (13%).     

Amiodarone: an effective alternative for recalcitrant supraventricular and ventricular tachycardias

Amiodarone was used in the treatment of 21 patients with supraventricular or ventricular arrhythmias which were refractory to conventional antiarrhythmic drugs, individually or in combination. Six of seven patients with supraventricular arrhythmias and 12 of 14 with ventricular tachycardia were controlled with amiodarone. Although side effects were common, only one patient was removed from treatment due to pulmonary fibrosis. We conclude that amiodarone is an effective antiarrhythmic drug for refractory ventricular and supraventricular arrhythmias.     

老年人心律失常的治疗

本文分析了抗心律失常药物对212例老年心血管病患者的治疗作用。结果表明:奎尼丁、乙胺碘呋酮、洋地黄和异搏定可以满意地控制室上性心律失常,而在室性心律失常的治疗中乙胺碘呋酮和慢心律的疗效最佳。顽固性复发性室性心律失常的治疗多数病例需联合用药。其优点是可以减小各种药物的剂量,降低毒副作用。本文还讨论了抗心律失常药物与左室功能之间的关系。     

Clinical use of amiodarone

Amiodarone is unique among the antiarrhythmic agents. Despite its unusual pharmacokinetics and its potential toxicity, it is successful in managing both supraventricular and ventricular arrhythmias. Therefore, it is destined to become an important drug in our antiarrhythmic armamentarium.     

A proposal for the clinical use of flecainide

Effective antiarrhythmic therapy requires a carefully considered approach, including an understanding of the arrhythmia, the underlying cardiac disease and the drug's pharmacokinetics. Flecainide is a new antiarrhythmic drug that may soon be released for general use. Flecainide demonstrates unsurpassed efficacy in chronic ventricular arrhythmias in stable patients and may become a first-choice drug because of its ease of administration, efficacy and favorable tolerance. Twice-daily dosing with 100 to 200 mg usually provides effective therapy. Clinical experience suggests flecainide to be indicated in the treatment of uniform and multiform ventricular premature complexes, coupled ventricular premature complexes, and episodes of nonsustained ventricular tachycardia. A lower response rate is observed in preventing induction of sustained ventricular tachycardia, and these patients should be carefully selected. Flecainide is promising in the treatment of supraventricular tachycardias using atrioventricular nodal or extranodal reentrant pathways, although this use is still investigational in the United States. The drug's use for arrhythmias during acute myocardial infarction requires further study. Flecainide possesses modest negative inotropic potential. Proarrhythmic or other adverse reactions have occurred primarily in settings of high drug level, poor ventricular function or refractory, malignant arrhythmias, suggesting caution in these groups.     

Clinical types of proarrhythmic response to antiarrhythmic drugs

The problem of drug-induced or drug-aggravated cardiac arrhythmias has been recognized for many years. Digitalis glycosides and class I, II, III, or IV antiarrhythmic drugs can cause severe sinus node dysfunction or atrioventricular block. Digitalis can cause a variety of supraventricular arrhythmias; atrial tachycardia with block and nonparoxysmal atrioventricular junctional tachycardia are the most characteristic. Recognition that class IA and class III antiarrhythmic drugs can aggravate arrhythmias or cause new arrhythmias in patients being treated for potentially malignant or malignant ventricular arrhythmias has intensified the interest in proarrhythmia in recent years. Several characteristic types of proarrhythmic response have been described. Torsades de pointes (multiform) ventricular tachycardia (VT) accompanied by prolongation of the QT interval can be caused by class IA and class III antiarrhythmic drugs as well as other drugs that bind to the membrane sodium channels of ventricular cells, for example, tricyclic antidepressants. Uniform VT in patients with malignant ventricular arrhythmias and poor left ventricular function is a characteristic proarrhythmic response to class IC antiarrhythmic drugs. Bidirectional VT or accelerated idioventricular rhythm are characteristic of digitalis toxicity. More difficult to establish as proarrhythmic responses are increased frequency of ventricular premature depolarizations and increased ease of inducing VT with programmed ventricular stimulation.     

Long-term low-dose amiodarone therapy in the management of ventricular and supraventricular tachyarrhythmias: Efficacy and safety

Background: Amiodarone hydrochloride has been in use for two decades for the control of ventricular and supraventricular arrhythmias. Established and emerging evidence indicates that amiodarone has an antiarrhythmic efficacy superior to that of most other drugs. Hypothesis: The study was undertaken to evaluate the efficacy and acceptability of low-dose amiodarone therapy in the long-term management of supraventricular and ventricular tachyarrhythmias. Methods: A total of 124 patients with symptomatic drug-refractory or life-threatening arrhythmias managed with low-dose oral amiodarone therapy over a 10-year period was analyzed retrospectively. Of these, 45 patients (36%) had ventricular arrhythmias, 52 (42%) had atrial arrhythmias, and 27 (22%) had atrioventricular reentry tachycardia. Loading doses of amiodarone 600 mg daily for 1 week were administered for supraventricular arrhythmias and 600–1200 mg daily for 2 weeks for ventricular arrhythmias. Maintenance daily doses were 194 ± 48 and 206 ± 55 mg, respectively. Mean treatment duration was 32 ± 28 months, with 326.3 patient years of therapy. Results: Of 39 patients with sustained ventricular tachyarrhythmias, the actuarial incidence of satisfactory arrhythmia control (absence of sudden cardiac death or nonfatal arrhythmia recurrence) was 78% at 1 year and 71 % at 2 years. Satisfactory control of supraventricular arrhythmias (mean ventricular rate < 100/min with significant symptomatic improvement for sustained atrial arrhythmias and < 1 attack per year for paroxysmal atrial or atrioventricular arrhythmias) was achieved in 73, 65, and 62% of patients at 1, 2, and 3 years, respectively. The cumulative incidence of amiodarone-related adverse effects was 5.8 per 100 patient years, with drug withdrawal required in 12 patients (9.7%). Fifteen patients had thyroid dysfunction, 2 had hepatic toxicity, and 1 developed nonfatal pulmonary fibrosis. Overall, the incidence of successful use of amiodarone (satisfactory arrhythmia control and freedom from side effects) was 67, 59, and 53% at 1, 2, and 3 years, respectively. Conclusions: The results of this study suggest that the efficacy of low-dose amiodarone therapy in the management of serious ventricular and supraventricular arrhythmias would be similar to those achieved with higher doses, but with a much more acceptable side effect profile.     

An approach to therapy of supraventricular tachyarrhythmias: An algorithm versus individualized therapy

Approaches to the treatment of supraventricular arrhythmias, including atrial fibrillation, atrial flutter, atrial tachycardia, atrioventricular (AV) reentrant tachycardia, and AV nodal reentrant tachycardia, continue to evolve. Within the past two decades, many new and effective treatments have become available. These include several new antiarrhythmic agents, ablative therapies, pacing and surgical modalities, and cardioversion/defibrillation techniques. This paper provides an algorithm for the treatment of these supraventricular arrhythmias which includes therapy for the acute episode as well as the prevention of subsequent episodes of the tachyarrhythmia.     

Propafenone: An Effective Agent for the Management of Supraventricular Arrhythmias

Propafenone in SVT. Propafenone is a sodium channel blocking antiarrhythmic drug. It also has β-adrenergic, potassium channel, and weak calcium channel blocking activity. The drug is metabolized in the liver with rates dependent on the debrisoquin phenotype. The saturable metabolism results in nonlinear pharmacokinetics. The metabolites retain sodium channel blocking activity but little β-adrenergic blocking activity. Both controlled and noncontrolled studies have documented its efficacy in a variety of supraventricluar arrhythmias. Intravenous propafenone is effective in converting atrial fibrillation to normal sinus rhythm. Chronic oral administration decreases the frequency of recurrence of atrial fibrillation and paroxysmal supraventricular tachycardia. The drug is particularly effective in the Wolff-Parkinson-White syndrome. The drug may produce SA block in patients with underlying sinus node dysfunction. Propafenone has comparatively few noncardiac side effects. It is a useful primary drug or an alternative to more commonly used drugs used for the treatment of supraventricular arrhythmias.     

Clinical studies of the antiarrhythmic efficacy of disopyramide phosphate (Norpace) (author's transl)]

The antiarrhythmic action of Norpace was investigated in three clinical studies. 1. A single blind placebo controlled study in 10 centers confirmed the antiarrhythmic action of Norpace in 120 patients with ventricular or supraventricular cardiac arrhythmias. It was shown by means of continuous ECG recordings that Norpace produced a statistically significant reduction in the frequency of both ventricular and supraventricular extrasystoles. Paroxysmal ventricular tachycardia was prevented in 70% of the patients. 2. In a double blind comparative study of Norpace and quinidine sulphate a similar antiarrhythmic action against ventricular and supraventricular extrasystoles was shown in both patient groups. In contrast, the tolerance of Norpace was markedly superior to quinidne sulphate. 3. An acute study of the action of Norpace was also conducted. Therapeutic plasma levels were attained within 2 1/2 hours following an initial single dose and within 60 to 120 minutes when this dose was doubled. Orally administered disopyramide phosphate has therefore proved effective in both the short and longer term treatment of various types of supraventricular and ventricular arrhythmias. Its antiarrhythmic properties are very similar to those of quinidine sulphate. The dosage of disopyramide phosphate should be sufficiently high and must be individualized. The dosage generally lies between 400 and 800 mg daily and should be given in 4 divided doses at intervals of 6 hours. To achieve rapid therapeutic effects an initial dose of 2 x 150 mg is recommended. This method of administration will produce effective therapeutic plasma levels within 1 to 2 hours. Due to possible negative inotropic effects it is necessary to digitalize patients with congestive heart failure and caution should be exercised in poorly compensated patients. Observed side effects were mainly of the anticholinergic type.     

Review: Electrolyte and antiarrhythmic drug interaction

When one considers the complex interaction of antiarrhythmic drugs, either among the various groups or in the presence of altered electrolytes, the number of possible antagonistic and synergistic actions becomes almost infinite. This overview has attempted to amalgamate present information concerning drug and electrolyte interactions. Fortunately, in the clinical setting one is usually operating within the physiologic range for serum electrolytes, and many of these alterations shown in laboratory studies may not be pertinent. It should be remembered, however, that when serum electrolyte derangements are present, the usual or expected effects of antiarrhythmic drugs may be masked, leading to erroneous therapy or to the conclusion that the therapy is either inadequate or useless.This summary also points out that marked beneficial effects can be achieved, particularly by the use of digitalis and propranolol, in slowing AV conduction in the presence of supraventricular arrhythmias and that low potassium completely nullifies the action of the quinidine-like or Group 1 agents.The antagonism of bretylium to quinidine-like agents should alert the clinician to the possibility that the administration of Group 1 drugs in the wake of Group 3 or possibly other antiarrhythmic drugs may either nullify or aggravate certain pharmacologic actions. Although it is true that quinidine, lidocaine, and procainamide can be used with increased efficacy in the presence of propranolol, the opposite may be true when they are used in the presence of bretylium. Precise monitoring of serum electrolytes would appear essential before and during antiarrhythmic drug therapy.     

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.     

Pediatric electrophysiology

Our understanding of pediatric arrhythmias continues to evolve through natural history studies of paroxysmal supraventricular tachycardia, the congenital long QT syndrome, and postoperative atrial and ventricular tachyarrhythmias. The influence of the autonomic nervous system on cardiovascular function may play a role in the sudden infant death syndrome, pallid breath-holding spells, and neurally mediated syncope; much work is necessary to understand these entities better. Therapeutic approaches to pediatric arrhythmias are extending beyond newer antiarrhythmic drugs and now include ablative therapy for many supraventricular tachyarrhythmias, both surgical and transcatheter. Advances in pacemaker therapy include novel implantation sites, down-sizing of devices, and the application of antitachycardia and rate-adaptive technologies.     

Latent Wolff-Parkinson-White syndrome as the electrophysiological and morphological basis of supraventricular tachycardia

The concealed Wolff-Parkinson-White (WPW) syndrome, the electrophysiologic and morphologic basis of cardiac arrhythmias, was shown to be a cause of the attacks of supraventricular tachycardia. The latter is rooted in the concealed WPW syndrome in about 30% of patients showing no electrocardiographic signs of pre-excitation. Electrophysiologic criteria of the diagnosis of supraventricular tachycardias due to the concealed WPW syndrome are listed. Concealed Kent's bundle was most commonly found on the left side. As regards antiarrhythmic therapy, disopyramide is one of the most effective drugs for patients with supraventricular tachycardias due to the concealed WPW syndrome.     

Congenital arrhythmia in a normal newborn

We describe a case, unique to the best of our knowledge, in which bigeminal supraventricular premature contractions were detected in a normal newborn. These arrhythmias disappeared spontaneously after the twelfth day of life. Since they do not appear to evolve towards paroxysmal supraventricular tachycardia, treatment with antiarrhythmic drugs is not recommended.     

Peri-operative supraventricular arrhythmias in coronary bypass surgery

One hundred consecutive admissions for coronary bypass surgery were studied to establish the incidence of peri-operative supraventricular arrhythmias, to monitor their evolution, and to identify their possible aetiological factors. No important arrhythmias were detected before the operation. Post-operatively, 24 patients (24%) developed supraventricular arrhythmias. Nineteen of them had atrial fibrillation or flutter (19%), 2 had supraventricular tachycardia (2%), and 3 had inappropriate sinus bradycardia (less than 45 min) (3%). Almost two-thirds of the arrhythmias occurred within the critical early post-operative period (63%). Haemodynamic compromise ushered the onset of arrhythmias in more than one-third of the patients in whom antiarrhythmic measures ensured prompt improvement (37.5%). Three-quarters of those with atrial fibrillation or flutter were back in sinus rhythm at the time of discharge from hospital (74%). The incidence of supraventricular arrhythmia was significantly higher in patients with demonstrable myocardial ischaemia prior to surgery, in patients who underwent adjunctive coronary endarterectomy, or in those in whom topical cardiac cooling was applied (50%, 45%, and 58%, respectively). Supraventricular arrhythmias are frequently encountered during the critical early post-operative period when serious but reversible haemodynamic compromise might be precipitated. Although the nature of the underlying myocardial insult remains obscure, supraventricular arrhythmia may be related more to defective myocardial preservation than to any specific underlying myocardial lesion.     

Concentration/response relations for the multiple antiarrhythmic actions of sotalol

Sotalol, one of the first beta-receptor antagonists synthesized, is a promising investigational agent with remarkable efficacy for treatment of patients with ventricular and supraventricular arrhythmias. Unlike other beta blockers, sotalol also possesses class III antiarrhythmic action, evidenced by prolongation of the myocardial action potential duration. This additional action probably accounts for the greater antiarrhythmic efficacy of sotalol compared with other beta blockers. Sotalol's class III antiarrhythmic action becomes apparent at concentrations higher than those necessary for significant beta-receptor antagonism, both in vitro and in human subjects. In a study correlating dosage and antiarrhythmic response with prolongation of rate-corrected QT (QTc) (a measure of class III action) and the degree of beta-receptor blockade (assessed by the reduction of the maximal exercise-induced heart rate), 11 of 17 patients had an antiarrhythmic response. Eight of these 11 responders had been unresponsive to conventional beta-receptor antagonists. The plasma concentration associated with significant QTc prolongation (2.55 micrograms/ml) was found to be much greater than that associated with 50% reduction in maximal slowing of heart rate (0.8 micrograms/ml). As with other beta-receptor antagonists, the activities of sotalol's 2 stereoisomers differ, with the I-isomer having far more beta-blocking activity. However, both isomers have equal class III antiarrhythmic activity. When increasing doses of the d-isomer of sotalol (50 to 400 mg every 12 hours) were evaluated in patients with chronic ventricular arrhythmias, arrhythmia frequency was suppressed greater than 80% in 3 patients and 50% in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolongation of cardiac refractory times in man by clofilium phosphate, a new antiarrhythmic agent

The electrophysiologic effects of clofilium phosphate, a new quaternary ammonium antiarrhythmic agent, were evaluated in 15 patients with a variety of cardiac dysrhythmias. Ten patients had ventricular dysrhythmias and five patients had supraventricular dysrhythmias. Clofilium was administered as a single bolus intravenously in doses ranging from 60 to 300 micrograms/kg during electrophysiologic testing. Blood pressure and heart rate were unchanged, and there were no significant side effects. Conduction time was unchanged in atrial tissue, ventricular tissue, atrioventricular node, and in the His-Purkinje system. QT intervals lengthened, atrial effective refractory period increased, and ventricular effective refractory period increased. The effective refractory period of the AV node was unchanged. Refractoriness of the bundle branches or His-Purkinje system was increased in eight patients. Inducible supraventricular arrhythmias were improved in four of four patients, and inducible ventricular arrhythmias were improved in at least five of nine patients. Clofilium is a model for an antiarrhythmic drug which should be useful in interrupting or suppressing reentrant arrhythmias because it increases refractoriness without major changes in conduction time.     

Antiarrhythmic drugs for supraventricular tachycardia

Many antiarrhythmic drugs are available for treatment of supraventricular tachycardia. Selection of the appropriate drug is helped by the identification of the site of origin, mechanism and pathway of the arrhythmia. For most types of supraventricular tachycardia >1 antiarrhythmic drug is available. Comparative studies between the effect of different antiarrhythmic drugs on the same arrhythmia are few, preventing scientifically proved advice on “the best” drug for a given arrhythmia. Familiarity with a limited number of antiarrhythmic drugs will increase therapeutic efficacy and reduce the incidence of unpleasant surprises to patient and physician.