Antiarrhythmic therapy

Cardiac arrhythmias are an important cause of morbidity and mortality approximately 400,000 people per year die from myocardial infarctions (MI) in the United States alone. Individuals with MI exhibit some form of dysrhythmia within 48 h. Post-mortem examinations of MI victims indicate that many die in spite of the fact that the mass of ventricular muscle deprived of its blood supply is often quite small. These data suggest that the cause of death is ventricular fibrillation and that the immediate availability of a safe and efficacious antiarrhythmic agent could have prolonged a number of Hves. The goals of antiarrhythmic therapy are to reduce the incidence of sudden death and to alleviate the symptoms of arrhythmias, such as palpitations and syncope. Several excellent reviews of the mechanisms of arrhythmias and the pharmacology of antiarrhythmic agents have been pubflshed (1,2). 

Explains the purpose of self-monitoring of pulse rate when receiving antiarrhythmic therapy. 

If severe symptoms are present, synchronized DCC should be instituted immediately to restore sinus rhythm. Precipitating factors should be corrected if possible. If VT is an isolated electrical event associated with a transient initiating factor (e.g., acute myocardial ischemia, digitalis toxicity), there is no need for long-term antiarrhythmic therapy after precipitating factors are corrected. 

An Overview of Class III Electrophysiological Agents A New Generation of Antiarrhythmic Therapy... 

PVC s alone with Class IC drugs was not sufficient to reduce mortality in the specific post-infarction population chosen for the CAST study. The failure of Class IC agents in the CAST study and their low efficacy in preventing induction of SVT during electrophysiological testing has increased the interest in alternative approaches to antiarrhythmic therapy, particularly towards Class III agents, a number of which are in Phase II clinical evaluation. 

Concomitant antiarrhythmic therapy Reserve concomitant use of disopyramide with other class lA antiarrhythmics or propranolol for life-threatening arrhythmias unresponsive to a single agent. Such use may produce serious negative inotropic effects or may excessively prolong conduction, particularly with cardiac decompensation. 

Transfer to sotalol from other antiarrhythmic therapy- Before starting sotalol, generally withdraw previous antiarrhythmic therapy under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient s clinical condition permits. Treatment has been initiated in some patients receiving IV lidocaine without ill effect. After discontinuation of amiodarone, do not initiate sotalol until the QT interval is normalized. 

Abstract Two thirds of the nearly half a million deaths per year in the United States due to sudden cardiac death (SCD) is attributed to coronary artery disease (CAD) and most commonly results from untreated ventricular tachyarrhythmias. Patients with ischemic cardiomyopathy and left ventricular dysfunction are at highest risk for SCD, but this still defines only a small subset of patients who will suffer SCD. Multiple lines of evidence now support the superiority of implantable cardioverter defibrillator (ICD) therapy over antiarrhythmic therapy for both primary and secondary prevention of SCD in advanced ischemic heart disease. Optimization of ICD therapy in advanced ischemic cardiomyopathy includes preventing right ventricular pacing as well as the use of highly effective anti-tachycardia pacing to reduce the number of shocks. While expensive, ICD therapy has been shown to compare favorably to the accepted standard of hemodialysis in cost effectiveness analyses. 

A review of these three trials concluded that, compared to antiarrhythmic therapy, ICD implantation for secondary prevention results in significant reductions in all-cause mortality (RR 0.76) and SCD (RR 0.50) [30]. A meta-analysis of secondary prevention trials found an absolute reduction in... 

The class IV-antiarrhythmics are the calcium antagonists, but remain limited to verapamil and possibly also diltiazem. The dihydropyridines (nifedipine and related compounds) are unsuitable for antiarrhythmic therapy. The antiarrhythmic activity of verapamil and diltiazem is based upon the impairment of AV conduction and heart rate. A few compounds may be considered to act as antiarrhyth-mics, but they are not included in the Vaughan-Williams classification. 

Clinical use of antiarrhythmic agents requires not only an accurate knowledge of the genesis of arrhythmias, but also an understanding of the precise mechanism of action of each agent. Antiarrhythmic therapy is complicated by the high incidence of severe and even fated adverse events. Most Na+... 

No data exist regarding the efficacy of antiarrhythmic therapy in mitral valve prolapse patients with hemodynamically significant mitral regurgitation. At present, /3-blockers seem preferable when ventricular performance permits. Class I agents should be used with careful follow-up by ambulatory monitoring and/or exercise testing to avoid any proar-rhythmic effects. 

Burkart F, Pflsterer M, Kiowski W, FoUath F, Burck-hardt D. Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias Basel Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol 1990 16 1711-8. 

Several important determinations must be made before initiation of any antiarrhythmic therapy ... 

The benefits of antiarrhythmic therapy are actually relatively difficult to establish. Two types of benefits can be envisioned reduction of arrhythmia-related symptoms, such as palpitations, syncope, or cardiac arrest or reduction in long-term mortality in asymptomatic patients. Among drugs discussed here, only 3 blockers have been definitely associated with reduction of mortality in relatively asymptomatic patients, and the mechanism underlying this effect is not established (see Chapter 10). 

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug therapy and the underlying heart disease appears important. 

Lazzara R, Scherlag BJ Current concepts of the genesis of ischemic arrhythmias and sudden coronary death in Lucchesi R, Dingell JV, Schwarz RP (eds) Clinical Pharmacology of Antiarrhythmic Therapy. New York, Raven Press, 1984, pp 9-23. 

Andersen ED. Long-term antiarrhythmic therapy with amiodarone high prevalence of thyrotoxicosis (11%). Eur Heart J 1981 2 199. 

Van Gelder IC, Brugemann J, Crijns HJ. Current treatment recommendations in antiarrhythmic therapy. Drugs. 1998 55 331-346. 

Premature ventricular contractions (PVCs) are commonly recorded in patients convalescing from myocardial infarction. Since such arrhythmias have been associated with an increased risk of sudden cardiac death, it had been the empiric practice of many physicians to treat PVCs, even if asymp-tomatic, in such patients. In CAST (Cardiac Arrhythmia Suppression Trial [CAST], Echt et al, 1991), an attempt was made to document the efficacy of such therapy in a controlled clinical trial. The effects of several antiarrhythmic drugs on arrhythmia frequency were first evaluated in an open-label fashion. Then, patients in whom antiarrhythmic therapy suppressed PVCs were randomly assigned, in a double-blind fashion, to continue that therapy or its corresponding placebo. 

Chest pain during septal ablation commonly occurs and is effectively managed by analgesic therapy. Intensive care unit monitoring is employed routinely postprocedure in anticipation of ventricular arrhythmias during the initial period of myocardial injury, Prophylactic antiarrhythmic therapy has not been used in our center,... 

Effect of long-term antiarrhythmic therapy on mortality based on placebo-controlled, randomized trials. 

As noted above, the antiarrhythmic drugs can modify impulse generation and conduction. More than a dozen such drugs that are potentially useful in treating arrhythmias are currently available. However, only a limited number of these agents are clinically beneficial in the treatment of selected arrhythmias. For example, the acute termination of ventricular tachycardia by lidocaine or supraventricular tachycardia by adenosine or verapamil are examples in which antiarrhythmic therapy results in decreased morbidity. In contrast, many of the antiarrhythmic agents are now known to have lethal proarrhythmic actions, that is, to cause arrhythmias. 

Kluger J, Leech S, Reidenberg MM, Lloyd V, Drayer DE. Long-term antiarrhythmic therapy with acetylprocaina-mide. Am J Cardiol 1981 48(6) 1124—32. 

Kosior D, Karpinski G, Wretowski D, Stolaiz P, Stawicki S, Rabczenko D, Torbicki A, Opolski G. Sequential prophylactic antiarrhythmic therapy for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation—one year follow-up. Kardiol Pol 2002 56 361-7. 

Natale A, Newby KH, Pisano E, Leonelli F, Fanelli R, Potenza D, Beheiry S, Tomassoni G. Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter. J Am Coll Cardiol 2000 35(7) 1898-904. 

Cairns JA. Antiarrhythmic therapy in the post-infarction setting update from major amiodarone studies. Int J Clin Pract 1998 52(6) 422-4. 

Kowey PR, Marinchak RA, Rials SJ, Bharucha DB. Intravenous antiarrhythmic therapy in the acute control of in-hospital destabilizing ventricular tachycardia and fibrillation. Am J Cardiol 1999 84(9A) R46-51. 

Hilleman DE, Mohiuddin SM, Garmon JM. Adverse reactions during acute and chronic class I antiarrhythmic therapy. Curr Ther Res 1992 51 730-8. 

Cowan JC, Coulshed DS, Zaman AG. Antiarrhythmic therapy and survival following myocardial infarction. J Cardiovasc Pharmacol 1991 18(Suppl 2) S92-8. 

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