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Published on 1 September 2001

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Treatment of cardiac tachyarrhythmias

Hanno L Tan
Department of Clinical and Experimental Cardiology
Academic Medical Center
University of Amsterdam
The Netherlands

The notion that cardiac antiarrhythmic drugs may be a double-edged sword with the potential of proarrhythmic effects in addition to antiarrhythmic effects has gained widespread recognition since the landmark CAST study,(1) which showed increased mortality in patients treated with various class IC drugs (Vaughan Williams classification – see Table 1) for the prevention of ventricular tachycardias (VTs). Subsequent analyses revealed that excess mortality afflicted certain subgroups, such as those with ischaemia and left ventricular dysfunction. In general, sodium channel blockade (class I drugs) may cause proarrhythmia both on ventricular and supraventricular levels.(2) An example of the latter is conversion of atrial fibrillation (AF) to atrial flutter (AFl) by flecainide, with subsequent enhanced AV nodal conduction resulting in 1:1 AV conduction and potentially life- threatening high ventricular rates.

Antiarrhythmic drugs that act by prolonging action potential duration and refractoriness (class IA and class III drugs) are notorious for their ability to cause polymorphic VT (torsade de pointes) when excessive action potential prolongation (possibly in patients with an increased susceptibility to the potassium-channel-blocking properties of these drugs) facilitates after­depolarisations.(3) Even well-known drugs such as digitalis and verapamil may cause proarrhythmia under certain conditions, in particular by causing AV block and facilitating accessory pathway conduction during AF in patients with Wolff–Parkinson–White (WPW) syndrome, thereby raising ventricular rates inadvertently.(4) Perhaps the only antiarrhythmic drugs devoid of serious proarrhythmia are b-blockers (class II, but not sotalol, which has additional potent class III effects and is classified as a class III drug) and amiodarone.(5) However, the efficacy of ­
b-blockers is often limited, while the unwieldy ­pharmacokinetics and impressive range of sometimes serious non-cardiac side-effects make amiodarone no drug of first choice. On the other hand, while class IC drugs have gained notoriety because of the CAST study, they rank among the most effective drugs for supra­ventricular tachycardias (SVTs), particularly AF.

The lesson from these observations is that anti-arrhythmic drug treatment should be tailored therapy, which takes into account individual patient characteristics. To obtain a more rational approach to choosing an antiarrhythmic drug, knowledge of the basic electrophysiological mechanisms of (pro)arrhythmia types and drug action is paramount.(6) Some brief guidelines and new developments are discussed here.

Sustained tachycardia
In all forms of sustained tachycardia that are not haemodynamically well tolerated, emergent DC cardioversion to restore sinus rhythm should be performed. If the tachycardia is haemodynamically well tolerated, drug therapy may be attempted; if drug treatment fails, DC cardioversion should be performed.

While adenosine may be helpful in distinguishing VT from SVT with aberrant conduction in cases of wide complex tachycardia, this distinction cannot always be made with certainty. When this is the case, procainamide should be administered and verapamil withheld. This is because verapamil is ineffective in most VT forms, and it has negative inotropic effects that may be particularly significant during sustained tachycardia; procainamide has less negative inotropic effects, and it may not only terminate VT but also be useful in most SVT forms (particularly atrioventricular reciprocating tachycardia [AVRT] and AF/AFl).

Ventricular and supraventricular ectopic beats
Ventricular or supraventricular ectopy in structurally normal hearts has no clinical significance. The primary management goal is reassurance. Provoking factors, such as caffeine, smoking and alcohol, should be avoided. If drug treatment is desired, b-blockers may be effective.

Supraventricular tachycardia utilising the AV node
Supraventricular tachycardia in which the AV node is part of the re-entry circuit includes atrioventricular nodal re-entrant tachycardia (AVNRT) and AVRT involving an accessory pathway – for example, WPW syndrome. Both tachycardia forms may be terminated by (transiently) blocking AV nodal conduction. If vagal measures fail, adenosine is the first choice because it combines a very high efficacy (close to 100% termination of AVNRT and AVRT) with a very brief plasma half-life. If adenosine is not well tolerated (for example, with chronic pulmonary disease) and for long-term prevention of AVNRT/AVRT episodes, verapamil may be used. In AVRT, the strategy may be aimed at blocking accessory pathway conduction instead of AV nodal conduction. This may be accomplished with class I drugs (like flecainide). In particular, patients with an accessory pathway who present with AF should not be given drugs that suppress AV nodal conduction, because this may facilitate accessory pathway conduction, thereby raising ventricular rate. Instead, class I drugs should be administered to slow accessory pathway conduction; these drugs have the added benefit that they may prevent and/or terminate AF. In patients with frequent AVNRT or AVRT episodes, radiofrequency (RF) catheter ­ablation may be considered.

Atrial fibrillation, atrial flutter and atrial tachycardia
It is generally believed that maintenance of sinus rhythm is preferable to controlling ventricular rate while accepting AF, although the first large trials addressing this issue await completion.(7) Termination of AF may be ­accomplished with flecainide, propafenone or ibutilide with a high reported success rate (50–90%). To maintain sinus rhythm, flecainide, propafenone, sotalol or amiodarone may be used. Some advocate combining flecainide with a b-blocker to avoid 1:1 AV conduction after conversion of AF to AFl. Although effective, particularly in vagally ­mediated AF (because it has vagolytic actions, as has disopyramide), flecainide should not be administered in patients with ischaemic heart disease or left ­ventricular dysfunction, because of proarrhythmia. Amiodarone is preferable, particularly in heart failure, because of a lack of negative inotropic action.

If sinus rhythm cannot be maintained and rate control must be instituted, digoxin, b-blockers or verapamil are the drugs of choice. If heart failure is present, digoxin or amiodarone may be used. While AF is the most common clinically significant tachyarrhythmia, drug treatment is often not sufficiently effective. It is expected that novel class III drugs will soon be introduced. They carry the promise of a (theoretically) more desirable mode of action (dofetilide, azimilide) or fewer non-cardiac side-effects (dronedarone). RF catheter ablation techniques to treat AF are being developed.(8) As a last resort, His bundle RF ablation with pacemaker implantation may be performed in drug-refractory AF.

No drugs are effective in converting AFl. Flecainide should be withheld because it may cause 1:1 AV conduction. On the other hand, RF catheter ablation of AFl is often effective. Rate control in AFl may be accomplished using the same strategies as in AF. Some atrial tachycardia (AT) forms may be terminated by adenosine. For chronic treatment, flecainide, propafenone, disopyramide, b-blockers, verapamil or amiodarone may be used. RF catheter ablation may be effective.

Ventricular tachycardia
VT usually results from structural heart disease, particularly ischaemic heart disease. Primary VT (VT during the first 24 hours after myocardial infarction) may be effectively treated with lidocaine or procainamide; during cardiopulmonary resuscitation, intravenous amiodarone may be even more effective.(9) However, for the long-term management of VT due to ischaemic heart disease, particularly in the presence of left ventricular dysfunction, antiarrhythmic drugs confer insufficient protection. It is now generally accepted that implantable defibrillators are superior in reducing total mortality than the most potent antiarrhythmic drug (amiodarone) in this patient category.(10) Antiarrhythmic drugs, such as amiodarone, sotalol and b-blockers, are ancillary treatments aimed at minimising the incidence of VT. Class IC drugs (flecainide, encainide, moricizine) are associated with increased mortality in patients with ischaemia and/or left ventricular dysfunction.

In addition to VT due to ischaemic heart disease, relatively rare VT forms exist and require specific therapy. Idiopathic VT, arising either from the right ventricular outflow tract or from the inferior left-sided ventricular septum, may be managed with adenosine, verapamil, b-blockers or RF ablation. Inherited long QT syndrome may be successfully managed with (non-selective) b-blockers. However, VT in long QT syndrome type 3 (based on sodium channel mutations) is strongly bradycardia-dependent. Thus b-blockers may be deleterious; furthermore, there is no convincing evidence for their efficacy. Defibrillator implantation should be performed in these patients. VT in some forms of arrhythmogenic right ventricular dysplasia and hypertrophic cardio-myopathy may be prevented by b-blockers. However, in malignant mutants (those associated with familial sudden death) a defibrillator should be implanted.


  1. Mason JW. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993;329:452-8.
  2. Wilde AAM. Proarrhythmia related to sodium channel blockade: ­mechanisms, monitoring, prevention and management. Card Electrophysiol Rev 1998;2:136-41.
  3. Tan HL, Hou CJY, Lauer MR, Sung RJ. Electrophysiologic ­mechanisms of the long QT syndromes and torsade de pointes. Ann Intern Med 1995;122:701-14.
  4. Sellers TD, Bashore TM, Gallagher JJ. Digitalis in the pre-excitation syndrome. Analysis during atrial ­fibrillation. Circulation 1977;56:260-7.
  5. Mattioni TA, Aheutlin TA, Sarmiento JJ, et al. Amiodarone in patients with previous drug-mediated torsade de pointes: long-term safety and efficacy. Ann Intern Med 1989;111:574-80.
  6. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms [abstract]. Circulation 1991;84:1831-51.
  7. Levy S, Breithardt G, Campbell RW, et al. Atrial fibrillation: current ­knowledge and recommendations for management. Working Group on Arrhythmias of the European Society of Cardiology. Eur Heart J 1998; 19:1294-320.
  8. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-66.
  9. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for ­resuscitation after out-of-hospital cardiac arrest due to ventricular ­fibrillation. N Engl J Med 1999;341:871-8.
  10. Moss AJ, Hall WJ, Cannom DS,et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933-40.

European Society of Cardiology

Further ­reading
Braunwald E, et al. Heart disease: a textbook of ­cardiovascular medicine. 6th edn. Philadelphia: Saunders; 2001
Zipes DP, Jalife J, Cardiac ­electrophysiology: from cell to bedside. 3rd edn. Philadelphia: Saunders; 2000

Forthcoming event
1–5 Sept 2001
European Society of Cardiology Annual Congress

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