The need for treatment of arrhythmias depends on the symptoms and the seriousness of the arrhythmia. Treatment is directed at causes. If necessary, direct antiarrhythmic therapy, including antiarrhythmic drugs, cardioversion-defibrillation, implantable cardioverter-defibrillators (ICDs), pacemakers (and a special form of pacing, cardiac resynchronization therapy), catheter ablation, surgery, or a combination, is used.
Most antiarrhythmic drugs are grouped into 4 main classes (Vaughan Williams classification) based on their dominant cellular electrophysiologic effect (see table Antiarrhythmic Drugs (Vaughan Williams Classification)).
-
Class I: Class I drugs are subdivided into subclasses a, b, and c. Class I drugs are sodium channel blockers (membrane-stabilizing drugs) that block fast sodium channels, slowing conduction in fast-channel tissues (working atrial and ventricular myocytes, His-Purkinje system).
-
Class II: Class II drugs are beta-blockers, which affect predominantly slow-channel tissues (sinoatrial [SA] and atrioventricular [AV] nodes), where they decrease rate of automaticity, slow conduction velocity, and prolong refractoriness.
-
Class III: Class III drugs are primarily potassium channel blockers, which prolong action potential duration and refractoriness in slow- and fast-channel tissues.
-
Class IV: Class IV drugs are the nondihydropyridine calcium channel blockers, which depress calcium-dependent action potentials in slow-channel tissues and thus decrease the rate of automaticity, slow conduction velocity, and prolong refractoriness.
Digoxin and adenosine are not included in the Vaughan Williams classification. Digoxin shortens atrial and ventricular refractory periods and is vagotonic, thereby prolonging AV nodal conduction and AV nodal refractory periods. Adenosine slows or blocks AV nodal conduction and can terminate tachyarrhythmias that rely upon AV nodal conduction for their perpetuation.
Antiarrhythmic Drugs (Vaughan Williams Classification)
Class I Antiarrhythmic Drugs
Class I antiarrhythmic drugs are
In the electrocardiogram (ECG), this effect may be reflected as widening of the P wave, widening of the QRS complex, prolongation of the PR interval, or a combination.
Class I drugs are subdivided based on the kinetics of the sodium channel effects:
The kinetics of sodium channel blockade determine the heart rates at which their electrophysiologic effects become manifest. Because class Ib drugs have fast kinetics, they express their electrophysiologic effects only at fast heart rates. Thus, an ECG obtained during normal rhythm at normal rates usually shows no evidence of fast-channel tissue conduction slowing. Class Ib drugs are not very potent antiarrhythmics and have minimal effects on atrial tissue.
Class Ic drugs have slow kinetics, so they express their electrophysiologic effects at all heart rates. Thus, an ECG obtained during normal rhythm at normal heart rates usually shows fast-channel tissue conduction slowing. Class Ic drugs are more potent antiarrhythmics.
Class Ia drugs have intermediate kinetics, so their fast-channel tissue conduction slowing effects may or may not be evident on an ECG obtained during normal rhythm at normal rates. Class Ia drugs also block repolarizing potassium channels, prolonging the refractory periods of fast-channel tissues. On the ECG, this effect is reflected as QT-interval prolongation even at normal rates. Class Ib drugs and class Ic drugs do not block potassium channels directly.
The primary indications are supraventricular tachycardia (SVT) for class Ia and Ic drugs and ventricular tachycardia (VTs) for all class I drugs.
Adverse effects of class I drugs include proarrhythmia, a drug-related arrhythmia worse than the arrhythmia being treated, which is the most worrisome adverse effect. All class I drugs may worsen VTs. Class I drugs also tend to depress ventricular contractility. Because these adverse effects are more likely to occur in patients with a structural heart disorder, class I drugs are not generally recommended for such patients. Thus, these drugs are usually used only in patients who do not have a structural heart disorder or in patients who have a structural heart disorder but who have no other therapeutic alternatives. There are other adverse effects of class I drugs that are specific to the subclass or individual drug.
Class Ia antiarrhythmic drugs
Class Ia drugs have kinetics that are intermediate between the fast kinetics of class Ib and the slow kinetics of class Ic. Their fast-channel tissue conduction slowing effects may or may not be evident on an ECG obtained during normal rhythm at normal rates. Class Ia drugs block repolarizing potassium channels, prolonging the refractory periods of fast-channel tissues. On the ECG, this effect is reflected as QT-interval prolongation even at normal rates.
Class Ia drugs are used for suppression of atrial premature beats, ventricular premature beats, supraventricular tachycardia, ventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular fibrillation. The primary indications are supraventricular and ventricular tachycardias.
Class Ia drugs may cause torsades de pointes ventricular tachycardia. Class Ia drugs may organize and slow atrial tachyarrhythmias enough to permit 1:1 AV conduction with marked acceleration of the ventricular response rate.
Class Ib antiarrhythmic drugs
Class Ib drugs have fast kinetics; they express their electrophysiologic effects only at fast heart rates. Thus, an ECG obtained during normal rhythm at normal rates usually shows no evidence of fast-channel tissue conduction slowing. Class Ib drugs are not very potent antiarrhythmics and have minimal effects on atrial tissue. Class Ib drugs do not block potassium channels directly.
Class Ib drugs are used for the suppression of ventricular arrhythmias (ventricular premature beats, ventricular tachycardia, ventricular fibrillation).
Class Ic antiarrhythmic drugs
Class Ic drugs have slow kinetics; they express their electrophysiologic effects at all heart rates. Thus, an ECG obtained during normal rhythm at normal heart rates usually shows fast-channel tissue conduction slowing. Class Ic drugs are more potent antiarrhythmics than either class Ia or class Ib drugs. Class Ic drugs do not block potassium channels directly.
Class Ic drugs may organize and slow atrial tachyarrhythmias enough to permit 1:1 AV conduction with marked acceleration of the ventricular response rate.
Class Ic drugs are used for suppression of atrial premature beats, ventricular premature beats, supraventricular tachycardia, ventricular tachycardias, atrial fibrillation, atrial flutter, and ventricular fibrillation.
Class II Antiarrhythmic Drugs
Class II antiarrhythmic drugs are
Beta-blockers affect predominantly slow-channel tissues (sinoatrial and atrioventricular nodes), where they decrease rate of automaticity, slow conduction velocity, and prolong refractoriness. Thus, heart rate is slowed, the PR interval is lengthened, and the AV node transmits rapid atrial depolarizations at a lower frequency.
Class II drugs are used primarily to treat supraventricular tachycardias, including sinus tachycardia, AV nodal reentry, atrial fibrillation, and atrial flutter. These drugs are also used to treat ventricular tachycardia to raise the threshold for ventricular fibrillation and reduce the ventricular proarrhythmic effects of beta-adrenoceptor stimulation.
Beta-blockers are generally well tolerated; adverse effects include lassitude, sleep disturbance, and gastrointestinal upset. These drugs are contraindicated in patients with asthma.
Class III Antiarrhythmic Drugs
Class III drugs are
Class III drugs prolong action potential duration and refractoriness in slow- and fast-channel tissues. Thus, the capacity of all cardiac tissues to transmit impulses at high frequencies is reduced, but conduction velocity is not significantly affected. Because the action potential is prolonged, rate of automaticity is reduced. The predominant effect on the ECG is QT-interval prolongation.
Class IV Antiarrhythmic Drugs
Class IV drugs are
These drugs depress calcium-dependent action potentials in slow-channel tissues and thus decrease the rate of automaticity, slow conduction velocity, and prolong refractoriness. Heart rate is slowed, the PR interval is lengthened, and the AV node transmits rapid atrial depolarizations at a lower frequency. These drugs are used primarily to treat SVTs. They may also be used to slow rapid atrial fibrillation or atrial flutter. One form of VT (left septal or Belhassen VT) can be treated with verapamil.
