Electrophysiologic study with catheter ablation is now the primary mode of therapy for most forms of recurrent supraventricular tachycardia. However, pharmacologic therapy for acute episodes and for the long-term management of patients for whom electrophysiologic studies and ablation are not available or appropriate is still an important clinical consideration. The proper use of drugs in these patients requires an understanding of multiple factors: the electrophysiologic mechanism responsible for the arrhythmia, the functional roles of the anatomic pathways involved, the pharmacology of the target tissues, and the properties of the drugs themselves.
Drugs may be used both as immediate therapy to terminate episodes of tachycardia or for long-term prophylactic therapy to maintain sinus rhythm long term. The most common supraventricular tachycardias (SVTs) involve reentry over a single circuit, and a very short duration of drug effect may be all that is necessary to break a single tachycardia episode. Prophylaxis of recurrent arrhythmias requires a different strategy than that for termination. In reentrant arrhythmias, complete and permanent conduction block in the circuits involved is achievable with drug therapy only rarely, and if the tissue is required for normal conduction, fixed block will not be desirable. Effective strategies may include facilitation of early termination via rate-related block in the atrioventricular (AV) node, drug-induced changes in conduction times, or production of block only in abnormal conduction pathways. Long-term suppression of automatic arrhythmias often requires approaches that eliminate or modify precipitating stimuli or that suppress or eliminate selectively the responsible anatomic focus. This chapter deals primarily with therapy for paroxysmal supraventricular tachycardia (PSVT) and atrial flutter.
Pharmacology of Supraventricular Tachycardias
Drug therapy of supraventricular arrhythmias is typically based on the concept of a “vulnerable target” at which drug treatment may be directed. The sinus node and the AV node have calcium-mediated action potentials and are more sensitive to direct effects of calcium channel blockers (CCBs) and adenosine and indirect, autonomically mediated effects of adenosine, β-adrenergic blockers, or cardiac glycosides. The primary pacemaker current in the sinus node—the “funny current,” or I f —is a new target for arrhythmias originating in the sinus node. Atrial muscle conduction is depressed by sodium channel blockers, and refractory periods are prolonged by potassium channel blockers. Enhanced or abnormal automaticity in atrial muscle may be due to many mechanisms; therefore drugs that block adenosine or β-adrenergic receptors, and calcium, sodium, and potassium channels may all be effective in selected cases. Most accessory pathways have electrophysiologic properties similar to those of atrial or ventricular muscle. Conduction and refractory periods of accessory pathways are most susceptible to sodium and potassium channel blockers, but some pathways sensitive to adenosine have been described. Although there are limitations to the Vaughan Williams classification of antiarrhythmic drugs, it may still be useful as a general guide for the selection of drug therapy ( Table 19-1 ).
| Electrocardiography | Electrophysiology | ||||||
|---|---|---|---|---|---|---|---|
| CLASS AND AGENTS | PR | QRS | QTc | JTc | AV | AP | AVN |
| Class Ia: Na + channel blockers (quinidine, procainamide, disopyramide) | NC | (↑) | ↑ | ↑ | ERP ↑ | ERP ↑ | ERP NC COND NC |
| COND ↓ | COND ↓ | ||||||
| Class Ic: Na + channel blockers (flecainide, propafenone, moricizine) | ↑ | ↑↑ | (↑) | NC | ERP ↑ | ERP ↑ | ERP ↑ |
| COND ↓↓ | COND ↓↓ | COND ↓ | |||||
| Class II: β-Adrenergic blockers (many preparations) | ↑ | NC | NC | NC | ERP NC COND NC | ERP NC COND NC | ERP ↑ |
| COND ↓ | |||||||
| Class III: K + channel blockers (amiodarone, sotalol, dofetilide) * | ↑ | NC | ↑↑ | ↑↑ | ERP (↑) | ERP ↑ | ERP ↑ |
| COND ↑ | COND ↑ | COND ↓ | |||||
| Class IV: Ca 2+ channel blockers (verapamil, diltiazem) | ↑ | NC | NC | NC | ERP NC COND NC | ERP NC COND NC | ERP ↑↑ |
| COND ↓↓ | |||||||
| Adenosine | ↑ | NC | NC | NC | ERP (A) ↓ | ERP ↓ | ERP ↑↑ |
| ERP (V) NC COND NC | COND ↑ | COND ↓↓ | |||||
| Digoxin | ↑ | NC | NC | NC | ERP (A) ↓ | ERP ↓/NC | ERP ↑ |
| ERP (V) NC COND NC | COND ↑/NC | COND ↑ | |||||
* Clinically available agents have other actions not related to K + channel blockade.
Evaluation of Therapy
Several types of studies have been used to establish the effectiveness of drug therapy in patients with supraventricular arrhythmias. The most reliable studies are randomized trials that compare the study drug with either a placebo control or a second active agent. The range of doses studied during the course of drug evaluation should include both minimally and maximally effective doses. When two agents are compared, it is important that each drug be tested at a dose expected to produce a maximal or near-maximal response.
For acute termination of an episode of tachycardia, the efficacy of a drug is relatively easy to evaluate. Patients who come to medical attention with an appropriate arrhythmia are entered into the trial; both spontaneous and stimulation-induced episodes of arrhythmia may be included. After an observation period to establish stability of the tachycardia, the patient is administered one or more doses of the drug under study or the active or inactive control. Total response is determined by the proportion of episodes converted within a specified period. The maintenance of normal rhythm after conversion for some prespecified time can serve as a secondary endpoint.
The prevention of arrhythmia induction in an electrophysiologic study during drug therapy is rarely used as an endpoint in patients with supraventricular arrhythmias for several reasons. First, radiofrequency ablation (RFA) has become the primary therapy for many supraventricular arrhythmias owing to its high success and low complication rates. The administration of a drug that blocks conduction in the target tissue during the study might interfere with the primary goal of the procedure. Second, the role of autonomic nervous system influences on arrhythmia initiation and maintenance may be profound, and in many cases, changes in autonomic tone can override drug effects.
Most of the common forms of PSVT and many cases of atrial flutter are now treated with catheter ablation as a first option when that modality is available; therefore only limited contemporary data are available about long-term drug therapy for common varieties of PSVT and atrial flutter. When placebo-controlled studies have been performed, they typically have used endpoints such as the total number of episodes and the time to first recurrence.
Paroxysmal Supraventricular Tachycardia
PSVT is a common arrhythmia with a prevalence of about 2.5 per 1000 adults. PSVT in the absence of structural heart disease can manifest at any age, but the first episode commonly occurs between age 12 and 30 years. In most patients, PSVT as a result of atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reentrant tachycardia (AVRT) is not causally associated with structural heart disease, although exceptions exist (e.g., Ebstein’s anomaly, familial preexcitation with cardiomyopathy). Atrial tachycardias may occur either in structurally normal or abnormal hearts. In normal patients, the physical examination during PSVT is significant mainly for the rapid heart rate. Prominent jugular venous pulsations, the “frog’s neck” finding, which are due to atrial contraction against closed AV valves, are characteristic of AVNRT. The patient’s history, physical examination, and ECG constitute an appropriate initial evaluation. Further diagnostic studies are indicated only if signs or symptoms that suggest structural heart disease are present. In patients with incessant tachycardia, the clinician should remember that a tachycardia-induced cardiomyopathy may develop that is completely reversible if the tachycardia is eliminated.
Mechanisms of Paroxysmal Supraventricular Tachycardia
Figure 19-1 illustrates the common forms of PSVT. The AV node sits in the triangle of Koch in the floor of the right atrium. Separate pathways, characterized by their conduction velocities as fast or slow, provide input into the AV node. If these pathways have different refractory periods, reentry using one pathway for anterograde conduction and one for retrograde conduction may occur. The P-wave position during AVNRT depends on the types of pathways used. In the most common form (slow pathway anterograde–fast pathway retrograde) the P wave is either not seen or is visible only in the terminal portion of the QRS ( Figure 19-2 ). If two slow pathways or fast anterograde and slow retrograde pathways form the circuit, the R-P′ interval will either be short or long, respectively. Although uncommon, AV block is possible during AVNRT if the block occurs distal to the turnaround point, where the pathways join.
In AVRT, an extranodal accessory pathway connects the atrium and ventricle. Accessory pathways may exhibit both anterograde and retrograde conduction, or they may show only antegrade (uncommon) or retrograde conduction. In the latter situation, the pathway is called a concealed pathway. When the pathway manifests anterograde conduction, ventricular preexcitation with a delta wave will be present on the surface ECG. A diagnosis of Wolff-Parkinson-White syndrome is made if the patient has PSVT. Accessory pathways usually manifest rapid AV conduction with no change in conduction velocity over a range of cycle lengths, but a minority of pathways may manifest longer conduction times at all rates. The most common form of AV reentry, termed orthodromic AVRT, uses the accessory pathway as the retrograde limb and the AV node–His as the anterograde limb, resulting in a narrow QRS ( Figure 19-3 ). Functional or fixed bundle branch block, a reversal of the circuit, termed antidromic AVRT, or the presence of two accessory pathways can lead to a wide QRS complex during PSVT owing to AV reentry. Accessory pathways can also conduct as passive bystanders during AVNRT or atrial tachycardias, but these patterns are less common. In AVRT the ventricle is an obligate part of the circuit; therefore AV block cannot occur.
Atrial tachycardia is the least common form of PSVT in normal individuals but may predominate in patients who have significant atrial scarring, especially those who have undergone earlier atrial surgery. Atrial tachycardias may be due to enhanced or triggered automaticity or to reentry. Because the AV node and ventricle are not required participants in the arrhythmia, AV block commonly occurs if there is a short atrial cycle length. The P-R and apparent R-P′ intervals depend on the response of the AV conduction system to the atrial rate. P-wave morphology is determined by the site of origin in the atrium. If the site of origin is within or involves the sinus node region, the terms sinus node reentrant or inappropriate sinus tachycardia are often applied.
Management of Acute Episodes of Paroxysmal Supraventricular Tachycardia
PSVT rarely is so poorly tolerated that it requires immediate termination with electrical cardioversion. Most episodes can be managed with physiologic maneuvers or drugs. The most common types of PSVT require intact one-to-one AV nodal conduction for continuation and are classified as AV nodal–dependent tachycardias. Because the refractory period of the AV node may be modified by vagal maneuvers and by many pharmacologic agents, and because prolongation of AV nodal refractoriness can lead to transient block, AV nodal conduction is the weak link targeted by most short-term therapies.
Many patients learn to terminate acute episodes of PSVT by using vagal maneuvers early during an episode. Valsalva is the most effective technique for adults, but carotid massage may also be effective. Facial immersion is the most reliable method for infants. Vagal maneuvers are less effective once a sympathetic response to PSVT has become established; therefore patients should try them soon after onset.
Oral antiarrhythmic drug tablets are not reliably absorbed during rapid PSVT, but some patients may respond to self-administration of crushed medications. In one small study, a combination of diltiazem (120 mg) plus propranolol (80 mg) was shown to be superior to both placebo and oral flecainide (approximately 3 mg/kg). Hypotension and bradycardia after termination are rare complications of this approach in otherwise healthy individuals.
Adenosine and the nondihydropyridine calcium antagonists, verapamil and diltiazem, are the intravenous (IV) drugs of choice for termination of PSVT. Adenosine is an endogenous purine nucleoside that slows AV nodal conduction and results in transient AV nodal block when administered during an episode of PSVT. Conduction in rapidly conducting accessory pathways is not affected by adenosine, but pathways with long refractory periods or slow conduction may exhibit block. Exogenous adenosine is cleared extremely rapidly from the circulation by cellular uptake and metabolism with an estimated half-life of less than 5 seconds. Adenosine effect is typically seen 15 to 30 seconds after rapid peripheral infusion as a first-pass phenomenon. Administration via a central line requires dose reduction. The effective dose range in adults is 2.5 to 25 mg. If no upper dosage limit is imposed, at least transient termination of AV node–dependent PSVT can be produced in essentially all patients. The recommended adult dosage is 6 mg followed if needed by a 12-mg dose. In pediatric patients, the dose range is 50 to 250 µg/kg using an upward dose titration. Because of the ultrashort duration of action, cumulative effects of sequential doses are not seen.
Minor side effects of transient dyspnea or chest pain are common with adenosine. Sinus arrest or bradycardia may occur but resolves quickly if appropriate upward dose titration is used. Atrial and ventricular premature beats are frequently seen with PSVT termination. A few patients with adenosine-induced polymorphic ventricular tachycardia (VT) and ventricular fibrillation have been reported. The majority of these patients had long baseline QT intervals during tachycardia and had long pauses during adenosine-induced AV block that led to bradycardia-dependent polymorphic VT. Adenosine shortens the atrial refractory period, and critically timed atrial ectopic beats may induce atrial fibrillation ( Figure 19-4 ). This may be a dangerous situation if the patient has an accessory pathway capable of rapid anterograde conduction, because adenosine may further shorten the effective refractory period of the pathway. Because adenosine is cleared so rapidly, reinitiation of PSVT after initial termination may occur. Repeat administration of the same dose of adenosine or substitution of a CCB is likely to be effective.
