American College of Cardiology

Blomström-Lundqvist ET AL., MANAGEMENT OF PATIENTS Supraventricular Arrhythmias
J Am Coll Cardiol 2003;42:1493–531

ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias

A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias)

V. SPECIFIC ARRHYTHMIAS

A. Sinus Tachyarrhythmias

Sinus tachycardia usually occurs in response to an appropriate physiological stimulus (eg, exercise) or to an excessive stimulus (eg, hyperthyroidism). Failure of the mechanisms that control the sinus rate may lead to an inappropriate sinus tachycardia. Excessive sinus tachycardia may also occur in response to upright posture (postural orthostatic tachycardia syndrome [POTS]). A re-entry mechanism may also occur within, or close to, the sinus node, resulting in so-called sinus node re-entrant tachycardia, which is also sometimes known as SA re-entry.

1. Physiological Sinus Tachycardia

The normally innervated sinus node generates an impulse approximately 60 to 90 times per minute and responds to autonomic influences. Nevertheless, the sinus node is a versatile structure and is influenced by many other factors, including hypoxia, acidosis, stretch, temperature, and hormones (eg, tri-iodothyronine, serotonin).

a. Definition

Sinus tachycardia is defined as an increase in sinus rate to greater than 100 bpm in keeping with the level of physical, emotional, pathological, or pharmacologic stress. Pathological causes of sinus tachycardia include pyrexia, hypovolemia, or anemia, which may result from infections, malignancies, myocardial ischemia, congestive cardiac failure, pulmonary emboli, shock, and thyrotoxicosis. Drugs that induce sinus tachycardia include stimulants (eg, caffeine, alcohol, nicotine); prescribed compounds (eg, salbutamol, aminophylline, atropine, catecholamines); and certain recreational/illicit drugs (eg, amphetamines, cocaine, “ecstasy,” cannabis) (100). Anticancer treatments, in particular anthracycline compounds such as doxorubicin (or Adriamycin) and daunorubicin, can also trigger sinus tachycardia as part of the acute cardiotoxic response that is predominantly catecholamine/histamine induced (101) or part of a late cardiotoxic response (102,103). Sinus tachycardia may signal severe underlying pathologies and often requires comprehensive evaluation. Atrial and sinus tachycardias may be difficult to differentiate.

b. Mechanism

Sinus tachycardia results from physiological influences on individual pacemaker cells and from an anatomical shift in the site of origin of atrial depolarization superiorly within the sinus node (104). If current activity is one of several mechanisms by which phase 4 diastolic depolarization is hastened, therefore increasing the heart rate, then an increase in cyclic adenosine monophosphate triggers opening of ion channels responsible for the pacemaker, or funny current (if), resulting in a faster heart rate due to more rapid attainment of threshold potential.

c. Diagnosis

In normal sinus rhythm, the P wave on a 12-lead ECG is positive in leads I, II, and aVF and negative in aVR. Its axis in the frontal plane lies between 0 and +90; in the horizontal plane, it is directed anteriorly and slightly leftward and can, therefore, be negative in leads V1 and V2 but positive in leads V3 to V6. The PR interval is normally between 120 ms and 200 ms (220 ms in the elderly). The P waves have a normal contour, but a larger amplitude may develop and the wave may become peaked (105). Sinus tachycardia is non- paroxysmal, thus differentiating it from re-entry.

d. Treatment

The mainstay in the management of sinus tachycardias primarily involves identifying the cause and either eliminating or treating it. However, beta blockade can be extremely useful and effective for physiological symptomatic sinus tachycardia triggered by emotional stress and other anxiety-related disorders (106-113); for prognostic benefit after myocardial infarction (114-117); for the symptomatic and prognostic benefits in certain other irreversible causes of sinus tachycardias, such as congestive cardiac failure (118-120); and for symptomatic thyrotoxicosis in combination with carbimazole or propylthiouracyl while these palliative agents take effect (121,122). Nondihydropyridine calcium-channel blockers, such as diltiazem or verapamil, may be of benefit in patients with symptomatic thyrotoxicosis, if beta blockade is contraindicated (123).

2. Inappropriate Sinus Tachycardia

a. Definition

Inappropriate sinus tachycardia is a persistent increase in resting heart rate or sinus rate unrelated to, or out of proportion with, the level of physical, emotional, pathological, or pharmacologic stress.

b. Mechanism

The underlying pathological basis for inappropriate sinus tachycardia is likely to be multifactorial, but two main mechanisms have been proposed:

1. Enhanced automaticity of the sinus node (125)
2. Abnormal autonomic regulation of the sinus node with excess sympathetic and reduced parasympathetic tone (126,127)

It is unclear whether these mechanisms are a direct result of impaired neural input into the sinus node or whether they represent an inherent abnormality within the sinus node itself

c. Presentation

A high proportion of patients with inappropriate sinus tachycardia are healthcare professionals, and approximately 90% are female (129). The mean age of presentation is 38 plus or minus 12 years. Although the predominant symptom at presentation is palpitations, symptoms such as chest pain, shortness of breath, dizziness, lightheadedness, and presyncope have also been reported. The degree of disability can vary tremendously, from totally asymptomatic patients identified during routine medical examination to individuals who are fully incapacitated. Clinical examination and routine investigations allow elimination of a secondary cause for the tachycardia but are generally not helpful in establishing the diagnosis.

d. Diagnosis

Inappropriate sinus tachycardia is diagnosed on the basis of invasive and noninvasive criteria (128,129):

1. The presence of a persistent sinus tachycardia (heart rate greater than 100 bpm) during the day with excessive rate increase in response to activity and nocturnal normalization of rate, as confirmed by a 24-hour Holter recording
2. The tachycardia (and symptoms) is nonparoxysmal
3. P-wave morphology and endocardial activation identical to sinus rhythm
4. Exclusion of a secondary systemic cause (eg, hyperthyroidism, pheochromocytoma, physical deconditioning)

e. Treatment

The treatment of inappropriate sinus tachycardia is predominantly symptom driven. The risk of tachycardia-induced cardiomyopathy (130) in untreated patients is unknown but likely to be small.

Although no randomized, double-blinded, placebo-controlled clinical trials exist, beta blockers may be useful and should be prescribed as first-line therapy in the majority of these patients. Anecdotal evidence suggests that nondihydropyridine calcium-channel blockers, such as verapamil and diltiazem, are also effective (131). Specific bradycardic agents (eg, If inhibitor ivabradine) may be valuable, but these agents are still under investigation (132).

Sinus node modification by catheter ablation remains a potentially important therapeutic option in the most refractory cases of inappropriate sinus tachycardia (133). Potential adverse effects include pericarditis, phrenic nerve injury, superior vena cava (SVC) syndrome, or need for permanent pacing. A number of case reports have recorded successful surgical excision (134,135) or radiofrequency (RF) ablation of the sinus node (136-138). There is also a case report of successful obliteration of the sinus node artery for the management of this disorder (139). The diagnosis of POTS (see Section V–A, 3) must be excluded before considering abla- tion. In a retrospective analysis of 29 cases undergoing sinus node modification for inappropriate sinus tachycardia (140), a 76% acute success rate (22 out of 29 cases) was reported. The long-term success rate has been reported to be 25% to 65%.

3. Postural Orthostatic Tachycardia Syndrome

Postural orthostatic tachycardia syndrome is part of a wide spectrum of disorders that exhibit autonomic dysfunction (142). These include severe orthostatic hypotension in the presence of autonomic neuropathy and vasovagal syncope in the absence of other evidence of autonomic dysfunction. Postural orthostatic tachycardia syndrome manifests as an excessive orthostatic tachycardia without significant orthostatic hypotension in those without overt autonomic neuropathy. It is associated with numerous other symptoms, such as exercise intolerance, palpitations, weakness, and lightheadedness; most of these symptoms are also autonomically mediated (143-145).

a. Definition

Postural orthostatic tachycardia syndrome is the diagnosis applied to individuals who present with orthostatic intolerance (ie, symptoms on standing that are relieved by recumbency) in the presence of a demonstrable exaggerated, persistent postural sinus tachycardia (greater than 30 bpm from baseline or greater than 120 bpm) within 10 minutes of an upright tilt in the absence of postural hypotension and any demonstrable autonomic neuropathy.

b. Mechanism

Many mechanisms have been proposed for POTS. These range from idiopathic hypovolemia (146) and reduced circulating blood volume (147) to splanchnic bed blood pooling (148,149) and reduced red cell mass resulting from an impaired erythropoietin response (150). There is little doubt that the etiology and pathophysiology of POTS is heterogeneous, although there are similar clinical characteristics (151). Two forms seem to predominate (152) The first is a central beta-hypersensitivity form in which the normal physiological baroreflex fails to terminate the tachycardia triggered by upright posture (153). In certain cases of this form of POTS, the basic abnormality responsible for the condition is a defective norepinephrine-transporter mechanism (154). This abnormality leads to a failure in the synaptic clearance of norepinephrine, resulting in an exaggerated sympathetic response to physiological stimuli. The second form of POTS, the so-called partial dysautonomic form, is seen in the majority of POTS patients. There appears to be a mild idiopathic peripheral autonomic neuropathy, wherein there is a failure of the peripheral vasculature to vasoconstrict appropriately during orthostatic stress, thereby resulting in an exaggerated tachycardia (145,155). This effect is likely to be due to partial sympathetic denervation, especially in the legs (156); arteries seem to be affected rather than veins (157). Emerging evidence suggests that there may be two further subgroups of this partial dysautonomic form-one that is centrally mediated and the other peripheral (158). There is, however, also evidence of autoantibodies to ganglionic nicotinic acetylcholine receptors in certain cases (159), and intrinsic sinus node abnormalities in others (160). In almost half of the cases of POTS, there may be a preceding viral illness; these patients have a better long-term prognosis than others (145,161).

c. Presentation

Patients with POTS present with palpitations, severe fatigue, exercise intolerance, presyncope, tremor, bowel hypomotility, and dizziness or lightheadedness. A significant proportion of patients also complain that they always feel cold and are unable to tolerate extreme heat (152). Furthermore, patients with POTS may be diagnosed as suffering from chronic fatigue syndrome (162). In fact, there appears to be a considerable overlap between the two ailments (163,164).

d. Diagnosis

1. Head-upright tilt testing exhibits an increase in heart rate of at least 30 bpm in the first 5 to 10 minutes or achieves heart rates well in excess of 120 bpm

2. Absence of orthostatic hypotension

3. Absence of a known cause of autonomic neuropathy

4. Provocation of orthostatic symptoms (165) Patients with the central beta hypersensitivity form of POTS tend to have high serum catecholamine levels (ie, nor- epinephrine greater than 600 ng/ml) and exhibit an excessive increase in supine heart rate in response to a low-dose isoproterenol infusion (heart rate increase greater than 30 bpm with a 1-mcg/min infusion) (152).

e. Treatment

As POTS becomes better understood and appropriately classified, management will be targeted according to the underlying cause. At present, there is little controlled data on long-term efficacy of therapy. Nevertheless, for the vast majority of patients, the management of POTS is medical. The use of ablative procedures involving the sinus node has been shown to worsen the symptoms. In one study, a group of seven patients with symptoms of POTS demonstrated that, although sinus node modification resulted in a reduction in the basal heart rate in five out of the seven patients, their symptoms persisted and in some cases worsened (142). In fact, four out of the five cases required insertion of a perma- nent pacemaker. The medical management of POTS can be divided into nonpharmacologic and pharmacologic.

NONPHARMACOLOGIC. The mainstay of nonpharmacologic treatment for all patients with POTS is volume expansion. All patients need five to eight 8-ounce (240 ml) glasses of fluids daily and a high-salt diet (10 to 15 grams daily) (161). Sleeping with the head of the bed elevated four inches (10 to 16 cm) (166,167) increases vasopressin secretion and expands plasma volume. Resistance training combined with the use of physical countermaneuvers has also been recommended (167). Radiolabeled erythrocytes have been used to demonstrate significant lower limb venous pooling in a range of patients with orthostatic intolerance (168). This study also demonstrated that heart rates could be returned to normal and symptoms could be relieved by inflation of military anti- shock trousers (MAST) to 45 mm Hg while patients were upright (168). The use of thigh-length compression stockings is, therefore, advocated in POTS patients. Anke pressure should be at least 30 mm Hg (152).

PHARMACOLOGIC. No single agent is appropriate for all cases of POTS, and combination therapy may often be necessary. The agent of choice will depend on the nature of the orthostatic intolerance and the tolerability of the agent. Beta blockers can be effective in the central beta-hypersensitive and in the partial dysautonomic forms of POTS because of unopposed alpha-receptor–mediated increase in peripheral vascular resistance (161,169). Fludrocortisone with or without bisoprolol has also been shown to improve symptoms in patients in whom idiopathic hypovolemia is present (169,170), but this requires high salt intake and regular monitoring of plasma potassium levels. Fludrocortisone has also been effectively combined with sleeping in the head-up tilt position (166). Centrally acting (eg, methylphenidate, clonidine) or peripherally acting agents (eg, midodrine) have also been effectively used (171,172). Phenobarbital has also been successfully used for the hyperadrenergic form of POTS but with the potential hazard of dependence (173). Disturbances in central serotonin production and regulation have also been implicated in the pathogenesis of POTS, and serotonin-specific uptake inhibitors have been used with some effect (174). The advantage of peripheral agents is that they are free of the centrally induced undesired effects. Octreotide, a predominantly splanchnic vasoconstrictor, has been successfully used, indicating that the splanchnic bed may also be an important site for blood pooling (175). In the most refractory cases, erythropoietin may be tried. Erythropoietin not only increases red cell mass but also has vasoconstrictor properties that may benefit certain patients. However, the evidence suggests that the patients most likely to respond to this therapy are those with orthostatic hypotension and not orthostatic tachycardia (150,176).

4. Sinus Node Re-entry Tachycardia

Although sinus node re-entry tachycardia was conceptualized as early as 1943 (177), it was only first demonstrated in the rabbit heart in 1968 (178). The phenomenon was first demonstrated during an electrophysiological study in a patient in 1985 (179).

a. Definition

Sinus node re-entry tachycardias arise from re-entrant circuits involving the sinus node's production of paroxysmal, often nonsustained bursts of tachycardia with P waves that are similar, if not identical, to those in sinus rhythm. They are usually triggered and terminated abruptly by an atrial premature beat.

b. Mechanism

Heterogeneity of conduction within the sinus node provides a substrate for re-entry (180,181), but it is still not known whether the re-entry circuit is isolated within the sinus node itself, whether perisinus atrial tissue is necessary, or whether re-entry around a portion of the crista terminalis is responsi- ble. However, the fact that this arrhythmia, like AVNRT, responds to vagal maneuvers and adenosine suggests that sinus node tissue is involved in the re-entrant circuit (182).

c. Presentation

The incidence of sinus node re-entry tachycardia in patients undergoing electrophysiological study for SVT ranges between 1.8 and 16.9% (183) and up to 27% for those with focal AT (184). Contrary to popular belief, there is a high incidence of underlying organic heart disease in patients with sinus node re-entry tachycardia (185). Patients present with symptoms of palpitations, lightheadedness, and presyncope. Syncope is extremely rare, as the rates of the tachycardia are rarely higher than 180 bpm. An important clue for diagnosis is the paroxysmal nature of the attacks.

d. Diagnosis

Sinus node re-entry tachycardia is diagnosed on the basis of invasive and noninvasive criteria (128). Clinically, the following features are highly suggestive of this arrhythmia:

1. The tachycardia and its associated symptoms are paroxysmal.

2. P-wave morphology is identical to sinus rhythm with the vector directed from superior to inferior and from right to left.

3. Endocardial atrial activation is in a high-to-low and right-to-left pattern, with an activation sequence similar to that of sinus rhythm.

4. Induction and/or termination of the arrhythmia occurs with premature atrial stimuli.

5. Termination occurs with vagal maneuvers or adenosine.

6. Induction of the arrhythmia is independent of atrial or AV-nodal conduction time.

e. Treatment

There have been no controlled trials of drug prophylaxis involving patients with sinus node re-entrant tachycardia. Clinically suspected cases of symptomatic sinus node re- entrant tachycardia may respond to vagal maneuvers, adenosine, amiodarone, beta blockers, nondihydropyridine calcium-channel blockers, or even digoxin. Patients whose tachyarrhythmias are well tolerated and easily controlled by vagal maneuvers and/or drug therapy should not be considered for electrophysiological studies (89). Electro- physiological studies are indicated for patients with frequent or poorly tolerated episodes of tachycardia that do not adequately respond to drug therapy and for patients in whom the exact nature of the tachycardia is uncertain and for whom electrophysiological studies would aid appropriate therapy. Radiofrequency catheter ablation of persistent sinus node re- entry tachycardias identified through electrophysiological study is generally successful (183,184,186-188).

B. Atrioventricular Nodal Reciprocating Tachycardia

1. Definitions and Clinical Features

Atrioventricular nodal reciprocating tachycardia is the most common form of PSVT. It is more prevalent in females; is associated with palpitations, dizziness, and neck pulsations; and is not usually associated with structural heart disease. Rates of tachycardia are often between 140 and 250 per minute.

Although the re-entrant circuit was initially thought to be confined to the compact AV node, a more contemporary view recognizes the usual participation of perinodal atrial tissue as the most common component of the re-entrant circuit (189). However, it has been shown convincingly that AVNRT may persist without participation of atrial tissue. Atrioventricular nodal reciprocating tachycardia involves reciprocation between two functionally and anatomically distinct pathways (190). In most cases, the fast pathway appears to be located near the apex of Koch’s triangle. This triangle is bounded by the tendon of Tadaro superiorly, and the tricuspid annulus is the base. The slow pathway extends inferoposterior to the compact AV-node tissue and stretches along the septal margin of the tricuspid annulus at the level of, or slightly superior to, the coronary sinus.

During typical AVNRT, the fast pathway serves as the retrograde limb of the circuit, whereas the slow pathway is the anterograde limb (ie, slow-fast AV-node re-entry). After conduction through the slow pathway to the His bundle and ventricle, brisk conduction back to the atrium over the fast pathway results in inscription of the shorter duration (40 ms) P wave during or close to the QRS complex (less than or equal to 70 ms) (Fig. 4) often with a pseudo-r´ in lead V1 (see Fig. 3). Less commonly (approximately 5 to 10%), the tachycardia circuit is reversed such that conduction proceeds by an anterograde route over the fast pathway and by a retrograde route over the slow pathway (ie, fast-slow AV-node re-entry, or atypical AVNRT) producing a long R-P tachycardia (ie, atypical AVNRT) (191), but other circuits may also be involved. The P wave, negative in leads III and aVF, is inscribed prior to the QRS. Infrequently, both limbs of the tachycardia circuit are composed of slowly conducting tissue (ie, slow-slow AV-node re-entry), and the P wave is inscribed after the QRS (ie, RP interval greater than or equal to 70 ms).

2. Acute Treatment

Acute evaluation and treatment of the patient with PSVT are discussed in Sections IV–A and IV–B.

3. Long-Term Pharmacologic Therapy

In patients with common, recurrent sustained episodes of AVNRT who prefer long-term oral therapy instead of catheter ablation, a spectrum of antiarrhythmic agents is available. Standard therapy includes nondihydropyridine calcium-channel blockers, beta blockers, and digoxin (192,193). In patients without structural heart disease who do not respond to AV-nodal–blocking agents, the class Ic drugs flecainide and propafenone have become the preferred choice (194-197). In most cases, class III drugs, such as sotalol or amiodarone, are unnecessary (198,199). Class Ia drugs, such as quinidine, procainamide, and disopyramide, have limited appeal due to their multidosing regimens, modest efficacy, and adverse and proarrhythmic effects (200- 202).

A major limitation in evaluating antiarrhythmic agents for treating AVNRT is the general absence of large multicenter, randomized, placebo-controlled studies. The diagnosis of the rhythm disturbance is often on the basis of the 12-lead ECG, but the correct diagnosis of AVNRT can be reliably assured only when confirmed by intracardiac recordings, which have, by necessity, limited the number of patients and centers willing to participate in studies. As a result, some of the information that follows is derived from extrapolation of data from studies in patients with PSVT, where AVNRT is not differentiated from AVRT.

a. Prophylactic Pharmacologic Therapy

CALCIUM-CHANNEL BLOCKERS,BETA BLOCKERS, AND DIGOXIN. Comments regarding the long-term efficacy of calcium-channel blockers, beta blockers, and digoxin taken orally in the management of AVNRT are limited by the small number of randomized patients studied. A small (11 patients), randomized, double-blinded, placebo-controlled trial showed that verapamil taken orally decreases the number and duration of both patient-reported and electrophysiologically-recorded episodes (203). A similar finding was demonstrated with doses of 360 to 480 mg/day with a trend toward greater effect with higher doses; however, the study was underpowered to detect a modest difference (204).

Oral digoxin (0.375 mg/day), verapamil (480 mg/day), and propranolol (240 mg/day) showed similar efficacy in 11 patients in a randomized, double-blinded, crossover study. There was no difference among the drugs with respect to frequency or duration of PSVT (192).

CLASS I DRUGS. The data showing efficacy of procainamide, quinidine, and disopyramide are from the older literature and are derived from small studies. These drugs are rarely used for treating AVNRT today (200-202).

Long-term benefits of oral flecainide in AVNRT were initially shown in an open-labeled study. At doses between 200 and 300 mg/day, flecainide completely suppressed episodes in 65% of patients (195). Several double-blinded, placebo- controlled trials have confirmed the efficacy of flecainide for prevention of recurrences (194,205). Events are reduced when compared with placebo, with an increase in the median time to the first recurrence and a greater interval between attacks. Open-labeled, long-term studies suggest excellent chronic tolerance and safety. In patients without structural heart disease, 7.6% discontinued the drug due to a suboptimal clinical response, and 5% discontinued it because of noncardiac (usually central nervous system) side effects (206). Class Ic agents (ie, flecainide and propafenone) are contraindicated for patients with structural heart disease. Moreover, class Ic drugs are often combined with beta- blocking agents to enhance efficacy and reduce the risk of one-to-one conduction over the AV node if atrial flutter occurs.

Flecainide appears to have greater long-term efficacy than verapamil. Although both drugs (median doses 200 mg/day and 240 mg/day, respectively) demonstrated an equivalent reduction in the frequency of episodes, 30% of patients had complete suppression of all symptomatic episodes with flecainide, whereas 13% had complete suppression with verapamil (207). Discontinuation rates due to adverse effects were equivalent, 19% and 24%, respectively. Propafenone is also an effective drug for prophylaxis of AVNRT. In a double-blinded, placebo-controlled trial, in which time to treatment failure was analyzed, the RR of treatment failure for placebo versus propafenone was 6.8 (208). A single-center, randomized, double-blinded, placebo- controlled study showed that propafenone (300 mg taken three times per day) reduces the recurrence rate to one fifth of that of placebo (197).

CLASS III DRUGS. Limited prospective data are available for use of class III drugs (eg, amiodarone, sotalol, dofetilide). Although many have been used effectively to prevent recurrences, routine use should be avoided due to their toxicities, including proarrhythmia (ie, torsades de pointes). A placebo- controlled trial found sotalol to be superior to placebo in prolonging time to recurrence of PSVT (199). With regard to dofetilide, a multicenter, randomized, placebo-controlled study showed that patients with PSVT had a 50% probability of complete symptomatic suppression with dofetilide over a 6-month follow up (500 mcg taken twice per day), whereas the probability of suppression in the control group was 6% (P less than 0.001). There were no proarrhythmic events (198). In this study, dofetilide was shown to be as effective as propafenone (150 mg taken three times per day).

There is a paucity of data regarding the effects of amiodarone on AVNRT (209). In one open-labeled study in the electrophysiology laboratory, IV amiodarone (5 mg/kg over 5 minutes) terminated tachycardia in seven out of nine patients. Treatment with oral amiodarone (maintenance dose 200 to 400 mg/day) for 66 plus or minus 24 days prevented recurrence and inducibility in all patients, with its predominant effect being the depression of conduction in the retrograde fast pathway (210). Of note, amiodarone has been shown to be safe in structural heart disease, particularly LV dysfunction.

b. Single-Dose Oral Therapy (Pill-in-the-Pocket)

Single-dose therapy refers to administration of a drug only during an episode of tachycardia for the purpose of termination of the arrhythmia when vagal maneuvers alone are not effective. This approach is appropriate to consider for patients with infrequent episodes of AVNRT that are prolonged (ie, lasting hours) but yet well tolerated (211). This approach obviates exposure of patients to chronic and unnecessary therapy between their rare arrhythmic events. It necessitates the use of a drug that has a short time to take effect (ie, immediate-release preparations). Candidate patients should be free of significant LV dysfunction, sinus bradycardia, or pre-excitation.

A single oral dose of flecainide (approximately 3 mg/kg) has been reported to terminate acute episodes of AVNRT in adolescents and young adults without structural heart disease (196), although it offered no benefit compared with placebo in other studies (211). Single-dose oral therapy with diltiazem (120 mg) plus propranolol (80 mg) has been shown to be superior to both placebo and flecainide in sequential testing in 33 patients with PSVT in terms of conversion to sinus rhythm (211). Favorable results comparing diltiazem plus propranolol with placebo have also been reported by others (212). Hypotension and sinus bradycardia are rare complications.

Single-dose therapy with diltiazem plus propranolol is associated with a significant reduction in emergency room visits in appropriately selected patients (211).

4. Catheter Ablation

Radiofrequency ablation for AVNRT originated in the observation that surgical dissection in discrete regions of the perinodal area could interrupt fast- or slow-pathway conduction (213,214). This finding led to the development of percutaneous, catheter-based techniques designed to modify or eliminate fast-pathway conduction. Energy (initially DC and later RF) was applied in the region of the apex of Koch's triangle, along the superior aspect of the tricuspid annulus (215,216). Success with this technique was associated with prolongation of the PR interval (ie, first-degree AV block), elimination of retrograde fast-pathway conduction, and non- inducibility of AVNRT. Success rates for this technique are approximately 90%. The major procedural risk is significant, 5 to 10% risk of complete AV block caused by proximity of the fast pathway to the His bundle (217).

Targeting the slow pathway along the posteroseptal region of the tricuspid annulus markedly reduces the risk of heart block and is the preferred approach. A prospective, randomized comparison of the fast- and slow-pathway approaches demonstrates equivalent success rates (218). Advantages of slow-pathway ablation include a lower incidence of complete AV block (1 vs. 8%) and the absence of the hemodynamic consequences of marked prolongation of the PR interval. Hence, slow pathway ablation is always used initially and fast pathway ablation is considered only when slow pathway ablation fails. Mapping to target discrete “slow-pathway” potentials was proposed originally (219), but an anatomical approach targeting the region between the coronary sinus ostium and the tricuspid annulus is also effective. A randomized study comparing an anatomical versus “slow-pathway wed no difference in success, ?number of RF applications, duration of ablation or fluoroscopy, or complications (220). In the fast-slow form of AVNRT, the slow pathway can be targeted directly by mapping the atrial exit site during tachycardia. In the slow-slow form of AVNRT, the retrograde slow pathway is likely to be composed of tissue originating from an extension of the AV node along the left side of the interatrial septum. Earliest retrograde atrial activation can be successfully and safely ablated within the ostium of the coronary sinus (221).

The NASPE Prospective Cardiac Ablation Registry includ- ed 1197 patients who underwent AV-nodal modification for AVNRT. Success was achieved in 96.1%, and the only significant complication was a 1% incidence of second-degree or third-degree AV block (222). These data have been confirmed by others (223). Atrioventricular block may complicate slow-pathway ablation due to posterior displacement of the fast pathway, superior displacement of the slow pathway (and coronary sinus), or inadvertent anterior displacement of the catheter during RF application. Pre-existing first-degree AV block does not appear to increase appreciably the risk of developing complete AV block (224), although caution is advised. The recurrence rate after ablation is approximately 3 to 7% (223,225,226).

Ablation of the slow pathway may be performed in patients with documented SVT (which is morphologically consistent with AVNRT) but in whom only dual AV-nodal physiology (but not tachycardia) is demonstrated during electrophysiological study (227). Because arrhythmia induction is not an available endpoint for successful ablation in this circumstance, the surrogate endpoint of an accelerated junctional rhythm during ablation is a good indication of slow-pathway ablation.

Slow-pathway ablation may be considered at the discretion of the physician when sustained (greater than 30 seconds) AVNRT is induced incidentally during an ablation procedure directed at a different clinical tachycardia.

Indications for ablation depend on clinical judgment and patient preference. Factors that contribute to the therapeutic decision include the frequency and duration of tachycardia, tolerance of symptoms, effectiveness and tolerance of antiar- rhythmic drugs, need for lifelong drug therapy, and the presence of concomitant structural heart disease. Catheter ablation has become the preferred therapy, compared with long- term pharmacologic therapy, for management of patients with AVNRT. The decision to ablate or proceed with drug therapy as initial therapy is, however, often patient specific, related to lifestyle issues (eg, planned pregnancy, competitive athlete, recreational pilot), affected by individual inclinations or aversions with regard to an invasive procedure or the chronicity of drug therapy, and influenced by the availability of an experienced center for ablation. Because drug efficacy is in the range of 30 to 50%, catheter ablation may be offered as first-line therapy for patients with frequent episodes of tachycardia. Patients considering RF ablation must be willing to accept the risk, albeit low, of AV block and pacemaker implantation.

C. Focal and Nonparoxysmal Junctional Tachycardia

1. Focal Junctional Tachycardia

a. Definition

Abnormally rapid discharges from the junctional region have been designated by a number of terms, each of which has deficiencies. For example, some refer to these disorders as “junctional ectopic tachycardia.” The problem with this term is redundancy because all pacemakers outside the sinus node are in fact ectopic. The term “automatic junctional tachycardia” suggests that the dominant mechanism is abnormal automaticity; however, mechanisms other than abnormal automaticity may be operative. The writing committee believes it reasonable to designate these arrhythmias as focal junctional tachycardia, which has a neutral connotation with regard to arrhythmic mechanism.

b. Diagnoses

The unifying feature of focal junctional tachycardias is their origin from the AV node or His bundle. This site of arrhythmia origin results in varied ECG manifestations because the arrhythmia requires participation of neither the atrium nor the ventricle for its propagation. The ECG features of focal junctional tachycardia include heart rates of 110 to 250 bpm and a narrow complex or typical BBB conduction pattern. Atrioventricular dissociation is often present (Fig. 10), although one-to-one retrograde conduction may be transiently observed. On occasion, the junctional rhythm is quite erratic, suggesting AF. Finally, isolated, concealed junctional extrasystoles that fail to conduct to the ventricles may produce episodic AV block by rendering the AV node intermit- tently refractory. During electrophysiological study, each ventricular depolarization is preceded by a His bundle deflection (228,229). The precise electrophysiological mechanism of this arrhythmia is thought to be either abnormal automaticity or triggered activity based on its response to beta-adrenergic stimulation and calcium-channel blockade (230,231).

c. Clinical Features

Focal junctional tachycardia, also known as automatic or paroxysmal junctional tachycardia, is a very uncommon arrhythmia. It is rare in the pediatric population and even less common in adults. Under the common umbrella of “focal junctional tachycardia” are several distinct clinical syndromes. The most prevalent among these, so-called “congenital junctional ectopic tachycardia” and “postoperative junctional ectopic tachycardia,” occur exclusively in pediatric patients and are, therefore, outside of the scope of this document.

Focal junctional tachycardia usually presents in young adulthood. It has been speculated that this form of arrhythmia is an adult extension of the pediatric disorder commonly termed “congenital junctional ectopic tachycardia.” If this is the case, then it appears to be more benign than is the pediatric form. This arrhythmia is usually exercise or stress related and may be found in patients with structurally normal hearts or in patients with congenital abnormalities, such as atrial or ventricular septal defects (230). The patients are often quite symptomatic and, if untreated, may develop heart failure, particularly if the tachycardia is incessant.

d. Management

Relatively little information is available about the response of rapid focal junctional tachycardia to suppressive drug therapy. Patients typically show some responsiveness to beta blockade. The tachycardia can be slowed or terminated with IV flecainide and shows some positive response to long-term oral therapy (232,233). Drug therapy is only variably successful, and ablative techniques have been introduced to cure tachycardia. Catheter ablation can be curative by destroying the foci adjacent to the AV node, but the procedure appears to be associated with risk (5 to 10%) of AV block (234-236). In one series, 17 patients with focal junctional tachycardia were referred for electrophysiological testing and possible catheter ablation. Ten of 11 patients undergoing RF catheter ablation in this series had acute tachycardia elimination. Eight patients remained symptom free during follow-up (228). The related pediatric disorder has been successfully treated with propafenone (237), sotalol (238), and amiodarone (239,240), although the latter is limited by its slow onset of action.

2. Nonparoxysmal Junctional Tachycardia

a. Definition and Clinical Features

Nonparoxysmal junctional tachycardia is a benign arrhythmia that is characterized by a narrow complex tachycardia with rates of 70 to 120 bpm. The arrhythmia mechanism is thought to be enhanced automaticity arising from a high junctional focus (68) or in response to a triggered mechanism (241). It shows a typical “warm-up” and “cool-down” pattern and cannot be terminated by pacing maneuvers. The most important feature about this tachycardia is that it may be a marker for a serious underlying condition, such as digitalis toxicity (242), postcardiac surgery, hypokalemia, or myocardial ischemia. Other associated conditions include chronic obstructive lung disease with hypoxia, and inflammatory myocarditis. Unlike the more rapid form of focal junctional tachycardia, there is commonly one-to-one AV association. In some cases, particularly in the setting of digitalis toxicity, anterograde AV-nodal Wenckebach conduction block may be observed (241,243).

The diagnosis must be differentiated from other types of narrow complex tachycardia, including AT, AVNRT, and AVRT. Usually, the clinical setting in which the arrhythmia presents and the ECG findings allow the clinician to ascertain the arrhythmia mechanism. However, in some cases, the mechanism may be determined only with invasive electrophysiological testing.

b. Management

The mainstay of managing nonparoxysmal junctional tachycardia is to correct the underlying abnormality. Withholding digitalis when junctional tachycardia is the only clinical manifestation of toxicity is usually adequate. However, if ventricular arrhythmias or high-grade heart block are observed, then treatment with digitalis-binding agents may be indicated. It is not unusual for automatic activity from the AV node to exceed the sinus rate, leading to loss of AV synchrony. This should be regarded as a physiological condition, and no specific therapy is indicated. Persisting junctional tachycardia may be suppressed by beta blockers or calcium- channel blockers (68). In rare cases, the emergence of a junctional rhythm is the result of sinus node dysfunction. Sympathetic stimulation of the AV-junction automaticity can lead to an AV-junctional rhythm that supersedes the sinus rhythm. In these cases, symptoms mimicking “pacemaker syndrome” may occur due to retrograde conduction from the AV junction to the atrium and resultant atrial contraction against closed AV valves, resulting in cannon A waves and possible hypotension. Atrial pacing is an effective treatment for this condition.

D. Atrioventicular Reciprocating Tachycardia (Extra Nodal Accessory Pathways)

Typical accessory pathways are extra nodal pathways that connect the myocardium of the atrium and the ventricle across the AV groove. Delta waves detectable on an ECG have been reported to be present in 0.15 to 0.25% of the general population (246,247). Pathway conduction may be intermittent. A higher prevalence of 0.55% has been reported in first-degree relatives of patients with accessory pathways (248). Accessory pathways can be classified on the basis of their location along the mitral or tricuspid annulus; type of conduction (decremental [ie, progressive delay in accessory pathway conduction in response to increased paced rates] or nondecremental); and whether they are capable of anterograde conduction, retrograde conduction, or both. Accessory pathways usually exhibit rapid, nondecremental conduction, similar to that present in normal His-Purkinje tissue and atrial or ventricular myocardium. Approximately 8% of accessory pathways display decremental anterograde or retrograde conduction (249). The term “permanent form of junctional reciprocating tachycardia” is used to refer to a rare clinical syndrome involving a slowly conducting, concealed, usually posteroseptal (inferoseptal) accessory pathway. This syndrome is characterized by an incessant SVT, usually with negative P waves in leads II, III, and aVF and a long RP interval (RP greater than PR).

Accessory pathways that are capable of only retrograde conduction are referred to as “concealed,” whereas those capable of anterograde conduction are “manifest,” demonstrating pre-excitation on a standard ECG. The degree of pre- excitation is determined by the relative conduction to the ventricle over the AV node-His bundle axis versus the accessory pathway. In some patients, anterograde conduction is apparent only with pacing close to the atrial insertion site, as, for example, for left-lateral-located pathways. Manifest accessory pathways usually conduct in both anterograde and retrograde directions (250). Those that conduct in the antero- grade direction only are uncommon, whereas those that conduct in the retrograde direction are common.

The diagnosis of WPW syndrome is reserved for patients who have both pre-excitation and tachyarrhythmias. Among patients with WPW syndrome, AVRT is the most common arrhythmia, accounting for 95% of re-entrant tachycardias that occur in patients with an accessory pathway.

Atrioventricular re-entry tachycardia is further subclassified into orthodromic and antidromic AVRT. During orthodromic AVRT, the re-entrant impulse conducts over the AV node and the specialized conduction system from the atrium to the ventricle and utilizes the accessory pathway for conduction from the ventricle to the atrium. During antidromic AVRT, the re-entrant impulse travels in the reverse direction, with anterograde conduction from the atrium to the ventricle occurring via the accessory pathway and retrograde conduction over the AV node or a second accessory pathway. Antidromic AVRT occurs in only 5 to 10% of patients with WPW syndrome. Pre-excited tachycardias can also occur in patients with AT, atrial flutter, AF, or AVNRT, with the accessory pathway acting as a bystander (ie, not a critical part of the tachycardia circuit). Atrial fibrillation is a potentially life-threatening arrhythmia in patients with WPW syndrome. If an accessory pathway has a short anterograde refractory period, then rapid repetitive conduction to the ventricles during AF can result in a rapid ventricular response with subsequent degeneration to VF (251-253). It has been estimated that one third of patients with WPW syndrome also have AF (254). Accessory pathways appear to play a pathophysiological role in the development of AF in these patients, as most are young and do not have structural heart disease. Rapid AVRT may play a role in initiating AF in these patients. Surgical or catheter ablation of accessory pathways usually eliminates AF as well as AVRT (255,256).

1. Sudden Death in WPW Syndrome and Risk Stratification

The incidence of sudden cardiac death in patients with WPW syndrome has been estimated to range from 0.15 to 0.39% (253) over 3- to 10-year follow-up (257,258). It is unusual for cardiac arrest to be the first symptomatic manifestation of WPW syndrome (253). Conversely, in about half of the cardiac arrest cases in WPW patients, it is the first manifestation of WPW syndrome (258). Given the potential for AF among patients with WPW syndrome and the concern about sudden cardiac death resulting from rapid pre-excited AF, even the low annual incidence of sudden death among patients with WPW syndrome is of note and supports the concept of liberal indications for catheter ablation.

Studies of WPW syndrome patients who have experienced cardiac arrest have retrospectively identified a number of markers that identify patients at increased risk (251,258- 262). These include 1) a shortest pre-excited R-R interval less than 250 ms during spontaneous or induced AF, 2) a history of symptomatic tachycardia, 3) multiple accessory pathways, and 4) Ebstein's anomaly. A high incidence of sudden death has been reported in familial WPW syndrome. This familial presentation is, however, exceedingly rare (263). Several noninvasive and invasive tests have been proposed as useful in risk-stratifying patients for sudden death risk. The detection of intermittent pre-excitation, which is characterized by an abrupt loss of the delta wave and normalization of the QRS complex, is evidence that an accessory pathway has a relatively long refractory period and is unlikely to precipitate VF (264). The loss of pre-excitation after administration of the antiarrhythmic drug procainamide has also been used to indicate a low-risk subgroup (262). Noninvasive tests are considered inferior to invasive electrophysiological assessment for risk of sudden cardiac death. For this reason, non- invasive tests currently play little role in patient management.

2. Acute Treatment

The approach to acute evaluation and management during a sustained regular tachycardia is addressed in Sections IV–A and IV–B. The approach to acute termination of these arrhythmias generally differs from that used for long-term suppression and prevention of further episodes of SVT.

a. Special Considerations for Patients With Wide-Complex (Pre-excited) Tachycardias

In patients with antidromic tachycardia, drug treatment may be directed at the accessory pathway or at the AV node because both are critical components of the tachycardia circuit. Atrioventricular nodal–blocking drugs would, however, be ineffective in patients who have anterograde conduction over one pathway and retrograde conduction over a separate accessory pathway because the AV node is not involved in the circuit. Adenosine should be used with caution because it may produce AF with a rapid ventricular rate in pre-excited tachycardias. Ibutilide, procainamide, or flecainide, which are capable of slowing the conduction through the pathway, are preferred.

Pre-excited tachycardias occurring in patients with either AT or atrial flutter with a bystander accessory pathway may present with a one-to-one conduction over the pathway. Caution is advised against AV-nodal–blocking agents, which would obviously be ineffective in this situation. Antiarrhythmic drugs, which prevent rapid conduction through the bystander pathway, are preferable, even if they may not convert the atrial arrhythmia. Similarly, it is preferable to treat pre-excited AF by IV ibutilide, flecainide, or procainamide. Patients with AVNRT and pre-excited tachycardia with a bystander accessory pathway may respond to AV- nodal–blocking drugs, which are usually discouraged because of the risk of AV-nodal blockade and acceleration of ventricular rate if AF occurs.

3. Long-Term Pharmacologic Therapy

Antiarrhythmic drugs represent one therapeutic option for management of accessory pathway mediated-arrhythmias, but they have been increasingly replaced by catheter ablation. Antiarrhythmic drugs that primarily modify conduction through the AV node include digoxin, verapamil, beta blockers, adenosine, and diltiazem. Antiarrhythmic drugs that depress conduction across the accessory pathway include class I drugs, such as procainamide, disopyramide, propafenone, and flecainide, as well class III antiarrhythmic drugs, such as ibutilide, sotalol, and amiodarone.

a. Prophylactic Pharmacologic Therapy

There have been no controlled trials of drug prophylaxis involving patients with AVRT; however, a number of small, nonrandomized trials have been performed (each involving fewer than 50 patients), and they have reported the safety and efficacy of drug therapy for maintenance of sinus rhythm in patients with supraventricular arrhythmias. A subset of the patients in these studies had AVRT as their underlying arrhythmia. Available data do not allow a comparison of the efficacy of these drugs relative to one another. The drugs available to treat AVRT include any drug that alters either conduction through the AV node (eg, nondihydropyridine calcium-channel blockers, beta blockers, digoxin) or a drug that alters conduction through the atrium, ventricle, or accessory pathway (eg, class Ia, Ic, or III antiarrhythmic agents). The available data are outlined below. Of note is that no studies have examined the efficacy of chronic oral beta blockers in the treatment of AVRT and/or WPW syndrome. The absence of studies specifically examining the role of beta- blocker therapy in the treatment of WPW syndrome likely reflects the fact that catheter ablation is the therapy of choice for these patients. Despite the absence of data from clinical trials, chronic oral beta-blocker therapy may be used for treatment of patients with WPW syndrome, particularly if their accessory pathway has been demonstrated during electrophysiological testing to be incapable of rapid anterograde conduction.

PROPAFENONE. The largest published study that reported the efficacy of propafenone in adult patients involved 11 individuals. Propafenone resulted in anterograde conduction block in the accessory pathway in 4 of 9 patients and retrograde block in 3 of 11 patients. Atrioventricular re-entry tachycardia was rendered noninducible in 6 of 11 patients. During 9 plus or minus 6 months of follow-up, none of the 10 patients discharged on a combination of propafenone and a beta blocker experienced a recurrence. No major side effects were reported (265). Other small trials have evaluated the efficacy of propafenone in the treatment of AVRT in children (266-269). The largest of these involved 41 children. Chronic administration of propafenone was effective in 69%. Side effects occurred in 25% of these patients (248).

FLECAINIDE. A number of studies have examined the acute and long-term efficacy of oral and IV flecainide in the treatment of patients with AVRT. The largest of these studies involved 20 patients with AVRT (270). The oral administration of flecainide (200 to 300 mg/day) resulted in an inability to induce sustained tachycardia in 17 of these 20 patients. The electrophysiological effects of flecainide were partially reversed by administration of isoproterenol. During 15 plus or minus 7 months of follow-up on oral flecainide treatment, 3 patients developed a recurrence of tachycardia. Other studies have reported similar findings (271-276). The addition of a beta blocker results in greater efficacy, with greater than 90% of patients achieving abolition of symptomatic tachy- cardia (270,277). In addition to studies that specifically focused on patients with a known AVRT, several randomized trials have evaluated the efficacy of flecainide in the treatment of patients with PSVT of undetermined tachycardia mechanism. One study enrolled 34 patients with PSVT in a double-blinded, placebo-controlled trial with an 8-week crossover trial design (205). Flecainide was shown to be superior to placebo; 8 of the 34 patients had a recurrence during flecainide therapy, compared with 29 of 34 patients having a recurrence on placebo (205). Treatment with flecainide also increases the time to first symptomatic event and time to subsequent events.

SOTALOL. The efficacy of oral sotalol in the prevention of AVRT has been reported in a single study (278), which involved 17 patients with an accessory pathway. Fourteen of 15 patients with inducible sustained tachycardia during electrophysiological testing continued to have inducible tachycardia after administration of IV sotalol. Thirteen of the 16 patients who were discharged taking oral sotalol were free of symptomatic recurrences during a median of 36 months of follow-up (278).

AMIODARONE. Several studies have evaluated the efficacy of amiodarone in the treatment of patients with accessory pathway-mediated tachycardias (279-282). However, these studies do not demonstrate that amiodarone is superior to class Ic antiarrhythmic agents or sotalol. As a result of these findings, combined with the well-recognized organ toxicity associated with amiodarone and the high rate of discontinuation of this drug, amiodarone generally is not warranted for treatment of patients with accessory pathways. Exceptions are for patients with structural heart disease who are not thought to be candidates for catheter ablation.

VERAPAMIL. The efficacy of verapamil in the prevention of AVRT has been reported in a single study, which involved seven patients (283). Four of the 17 patients continued to have inducible AVRT during electrophysiological testing despite treatment with oral verapamil. Adequate follow-up data in these patients were not provided. Intravenous verapamil can precipitate hemodynamic deterioration during AF. Verapamil and diltiazem should not be used as the sole therapy for patients with accessory pathways that might be capable of rapid conduction during AF. This concern also applies to digoxin, which also should not be used in this situation.

OTHER DRUGS. No studies have been performed to determine the short- or long-term efficacy of procainamide or quinidine in the treatment of AVRT.

b. Single-Dose Oral Therapy (Pill-in-the-Pocket)

Some patients with infrequent episodes of tachycardia may be managed with the single-dose, “pill-in-the-pocket” approach: taking an antiarrhythmic drug only at the onset of a tachycardia episode (211). This approach to treatment is reserved for patients without pre-excitation and with uncommon and hemodynamically tolerated tachycardia. A recent study reported that 94% of induced PSVT episodes were terminated in the electrophysiology laboratory within 32 minutes plus or minus 22 minutes by administration of a combination of diltiazem (120 mg) plus propranolol (80 mg) (211). This treatment was successful in terminating PSVT within 2 hours during outpatient follow-up in 81% of patients. Another finding of this study was that flecainide, when given as a single dose for acute termination of PSVT, was significantly less effective than the combination of diltiazem and propranolol.

4. Catheter Ablation

Catheter ablation of accessory pathways is performed in conjunction with a diagnostic electrophysiological test. The purposes of the electrophysiological test are to confirm the presence of an accessory pathway, determine its conduction characteristics, and define its role in the patient’s clinical arrhythmia. Once the arrhythmia is localized, ablation is performed using a steerable ablation catheter. There have been no prospective, randomized clinical trials that have evaluated the safety and efficacy of catheter ablation of accessory pathways; however, the results of catheter ablation of accessory pathways have been reported in a large number of single-center trials (284-288), one multicenter trial (225), and several prospective registries (222,289,290). The initial efficacy of catheter ablation of accessory pathways is approximately 95% in most series (225,284-288). The success rate for catheter ablation of left free-wall accessory pathways is slightly higher than for catheter ablation of accessory path- ways in other locations. After an initially successful procedure, resolution of the inflammation or edema associated with the initial injury allows recurrence of accessory path- way conduction in approximately 5% of patients. Accessory pathways that recur can usually be successfully ablated during a second session. Complications associated with catheter ablation of accessory pathways result from radiation exposure, vascular access (eg, hematomas, deep venous thrombosis, arterial perforation, arteriovenous fistula, pneumothorax), catheter manipulation (eg, valvular damage, microemboli, perforation of the coronary sinus or myocardial wall, coronary artery dissection, thrombosis), or delivery of RF energy (eg, AV block, myocardial perforation, coronary artery spasm or occlusion, transient ischemic attacks, cerebrovascular accidents [284]) (222,225,285-290). The procedure-related mortality reported for catheter ablation of accessory pathways ranges from 0 to 0.2% (222,225,284-290). The voluntary Multicentre European Radiofrequency Survey (MERFS) reported data from 2222 patients who underwent catheter ablation of an accessory pathway (290). The overall complication rate was 4.4%, including 3 deaths (0.13%). The 1995 NASPE survey of 5427 patients who underwent catheter ablation of an accessory pathway reported a total of 99 (1.82%) significant complications, including 4 procedure- related deaths (0.08%) (289). Among the 500 patients who underwent catheter ablation of an accessory pathway as part of a prospective, multicenter clinical trial, there was 1 death (0.2%). This patient died of dissection of the left main coronary artery during an attempt at catheter ablation of a left free-wall accessory pathway (225). The most common major complications are complete AV block and cardiac tamponade. The incidence of inadvertent complete AV block ranges from 0.17 to 1.0%. Most occur in the setting of attempted ablation of septal accessory pathways located close to the AV junction. The frequency of cardiac tamponade varies between 0.13 and 1.1%.

5. Management of Patients With Asymptomatic Accessory Pathways

An ECG pattern of pre-excitation is occasionally encoun- tered in a subject who has no symptoms of arrhythmia. The role of electrophysiological testing and catheter ablation in asymptomatic patients with pre-excitation is controversial. One-third of asymptomatic individuals younger than 40 years of age when pre-excitation was identified eventually developed symptoms, whereas no patients in whom pre-excitation was first uncovered after the age of 40 years developed symptoms (253). Most patients with asymptomatic pre-excitation have a good prognosis; cardiac arrest is rarely the first manifestation of the disease (258). Prior studies have reported that approximately 20% of asymptomatic patients will demonstrate a rapid ventricular rate during AF induced during electrophysiological testing (257,291). However, during follow-up, very few patients developed symptomatic arrhythmias, and none of these individuals experienced a cardiac arrest (257,291). The positive predictive value of invasive electrophysiological testing is considered to be too low to justify routine use in asymptomatic patients (89,258,292). The decision to ablate pathways in individuals with high-risk occupations, such as school bus drivers, pilots, and scuba divers (292), is made on the basis of individual clinical considerations (89). These recommendations are likely to remain unchanged despite the results of a study that identified the results of electrophysiological testing as an important predictor of arrhythmic events in patients with asymptomatic pre-excitation (293). This study reported the follow-up of 212 patients with asymptomatic pre-excitation, all of whom underwent a baseline electrophysiological study. After 38 plus or minus 16 months of follow-up, 33 patients became symptomatic, and 3 of these patients experienced VF (resulting in death in 1 patient). The most important factor in predicting outcome was the inducibility of AVRT or AF during the baseline electrophysiological study. The presence of multiple accessory pathways was also identified as a predictor of future arrhythmic events. Of the 115 noninducible patients, only 3.4% developed a symptomatic supraventricular arrhythmia during follow-up. In contrast, 62% of the 47 inducible patients developed a symptomatic arrhythmia during follow-up (including the 3 patients who experienced VF). Patients with asymptomatic pre-excitation should be encouraged to seek medical expertise whenever arrhythmia- related symptoms occur. The potential value of electrophysiological testing in identifying high-risk patients who may benefit from catheter ablation must be balanced against the approximately 2% risk of a major complication associated with catheter ablation.

6. Summary of Management

In general, patients who have WPW syndrome (pre-excitation and symptoms), and particularly those with hemodynamic instability during their arrhythmia, should undergo catheter ablation as first-line therapy. Patients who experience uncommon, minimally symptomatic episodes of SVT who do not have evidence of pre-excitation can be treated with a variety of approaches. These patients with concealed accessory pathways can be managed as patients with AVNRT. Patient preference is always an important consideration. Catheter ablation has sufficient efficacy and low risk to be used for symptomatic patients, either as initial therapy or for patients experiencing side effects or arrhythmia recur- rence during drug therapy.

E. Focal Atrial Tachycardias

1. Definition and Clinical Presentation

Focal ATs are characterized by regular atrial activation from atrial areas with centrifugal spread (294). Focal ATs are usually manifest by atrial rates between 100 to 250 bpm and rarely at 300 bpm. Neither the sinus nor the AV node plays a role in the initiation or perpetuation of the tachycardia.

Nonsustained AT is frequently found on Holter recordings and seldom associated with symptoms. Sustained focal ATs are relatively rare; they are diagnosed in about 10 to 15% of patients referred for catheter ablation of SVT (295,296). The prevalence of focal AT has been calculated to be 0.34% in asymptomatic patients versus 0.46% in symptomatic patients (297). Focal ATs account for 10 to 23% of SVTs in children with normal hearts and a much higher percentage in children with congenital heart disease (298-302). The outlook of patients with focal AT is usually benign with the exception of incessant forms, which may lead to tachycardia-induced cardiomyopathy (303). In adults, focal AT can occur in the absence of cardiac disease, but it is often associated with underlying cardiac abnormalities (184,186,295,304-309). Atrial tachycardia, usually with AV block, may be produced by digitalis excess. This arrhythmia may be exacerbated by hypokalemia. Focal ATs may present as either paroxysmal or permanent tachycardias.

2. Diagnosis

In ATs, the P waves generally occur in the second half of the tachycardia cycle (see Section I–B). Therefore, in ATs, the P wave is frequently obscured by the T wave of the preceding QRS complex (Fig. 11). The PR interval is directly influenced by the tachycardia rate. The presence of AV block during tachycardia excludes AVRT and makes AVNRT very unlikely. During ATs, an isoelectric baseline is usually present between P waves, and it is used to distinguish AT from typical or atypical flutter (ie, saw-toothed or sinusoidal P- wave morphologies) (Figs. 12 and 13). However, in the presence of rapid rates and/or atrial conduction disturbances, P waves can be very wide without an isoelectric baseline, thus mimicking atrial flutter (294). It should also be emphasized that an ECG pattern of AT with discrete P waves and isoelectric baselines does not rule out macro–re-entrant tachycardia, especially if complex structural heart disease is present and/or there has been surgery for congenital heart disease. The diagnosis of AT can be established with certainty only by an electrophysiological study, including mapping and entrainment. Although definite localization of the source of AT requires intracardiac mapping, the P-wave morphology on the 12- lead surface ECG is different from sinus rhythm and may be useful for the determination of the site of origin of the focal AT (310). A positive or biphasic P-wave morphology in surface lead aVL and a negative or biphasic P wave in lead V1 favors a right atrial origin. A negative P wave in leads I or aVL, or a positive P wave in lead V1, favors a left atrial origin. In addition, negative P waves in the inferior leads are suggestive of a caudal origin, whereas a positive P wave in those leads suggests a cranial origin (310). Of interest, the P waves during sinus rhythm may be similar to those originating from the high crista terminalis or right superior pulmonary vein (311). The latter site will, however, often show a positive P wave in lead V1; hence, a change in P-wave polarity from sinus rhythm should arouse suspicion of a right superior pulmonary vein (PV) site. Multilead body surface potential mapping can be used to help localize the tachycardia site of origin (312).

3. Site of Origin and Mechanisms

Focal ATs are not randomly distributed but rather tend to cluster over certain anatomical zones. The majority of right- sided ATs originate along the crista terminalis from the SA node to the AV node (313,314), but other right atrial sites include the atrial septum, atrial appendages, Koch’s triangle, and the tricuspid annulus (314-321). Conversely, several venous structures have been demonstrated to have atrial myocardial extensions that may contain a tachycardia focus, such as SVC or coronary sinus ATs (322-325). In the left atrium, foci are often found in the pulmonary veins, in the atrial septum, or on the mitral annulus (326); in many cases, they are generators for AF.

Focal ATs are characterized by radial spread of activation from a focus, with endocardial activation not extending through the entire atrial cycle. The mechanism of focal discharge is difficult to ascertain by clinical methods. Available information suggests that focal activity can be caused by abnormal or enhanced automaticity, triggered activity (due to delayed afterdepolarization), or micro–re-entry (306,327, 328). Automatic ATs could arise from atrial foci in which spontaneous phase 4 depolarization occurs in cells with normal or abnormal resting membrane potentials. The progressive increase in atrial rate with tachycardia onset (ie, “warm- up”) and/or progressive decrease before tachycardia termination (ie, “cool- down”) are suggestive of an automatic mechanism (329). Typical automatic ATs may arise spontaneously or increase their rate of discharge in response to adrenergic stimulation. However, inducibility of re-entrant and triggered ATs is also enhanced by catecholamines (306,327- 331). Automatic ATs tend to be incessant, especially in children, whereas those attributed to triggered activity may be either incessant or paroxysmal (305,327-331).

a. Drug-Induced Atrial Tachycardia

The drug most commonly associated with induction of focal AT is digitalis. This drug-induced AT is usually characterized by development of AT with AV block; hence, the ventricular rate is not excessively rapid. Serum digoxin levels are helpful for diagnoses. Treatment consists of discontinuing the digitalis. In cases of persistent advanced AV block, digitalis- binding agents may be considered (332).

4. Treatment

The efficacy of antiarrhythmic drugs is poorly defined because the clinical definition of focal ATs is often not very rigorous. No large studies have been conducted to assess the effect of pharmacologic treatment on patients with focal ATs, but both paroxysmal and incessant ATs are reported to be difficult to treat medically.

a. Acute Treatment

On rare occasions, ATs may be terminated with vagal maneuvers. A significant proportion of ATs will terminate with administration of adenosine. Adenosine-sensitive ATs are usually focal in origin (306,315,316,333,334). Persistence of the tachycardia with AV block is also a common response to adenosine. In addition, ATs that are responsive to IV verapamil or beta blockers have been reported. It is conceivable that the mechanism of AT in these patients relates either to micro–re-entry, involving tissue with slow conduction, or to triggered activity. Class Ia or class Ic drugs may suppress automaticity or prolong action-potential duration and, hence, may be effective for some patients with AT (335).

For patients with automatic AT, atrial pacing (or adenosine) may result in transient postpacing slowing but no tachycardia termination. Similarly, DC cardioversion seldom terminates automatic ATs, but DC cardioversion may be successful for those in whom the tachycardia mechanism is micro–re-entry or triggered automaticity. An attempt at DC cardioversion should, therefore, be considered for patients with drug-resistant arrhythmia.

The usual acute therapy for AT consists of IV beta blockers or calcium-channel blockers for either termination, which is rare (336,337), or to achieve rate control through AV block, which is often difficult to achieve. Direct suppression of the tachycardia focus may be achieved by use of IV class Ia and Ic (338,339) or class III (340) (eg, sotalol, amiodarone) (209,336,341) agents. Intravenous class Ia or Ic agents may be taken by patients without cardiac failure, whereas IV amiodarone is preferred for those with poor ventricular function (303,342).

b. Long-Term Pharmacologic Therapy

The available studies pertaining to long-term pharmacologic therapy are observational, and there are problems in discerning whether the tachycardias were carefully differentiated from other mechanisms (ie, AVRT or AVNRT) or from other forms of AT. Review of the available data supports a recommendation for initial therapy with calcium-channel blockers or beta blockers because these agents may prove to be effective and have minimal side effects. If these drugs are unsuc- cessful, then class Ia (342), class Ic (flecainide [335,336,339, 343, 344)], propafenone [209,336]) in combination with an AV-nodal–blocking agent, or class III agents (sotalol and amiodarone) may be tried because they may prove to be effective. The potential benefit should be balanced with the potential risks of proarrhythmia and toxicity. Because ATs commonly occur in older patients and in the context of structural heart disease, class Ic agents should be used only after coronary artery disease is excluded.

c. Catheter Ablation

Several mapping techniques have been described to search for a possible ablation site for focal ATs. Regardless of whether the arrhythmia is due to abnormal automaticity, triggering, or micro–re-entry, focal AT is ablated by targeting the site of origin of the AT. Electrograms at such sites are often fractionated and prolonged, and the activation time is generally 30 to 100 ms before the onset of the P wave (184,186,304,305,307-309,345). High-density mapping techniques using an electroanatomical map can facilitate suc- cessful ablation.

Pooled data from 514 patients (346) who underwent catheter ablation for focal AT (301) showed an 86% success rate, with a recurrence rate of 8% (184,186,304,305,