PRACTICAL THERAPEUTICS ----

Drugs 42 (6): 974-983, 1991 00 12-6667/91/00 12-0974/$05.00/0 © Adis International Limited. All rights reserved. DRUl88

Cardiac Arrhythmias in Childhood Diagnostic Considerations and Treatment

Janette F. Strasburger Children's Memorial Hospital, Chicago, Illinois, USA

Contents 974 975 975

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Summary

Summary I. Diagnostic Techniques 1.1 Associated Conditions 2. Antiarrhythmic Drug Classifications 3. Treatment of Arrhythmias in Children Without Heart Disease 3.1 Supraventricular Tachycardia 3.2 Ventricular Tachycardia 4. Arrhythmias in Patients with Congenital Heart Disease or Cardiomyopathy 4.1 Ventricular Tachycardia 4.2 Primary Atrial Tachycardia 4.3 Junctional Ectopic Tachycardia 5. Conclusions

Determining safe and effective antiarrhythmic therapy in paediatric patients requires definition of the mechanism of the arrhythmia, determination of associated risk factors for treatment (such as the presence of congenital cardiac defects, myocarditis or cardiomyopathy), and monitoring for potential drug side effects related to the treatment. A number of modalities for noninvasive evaluation of arrhythmias is available, including ECG, 24-hour ambulatory Holter monitoring, and transtelephonic ECG transmission. Arrhythmias requiring medical treatment in children with normal cardiac anatomy and function include supraventricular tachycardia (SVT), ventricular tachycardia (VT) and primary atrial tachycardias. SVT is treated acutely with vagal manoeuvres or drugs which slow AV conduction [adenosine (adenine riboside), edrophonium, phenylephrine or verapamil]. When medical conversion is not achieved, transoesophageal overdrive pacing or direct current (DC) cardioversion may be required. Long term drug therapy for SVT includes first-line treatment with digoxin, verapamil or propranolol. Ventricular tachycardia is managed acutely with DC cardioversion and intravenous lidocaine (lignocaine). Chronic drug regimens include mexiletine, propranolol or amiodarone. In children with structural congenital heart disease or myocardial dysfunction, hazards of drug therapy for arrhythmias include depression of cardiac function, proarrhythmia (drug-induced worsening of arrhythmias), and conduction abnormalities. Care must be taken to choose medication regimens which are likely to be effective with minimum risk of potentiating abnormal haemodynamics or conduction.

975

Arrhythmias in Childhood

Arrhythmias in healthy children are relatively common, but rarely require treatment. Often these benign arrhythmias, such as premature atrial contractions (PAC) or marked sinus (or respiratory) arrhythmias, are discovered during a routine examination, or while the child is being monitored in a hospital or clinic setting for illness. In a study of healthy children undergoing 24-hour cardiac monitoring, 20% had PACs, 20% had junctional rhythm, and 2 to 3% had Wenckebach atrioventricular (AV} block (Gillette 1982; Southall et al. 1977). Benign arrhythmias are usually not associated with symptoms such as palpitations, syncope or chest pain, or with signs of congestive heart failure.

1. Diagnostic Techniques Not all arrhythmias in childhood are benign. Potentially serious arrhythmias account for about 10% of average paediatric cardiology practice. Specialists in the diagnosis and treatment of arrhythmias, electrophysiologists, use a number oftools to approach the diagnosis and mechanism of an arrhythmia. The most commonly used techniques are electrocardiograms (ECG), 24-hour ambulatory monitoring, transtelephonic ECG transmission, and programmed electrical stimulation of the heart during cardiac catheterisation - called electrophysiological study (EPS). Since many rapid or 'tachy'arrhythmias in children are supraventricular, a new technique of pacing from the oesophagus [transoesophageal atrial pacing (TEP)] has become very popular, both for diagnosing tachycardias, and for treating atrial flutter and supraventricular tachycardia (SVT). TEP is less dangerous and, in many acute circumstances, just as effective in treating supraventricular tachyarrhythmias as antiarrhythmic drug administration, catheter EPS or direct current (DC) cardioversion, and has fewer side effects (Benson 1987). 1.1 Associated Conditions

Cardiac arrhythmias are a common early and late complication of surgery for congenital cardiac defects. Arrhythmias are also seen in association

with myocarditis or myocardial ischaemia, cardiomyopathy, drug ingestions, hypoxia and metabolic disturbances and increased intracranial pressure, and can even be an adverse effect .of antiarrhythmic drug therapy itself. Serious arrhythmias are accompanied by symptoms and, in some cases, an increased risk of sudden death (Benson et al. 1983; Garson & McNamara 1985). The purpose of treatment, then, is to decrease symptoms, and reduce the potential for sudden death. While some forms of treatment of arrhythmias, such as pacemaker implantation for surgical heart block, are very effective in reducing the risk of sudden death, other forms of treatment are more controversial. In fact, most antiarrhythmic drugs have not been shown to reduce mortality in adults or in children, and newer drugs-may eyen potentiate the risk of sudden death [Cardiac Arrhythmias Suppression Trial (CAST) 1989; Ruskins 1989]. Therefore, newer forms of pacing therapy, such, as implantable antitachycardia pacemakers with defibrillation capability, may in the future have a greater impact on survival in children with life-threatening arrhythmias than antiarrhythmic drugs alone.

2. Antiarrhythmic Drug Classifications The most common classification for antiarrhythmic drugs is a modification of that devised by Vaughan Williams, which classifies drugs according to their mechanism of action (table I) [Vaughan Williams 1984]. The drugs most commonly used in the treatment of arrhythmias in , children are ,listed in table II.

3. Treatment 0/ Arrhythmias in Children Without Heart Disease While children with congenital heart disease and children with structurally normal hearts can both have potentially serious arrhythmias, the risks of the arrhythmias and the risks and types of treatment can be different (Garson & McNamara 1985; Southall et al. 1977).

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Table I. Antiarrhythmic drug classification

Class

Drug

Effect

Digitalis

Digoxin

Vagolytic

Ouinidine Procainamide Disopyramide lidocaine (lignocaine) Mexiletine Tocainide Phenytoin Encainide

tERP/APD, tEAP,

glycoside I IA

IB

IC

Sodium channel blockade ~conduction

tAPD, tORS duration tERP/APD, tAPD

~conduction, tORS

duration

II

III

IV

Flecainide Propranolol

tAPD /3-Adrenergic blockade

Atenolol Metoprolol Others Amiodarone Bretylium Sotalol Verapamil

tAPD, tORS duration

Calcium channel blockade

= effective refractory period; = action potential duration; t = increase; ~ = decrease.

Abbreviations and symbols: ERP

APD

Arrhythmias in children without heart disease have a good prognosis, but it is important to rule out subtle cardiac abnormalities such as mild Ebstein's malformation of the tricuspid valve, and mild ventricular dysfunction, which may not be readily apparent on a chest radiograph, ECG and examination. Echocardiography is useful for this purpose.

3.1 Supraventricular Tachycardia

The most common arrhythmia requiring treatment in the child without heart disease is (SVT), which occurs in about 1 in 1000 children, and most commonly affects infants less than 1 year of age (Ko et al. 1991). About 10% of children with SVT

have congenital heart defects. The prevalent form of SVT is a reciprocating (back and forth) tachycardia which involves the AV node (with rare exceptions) and either an accessory AV connection (50 to 60%) or a retrograde AV nodal pathway (10 to 20%) [Ludomirsky & Garson 1990]. Rarer types of atrial tachycardias such as atrial ectopic tachycardia, primary atrial tachycardia and chaotic atrial tachycardia, account for the remaining tachycardial mechanisms in children with normal hearts. Primary atrial tachycardias, such as atrial flutter, are very common in premature infants and in the fetus, and may account for as many as 50% of tachycardias in this age group (Strasburger & Benson 1989). Thus, in older infants and children, drugs which slow conduction at the AV node, such as digoxin, propranolol, and verapamil, may be very effective in preventing supraventricular tachycardias. Cardioselective {j-adrenoceptor antagonists, such as atenolol, which are less likely to cause bronchospasm than propranolol, may be required for children with asthma. About 22% of children with SVT have the WolffParkinson-White syndrome (WPW) manifest on ECG. Some of these children may have very rapid conduction to their ventricle during atrial flutter or fibrillation. Since atrial flutter and fibrillation are uncommon in children, sudden death is rare. However, digoxin and verapamil have been shown to shorten conduction over the accessory connection in adult patients, and should generally be avoided in adolescents with WPW (Gallagher et al. 1978). Verapamil is also contraindicated for intravenous use for acute management of SVT in infants under 1 year of age because of severe hypotension which can result from the calcium-blocking effects of the drug (Epstein et al. 1986). Procainamide, quinidine, and disopyramide may be effective for prophylaxis against resistant SVT. While more potent drugs such as encainide, flecainide and amiodarone are highly effective, the risk of side effects, including death, is significant and may approach the risk of surgical or catheter ablation treatment of the arrhythmia (Dick et al.

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Arrhythmias in Childhood

Table II. Antiarrhythmic drug dosing in children Class, drug

Maintenance dose (mg/kg/day)

Frequency

Therapeutic serum concentration

8-10 l'9/kg/day

q12h

50-100

q4h

1 mg/kg 10-15 mg/kg (over 1h) 0.1 mg/kg (over 5 min) 5 mg/kg 0.1-0.15 mg/kg

20-50 I'g/kg/min 4.0-7.0

Cont. info q12-24h

0.9-2.6 nmol/L (0.7-2.0 I'g/L) Procainamide 17-34 I'mol/L (4-8 mg/L) Procainanide + NAPA 15-30 mg/L 6.4-21.5 I'mol/L (1.5-5.0 mg/L) 40-80 I'mol/L (10-20 mg/L)

Repeat q2h prn

q4h

190-385 nmol/L (50-100 I'9/L)

40-50 I'g/kg/TDD 3-5 mg/kg q3h x 3 doses

10-15 l'9/kg/day 15-60

bid, qd qid, tida

0.9-2.6 nmol/L (0.7-2.0 I'g/L) 6.2-15.4 I'mol/L (2.0-5.0 mg/L)

50-125 10-20 2.5-5.0 mg/kg/q8h 10-30 4.0-7.0 1.5-4.0 2.0-4.0 2.0-6.0 0.7-1.4 10-60 5.0-10 1.5-4.5 4.0-8.0

qid qid, bida tid, bid tid, bid bid, qd tid, qid bid qid, qdB bid, qd bid, qd qd bid tid, qdB

See above 6-15I'mol/L (2.0-5.0 mg/L) 0.75-2.0 mg/L 4-10 mg/L See above ODE < 350 mg/L 200-1000 I'9/L See above

Loading dose

Intravenous administration Digoxin 30-40 I'g/kg/TDD (over 16-24h) IA Procainamide 15 mg/kg (over 15-30 min) IB Lidocaine (lignocaine) Phenytoin II Propranolol III Bretylium IV Verapamil Oral administration Digoxin IA Quinidine Procainamide Disopyramide IB Mexiletine Tocainide Phenytoin IC Encainide Flecainide II Propranolol Atenolol Metoprolol III Amiodarone Sotalol IV Verapamil

10-15 mg/kg/day

Repeat x 1 Repeat q15 min prn

50-2OO l'g/L

1.5-2.5 I'g/L 0.5-2.0 gIL (pk) 50-200I'g/L

a Sustained release preparation frequency. = total digitalising dose; q2h prn = every 2 hours as needed; q15 min prn = every 15 minutes as needed; q3h = every 3 hours; q12h = every 12 hours; q4h = every 4 hours; q8h = every 8 hours; q12-24h = every 12 to 24 hours; cont. info = continuous infusion; bid = twice daily; qd = once daily; qid = 4 times daily; tid = 3 times daily; ODE = O-demethylencainide; NAPA = N-acetyl procainamide; pk = peak.

Abbreviations: TDD

1986; Perry et al. 1989; Strasburger et al. 1983). Clinical use of sotalol is limited at present but it shows promise of being effective for resistant SVT. Proarrhythmia has also been reported with this drug (Maragnes et al. 1990). The best therapies for acute conversion of SVT are vagal manoeuvres (ice bag application to the face for 15 to 20 seconds in infants) or drugs which promote a vagal response, such as adenosine (adenine riboside) [Faulds et al. 1991], phenylephrine

or edrophonium (Till et al. 1989). If these fail, IV verapamil can be used in older children with recurrent SVT, where the underlying Stat~s of the sinus node is known. Rapid overdrive pacing methods are otherwise safest, and transoesophageal high-rate atrial pacing is especially useful in this clinical setting. Acute and chronic treatment strategies for the management of supraventricular tachycardias in children are outlined in figures 1 and 2.

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978

3.2 Ventricular Tachycardia

Determine mechanism (ECG)

If no conversion: adenosine, edrophonium or phenylephrine

If no conversion: transoesophageal recording if mechanism uncertain

Fig. 1. Acute management scheme for the treatment of supraventricular tachycardia in children. Abbreviation: ECG = electrocardiogram.

Although very rare, ventricular tachycardia (VT) can occur in children with structurally normal hearts. Endomyocardial biopsy often discloses subtle ultrastructural abnormalities. Ventricular tachycardia and ventricular fibrillation commonly occur in young patients who have been resuscitated from unexplained cardiac arrest (Benson 1983). In the acute setting, VT with haemodynamic compromise should be treated with DC cardioversion. In stable patients, intravenous lidocaine (lignocaine) is the drug of choice. For refractory or incessant ventricular tachycardia, judicious administration of propranolol, procainamide, phenytoin or combination treatment may be req~ired to control VT. During cardiac arrest and refractory ventricular fibrillation, bretylium is indicated (fig. 3). Amiodarone or mexiletine have been very effective agents for prevention ofVT, with long term efficacy of about 60% for mexiletine and somewhat higher for amiodarone (Moak et al. 1987). Mexiletine is less effective for ventricular arrythmias in children with structurally normal hearts. Side effects from amiodarone in children are generally seen with prolonged therapy and inclu~e thyroid dysfunction, liver enzyme elevation, and photosensitivity-induced skin reactions (Garson et al. 1984). Use of sunscreen is necessary. Mexiletine causes gastrointestinal side effects in up to 40% of children, and tremors or headaches in < 10%. Liver enzyme elevation can also be seen. Tocainide is similar to mexiletine but has been reported to cause granulocytopenia in adult patients. These agents should be initiated during hospitalisation, as worsening of the arrhythmia (proarrhythmia) occurs in 2 to 6% of patients. Class IA drugs such as procainamide, quinidine and disopyramide may also be effeetive in preventing recurrence of VT, but these drugs have more negative inotropic effects than mexiletine or amiodarone. In some cases, combinations of drugs may be needed. Mexiletine and quinidine have been used in combination in adult patients, but experience with combination therapy in paediatrics is limited.

979

Arrhythmias in Childhood

I

.

.

I

1111111 aVT epIeode

l

Full cardiac evaluation

Wolff-Parllinson-White syndrome

.no

I

yes . .

Propranolol or no treatment

I

l

Verapamil, propranolol, digoxin or no treatment

l

I

.

J I

.

-y Congen~al

I

heart disease

1

Ventricular function poor: digoxin, procainamide or amiodarone

-+

Ventricular function good: digoxin, propranolol, verapamil, procainamide or no treatment

•

RKurrent SVT."."

Assess drug concentrations and patient compliance

I

+

•

Compliance inadequate

I

Patient education

I

t

~r

I

Concentrations and compliance adequate

..-

~

Poor cardiac function: amlodarone

I

Nonnel cardiac function: procainamide quinidine disopyramide

X

Compliance adequate , but concentrations low

l

X

Increase dose

J

Recurrent SVT epIeodM deIpIte u.tmenI

~ Full electrophysiological evaluation Consider non pharmacological treatment : Ant~achycardia pacing Surgical or catheter ablation Or Flacainide Amiodarone Other combination treatment

Fig_ 2.

Chronic management techniques for the treatment of supraventricular tachycardia (SVT) in children.

J

J

980

Drugs 42 (6) 1991

I

Acute management

I

Wide OAS tachycardia

...

Patient stable: lidocaine overdrive ventricular pacing

9-

I

I I

+

Patient unstable: DC cardioversion

r----4

.

I

I

I

,

If cardioversion refractory

+

~

Patient unstable: bretylium

Patient relatively stable: procainamide propranolol phenytoin combination treatment

I I I

+

Congenital heart disease: consider surgery to improve haemodynamics. medical management or cardiac transplantation .

•

I

Good ventricular function: mexilitine procainam ide phenytoin amiodarone

.

Chronic management

Acute management

I Complete electrophysiological and haemodynamic evaluation

,

I I I

+

Long QT syndrome: propranolol mexilitine

...

Poor ventricular function: amiodarone lidocaine mexilitine

Fig. 3. Acute and chronic management schemes for the treatment of ventricular tachycardia (VT) in children.

981

Arrhythmias in Childhood

Potentiation of side effects is common, and doses for each drug should be kept as low as possible. Both class I drugs and amiodarone cause prolongation ofthe QT interval on the ECG and should be avoided in patients with underlying prolonged QT. Propranolol, mexiletine or tocainide, alone or in combination, are used for patients with underlying QT prolongation. While flecainide and encainide have been used in adult patients with refractory VT, a recent interinstitutional study in paediatric patients found a high incidence of proarrhythmia with these 2 drugs, especially in patients with cardiac dysfunction (Fish et al. 1989). We therefore recommend that patients treated with encainide or flecainide undergo EPS testing during initiation, and even this may not fully define patients at risk of proarrhythmia. One type of exercise-related ventricular tachycardia is very characteristic in that the ECG during tachycardia has right bundle branch block, and left axis deviation (Belhassen et al. 1984). This form of ventricular tachycardia responds to verapamil; however, verapamil is generally not effective for other types of VT, and may produce hypotension when administered intravenously during VT.

4. Arrhythmias in Patients with Congenital Heart Disease or Cardiomyopathy 4.1 Ventricular Tachycardia In long term follow-up of paediatric patients who have undergone repair or palliation of cardiac defects, the risk of sudden death may be significant (double outlet right ventricle 15%; tetralogy of Fallot 4%; Mustard operation for transposition of the great arteries 4 to 9%). Most patients who have experienced symptoms such as syncope or cardiac arrest have inducible ventricular tachycardia or ventricular fibrillation at EPS, and it is thought that these symptoms are most commonly related to tachy- rather than bradyarrhythmias. Monomorphic VT is the most common form ofVT, and is probably due to re-entry in areas of ventricular fibrosis. Many patients have abnormal haemodynamics. The treatment, whenever possible, is to im-

prove the patient's haemodynamics, usually surgically, but when this is not possible, the treatment regimens outlined previously for ventricular tachycardia should be utilised (see section 3.2 and fig. 3). In postoperative patients, complications may arise that are not usually seen in children without heart disease. These include potentiation of congestive heart failure or sick sinus syndrome (described below), conduction block due to prior injury to the conduction system, and drug-drug interactions. Digoxin serum concentrations are increased by quinidine, amiodarone, flecainide and verapamil (Marcus 1985). Amiodarone has potent effects on sinus node function, and in symptomatic patients with sick sinus syndrome it is recommended that a permanent pacemaker be implanted prior to therapy (Frye et al. 1984). 4.2 Primary Atrial Tachycardia Several cardiac surgical procedures involve extensive atrial reconstruction and have a high incidence of postoperative atrial arrhythmias. The most common are the Fontan operation for tricuspid atresia, the Mustard and Senning (atrial baffle) operations for transposition of the great arteries, and atrial septal defect closure (Paul 1989; Shen et al. 1990). Tachycardia and bradycardia are both present in a condition called 'sick sinus syndrome' or tachy-brady syndrome. The incidence of tachybrady syndrome approaches 50% 10 years after the Mustard operation. Postoperative tachyarrhythmias in these patients may be hard to recognise: the arrhythmias do not require the AV node for perpetuation (primary atrial tachycardias, or atrial flutter), and 2: 1 AV block during tachycardia is common. AV block results in slower heart rates in tachycardia, often between 130 and 150 beats/min. The atrial rates are 260 to 300 beats/min. These arrhythmias are very stable, and some patients can remain in tachycardia for months before congestive heart failure develops. Primary atrial tachycardias are also very resistant to conversion with antiarrythmic agents. Com-

Drugs 42 (6) 1991

982

binations of digoxin and quinidine rarely or infrequently result in conversion to sinus rhythms, and for this reason transoesophageal pacing has become the mainstay of acute management. Since the arrhythmia is relatively well tolerated, and may not recur for months after the initial episode, treatment with antiarrhythmic therapy other than digoxin may not be necessary. if recurrences become frequent, the addition of procainamide or quinidine is often effective in decreasing the frequency of tachycardia episodes. These drugs require frequent dosing, and treatment failure is often due to inability to maintain therapeutic drug concentrations. When true treatment failures occur, amiodarone may be effective, but in less than 10% of patients no drug combination maintains normal rhythm. For these patients, antitachycardia pacing, combined with antiarrhythmic therapy, is usually employed. The addition of amiodarone usually requires insertion of a permanent pacemaker in patients with significant bradycardia. 4.3 Junctional Ectopic Tachycardia Junction ectopic tachycardia (JET) [fig. 4] occurs soon after operations involving suturing near the AV node and bundle of His, such as tetralogy of Fallot repair. AV dissociation is usually present with atrial rates in the normal range. The tachycardia is incessant and extremely resistant to treatment. It usually resolves after 7 to 10 days. Initial junctional rates in excess of 200/min cause severe haemodynamic compromise. Cooling of the core body temperatue to 35°C usually slows the tachycardia rates. Digoxin is sometimes also helpful, but procainamide is the most effective of the currently available drug therapies for slowing very rapid JET. Rarely propafenone has been used intravenously, but experience with this treatment is limited (Bash et al. 1987).

5. Conclusions The most common arrhythmia requiring treatment in children is supraventricular tachycardia. It is usually treated with digoxin, a {3-blocker, or

Provide adequate analgesia Correct hypovolaemia Decrease catecholamines Maintain normothermia

Digoxin Procainamlde Cool core body temperature slowly to 35°C Atrial pacing

Observe ? Digoxin Atrial pacing

If no slowing In rale: Further cooling Propafenone Paired ventricular pacing

Fig. 4. Treatment scheme for the acute management of junctional ectopic tachycardia in children.

with a class IA agent such as procainamide or quinidine. When treatment failure occurs, more potent antiarrhythmic agents such as the class IC agents, or amiodarone may be necessary. Atrial flutter is less likely to respond to pharmacological treatment acutely, and rapid overdrive pacing remains a mainstay in its treatment. Ventricular tachycardia is usually initially treated with lidocaine intravenously, and chronic management is commonly achieved with mexiletine or amiodarone. Since ventricular arrhythmias are more likely to be associated with cardiac disease and risk of sudden death, it is important to select medications which provide a long half-life and few side effects, thus enhancing patient compliance. Drug therapy is only one of several forms of acute and long term treatment of arrhythmias in children. The treatment goals should be to elimi-

Arrhythmias in Childhood

nate symptoms or to decrease the potential risk of arrhythmia-related ventricular dysfunction or sudden death. Thus, knowledge of the mechanism of tachycardia and the clinical condition of the patient are required in order to guide the clinician in appropriate drug selection.

References Bash SE. Shah JJ, Albers WH, Giess DM. Hypothermia for the treatment of postsurgical greatly accelerated junctional ectopic tachycardia. Journal of the American College of Cardiology 105: 1095-1099, 1987 Belhassen B, Shapira I. Pelleg A, Coperman I, Kauli N, et al. Idiopathic recurrent sustained ventricular tachycardia responsive to verapamil: an ECG electrophysiologic entity. American Heart Journal 108 (4): 1034-1037, 1984 Benson Jr DW. Transesophageal electrocardiography and cardiac pacing: state of the art. Circulation 75: III-86-III-90, 1987 Benson DW, Benditt DG, Anderson RW, Dunnigan A, Pritzker MR, et al. Cardiac arrest in young, ostensibly healthy patients: clinical, hemodynamic, and electrophysiologic findings. American Journal of Cardiology 52: 65-69, 1983 Cardiac Arrhythmias Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. New England Journal of Medicine 321 (6): 406-412, 1989 Dick M, Scott W A. Amiodarone in pediatric patients. Clinical Progress in Electrophysiology and Pacing 4: 522-527, 1986 Epstein ML, Seibel MA, Hill MR, et al. Pharmacokinetics of chronic oral verapamil therapy in infants. Circulation 74: 77, 1986 Faulds D, Chrisp P, Buckley MM-T. Adenosine. An evaluation of its use in cardiac diagnostic procedures. and in the treat-

ment of paroxysmal supraventricular tachycardia. Drugs 41: 596-624, 1991 Fish FA, Gillette PC, Benson Jr DW, for the Pediatric Electrophysiology Group. Incidence of cardiac arrest and proarrhythmia in young patients receiving flecainide or encainide. Abstract 1539. Circulation 80 (4): 11-387, 1989 Frye RL, Collins JJ, DiSanctis RW, Dodge HT, Drehus LS, et al. Guidelines for permanent cardiac pacemaker implantation. Circulation 70: 2, 1984 Gallagher JJ, Pritchett ELC, Sealy WC, Rasell J, Wallace AG. The preexcitation syndromes. Progress in Cardiovascular Diseases 20 (4): 285-327, 1978 Garson Jr A, Gillette PC, McVey P, et al. Amiodarone treatment of critical arrhythmias in children and young adults. Journal of the American College of Cardiology 4: 749-755, 1984 Garson Jr A, McNamara DC. Sudden death in a pediatric cardiology population, 1958-1983: relation to prior arrhythmias. Journal of the American College of Cardiology 5 (Suppl. 6): 134B-137B,1985 Garson Jr A, Porter CBJ, Gillette PC, McNamara DG. Induction of ventricular taChycardia during electrophysiologic study after repair of tetralogy of Fallot. Journal of the American College of Cardiology I (6): 1493-1502, 1983

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Gillette PC, Garson Jr A (Eds). Noninvasive diagnostic techniques. In Pediatric arrhythmia: electrophysiology and pacing, pp. 205-216, WB Saunders CO., Philadelphia 1982 Joint American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures, Subcommittee on Pacemaker Implantation. Guidelines for permanent cardiac pacemaker implantation. Circulation 70: 331-339A, 1984 Ko JK, Deal BH, Strasburger JF, Benson JR DW. Supraventricular tachycardia mechanisms and their age distribution in pediatric patients. Journal in press, 1991 Ludomirsky A, Garson Jr A. Supraventricular tachycardia. In Gillette PC & Garson Jr A (Eds) Pediatric arrhythmia: electrophysiology and pacing, pp. 380-426, WB Saunders Co., Philadelphia, 1990 Maragnes P, Fornier A, Kratz C, Houyel L, Davignon A, et al. Efficacy of sotalol in the pediatric population. Abstract. Circulation 82 [Suppl.] III-224, 1990 Marcus FI. Pharmacokinetics: interactions between digoxin and other drugs. Journal of the American College of Cardiology 5 (5): 81 A-82A, 1985 Moak JP, Smith RT, Garson Jr A. Mexilitine: an effective antiarrhythmic agent for treatment of ventricular arrhythmias in children with congenital heart disease. Journal of the American College of Cardiology 10: 824-829, 1987 Paul M. Complete transposition of the great arteries. In Adams FH et al. (Eds) Heart disease in infants, children and adolescents, 4th ed., pp. 371-423, Williams and Wilkins, Baltimore, 1989 Perry JC, McQuinn R, Smith RT, et al. F1ecainide acetate for resistant arrhythmias in the young: efficacy and pharmacokinetics. Journal of the American College of Cardiology 14: 185193, 1989 Ruskins IN. The Cardiac Arrhythmias Suppression Trial (CAST). New England Journal of Medicine 321 (6): 386-388, 1989 Shen WoK, Holmes DR, Porter CJ, McGoon DC, Filstrup SM. Sudden death after repair of double-outlet right ventricle. Circulation 81: 128-129, 1990 Southall DP, Orrell MJ, Talbot JF, Brinton RJ, Vulliam DG, et al. Study of cardiac arrhythmias and other forms of conduction abnormality in newborn infants. British Medical Journal 2: 597599, 1977 Strasburger JF, Benson Jr DW. Mechanisms of tachycardia in the premature infant and fetus. Abstract 1875. Circulation 80 (4): 11-471, 1989 Strasburger JF, Moak JP, Smith RT, et al. Encainide for refractory supraventricular tachycardia in children. American Journal of Cardiology 58: 49c-54c, 1983 Till J, Shinebourne EA, Rigby ML, Clarke B, Ward DE, et al. Efficacy and safety of adenosine in the treatment of supraventricular tachycardia in infants and children. British Heart Journal 62: 204-211, 1989 Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. Journal of Clinical Pharmacology 24: 129-147, 1984

Correspondence and reprints: Dr Janelle F. Strasburger. Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL60614, USA.