CHARACTERISTICS OF AT/Gillette, Garson 15. Gutgesell HP, Gillette PC, McNamara DG: The response of the sinoatrial node to rapid atrial stimulation. Pediat Res 8: 350, 1974 16. Gillette PC, Mullins CE: Atrioventricular conduction in children: Response to rapid atrial stimulation and premature atrial stimulation. Cardiovasc Dis 2: 41, 1975 17. Godman MJ, Roberts NK, Izukawa T: Late postoperative conduction disturbances after repair of ventricular septal defect and tetralogy of Fallot: Analysis by His bundle recordings. Circulation 49: 214, 1974 18. Gillette PC: Electrophysiologic studies of surgical complete atrioventricular block. Cardiovasc Dis 1: 95, 1974 19. Anderson PAW, Rogers MC, Canent RV, Jarmakani JMM, Jewett PH, Spach MS: Reversible complete heart block following cardiac surgery: Analysis of His bundle electrograms. Circulation 46: 514, 1972 20. Niederhauser H, Simonin P, Friedli B: Sinus node function and conduction system after complete repair of tetralogy of Fallot. Circulation 52: 214, 1975 21. Hougen T, Dick M, Freed M, Keane J: His bundle electrograms following intracardiac repair of tetralogy of Fallot. Circulation 51: 197, 1975 22. Yabek SM, Jarmakani JM, Roberts N: Postoperative trifascicular block complicating tetralogy of Fallot repair. Pediatrics 58: 236, 1976 23. Neches WH, Park SC, Mathews RA, Garcia JM, Lenox CC, Zuberbuhler JR: Tetralogy of Fallot: Postoperative electrophysiologic studies.

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Proceedings of the Section of Cardiology of the American Academy of Pediatrics, 1976 24. Sung RJ, Tamer DM, Agha AS, Castellanos A, Myerburg RJ, Gelband H: Etiology of the electrocardiographic pattern of "incomplete right bundle branch block" in atrial septal defect: An electrophysiological study. J Pediatr 87: 1182, 1975 25. Pahlajani DB, Serratto M, Mehta A, Miller RA, Hastreiter A, Rosen KM: Surgical bifascicular block. Circulation 52: 82, 1975 26. Naylor V: Response to exercise in patients after total surgical correction of tetralogy of Fallot. Circulation 54: 671, 1976 27. Wessel HU, Cole RB, Guerrero L, Paul MH: Incidence and clinical significance of dysrhythmias in corrected tetralogy. Proceedings of the Section on Cardiology of the American Academy of Pediatrics, 1976 28. Gillette PC, El-Said G, Sivarajan N, Mullins CE, McNamara DG: Electrophysiological abnormalities after Mustard operation for transposition of the great arteries. Br Heart J 36: 186, 1974 29. El-Said GM, Gillette PC, Mullins CE, Nihill MR, McNamara DG: Significance of pacemaker recovery time after Mustard's operation for transposition of the great arteries. Am J Cardiol 38: 448, 1976 30. El-Said GM, Gillette PC, Cooley AC, Mullins CE, McNamara DG: Protection of the sinus node in Mustard's operation. Circulation 53: 788, 1976

Electrophysiologic and Pharmacologic Characteristics of Automatic Ectopic Atrial Tachycardia PAUL C. GILLETTE, M.D.,

AND

ARTHUR GARSON, JR., M.D.

SUMMARY In seven children six weeks to nine years of age, the diagnosis of chronic atrial tachycardia due to an automatic ectopic focus was established by clinical course, by the recording of intracardiac electrograms, and by atrial stimulation during cardiac catheterization. Both overdrive atrial pacing and programmed premature atrial stimulation failed to influence the tachycardia. Digoxin reestablished sinus rhythm in one patient while it slowed the tachy-

cardia rate slightly in six. Propranolol with digoxin was effective in restoring sinus rhythm in three cases, ineffective in one, and slowed the rate in two. Diphenylhydantoin was effective in one of two patients in whom it was used. Reserpine restored sinus rhythm in the one patient to whom it was given. Although automatic ectopic atrial tachycardias are difficult to manage, an aggressive diagnostic and pharmacologic program results in a high degree of control.

NEW ELECTROPHYSIOLOGICAL TECHNIQUES have allowed the classification of atrial tachycardia into two major types: automatic ectopic focus and re-entry.'-" The ectopic focus type is rare in adults but often occurs in children.', 4 11 It is likely that treatment of these two types of tachycardia will be different."' 13 It is the purpose of this report to observe the response of ectopic atrial tachycardia to atrial pacing and to long term drug treatment.

electrode catheters were inserted percutaneously into the femoral veins and positioned in the right heart under fluoroscopic and electrocardiographic control for His bundle potential and atrial recording as previously reported.'4 In one case, an additional quadripolar electrode catheter was positioned in the coronary sinus after percutaneous insertion in a left antecubital vein. Right atrial pacing at a rate slightly faster than the existing tachycardia was carried out in six patients with a Med Data MD-1 rapid stimulator, and recordings were made during abrupt termination of pacing. In five subjects, single, progressively more premature atrial beats were then introduced during existing tachycardia by coupling to the atrial electrogram with a Medtronic 5837 stimulator. External cardioversion with 2 watt seconds/kg of body weight was done in six patients. In three subjects who had periods of sinus rhythm during the study, premature atrial beats were coupled into their sinus rhythm. In four subjects, propranolol 0.1 mg/kg i.v., over ten minutes was given during the study and in three, xylocaine, 1 mg/kg/i.v. bolus was also administered. In each case, digoxin was selected as the initial drug for chronic treatment of their tachycardia. If digoxin proved ineffective, a second drug was added. Before declaring any drug ineffective, the dose was increased until clinical signs of mild toxicity developed or the serum level was in the upper

Methods Seven patients, six weeks to nine years of age were studied. Each subject was first evaluated by history and physical examination, 15 lead electrocardiography and chest roentgenography. All medications were discontinued 24 hours before the study. All except the youngest were sedated with meperidine 2 mg/kg, chlorpromazine 0.5 mg/kg, and promethazine 0.5 mg/kg, 30 minutes before the study. Two From the Section of Cardiology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital and the Clayton Foundation for Research, St. Luke's Episcopal Hospital, Houston, Texas. Supported in part by Grant HL-5756 from the NIH and USPHS Grant RR-00188 from the General Clinical Research Branch, NIH. Address for reprints: Paul C. Gillette, M.D., Section of Pediatric Cardiology, Texas Children's Hospital, 6621 Fannin, Houston, Texas 77030. Received March 10, 1977; revision accepted May 27, 1977.

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FIGL1R[ 1 The onset of an automatic ectopic suprav)entricular tachycardia recorded on lead II of the surface electrocardiogram ofpatient 1. There is a gradual increase in rate, together th a gradual increase in PR interval. P aves are clear/i vtisible except at the fastest rate.

part of the effective range. The results of treatment were observed clinically by electrocardiogram and by 12 and 24 hour ambulatory tape recordings of ECG at follow-up periods ranging from six months to seven years. Results

Surface electrocardiography showed repetitive tachycardia in four patients and persistent tachycardia in three, according to the definition of Keane et al."3 (figs. 1 and 2). Distinct P waves could be seen in the tracing of each of the seven. The rate of the tachycardia varied from day to day and minute to minute. The mechanism of tachycardia was determined in each case to be an automatic ectopic focus, based on the criteria of Goldreyer et al.3 and Scheinman et al.4 The tachycardia could not be started or stopped by either overdrive atrial

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pacing or single premature atrial beats. The initial complex of the tachycardia had the same P wave morphology and atrial activation sequence as the ensuing complexes. In all cases, the ectopic focus was in the atrium. By recording from the high and low right atrium the ectopic focus was low atrial in two patients, near the sinus node in two, and approximately equidistant in the others (table 1). In patient 7, in whom left atrial depolarization was recorded from an electrode in the coronary sinus, the left atrium showed the earliest depolarization (fig. 3). There was an associated cardiomyopathy present in patients 4, 6 and 7. As these patients all had tachycardia, it was impossible to establish whether the cardiomyopathy was primary or secondary to tachycardia. Overdrive atrial pacing temporarily depressed the rate of the ectopic focus in all six cases in which this was performed.

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FIGURE 2. Fifteen lead electrocardiogram ofpatient 7 during left atrial automatic ectopic tachycardia. The P waves are negative in leads I and a V, positive in II, III, and aVF, and show a dome and dart pattern in the right precordial leads.

CHARACTERISTICS OF AT/Gillette, Garson The degree of depression was variable as was the escape mechanism after pacing. The mechanism was sinus for one to four beats in three cases and ectopic in four. In no instance did overdrive pacing suppress the ectopic mechanism for over two seconds. Introduction of single premature beats during tachycardia resulted in a pause which became progressively less than compensatory as the premature atrial contraction was introduced earlier into the atrial cycle (fig. 4). The shape of the curve showing this relationship is similar to that recorded by introducing premature beats during sinus rhythm in normal subjects (fig. 5). This curve is qualitatively different from that obtained from patients with re-entry mechanism atrial tachycardia (fig. 6). Cardioversion was unsuccessful in all patients. In all patients, digoxin was the first drug given. In patient 3, digoxin completely suppressed the tachycardia for one year and there was no recurrence after stopping treatment during a two-year follow-up. In the other five patients, although digoxin aided in the control of congestive heart failure, it did not depress the tachycardia rate significantly. Propranolol, 1-3 mg/kg/day in four divided doses, together with digoxin was the next regimen tried in six cases. In one patient, propranolol had no detectable effect on rate or rhythm. In three patients, propranolol suppressed the ectopic focus completely and allowed sinus rhythm to resume. One of these three had no recurrence on discontinuing the drug after one year, while the other two continued to require the drug. Propranolol decreased the rate of the other two patients' tachycardias from 180-240 beats/min to 90-125 beats/min, but the focus remained unchanged (GC in table 1). Diphenylhydantoin (DPH) was used in the other two patients. In each, oral digoxin was continued while the DPH was administered, initially intravenously, at a dose of 4 mg/kg every six hours until the serum level was greater than 20 mg/ml (therapeutic range for seizures, 10-18 mg/ml). In case 2, on a day when the DPH level was 30 mg/ml, the

573

TABLE 1.

Case/Age/Sex

Site

1/9 y/F 2/8 m/F

HA LoA MA LoA LoA HA LA

3/4 m/F 4/2 y/M 5/6 wk/F

6/3 m/F

7/5 y/M

Response to Digoxin + Digoxin + Result DPH propranolol

Digoxin

NA + NA NA NA NA

+ + + = -

+ NA

+ +

-

Abbreviation: HA = high right atrium; LoA = low right atrium; MA = midatrium; LA = left atrium; NA = not attempted; GC = good control; NSR = normal sinus rhythm; + = effective; - = not effective; --

partially effective in relief of symptoms; DPH

=

dipheny lhydantoin.

patient was in sinus rhythm for 20 hours out of 24. For the remainder of the time, she was in ectopic tachycardia but at a rate of only 120. Careful neurologic examination failed to reveal any sign of DPH toxicity. In the other patient, DPH failed to influence the tachycardia. Reserpine was used in this patient when digoxin, propranolol, DPH and quinidine had failed. It was administered initially intramuscularly, followed by 0.18 mg/ day orally (body weight 7 kg). This resulted within 18 hours in sinus rhythm, which was maintained for nine months. At that time, it was felt that she was depressed psychologically, and the dose was decreased. The tachycardia then resumed. When the dose was again increased, sinus rhythm resumed. The depression was not considered to be as significant as the tachycardia. Digoxin and DPH were continued with reserpine.

Discussion The diagnosis of automatic ectopic focus atrial tachycardia may be suspected from the surface ECG. In all of our patients, P waves were clearly visible. This is the exception in cases of re-entry atrial tachycardia. The onset of tachy-

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FIGURE 3. Left atrial automatic ectopic tachycardia. Recorded are surface leads I, II and III simultaneously with high right atrial (HRA), distal coronary sinus (DCS), and His bundle electrocardiogram (HBE). After a single blocked premature atrial stimulus, the P wave is dissociated from the T wave and it can be seen that the P wave in lead I is negative. The first depolarization of the ectopic focus is recorded by the coronary sinus catheter.

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Fi(-EL RI 4. Respons e of a n ectopic atrial tachvcardia to a single premature atrial beat in patient 1. The tachycardia cycle length of 385 m.sec is interrupted hy a premature stimulus at 290 msec which is not conducted to the bundle of His. The tachscardia th en res unies after a less than compensa tory pause. Recorded are surface leads I a V., V,ltogether with a high right atrial electrograni (HRA) and a His bundle electrogram.

cardia was gradual in many cases (fig. 1). In cases of repetitive tachycardia the shape of the P wave of the first beat was the same as that of the subsequent beats. The PR interval during tachycardia was often but not always normal, whereas a prolonged PR interval is a hallmark of reentry tachycardias. The diagnosis of an ectopic focus is confirmed by intracardiac stimulation studies.3 5 11 In case 7, the intracardiac studies also confirmed that the ectopic focus was in the left atrium. This had already been suggested by the negative P waves in leads I and aV, on the surface ECG (fig. 2). This is the first confirmation of the ECG diagnosis of a left atrial spontaneous ectopic focus in man. This confirms that the diagnosis of left atrial rhythm 400

can be made based on the criteria of negative P waves in leads I and aV, positive P waves in II, III and aV6,.6 18 This patient also demonstrated notched P waves in lead V,, suggestive of the dome and dart pattern.16 Recent studies by Wit and Cranefield15 have shown that it is possible to trigger repetitive extrasystoles and sustained tachycardias in cardiac fibers with slow action potentials.'0 These rhythms were not thought to be due to re-entry, thus casting some doubt on currently used clinical techniques or differentiating re-entry from ectopic foci. These fibers were under abnormal conditions of external potassium and catecholamine stimulation and the situation may not be clinically applicable in the absence of myocardial infarction. In any event, the clinical electrophysiologic division into ectopic versus re-entry mechanisms is useful in that it

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Graph of the tYpical response of an atrial ectopic

tachYecardia to single programmed atrial extra stimulus in patient 5. A IA2 represen ts the interval from a spontan eous atrial ec topic beat to the premature beat. A2A 3 represen ts the interdurinig

tach'vcardia

val fromi the premature beat to the next beat which was always from the ectopic focus in this case. The dots represent the control state and the -vs represent a repeat study after intravenous propranolol. Propranolol markedlli depressed the automaticitY oJ the ectopic

foCUS.

300 I

CL 350msec

100

200

300

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F[CURLE 6. Graph of the response of a re-entry supraventricular tachYcardia to progressively more premature stimuli. As the preiiiaturity increased, the return cycle lengthened gradually until the re-entrsv cycle was broken and a sinus beat intervened as evidenced bY a marked sudden increase in return cycle length.

CHARACTERISTICS OF AT/Gillette, Garson separates patients into two groups which respond differently to management. Infants and children with automatic ectopic atrial tachycardia are usually very difficult management problems. Based on our studies and those of others,'2' 13 it is evident that one reason for this is the ineffectiveness of digoxin. Electrical cardioversion and overdrive pacing are also ineffective because they only suppress the focus for, at most, a few seconds. Electroversion was unsuccessful in each of six patients in whom it was attempted in this series. Each of the seven patients had either overdrive pacing or electroversion. The majority of our cases seem to be similar to those which are classified as chronic atrial tachycardia by Keane and Nadas"3 and by Jacobsen et al.12 They also noted the difficulty in treatment and the serious side effects such as strokes and congestive heart failure in some patients. Others persist in tachycardia for years without symptoms. The properties of these ectopic pacemakers are similar to those of the sinus node in that they are responsive to changes in autonomic tone and the rate varies from time to time. The response to premature atrial stimulation is also similar to the sinus node in that the ectopic pacemaker is reset by the premature beat to a degree proportional to the prematurity. Although the use of antidysrhythmic agents is still empiric, we believe that if an ectopic focus is suspected, certain drugs are more likely to be effective. Digoxin is the most frequently successful agent in breaking re-entry circuits,19 but as shown in this study it is rarely successful in ectopic foci. It should still be used routinely since it aids in the prevention of congestive heart failure and may slow the ventricular rate due to A-V block. Propranolol is frequently effective in both forms of tachycardia. Signs of congestive heart failure must be watched for, particularly if there is an associated cardiomyopathy. Xylocaine may be a useful drug for acutely slowing the rate of the supraventricular ectopic focus. In cases in which second degree A-V block is present, however, the ventricular rate may be increased when one to one conduction occurs as in one of our cases. It is possible that a xylocainelike drug for oral usage will be developed and may be effective in this condition. Diphenylhydantoin may be effective both acutely and for chronic administration. It appears that the therapeutic and toxic blood levels are very close to each other, and this limits its effectiveness for long term management. Reserpine is the final drug with which we have had a favorable response. Further studies on more patients will be necessary before its effectiveness can be evaluated.

575

Surgical treatment should be possible in extremely severe cases and could consist of the direct removal of the ectopic focus or division of the bundle of His with insertion of a pacemaker. In this study we have achieved complete control of the tachycardia with resumption of sinus rhythm in five of seven cases. In the other two, the rate was slowed to a level associated with relief of symptoms. Atrial ectopic tachycardias are not uncommon in children. Although their management is difficult, it may be successful if drug combinations are used rationally. References I. Bigger JT Jr, Goldreyer BN: The mechanism of supraventricular tachycardia. Circulation 42: 673, 1970 2. Goldreyer BN, Bigger JT Jr: Site of reentry in paroxysmal supraventricular tachycardia in man. Circulation 43: 15, 1971 3. Goldreyer BN, Gallagher JJ, Damato AN: The electrophysiologic demonstration of atrial ectopic tachycardia in man. Am Heart J 85: 205, 1973 4. Scheinman MM, Basu D, Hollenberg M: Electrophysiologic studies in patients with persistent atrial tachycardia. Circulation 50: 266, 1974 5. Rosen KM, Mehta A, Miller RA: Demonstration of dual atrioventricular nodal pathways in man. Am J Cardiol 33: 291, 1974 6. Denes P, Wu D, Dhingra RC, Chuquimia R, Rosen KM: Demonstration of dual A-V nodal pathways in patients with paroxysmal supraventricular tachycardia. Circulation 48: 549, 1973 7. Paulay KL, Varghese PJ, Damato AN: Sinus node re-entry: An in vivo demonstration in the dog. Circ Res 32: 455, 1973 8. Narula OS: Sinus node reentry: A mechanism for supraventricular tachycardia. Circulation 50: 114, 1974 9. Goldreyer BN, Damato AN: The essential role of atrioventricular conduction delay in the initiation of paroxysmal supraventricular tachycardia. Circulation 43: 679, 1971 10. Rosen KM: A-V nodal reentrance: An unexpected mechanism of paroxysmal tachycardia in a patient with preexcitation. Circulation 47: 1267, 1973 11. Gillette PC: The mechanisms of supraventricular tachycardia in children. Circulation 54: 133, 1976 12. Jacobsen JR, Andersen ED, Sandoe E, Videbaek J, Wennevold A: Chronic supraventricular tachycardia in infancy and childhood. Acta Paediatr Scand 64: 597, 1975 13. Keane JF, Plauth WH, Nadas AS: Chronic ectopic tachycardia of infancy and childhood. Am Heart J 84: 748, 1972 14. Gillette PC, Reitman MJ, Gutgesell HP, Vargo TA, Mullins CE, McNamara DG: Intracardiac electrography in children and young adults. Am Heart J 89: 36, 1975 15. Wit AL, Cranefield PF: Triggered activity in cardiac muscle fibers of the simian mitral valve. Circ Res 38: 85, 1976 16. Cohen J, Scherf D: Consideration on impulse formation in the left atrium and its diagnosis by electrocardiogram. Am J Cardiol 31: 799, 1973 17. MacLean WAH, Karp RB, Kouchoukos NT, James TN, Waldo AL: P waves during ectopic atrial rhythms in man. Circulation 52: 426, 1975 l8. Lau SH, Cohen SI, Stein E, Haft JI, Rosen KM, Damato AN: P waves and P loops in coronary sinus and left atrial rhythms. Am Heart J 79: 201, 1970 19. Wellens JHH, Duren DR, Liem KL, Lie KI: Effect of digitalis in patients with paroxysmal atrioventricular nodal tachycardia. Circulation 52: 779, 1975