- Email: [email protected]
Natural history of isolated atrial flutter in infancy
Natural history of isolated atrial flutter in infancy Alan M e n d e l s o h n , MD, M a c d o n a l d Dick II, MD, a n d G e r a l d A. Serwer, MD From the Division of Pediatric Cardiology, C, S. Mott Children's Hospital, and the Department of Pediatrics, University of Michigan, Ann Arbor To clarify the natural history of isolated (i.e., without associated c o n g e n i t a l cardiac anomalies) atrial flutter in infancy, we reviewed the clinical course in nine patients who were seen with this arrhythmia in the first year of life (range I d a y to 4 months). Atrial flutter was identified by the typical sawtooth pattern in leads II, III, and aVF of the surface e l e c t r o c a r d i o g r a m or the pattern of atrial flutter on an atrial electrogram recorded through the esophagus. The mean c y c l e length of the atrial flutter was 151 msec (atrial rate 397 beats/min). Six of the nine patients had other perinatal problems, such as immune and nonimmune hydrops fetalis (two patients), p n e u m o n i a (one patient), a n e m i a (five patients), or low birth weight (one patient). In all patients the rhythm reverted to normal, either spontaneously (two patients), wlth overdrive p a c i n g (four patients), or after oral d i g o x i n therapy (three patients). No consistent temporal relationship between d i g o x i n administration and conversion was observed; conversion was instantaneous in the four patients who received atrial overdrive pacing. Four patients were discharged receiving d i g o x i n therapy (6 months to 1 year). One patient had supraventricular t a c h y c a r d i a after discharge that was controlled with digoxin. No recurrence of atrial flutter was observed a m o n g the nine patients during a mean follow-up of 6.8 years (range 0.2 to 20 years). We c o n c l u d e that isolated atrial flutter in infancy is rare, has a g o o d prognosis, may be related to transient perinatal events, and often spontaneously converts to normal sinus rhythm; however, when it does not, it will respond to transesophageal pacing. Acute and chronic d i g o x i n therapy is p r o b a b l y unnecessary. (J PEDIATR1991; 119:386-91)
Atrial flutter is an uncommon arrhythmia in infancy. Patients with primary arrhythmias (i.e., no associated structural heart disease) represent 7% of the approximately 18,000 patients seen in our pediatric cardiac clinics; however, only nine of these patients have had isolated (i.e., not associated with other forms of heart disease) atrial flutter during infancy. Digoxin, which was virtually the only available therapy for many years, 1,2 direct current cardioversion, 3 and atrial overdrive pacing 4, 5 have been advanced as initial therapy. Dunnigan et al. 5 and Martin and Submitted for publication Jan. 24, 1991; accepted March 25, 1991. Reprint requests: Macdonald Dick II, MD, F1310, Box 0204, C.S. Mott Children's Hospital, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0204. 9/20/29699
386
Hernandez 2 have reported mean follow-up periods of 1.9 and 3,4 years, respectively, but an extensive natural history of infants with isolated atrial flutter is unavailable. To clarify the clinical course of infants with isolated atrial flutter and to determine optimal initial therapy, as well as the need for long-term digoxin prophylaxis, we reviewed our experience in nine infants with isolated atrial flutter. METHODS The Cardiac Diagnostic Database of the Division of Pediatric Cardiology, Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan, was searched to identify all patients with atrial flutter; those individuals in whom atrial flutter appeared after the first year of life or who had associated heart disease were excluded. Atrial flutter was defined electrocardiographically by the appear-
Volume 119 Number 3
Isolated atrial flutter in infancy
387
~lllllllllllll(llllllEliliilliillllllllllllllli,~,, ~q~i,~,,,,,~ ,~,,,,~ 84i/~i~,t, 84
ESOPN
IIIIlIfIlltlllIIIIIIIIII NilIIIIIIIIINilIttlItttIIIl!il}[gi!i;l~', illil;ll'ltlIil)lllHlIIIIIIIIllll{i lili,/ll
lI[lIl[[llllHlt[ll/II/llHIlllII]IHII/l/II/lllil/illliiill tllIHl ;i;~ililliil] H]I III1111IIIlIlllll II1!;III 1111}111
~H~[~lH~HII[IIII~IN~l~1~1ll1~1lll~llll~1~l~ll~i~1~1ll[~I]?i~i~1111~1I~I~1~tt~H~ 1
Fig. t. Electrocardiographic tracings of atrial flutter. A, Simultaneous surface (/earl II) electrocardiogram {upper) and transesophageal (ESOPH} atrial electrogram (lower) demonstrate atrial flutter with 3:1 block. Note constant we/l-formed atrial eleetrograms in esophageal tracing. B and C, Continuous electrocardiogram demonstrates atrial flutter. Rhythm was converted by transesophageal overdrive pacing (S) to normal sinus rhythm. D, Surface (upper) and transesophageal (lower) etectrograms demonstrates normal sinus rhythm and 1:1 atrioventricular conduction after conversion. These tracings were recorded from patient 6.
ance of a regular sawtooth pattern on the surface electrocardiogram with variable atrioventricular conduction (Fig. 1)6 Patients with electrocardiograms demonstrating variable or poorly formed P waves with varying PR intervals and irregular RR intervals were excluded from the analysis. Transesophageal atrial (and ventricular) recordings were used when available to assist in the diagnosis; this technique was important in a 2-month-old infant in whom the surface electrocardiogram demonstrated intermittently wellformed sawtooth pattern P waves in electrocardiographic leads II, 1II, and aVF. His transesophageal recording demonstrated well-formed atrial electrograms at a cycle length of 120 msec alternating with low-amplitude polyphasic multiform atrial activation waveforms, demonstrating a mixed atrial flutter/fibrillation pattern (Fig. 2); he was excluded. Absence of associated cardiac disease was confirmed at the time of diagnosis in alI patients by physical
examination, chest radiographs, and two-dimensional or M-mode echocardiograms (except in patient 1, in whom no echocardiogram was available). The medical records were scrutinized for abnormalities in the prenatal and perinatal course, including maternal illness, gestational age, birth weight, neonatal course, hemoglobin level, and other associated noncardiac disease. The cycle length of the atrial flutter was measured either on the surface electrocardiogram or through transesophageal electrograms and the atrioventricular conduction pattern by the ventricular response. All therapeutic trials were evaluated and time from initiation of first therapy to conversion of the atrial flutter was noted. Programmed transesophageal atrial extrastimulation was performed in three patients (after conversion) in an effort to identify electrophysiologic properties that might contribute to the atrial flutter. Short-term follow-up noted both discharge medications
388
Mendelsohn, Dick, and Serwer
The Journal of Pediatrics September 1991
Table. Patient data
Pt. No./sex
Age at onset
Perinatal period
Birth weight (kg)
Hemoglobin (gm/dl)
Atrial flutter cycle length (msec) /conduction
1/Male
6 wk
42 wk gestation, pneumonia, biliary atresia
5.1
8.0
160/2:1
2/Female
1 day
3.2
10.7
130/2:1
3/Female
4 mo
35 wk gestation, nonimmune hydrops fetalis, Apgar 2/5 40 wk gestation, uncomplicated
3.6
10.8
200/2:1
4/Female 5/Male 6/Female
Prenatal 1 day Prenatal
39 wk gestation, uncomplicated 35 wk gestation, uncomplicated 40 wk gestation, renal cysts
3.8 2.2 2.8
16.9 21.2 16.3
165/2:1 135/2:1 160/3:1
7/Female
Prenatal
32 wk gestation, immune hydrops fetalis, respiratory distress syndrome, Apgar 4/7
2.6
12.7
125/2:1
8/Male
1 day
4,4
17.1
150/2:1
9/Female Mean
1 day
41 wk gestation, maternal diabetes mellitus 32 wk gestation, Polyhydramnios 37.3 wk
2.0 3.27
11 13.9
135/2:1 151
and evaluation 2 to 6 months after the presenting episode; Holter tracings were available in three patients between 2 and 6 months after cardioversion. Long-term follow-up extended to the last known contact at our institution; at that encounter recurrence of tachycardia, cardiac medications, an electrocardiogram, and other clinical events were noted. RESULTS The clinical data of the nine patients are summarized in the Table. The diagnosis was made before birth by fetal echocardiogram in four patients, on the first day of life in three patients, at 6 weeks of age in one patient, and at 4 months in one patient. Seven of nine patients had Apgar scores of 9 or 10 at 5 minutes of life. Six of the nine patients had perinatal complications (Table). Four of the infants were born at less than 35 weeks of gestation and two were born after 40 weeks. Patient 7 had a 5-minute Apgar score of 7; this infant was born prematurely at 32 weeks' gestational age, and the perinatal period was complicated by immune fetal hydrops and respiratory distress syndrome. Patient 2 was born at 35 weeks of gestation with nonimmune fetal hydrops; no fetal tachycardia had been detected in this patient. Only one infant weighed less than 2000 gm at birth. Five patients were born with relative anemia for gestational age (hemoglobin levels between 8.0 and 12.7 gm/dl). In the postnatal period, patients 7 and 9 had symptoms of the respiratory distress syndrome requiring mechanical ventilation for 5 days and surfactant therapy.
The mean atrial flutter cycle length was 151 msec (atrial rate 397 beats/min). Conversion from atrial flutter to normal sinus rhythm occurred spontaneously (<24 hours) in two patients and possibly spontaneously in three others because conversion occurred between 10 and 24 hours after oral digoxin administration. Patients were initially administered loading doses according to a standard 24-hour schedule (one third of loading dose every 8 hours) and then given 8 to 10 #g/kg/day. The atrial flutter in four patients converted after atrial overdrive pacing through either the esophagus (three patients) or intracardiac electrodes (one patient). One patient (No. 8), after conversion from atrial flutter at 15 minutes of age, had orthodromic reciprocating tachycardia that was promptly converted to sinus rhythm with transesophageal pacing. Programmed atrial stimulation in three infants failed to induce the atrial flutter after each arrhythmia had been converted. One patient (No. 6) underwent atrial stimulation studies while receiving digoxin and again 6 days later without digoxin; the atrial effective refractory periods (shortest cycle length at which atrial conduction could not be achieved) at the same drive cycle length were similar (180 and 150 msee, respectively). Four of the nine patients were discharged home taking digoxin, two for 6 months and two for more than 1 year. Follow-up electrocardiograms in all nine subjects and 24-hour Holter electrocardiographic tracings in three demonstrated normal sinus rhythm with normal PR intervals, no preexcitation, and normal atrioventricular conduction. All patients were
Volume 119 Number 3
Isolated atrial flutter in infancy
389
Table. Cont'd.
Pt. No,
Treatment (acute)
Conversion by acute treatment
1
Digoxin, quinidine Direct-current cardioversion Spontaneous Digoxin
No No Yes Yes
24 hr
Digoxin, 6 mo
20
28 hr
Digoxin, 1 yr
9.6
Digoxin, propranolol Pacing (intracardiac) Digoxin Digoxin Digoxin, verapamil Pacing (esophageal)
Instantaneous
None
9.2
1189 hr 12 hr Instantaneous
Digoxin, 6 mo None None
7.1 5.8 5.4
Maternal digoxin Pacing (esophageal)
No Yes Yes Yes No No Yes No Yes
Instantaneous
2.2
8
Pacing (esophageal)
Yes
Instantaneous
Digoxin, 1 yr (for supraventricular tachycardia) None
9
Spontaneous
Yes
22 hr
None
0.2 6.8
2 3 4 5 6
7
free of symptoms without recurrence for a mean of 6.8 years (range 0.2 to 20 years). DISCUSSION This study underscores the previously noted favorable clinical course after conversion of isolated atrial flutter to normal sinus rhythm in infants. 1,2 In contrast to some authors], 2 however, we could not demonstrate any difference between those patients who were diagnosed to have atrial flutter before birth, at birth, or later in the first year of life by either atrial flutter cycle length, response to therapy, or outcome. Moiler et al. 3 reported that 8% of infants with atrial flutter have associated cardiac anomalies. Our subjects (by design) were free of associated heart disease, but only one other patient less than 1 year of age in our data base has had both atrial flutter and associated (unoperated) structural heart disease (transposition of the great arteries). Dunnigan et al. 5 reported four of eight patients with atrial flutter in infancy who fulfill the criteria used in this report; three of these four infants with isolated atrial flutter had successful cardioversions with atrial overdrive pacing. AIthough several authors 13 " note the lack of a temporal relationship between digoxin therapy and conversion of atrial flutter, all but Dunnigan et al. suggest digoxin as the first therapeutic agent and recommend chronic digoxin therapy. Among our patients there was no difference between patients treated for 6 months or longer with digoxin and those not so treated. Thus we agree with Dunnigan et al. 5
Interval to conversion
Fallow-up treatment
Follow-up interval (yr)
1.5
that isolated atrial flutter will either spontaneously convert or respond promptly to overdrive pacing. Chronic digoxin therapy may be useful only for those patients with mixed atrial flutter/fibrillation or other forms of supraventricular tachycardia. The determinants of atrial flutter in these infants are largely unknown; however, considerable experimental work during the last decade has addressed possible factors. 6-8 Atrial flutter is a sustained tachyarrhythmia with atrial rates from 240 to 360 beats/min characterized by typical P-wave morphology (sawtoothed pattern P waves in leads II, III, and AVF). The mechanism is a circus movement of atrial electrical activation around anatomic structures such as the vena caval orifices, scars, or the tricuspid valve or functional alterations such as inhomogeneity of repolarization within the atria. Initiation of the tachycardia may be dependent on spontaneous atrial premature beats and areas of slow conduction. In canine models 6 and most likely in adult patients the anatomic substrate is essential to maintenance of atrial flutter; further, these structures must be large enough to ensure sufficient length in the macroreentrant (>1 cm) circuit that can allow for repolarization and recovery and, thus, maintain reentry. A potential macroreentrant circuit in a fetal or infant atrium, by size differences alone, would be smaller. This difference in size along with normal to accelerated (relative to diseased or adult hearts) conduction within the atrium most likely accounts for the very rare finding of atrial flutter in this age
390
Mendelsohn, Dick, and Serwer
The Journal of Pediatrics September 1991
f'
I
1 sec
~i,
~
I
I
I'!
!
t
A
I
i'/
f/
III
, B
,
Eso
J
t
t
I
I
Fig. 2. Mixed atrial fibrillation/flutter. A and B, Continuous tracings of surface (leads I, lI, and ]1I) electrocardiogram and transesophageaI (Eso) atrial and ventricular electrograms demonstrate mixed forms of atrial flutter and fibrillation. A, Well-formedlarge atrial electrograms with cycle length of 120 msec (atrial rate 500 beats/rain). B, Spontaneous transient change in the atrial electrogram configuration compatible with atrial fibrillation and a spontaneous return to more well-formed atrial electrogram suggestive of atrial flutter.
group. On the other hand, very small microreentrant loops (as small as 1 cm) can be sustained if there are contiguous areas of inhomogeneity of repolarization and if the effective refractory period of the tissue is uniformly short. The microreentrant form of atrial flutter may play a role in the atypical form such as that seen in the patient we excluded. In this patient and similar ones reported by others, 2' 3, 9 the extremely rapid cycle length (<125 msec) may lead to cycle-to-cycle changes in the activation pattern. This may represent a potentially unstable state between atrial flutter and fibrillation6 and perhaps muitifocal atrial tachycardia, accounting, in part, for the failure of electrical conversion. These patients may have a different natural history than that of the patients presented herein. Pickoff et al.7 have shown that the neonatal canine heart has increased vulnerability to induction of a repetitive atrial response compared with that in older puppies and adult dogs. These findings, along with those outlined above, are possibly relevant to the occurrence of atrial flutter in our patients. Six of our nine patients had perinatal complications that could produce circulatory changes in the fetus and
newborn. Fluid retention (present in the cases of hydrops fetalis and perhaps the patients with anemia and renal cystic disease) could lead to fetal/neonatal conditions capable of producing local functional changes, such as spontaneous premature atrial beats, increased vulnerability to induction of repetitive responses, and altered conduction and refractoriness from distended atria. This distension may produce stretching of atrial tissue to a length sufficient to support the very fast cycle length (mean 151 msec) of atrial flutter in our patients. Once these transient conditions are corrected, by either conversion of atrial flutter or measures directed toward the underlying disorders, the tachyarrhythmia may not recur. The clinical course in our patients, as well as the failure to induce atrial flutter by extrastimulation in three infants, supports this interpretation. This study confirms the excellent outcome of infants with isolated atrial flutter. J, 2 It stands in contrast to the poor prognosis observed by others, 3 in part because we differentiated atrial flutter from mixed forms of atrial fibrillation/ flutter and excluded patients with underlying structural heart disease; the latter may be a stronger determinant of
Volume 119 Number 3
Isolated atrial flutter in infancy
outcome than the arrhythmia alone. 1~ Because of the low incidence of this arrhythmia in infancy, a prospective, randomized study Comparing pharmacologic versus pacing cardioversion is not feasible. Nonetheless, our experience, along with that of others, 2,3, 5, 9 suggests that treatment with digoxin may not be necessary. Recent studies regarding the mechanism(s) of atrial flutter 6-8 provide a firm foundation for both differentiating the spectrum of atrial flutter and initiating transesophageal atrial recording and pacing. Once conversion is achieved, recurrence is rare. Although two (or five) patients in this study had spontaneous conversion of the tachycardia, the prolonged course of atrial flutter in one patient, the advantage of electrical cardioversion :in converting reentrant arrhythmias, and the favorable response and safety of transesophageal overdrive pacing lead us to recommend this technique for acute conversion of isolated atrial flutter in infants. REFERENCES 1. Rowland TW, Mathew R, Chameides L, Keane JF. Idiopathic atrial flutter in infancy: a review of eight cases. Pediatrics 1978;61:52-6.
391
2. Martin TC, Hernandez A. Atrial flutter in infancy. J PEDIATR 1982;100:239-42. 3. Moller JH, Davachi F, Anderson RC. Atrial flutter in infancy. J PEDIATR 1969;75:643-51. 4. Campbell RM, Dick M, Jenkins JM, et al. Atrial overdrive pacing for conversion of atrial flutter in children. Pediatrics 1985;75:730-6. 5. Dunnigan A, Benson DW, Benditt DG. Atrial flutter in infancy: diagnosis, clinical features and treatment. Pediatrics 1985;75:725-9. 6. Boineau JP. Atrial flutter: a synthesis of concepts. Circulation 1985;72:249-57. 7. Pickoff AS, Singh S, Flinn CJ, McCormack J, Stolfi A, Gelband H. Atrial vulnerability in the immature canine heart. Am J Cardiol 1985;55:1402-6. 8. Frame LH, Page RL, Boyden PA, Fenoglio J J, Hoffman BF. Circus movement in the canine atrium around the tricuspid ring during atrial flutter and during reentry in vitro. Circulation 1987;76:1155-75. 9. Rodriguez-Coronel A, Sueblingvong V, Hastreiter AR. Clinical forms of atrial flutter in infancy. J PEDIATR1968;73:6976. 10. Garson A Jr, Bink-Boelkens M, Hesslein PS, et al. Atrial flutter in the young: a collaborative study of 380 cases. J Am Coil Cardiol 1985;6:871-8.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the 1991 issues of THE JOURNAL OF PEDIATRICS are available to subscribers (only) from the Publisher, at a cost of $52.00 for domestic, $71.64 for Canadian, and $68.00 for international subscribers, for Vol. 118 (January-June) and Vol. 119 (July-December), shipping charges included. Each bound volume contains subject and author indexes, and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram, with the Journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318, USA/800-325-4177, ext. 4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular Journal subscription.
Atrial flutter is an uncommon arrhythmia in infancy. Patients with primary arrhythmias (i.e., no associated structural heart disease) represent 7% of the approximately 18,000 patients seen in our pediatric cardiac clinics; however, only nine of these patients have had isolated (i.e., not associated with other forms of heart disease) atrial flutter during infancy. Digoxin, which was virtually the only available therapy for many years, 1,2 direct current cardioversion, 3 and atrial overdrive pacing 4, 5 have been advanced as initial therapy. Dunnigan et al. 5 and Martin and Submitted for publication Jan. 24, 1991; accepted March 25, 1991. Reprint requests: Macdonald Dick II, MD, F1310, Box 0204, C.S. Mott Children's Hospital, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0204. 9/20/29699
386
Hernandez 2 have reported mean follow-up periods of 1.9 and 3,4 years, respectively, but an extensive natural history of infants with isolated atrial flutter is unavailable. To clarify the clinical course of infants with isolated atrial flutter and to determine optimal initial therapy, as well as the need for long-term digoxin prophylaxis, we reviewed our experience in nine infants with isolated atrial flutter. METHODS The Cardiac Diagnostic Database of the Division of Pediatric Cardiology, Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan, was searched to identify all patients with atrial flutter; those individuals in whom atrial flutter appeared after the first year of life or who had associated heart disease were excluded. Atrial flutter was defined electrocardiographically by the appear-
Volume 119 Number 3
Isolated atrial flutter in infancy
387
~lllllllllllll(llllllEliliilliillllllllllllllli,~,, ~q~i,~,,,,,~ ,~,,,,~ 84i/~i~,t, 84
ESOPN
IIIIlIfIlltlllIIIIIIIIII NilIIIIIIIIINilIttlItttIIIl!il}[gi!i;l~', illil;ll'ltlIil)lllHlIIIIIIIIllll{i lili,/ll
lI[lIl[[llllHlt[ll/II/llHIlllII]IHII/l/II/lllil/illliiill tllIHl ;i;~ililliil] H]I III1111IIIlIlllll II1!;III 1111}111
~H~[~lH~HII[IIII~IN~l~1~1ll1~1lll~llll~1~l~ll~i~1~1ll[~I]?i~i~1111~1I~I~1~tt~H~ 1
Fig. t. Electrocardiographic tracings of atrial flutter. A, Simultaneous surface (/earl II) electrocardiogram {upper) and transesophageal (ESOPH} atrial electrogram (lower) demonstrate atrial flutter with 3:1 block. Note constant we/l-formed atrial eleetrograms in esophageal tracing. B and C, Continuous electrocardiogram demonstrates atrial flutter. Rhythm was converted by transesophageal overdrive pacing (S) to normal sinus rhythm. D, Surface (upper) and transesophageal (lower) etectrograms demonstrates normal sinus rhythm and 1:1 atrioventricular conduction after conversion. These tracings were recorded from patient 6.
ance of a regular sawtooth pattern on the surface electrocardiogram with variable atrioventricular conduction (Fig. 1)6 Patients with electrocardiograms demonstrating variable or poorly formed P waves with varying PR intervals and irregular RR intervals were excluded from the analysis. Transesophageal atrial (and ventricular) recordings were used when available to assist in the diagnosis; this technique was important in a 2-month-old infant in whom the surface electrocardiogram demonstrated intermittently wellformed sawtooth pattern P waves in electrocardiographic leads II, 1II, and aVF. His transesophageal recording demonstrated well-formed atrial electrograms at a cycle length of 120 msec alternating with low-amplitude polyphasic multiform atrial activation waveforms, demonstrating a mixed atrial flutter/fibrillation pattern (Fig. 2); he was excluded. Absence of associated cardiac disease was confirmed at the time of diagnosis in alI patients by physical
examination, chest radiographs, and two-dimensional or M-mode echocardiograms (except in patient 1, in whom no echocardiogram was available). The medical records were scrutinized for abnormalities in the prenatal and perinatal course, including maternal illness, gestational age, birth weight, neonatal course, hemoglobin level, and other associated noncardiac disease. The cycle length of the atrial flutter was measured either on the surface electrocardiogram or through transesophageal electrograms and the atrioventricular conduction pattern by the ventricular response. All therapeutic trials were evaluated and time from initiation of first therapy to conversion of the atrial flutter was noted. Programmed transesophageal atrial extrastimulation was performed in three patients (after conversion) in an effort to identify electrophysiologic properties that might contribute to the atrial flutter. Short-term follow-up noted both discharge medications
388
Mendelsohn, Dick, and Serwer
The Journal of Pediatrics September 1991
Table. Patient data
Pt. No./sex
Age at onset
Perinatal period
Birth weight (kg)
Hemoglobin (gm/dl)
Atrial flutter cycle length (msec) /conduction
1/Male
6 wk
42 wk gestation, pneumonia, biliary atresia
5.1
8.0
160/2:1
2/Female
1 day
3.2
10.7
130/2:1
3/Female
4 mo
35 wk gestation, nonimmune hydrops fetalis, Apgar 2/5 40 wk gestation, uncomplicated
3.6
10.8
200/2:1
4/Female 5/Male 6/Female
Prenatal 1 day Prenatal
39 wk gestation, uncomplicated 35 wk gestation, uncomplicated 40 wk gestation, renal cysts
3.8 2.2 2.8
16.9 21.2 16.3
165/2:1 135/2:1 160/3:1
7/Female
Prenatal
32 wk gestation, immune hydrops fetalis, respiratory distress syndrome, Apgar 4/7
2.6
12.7
125/2:1
8/Male
1 day
4,4
17.1
150/2:1
9/Female Mean
1 day
41 wk gestation, maternal diabetes mellitus 32 wk gestation, Polyhydramnios 37.3 wk
2.0 3.27
11 13.9
135/2:1 151
and evaluation 2 to 6 months after the presenting episode; Holter tracings were available in three patients between 2 and 6 months after cardioversion. Long-term follow-up extended to the last known contact at our institution; at that encounter recurrence of tachycardia, cardiac medications, an electrocardiogram, and other clinical events were noted. RESULTS The clinical data of the nine patients are summarized in the Table. The diagnosis was made before birth by fetal echocardiogram in four patients, on the first day of life in three patients, at 6 weeks of age in one patient, and at 4 months in one patient. Seven of nine patients had Apgar scores of 9 or 10 at 5 minutes of life. Six of the nine patients had perinatal complications (Table). Four of the infants were born at less than 35 weeks of gestation and two were born after 40 weeks. Patient 7 had a 5-minute Apgar score of 7; this infant was born prematurely at 32 weeks' gestational age, and the perinatal period was complicated by immune fetal hydrops and respiratory distress syndrome. Patient 2 was born at 35 weeks of gestation with nonimmune fetal hydrops; no fetal tachycardia had been detected in this patient. Only one infant weighed less than 2000 gm at birth. Five patients were born with relative anemia for gestational age (hemoglobin levels between 8.0 and 12.7 gm/dl). In the postnatal period, patients 7 and 9 had symptoms of the respiratory distress syndrome requiring mechanical ventilation for 5 days and surfactant therapy.
The mean atrial flutter cycle length was 151 msec (atrial rate 397 beats/min). Conversion from atrial flutter to normal sinus rhythm occurred spontaneously (<24 hours) in two patients and possibly spontaneously in three others because conversion occurred between 10 and 24 hours after oral digoxin administration. Patients were initially administered loading doses according to a standard 24-hour schedule (one third of loading dose every 8 hours) and then given 8 to 10 #g/kg/day. The atrial flutter in four patients converted after atrial overdrive pacing through either the esophagus (three patients) or intracardiac electrodes (one patient). One patient (No. 8), after conversion from atrial flutter at 15 minutes of age, had orthodromic reciprocating tachycardia that was promptly converted to sinus rhythm with transesophageal pacing. Programmed atrial stimulation in three infants failed to induce the atrial flutter after each arrhythmia had been converted. One patient (No. 6) underwent atrial stimulation studies while receiving digoxin and again 6 days later without digoxin; the atrial effective refractory periods (shortest cycle length at which atrial conduction could not be achieved) at the same drive cycle length were similar (180 and 150 msee, respectively). Four of the nine patients were discharged home taking digoxin, two for 6 months and two for more than 1 year. Follow-up electrocardiograms in all nine subjects and 24-hour Holter electrocardiographic tracings in three demonstrated normal sinus rhythm with normal PR intervals, no preexcitation, and normal atrioventricular conduction. All patients were
Volume 119 Number 3
Isolated atrial flutter in infancy
389
Table. Cont'd.
Pt. No,
Treatment (acute)
Conversion by acute treatment
1
Digoxin, quinidine Direct-current cardioversion Spontaneous Digoxin
No No Yes Yes
24 hr
Digoxin, 6 mo
20
28 hr
Digoxin, 1 yr
9.6
Digoxin, propranolol Pacing (intracardiac) Digoxin Digoxin Digoxin, verapamil Pacing (esophageal)
Instantaneous
None
9.2
1189 hr 12 hr Instantaneous
Digoxin, 6 mo None None
7.1 5.8 5.4
Maternal digoxin Pacing (esophageal)
No Yes Yes Yes No No Yes No Yes
Instantaneous
2.2
8
Pacing (esophageal)
Yes
Instantaneous
Digoxin, 1 yr (for supraventricular tachycardia) None
9
Spontaneous
Yes
22 hr
None
0.2 6.8
2 3 4 5 6
7
free of symptoms without recurrence for a mean of 6.8 years (range 0.2 to 20 years). DISCUSSION This study underscores the previously noted favorable clinical course after conversion of isolated atrial flutter to normal sinus rhythm in infants. 1,2 In contrast to some authors], 2 however, we could not demonstrate any difference between those patients who were diagnosed to have atrial flutter before birth, at birth, or later in the first year of life by either atrial flutter cycle length, response to therapy, or outcome. Moiler et al. 3 reported that 8% of infants with atrial flutter have associated cardiac anomalies. Our subjects (by design) were free of associated heart disease, but only one other patient less than 1 year of age in our data base has had both atrial flutter and associated (unoperated) structural heart disease (transposition of the great arteries). Dunnigan et al. 5 reported four of eight patients with atrial flutter in infancy who fulfill the criteria used in this report; three of these four infants with isolated atrial flutter had successful cardioversions with atrial overdrive pacing. AIthough several authors 13 " note the lack of a temporal relationship between digoxin therapy and conversion of atrial flutter, all but Dunnigan et al. suggest digoxin as the first therapeutic agent and recommend chronic digoxin therapy. Among our patients there was no difference between patients treated for 6 months or longer with digoxin and those not so treated. Thus we agree with Dunnigan et al. 5
Interval to conversion
Fallow-up treatment
Follow-up interval (yr)
1.5
that isolated atrial flutter will either spontaneously convert or respond promptly to overdrive pacing. Chronic digoxin therapy may be useful only for those patients with mixed atrial flutter/fibrillation or other forms of supraventricular tachycardia. The determinants of atrial flutter in these infants are largely unknown; however, considerable experimental work during the last decade has addressed possible factors. 6-8 Atrial flutter is a sustained tachyarrhythmia with atrial rates from 240 to 360 beats/min characterized by typical P-wave morphology (sawtoothed pattern P waves in leads II, III, and AVF). The mechanism is a circus movement of atrial electrical activation around anatomic structures such as the vena caval orifices, scars, or the tricuspid valve or functional alterations such as inhomogeneity of repolarization within the atria. Initiation of the tachycardia may be dependent on spontaneous atrial premature beats and areas of slow conduction. In canine models 6 and most likely in adult patients the anatomic substrate is essential to maintenance of atrial flutter; further, these structures must be large enough to ensure sufficient length in the macroreentrant (>1 cm) circuit that can allow for repolarization and recovery and, thus, maintain reentry. A potential macroreentrant circuit in a fetal or infant atrium, by size differences alone, would be smaller. This difference in size along with normal to accelerated (relative to diseased or adult hearts) conduction within the atrium most likely accounts for the very rare finding of atrial flutter in this age
390
Mendelsohn, Dick, and Serwer
The Journal of Pediatrics September 1991
f'
I
1 sec
~i,
~
I
I
I'!
!
t
A
I
i'/
f/
III
, B
,
Eso
J
t
t
I
I
Fig. 2. Mixed atrial fibrillation/flutter. A and B, Continuous tracings of surface (leads I, lI, and ]1I) electrocardiogram and transesophageaI (Eso) atrial and ventricular electrograms demonstrate mixed forms of atrial flutter and fibrillation. A, Well-formedlarge atrial electrograms with cycle length of 120 msec (atrial rate 500 beats/rain). B, Spontaneous transient change in the atrial electrogram configuration compatible with atrial fibrillation and a spontaneous return to more well-formed atrial electrogram suggestive of atrial flutter.
group. On the other hand, very small microreentrant loops (as small as 1 cm) can be sustained if there are contiguous areas of inhomogeneity of repolarization and if the effective refractory period of the tissue is uniformly short. The microreentrant form of atrial flutter may play a role in the atypical form such as that seen in the patient we excluded. In this patient and similar ones reported by others, 2' 3, 9 the extremely rapid cycle length (<125 msec) may lead to cycle-to-cycle changes in the activation pattern. This may represent a potentially unstable state between atrial flutter and fibrillation6 and perhaps muitifocal atrial tachycardia, accounting, in part, for the failure of electrical conversion. These patients may have a different natural history than that of the patients presented herein. Pickoff et al.7 have shown that the neonatal canine heart has increased vulnerability to induction of a repetitive atrial response compared with that in older puppies and adult dogs. These findings, along with those outlined above, are possibly relevant to the occurrence of atrial flutter in our patients. Six of our nine patients had perinatal complications that could produce circulatory changes in the fetus and
newborn. Fluid retention (present in the cases of hydrops fetalis and perhaps the patients with anemia and renal cystic disease) could lead to fetal/neonatal conditions capable of producing local functional changes, such as spontaneous premature atrial beats, increased vulnerability to induction of repetitive responses, and altered conduction and refractoriness from distended atria. This distension may produce stretching of atrial tissue to a length sufficient to support the very fast cycle length (mean 151 msec) of atrial flutter in our patients. Once these transient conditions are corrected, by either conversion of atrial flutter or measures directed toward the underlying disorders, the tachyarrhythmia may not recur. The clinical course in our patients, as well as the failure to induce atrial flutter by extrastimulation in three infants, supports this interpretation. This study confirms the excellent outcome of infants with isolated atrial flutter. J, 2 It stands in contrast to the poor prognosis observed by others, 3 in part because we differentiated atrial flutter from mixed forms of atrial fibrillation/ flutter and excluded patients with underlying structural heart disease; the latter may be a stronger determinant of
Volume 119 Number 3
Isolated atrial flutter in infancy
outcome than the arrhythmia alone. 1~ Because of the low incidence of this arrhythmia in infancy, a prospective, randomized study Comparing pharmacologic versus pacing cardioversion is not feasible. Nonetheless, our experience, along with that of others, 2,3, 5, 9 suggests that treatment with digoxin may not be necessary. Recent studies regarding the mechanism(s) of atrial flutter 6-8 provide a firm foundation for both differentiating the spectrum of atrial flutter and initiating transesophageal atrial recording and pacing. Once conversion is achieved, recurrence is rare. Although two (or five) patients in this study had spontaneous conversion of the tachycardia, the prolonged course of atrial flutter in one patient, the advantage of electrical cardioversion :in converting reentrant arrhythmias, and the favorable response and safety of transesophageal overdrive pacing lead us to recommend this technique for acute conversion of isolated atrial flutter in infants. REFERENCES 1. Rowland TW, Mathew R, Chameides L, Keane JF. Idiopathic atrial flutter in infancy: a review of eight cases. Pediatrics 1978;61:52-6.
391
2. Martin TC, Hernandez A. Atrial flutter in infancy. J PEDIATR 1982;100:239-42. 3. Moller JH, Davachi F, Anderson RC. Atrial flutter in infancy. J PEDIATR 1969;75:643-51. 4. Campbell RM, Dick M, Jenkins JM, et al. Atrial overdrive pacing for conversion of atrial flutter in children. Pediatrics 1985;75:730-6. 5. Dunnigan A, Benson DW, Benditt DG. Atrial flutter in infancy: diagnosis, clinical features and treatment. Pediatrics 1985;75:725-9. 6. Boineau JP. Atrial flutter: a synthesis of concepts. Circulation 1985;72:249-57. 7. Pickoff AS, Singh S, Flinn CJ, McCormack J, Stolfi A, Gelband H. Atrial vulnerability in the immature canine heart. Am J Cardiol 1985;55:1402-6. 8. Frame LH, Page RL, Boyden PA, Fenoglio J J, Hoffman BF. Circus movement in the canine atrium around the tricuspid ring during atrial flutter and during reentry in vitro. Circulation 1987;76:1155-75. 9. Rodriguez-Coronel A, Sueblingvong V, Hastreiter AR. Clinical forms of atrial flutter in infancy. J PEDIATR1968;73:6976. 10. Garson A Jr, Bink-Boelkens M, Hesslein PS, et al. Atrial flutter in the young: a collaborative study of 380 cases. J Am Coil Cardiol 1985;6:871-8.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the 1991 issues of THE JOURNAL OF PEDIATRICS are available to subscribers (only) from the Publisher, at a cost of $52.00 for domestic, $71.64 for Canadian, and $68.00 for international subscribers, for Vol. 118 (January-June) and Vol. 119 (July-December), shipping charges included. Each bound volume contains subject and author indexes, and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram, with the Journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318, USA/800-325-4177, ext. 4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular Journal subscription.