Prolonged QT interval in neonates: Benign, transient, or prolonged risk of sudden death Elizabeth Villain, MD,” Marilyn Arthur Garson, Jr., MD.b Paris,

Levy, MD,a Jean Kachaner, MD,a and France, and Houston, Texas

Prolongation of the QT interval on the electrocardiogram in certain individuals is associated with an increased incidence of life-threatening arrhythmias and sudden death. When discovered in a newborn, a long QT interval may be the marker of a true long QT syndrome (LQTS) with its attendant risk of sudden death, or simply a transient electrocardiographic abnormality. To determine the factors relating to prognosis, we reviewed the records of 15 infants who had a long QT interval in the neonatal period without an underlying cause. METHODOLOGY

The patient population consisted of patients from Hopital Necker Enfants-Malades, Paris (patients No. 1 to 9) and from Texas Children’s Hospital, Houston (patients No. 10 to 15). Each patient had a standard la-lead electrocardiogram (ECG), which was repeated daily during hospitalization. Each ECG was measured by the same investigator (EV). The QT interval’ was measured from the onset of the Q wave to the end of the T wave in lead II; the corrected QT for heart rate (QT,) was then obtained by Bazett’s formula, dividing the observed QT interval in seconds by the square root of the preceding R-R interval. A value greater than 0.45 second was considered as a prolonged QT. Patients with metabolic abnormalities or neurologic disorders were excluded, as were neonates whose QT returned to normal by the fourth day of life.

From %ervice de Cardiologie PQdiatrique, DBpartement de PQdiatrie, Hopita1 des Enfants-Malades; and bThe Lillie Frank Abercrombie, Section ot Cardiology, Department of Pediatrics. Baylor College of Medicine, and Texas Children’s Hospital. Received

for publication

Nov.

25, 1991;

accepted

Jan.

:i. 1992.

Reprint requests: Dr. Elizabeth Villain, Service de Cardiologie Pkdiatrique. D&partement de PPdiatrie, Hopital des Enfants-Malades, 149 rue de SBvres. 75743 Paris Cedex 15. France.

411137724

194

OBSERVATIONS Clinical data.

Fifteen neonates met these criteria. There were eight boys and seven girls. Five of them had intrauterine bradycardia, one with hydrops fetalis. Three were premature. In nine newborns, the initial ECG was performed because of bradycardia (six patients), irregular heart rate (two patients), or long QT in a sibling (one patient); six patients were referred because of symptoms of cardiac failure, syncope or apnea with pallor, or seizures. Two patients were siblings. A familial history of a long QT syndrome or of unexplained sudden death was found in four cases (Table I). Surface electrocardiography. All patients had a long QT,, ranging from 0.46 second to more than 0.70 second (mean = 0.58 second). Tracings of 11 patients also showed abnormal repolarization, with ST segment deformation or an inverted T wave (Fig. 1). Heart rate ranged from 80 to 140 beatslmin. When they were in sinus rhythm with normal atrioventricular conduction, 10 patients had bradycardia of 100 beatslmin or less. Cardiac arrhythmias occurred in eight patients. Transient first- and second-degree atrioventricular block (Mobitz type I and II) was seen in eight caseswhen the sinus rate was more than 120 to 150 beats/min; variable bundle branch block was associated with atrioventricular block in four of these patients. Life-threatening ventricular arrhythmias with tracings of “torsades de pointes” (five patients) or monomorphic ventricular tachycardia (two patients) were observed in six infants; all six patients had both documented block and ventricular arrhythmias (Fig. 2). Treatment. $-Blocking drugs, oral propranolol(2 to 5 mg/kg), or acebutolol (10 mg/kg) were given to 12 patients. Patient No. 4 received intravenous isoproterenol, which was not effective in preventing torsades de pointes. In patient No. 7, intravenous verapamil suppressed torsades de pointes, but was followed by cardiovascular collapse. A temporary pacing

Volume Number

124 1

Prolonged

Fig. 1. Idiopathic long QT syndrome. Top tracings, Electrocardiogram (QT, > 0.60 second) with ST deformation and a biphasic T wave. Lower Persistence of QT prolongation, with repolarization abnormalities.

Table

--

~_

I. Patient

Putient %(I.

QT in

neonates on sudden death

195

at 8 days of age. QT prolongation tracing, Same infant at 12 months.

data Fam

Presentation

Sinus (beatslmin)

1

0

Syncope

95

2 3 4 5 6 7 8 9 10 11 12 13 14 15

+ 0 0 0 + + 0 0 0 + 0 0 0 0

CF Brady CF Brady Fam Irreg HR Brady Apnea Brady Brady Seizures Syncope Irreg. HR Brady

110

100 80 95 95 140

80 120 90 . 80 100 140 135 70

Aceb. Acebutolol; AVB, atriaventricular block; Brady, bradycardia; nol; LQTS, long QT syndrome; PM, pacemaker; Prop, propranolol; tricuiar tachyrardia; f, positive; 0, negative; D. death.

QT, (see) 0.65 0.70 0.70 0.68 0.70 0.62 0.60 0.4x 0.4X 0.52 0.57 0.67 0.41 0.48 0.46

Arrhythmias

Treatment

Tors,AVB VT, AVB Tors, AVB Tors, AVB AVB AVB Tom, AVB

Prop,TP Prop, TP Prop,TP, PM Iso, TP Aceb Prop TP. PM, Prop, Ver Aceb

Tors. AVB

Prop Prop Prop Prop Prop

D I> D D 24 mo, LQTS 7 yr, LQTS 11 yr, LQTS 18 mo, 0.40 12 mo, 0.40 6 yr, LQTS 10 yr, LQTS 10 yr. LQTS 11 yr. 0.40

-

6 mo, 0.38 12 mo, 0.40

CF, cardiac failure; Fnm, family history; Irreg HR. irregular heart rate; Iso. isoprotereTars, torsades de pointes; 77’. temporary pacing: VW, verapamil: VT. monomorphic ven-

catheter was used in five children; two of them subsequently underwent implantation of a permanent epicardial ventricular pacemaker. Two infants were not treated. Follow-up

Deaths. Of the 15 infants, 4 died in the first month of life. Two (patiems No. 1 and 4) died of intractable ventricular arrhythmia. Patient No. 2 died 24 hours after removal of a temporary pacing catheter for low cardiac output related to atrioventricular (AV) block and bradycardia; the parents had refused permanent pacing. The last death (patient No. 3) was related to

a pacemaker infection; at the time of death, the patient was being treated with propranolol and his hemodynamic status was good, with no ventricular arrhythmia. All the infants who died had a very long QT (QT, > 0.65 second) with abnormal ST segments. Each had the combination of AV block and ventricular arrhythmias. Survivors. Follow-up among survivors ranged from 2 to 12 years (mean = 6 years). At follow-up, the QT, was more than 0.50 second in six cases, and these children are still treated with P-blocking agents, propranolol (three patients), nadolol (two patients), or

196

Villain

*.

it

r/l.

‘f-f-y+-r-$~F

Rs

Amervxn

_- .- 1 . _.^ ._

- .

1

acebutolol (one patient ). There were no cotnplic~ttions in this group, except. transient hypoglyc,emia because ot’&blocking agents (two patients). Two putients still have a transient Mobitz I AV block when the sinus rate is greater than 120 beats/min (patients No. 6 and 7): one of these ha:< a \.etttr.i~~ular pacemaker. In five cases, prolongation 01’ 1he 147 wits transient. and the QT returned to normal between 2 and 7 tnonths of’ age (Fig. 3). Patient No. 12. who had syncope shortly after birth. is still being treat,ed, although the QT is now normal. Proprano:ol was discontinued between 6 and 12 months ot’ age in the last two patient.s. COMMENTS

In this group of’ infants. the idiopathic long Q’I syndrome was fatal in t.he first weeks of life in .I of’ 15; among the 11 early survivors, the QT prolongation later disappeared in five. Data on t.he QT interval in inf’anls art’ limited, iire ol’ten based 011sniall 5raries:.

Heart

July 1992 Journal

and do not provide longitudinal information.“.,’ In 1982, Schwart.zd published a prospective st.udy involving 42OFinormal infants, 3946 ot’ them being 1 days old at the time of t,he first electrocardiogram. This age was selected t,o avoid the variability of the QT interval t.hat may be observed in the first days ot lit’e. The QT, was 0.39’i I 0.018 second in f’ull-tern] and 0.301 1 0.024 second in a group ot I 18 premat urc’ babies; values greater than 0.451 second i+3 SD) were considered as a prolonged QT interval. In Schwart,z’s study, 35 newborns had prolongation of the QT interval; none of t,hese infants was treated. Thirty remained asymptomatic and had normalization of’ their electrocardiogram within the first 2 years. Three were lost to f’ollow-up, hut two died suddenly. The first one died at 1 month: he had a verb long QT interval (QT, = O..Sci second) with sinIts bradycardia and abnormal repolarization. The othet one was born prematurely. had a Q?‘,. ctf’O.46second. and he died at 2 months 01’age: he hatI ;I twin whose Ij’l’! was also prolonged (0.46 second) and ret,urned to normal. i ‘ases of’ temporary prolongation d I he QT inter1.~1have been reported. sometimes with document.etl lit’r-ihreatening arrhythmias.” Among ‘)ur 15 p:rtients, file had a transient long QT interval. This is ti111tiec*essaril>benign. since 2 of’ 15 had had symptenth l’hosf> whose QT interval nortnalizrd later all had ii I)‘J’, (II’ less i ban 0.50 second at i days of’ age, had 1tt1 ;j\: l)lock. no documented \tAntricular arm rli?? hmias. and rare repolarization abnormalities. ‘l’ttese tindings are consistent with Schwartz’s results; it.1Iii:, ht rttiy. all infants with a transient long QT i~i1~ri-al had initial values T interval and major ST segment changes; the in these patients is high, esperisk of’ scldden death cially in the tirst weeks of life. In those with the comhinat ion of’ a long QT, interval and AV block, early I t’t’atrne1!1 \cit t! -: blockers and parin:: ~.l!o~rldhe COII

vohne Number

124 1

Prolonged

Fig. 3. Transient repolarization deformation 01’ the ST segment, 6 and 12 months elf ag:r.

SUMMARY the factors

relating

197

abnormalities. ECG tracings of patient No. 9 at 15 days of age. There is with a QT,, of 0.18 second. The QT interval returned to normal between

sidered. .4fter the lust weehs of life, if arrhythmias are controlled with treatment, the prognosis appears to l)e good, although further follow-up is required. In conclusion, pr!)longation of the QT interval in neonates may be transient or may represent an early form of the long QT syndromes. The length of the QT interval at 4 days l)f’ age may provide data on the prognosis. In all infants with a QT, less than 0.50 second, the abnormality was transient, disappearing by 1 year of age. Both infants presenting with a QT, of Cl.50to 0.59 second continue to have a prolonged QT interval, but are asymptomatic. Of those eight with a QTC > 0.60 second, all had second-degree AV block, six had “torsades de pointes,” and four died.

7’0 determine

47 in rwonat~s on sudden drath

to prognosis,

the

records of 15 neonates with persistent prolongation of t.he QT int,erval on t,he electrocardiogram after the fourth day of life were reviewed. Patient,s were admitted for symptoms (syncope, cardiac failure, or seizures), abnormal auscult ation with an irregular heart rat.e or bradycardia, or because of a family history of a long QT syndrome. All infants had a long Q1’ 0.60 second were associated with severe arrhythmias and four of eight infants died. REFERENCES

I. Garstrn A. The normal The electrocardiogram Lea & Febiger,

electrocardiogram. In: Garson A, ed. in infants and children. Philadelphia:

1983:71-6.

2. Weinstein S, Steinschneider

A. Q’I‘C and RR intervals in victims of the sudden infant death syndrome. Am .J Ibis Child 1985;1:39:987-9. :i. \Veintraub RG, C&J RIM, Wilkinson ,J. The congenital lung QT syndromes in childhood. .I Am (“011 rardiol 1990:16:674811. -1. Schwartz PJ. Montemerlo M, Facchini M, et al. The QT interval throughout the tirst six months of life: a prospective study. Circulation 198‘;66:496-501. 5. Hat&e A. Hellov C, Fermont L,, PiCchaud .JF, Iiachaner J. Allongemrnt de i’espace Q?’ avec bloc auriculoventriculaire f’onctionnel chez le nouveau-G et lc jeune nourrisson. Arch Fr Pediatr IYXl;XH:657-62.