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Hereditary Long QT Syndrome in Pregnancy: Antenatal and Intrapartum Management Options

June 14, 2007

By Papantoniou, Nicolaos Katsoulis, Ioannis; Papageorgiou, Ioannis; Antsaklis, Aris

Abstract Long QT syndrome is a rare but severe cardiac arrhythmia. We report the antenatal and intrapartum management of a primigravida carrying the hereditary form of the disease and specifically the Romano-Ward syndrome. A multidisciplinary approach and close obstetric surveillance are mandatory for a good maternal and perinatal outcome. Follow-up of the neonate is equally important.

Keywords: Hereditary long QT syndrome, antenatal care

Introduction

Pregnancy is associated with a variety of cardiovascular changes that normal women can physiologically tolerate, but which are responsible for clinical decompensation in patients with structural heart defects. However, the effect of pregnancy on patients with cardiac rhythm disorders is not well characterized. Previous studies have focused primarily on patients with supraventricular arrhythmias. Increasingly, there is interest in other forms of arrhythmias and the effect of pregnancy on them. Long QT syndrome (LQTS) is a cardiac disorder characterized by an abnormality in cardiac repolarization that leads to prolongation of the QT interval (>0.44 seconds), T-wave changes, and torsade de pointes (TdS) on surface electrocardiograms (ECGs). We report a case of hereditary LQTS in pregnancy and the management options used for the antenatal and intrapartum care of the patient. Our aim is to present this rare but severe form of arrhythmia, how this can complicate pregnancy, and most importantly to present safe options for management.

Case report

A 26-year-old primigravida affected by LQTS at 36 weeks plus 2 days of gestation was admitted to the high-risk pregnancy ward in order to be assessed for further management, the time and mode of delivery. She suffers from the hereditary form of LQTS with a dominant pattern of inheritance, not combined with deafness, which is known as the Romano-Ward syndrome. This had been diagnosed 11 years previously, after an episode of recurrent loss of consciousness during swimming. She had a strong family history, including the sudden cardiac death of her sister during adolescence. Her grandmother, father and another sister have also suffered with this syndrome. Ten years previously she had been given a pacemaker, which had been replaced 5 years later and was still in place at this time. She was additionally being treated with beta-blockers.

During the antenatal period the patient attended the high-risk pregnancies clinic at regular monthly intervals until 24 weeks, and she was also regularly reviewed by a consultant cardiologist. Thereafter she was monitored with regular ultrasound scans every 15 days for growth assessment, biophysical profiles and Doppler studies. The pregnancy was uneventful for the mother and the fetus and she was finally admitted at 36 weeks for delivery. At the time of her pre-labor admission, the patient was evaluated by the attendant consultant cardiologist and had cardiac ultrasound assessment as well as technical assessment of the pacemaker and all was revealed to be in order. An obstetric ultrasound scan revealed oligohydramnios (amniotic fluid index (AFI) 7 cm at 36 weeks), but with normal estimated fetal weight (3150 g) and biophysical profile (8/10), as well as umbilical artery Doppler studies (pulsatility index (PI) 1.00). On the basis of the presence of oligohydramnios, in the absence of other findings, but with lung maturity having been reached, the decision was taken to deliver the baby. The mode suggested by the cardiologist was cesarean section under general anesthesia; thus the patient would avoid the strain associated with labor, which could provoke arrhythmias. Moreover the maternal surveillance at delivery and the immediate postpartum period are optimal in an operating theatre and intensive care unit. An unfavorable Bishop score was an additional indication for cesarean section. She had an uneventful elective lower segment cesarean section at 36 weeks plus 6 days of gestation and delivered a female neonate of 2800 g with 9/10 1-min Apgar score. During the postpartum period she had an uncomplicated recovery under continuous ECG monitoring. The neonate was investigated thoroughly with regard to cardiac function, with ECG and ultrasound studies, and has not shown any evidence of cardiac disease. Genetic counseling was offered for the short-term follow-up and the baby is being followed up at monthly intervals with ECGs.

Discussion

The incidence of arrhythmias varies between men and women; the main predisposing factor is the effect of the reproductive hormones on the electrophysiologic structure of the heart. Women are at lower risk of sudden cardiac death overall, but they have a high risk of presenting with the LQTS [I]. This is a hereditary disorder of cardiac ion channels causing abnormal electrical activation of the heart and leading to life-threatening ventricular tachycardia.

More than 300 mutations have been identified in five genes encoding subunits of cardiac potassium and sodium channels. These genes are KCNQl, KCNH2, SCN5A, KCNE1, KCNE2 located on chromosomes 11, 7, 3 and 4, and genetic testing is now available [2]. These mutations are responsible for the Romano-Ward syndrome, which is the hereditary LQTS with dominant autosomal transmission not combined with deafness. Our patient had been diagnosed with Romano-Ward syndrome 11 years previously after recurrent loss of consciousness. Mutations of the minK gene are responsible for the much rarer Jervell-Lange-Nilsen syndrome, with recessive autosomal pattern of inheritance, which is also a hereditary LQTS combined with congenital sensorineural deafness [3]. Recently a new variant of the LQTS has been described, called Andersen syndrome, which is also transmitted with autosomal dominant pattern and affects both the cardiac and skeletal muscles. The responsible mutation affects the KCNJ2 gene of chromosome 17 [4]. There is also an acquired drug- related form of the syndrome and women are also more susceptible to it. The incidence of hereditary LQTS in the USA is 1:5000. In our department it was the first case managed throughout pregnancy. Syncope, ventricular tachycardia, or sudden cardiac death in the absence of structural heart disease is the typical presentation, even during childhood.

Pregnancy can precipitate all cardiac arrhythmias not previously present, in seemingly well individuals. Risk of arrhythmias is relatively higher during labor and delivery. Potential factors that can promote this presentation in pregnancy include the direct effect of the hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia of pregnancy, and underlying heart disease [5]. For the LQTS the critical period is labor and the puerperium, although the antenatal period is equally important for the well-being of the mother, who must be under surveillance throughout pregnancy. Pregnant women diagnosed with LQTS should also be treated with beta-blockers for primary prevention of cardiac arrhythmias, although these are associated with intrauterine growth restriction, thus close fetal growth assessment is mandatory. The mode of delivery suggested by most physicians, including at our center, is by elective cesarean section to reduce the stress related with vaginal birth and possible provocation of arrhythmias. There is a consensus for general anesthesia and that was the case in our unit, with the physicians involved (obstetrician, cardiologist and the anesthetist) agreed on this; nevertheless regional anesthesia has been utilized by others [6].

The genetic feature of the disorder puts the fetus at risk as well. Prenatal diagnosis of the syndrome is possible indirectly with the evidence of sinus bradycardia in the cardiotocogram during delivery or in pregnancy [7], and directly invasively by genotyping [8]. Non-invasively, prenatal diagnosis can be made by magnetocardiography, which reveals the prolongation of the QT interval. The latter is a new non-invasive method used over the maternal abdomen that permits analysis of all parts of the PQRST waveform [9]. Postnatal electrocardiography should be performed in these children to rule out or confirm a prolongation of the QT interval, as 4% of the congenital LQTS may happen within the first year of life and the more marked the ECG findings are, the greater is the risk of sudden death for the neonate [10]. Cardiac arrhythmia may be present from the beginning of fetal life and instant fetal death may occur in utero during the third trimester. In cases with recurrent fetal loss during the third trimester, in an otherwise seemingly well mother, the likelihood of mosaicism for the LQTS must be investigated [11]. Also the LQTS has strongly been linked with sudden infant death syndrome (SIDS) as in several cases of SIDS mutations for LQTS have been identified [12]. In the present case report the neonatal and infantile periods have been uneventful. The infant is being monitored at monthly intervals with normal ECGs, and genetic investigation is expected to be carried out in the near future.

References

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11. Todd E. Miller, Elicia Estrella, Robert J. Myerburg, Jocelyn Garcia de Viera, Niberto Moreno, Paolo Rusconi, Mary Ellen Aheam, Lisa Baumbach, Grace Wolff, Nanette H. Bishopric. Recurrent third- trimester fetal loss and maternal mosaicism for long-QT syndrome. Circulation 2004;109:3029-3039.

12. Schwartz PJ. Stillbirths, sudden infant deaths and long-QT syndrome. Circulation 2004;109:2930-2932.

NICOLAOS PAPANTONIOU, IOANNIS KATSOULIS, IOANNIS PAPAGEORGIOU, & ARIS ANTSAKLIS

1st Department of Obstetrics and Gynecology, University of Athens, Greece

(Received 1 June 2005; revised 4 July 2005; accepted 26 January 2007)

Correspondence: Nicolaos Papantoniou, 82 Vassilissis Sofias Ave., 11528 Athens, Greece. Tel: +30 693 2202691. Fax: +30 210 7488648. E- mail: npapant@med.uoa.gr

Copyright Taylor & Francis Ltd. May 2007

(c) 2007 Journal of Maternal – Fetal & Neonatal Medicine. Provided by ProQuest Information and Learning. All rights Reserved.