Scholarly article on topic 'Successful prenatal management of ventricular tachycardia and second-degree atrioventricular block in fetal long QT syndrome'

Successful prenatal management of ventricular tachycardia and second-degree atrioventricular block in fetal long QT syndrome Academic research paper on "Clinical medicine"

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HeartRhythm Case Reports
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{"Congenital long QT syndrome" / "Ventricular arrhythmia" / "Prenatal management" / "Ventricular tachycardia/torsades de pointes" / "Fetal magnetocardiography"}

Academic research paper on topic "Successful prenatal management of ventricular tachycardia and second-degree atrioventricular block in fetal long QT syndrome"

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Successful prenatal management of ventricular tachycardia and second-degree atrioventricular block in fetal long QT syndrome

Akira Miyake, Heima Sakaguchi, Aya Miyazaki, Takekazu Miyoshi, Takeshi Aiba, Isao Shiraishi

Heart Rhythm^ocate/buildenv

PII: S2214-0271(16)30106-3


Reference: HRCR291

To appear in: HeartRhythm Case Reports

Received date: 10 March 2016 Revised date: 25 August 2016 Accepted date: 1 September 2016

Cite this article as: Akira Miyake, Heima Sakaguchi, Aya Miyazaki, Takekazu Miyoshi, Takeshi Aiba and Isao Shiraishi, Successful prenatal management of ventricular tachycardia and second-degree atrioventricular block in fetal long QT syndrome, HeartRhythm Case Reports,'.hrcr.2016.09.001

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Successful prenatal management of ventricular tachycardia and second-degree atrioventricular block in fetal long QT syndrome

Akira Miyake MDa), Heima Sakaguchi MDa), Aya Miyazaki MDa), Takekazu Miyoshi MDb), Takeshi Aiba MDc), Isao Shiraishi MDa)

a) Department of Pediatric Cardiology, b) Department of Perinatology and Gynecology, and c) Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan

Address correspondence to: Dr. Heima Sakaguchi

Department of Pediatric cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan Phone: +81-6-6833-5012; Fax: +81-6-6872-7486 E-mail:

Conflicts of interest: none

Short title: Prenatal management of fetal LQTS and torsade des pointes Word count: 2119 words

Keywords: congenital long QT syndrome, ventricular arrhythmia, prenatal management, ventricular tachycardia/torsade de pointes, fetal magnetocardiography

Abbreviations: LQTS = long QT syndrome; AVB = atrioventricular block; fMCG = fetal magnetocardiography; TdP = torsade de pointes; VT = ventricular tachycardia; bpm = beats per minute; ECG = electrocardiography; ICD = implantable cardioverter defibrillator


Long QT syndrome (LQTS) is an inherited channelopathy that causes sudden death in all ages due to polymorphic ventricular tachycardia. Although uncommon, individuals affected by certain LQTS mutations present in utero with ventricular tachycardia with/without 2° atrioventricular block (AVB). Fetuses manifesting these rhythms are at risk of intrauterine heart failure and fetal demise.1

Fetal LQTS can be suspected by echocardiography, but is diagnosed by fetal magnetocardiography (fMCG) which can be performed from mid-second trimester to term.2 Findings of a prolonged QTc interval and the distinct characteristics of Torsade des pointes (TdP) in a fetus with ventricular tachycardia (VT) and either sinus bradycardia or 2° AVB confirms the clinical suspicion of LQTS. Transplacental antiarrhythmic drug administration is effective for rescuing fetuses that have developed, or are at high risk of developing, fetal hydrops.3 fMCG can also monitor transplacental antiarrhythmic drug treatment given to rescue the fetuses. The purpose of this report is to describe the treatment of two LQTS fetuses with hydrops and complex arrhythmia guided by fMCG.

Case reports

Case 1

A 32-year-old woman in the 28th week of her 5th pregnancy was referred to our institution with a 3 weeks history of fetal bradycardia (fetal heart rate 60 beats per minute (bpm)). She had no personal or family histories of cardiac arrest, seizures, or syncope. Of her 4 pregnancies, only one had ended in a miscarriage. The initial fetal echocardiogram at our institution revealed a structurally normal heart with normal size, function and 2° AVB (V rate 60 bpm, atrial rate 120 bpm). Her antibody screen was negative for anti-SSA and anti-SSB antibodies. One week later, a follow-up fetal echocardiogram showed a ventricular rate of 220 bpm (atrial rate was 130 bpm) (Figure 1A). An fMCG was then performed which revealed non-sustained VT alternating with sinus rhythm (rate 130 bpm) (Figure 1B). The VT was present about 75% of the time. The QTc interval was 591 ms (Figure 1C).

Over the ensuing days, the TdP continued and the fetus developed severe hydrops. We therefore decided to administer an intravenous loading dose of magnesium (4 g) followed by a continuous infusion (1-1.4 g/h) to maintain a maternal serum level of 1.2-1.4 (normal = 0.65-1.05 mmol/L). The mother's baseline magnesium level was 0.72 mmol/L. Within 3 days of magnesium infusion the

frequency of TdP decreased (by fMCG the fetus was in sinus rhythm 80% of the time). Because of

the concern for an SCN5A R1623Q mutation, we began treatment with mexiletine (600 mg orally

per day). The fetus remained in sinus rhythm (rate 100 bpm) with continuous magnesium infusion

and oral mexiletine given to the mother. At 35 weeks the fetus became bradycardia and was found to

be in 2° AVB.

The mother underwent an elective cesarean section at 35 weeks gestation and a 2334-g male

infant was delivered. The heart rate at birth was 56 bpm due to functional second degree AVB with

2:1 conduction (Figure 2A). Immediately after delivery, temporary transvenous pacing wires were

placed. On the second day of life, a permanent pacemaker was implanted. We also administered oral

mexiletine (4 mg/kg/day) and intravenous propranolol (0.02 mg/kg/hour); no VT was observed. On

the 14th day of life, the infant's electrocardiography (ECG) showed sinus rhythm with a left

bundle-branch block pattern (Figure 2B). On the 40th day of life, the mexiletine blood levels

declined, and TdP occurred despite ventricular pacing (VVI 80 bpm). The TdP spontaneously


The VVI pacing rate was increased to 110 bpm. At the age of 5 months, weighing 6.6 kg, we

placed an implantable cardioverter defibrillator (ICD). The shock lead was implanted

subcutaneously through the left thoracodorsal region, and the generator was placed under the right

abdominal rectus muscle (Figure 2C). Following implantation of the ICD, The child did not

experience any appropriate or inappropriate shocks during 4 years of follow-up. He received oral

mexiletine (12 mg/kg/day) and propranolol (2 mg/kg/day).

Genetic testing of this case revealed a KCNH2 missense mutation (S624R). To date, there has

been no functional analysis of this mutation. His mother's QTc was 440 ms, and his father's was 390

ms. Neither of the parents had any mutation in this locus. However, we did not exclude parental

germinal mosaicism.

Case 2

A 35-year-old woman was referred to our institution at 24 weeks of gestation because of a fetal

pericardial effusion and fetal tachycardia. The family history was positive for a paternal KCNH2

missense mutation (T613M) diagnosed after a syncopal episode. The fetal echocardiogram revealed

a peristent tachycardia with AV dissociation (Figure 3A). The fMCG confirmed the clinical

diagnosis of VT with a rate of 220 bpm (Figure 3B) with a prolonged (511 ms) QTc interval during

brief (< 20% of the recording time) episodes of sinus rhythm (rate 110-120 bpm) (Figure 3C). The

mother was admitted to the hospital for continuous intravenous magnesium treatment to terminate

the fetal VT. However, despite maternal serum magnesium levels of 1.28 mmol/L (normal range

0.65-1.05 mmol/L), the VT persisted and the fetus became hydropic (Figure 3D). Ten days after the

mother was on magnesium, we initiated propranolol (initial dose 60-120 mg orally per day),

following which the VT resolved. We continued magnesium by a continuous infusion (1.4 g/h) after

we started propranolol. fMCG revealed a decreased fetal sinus rate from 120 to 110 bpm. The

hydrops then improved gradually. The mother's daily total heart beats decreased from 129,108 to

103,206 (average heart rate decreased from 90 to 71 bpm) after propranolol administration

indicating beta adrenergic blocking effect. Subsequently, the fetal sinus rhythm (rate 110bpm) was

maintained. A 2010-g female infant was delivered by elective cesarean delivery at 37 weeks of

gestation. After birth, the infant's ECG showed an intermittent left bundle-branch block pattern. On

the fifth day of life, she developed 2° AVB with a ventricular rate of 60-80 bpm and metabolic

acidemia due to poor cardiac output. She urgently underwent temporary epicardial ventricular pacing

lead implantation. At the age of 3 months, sustained VT occurred immediately after permanent

pacemaker implantation and was successfully terminated by cardioversion. Hypokalemia (serum

potassium level was 2.9 mmol/L) during intensive care likely contributed to the VT. VT did not

recur after the potassium was corrected. Her genetic testing identified the KCNH2 missense

mutation (T613M), identical to that of her father. She received oral mexiletine (7 mg/kg/day) and

propranolol (3 mg/kg/day) with pacing (VVI 110 bpm) for 23 months.


In rare severe cases of congenital LQTS, VT/TdP or the combination of TdP and 2° AVB during

fetal life can cause fetal hydrops and intrauterine fetal demise.4 We report the successful intrauterine

management of two fetuses with ventricular arrhythmias and hydrops. Both had KCNH2 mutations

in the pore region.5 But effective intrauterine management was different.

Fetal-onset LQTS is a rare and difficult-to-diagnose condition. In utero, the fetal presentation of

LQTS can manifest as a reduced baseline fetal heart rate < 3rd percentile for gestational age or 2 SD

below the mean for normal fetuses.1 In more severe cases, ventricular tachycardia, 2° AVB and

hydrops may be present.6 Fetal LQTS has been successfully diagnosed by fMCG.2 In the present

cases, fMCG proved useful for revealing the fetal arrhythmia and determining the correction of the

fetal QT interval.

Intervention should be considered for fetal hydrops due to TdP or sustained VT. There are two

types of intervention: delivery or fetal therapy. Intrauterine management of the fetus with LQTS can

control the potentially lethal ventricular arrhythmias and postpone delivery, thus avoiding ICD or

pacemaker implantation in a premature infant and other morbidities of prematurity. A few previous

reports have detailed the fetal treatment in such cases, but the effective drugs differed between the

reports and a consensus regarding appropriate drug selection has not yet been established.3 In Case 1,

magnesium was effective for the VF/TdP. Magnesium has successfully restored sinus rhythm in

several case reports,7 but in our second case beta-blockers were effective for the sustained VT.

Magnesium not only reduced the occurrence of one type of early after-depolarization but also

abolished it, providing an insight into the mechanism of TdP.8 Beta-blockers have a transplacental

transfer rate of only 25-30%, and their therapeutic effect for TdP is limited.1 However, Chang et al.

described successful transplacental therapy for VT using a beta-blocker.9 In our case, the fetal heart

rate during sinus rhythm decreased from 120 to 110 bpm during treatment with propranolol which

may indicate drug effect despite the unfavorable pharmacokinetics. Transplacental antiarrhythmic

drug administration is an effective treatment for the rescue of fetuses that have developed or have a

high risk of developing fetal hydrops. However, the selection of the appropriate drugs in these cases

has not yet been established and requires further study.


Severe cases of LQTS presenting during fetal life with VT/TdP and hydrops can be successfully

treated in utero. Historically, and in the first case described here, intravenous magnesium given to

the mother has a high likelihood of terminating VT/TdP. But, if magnesium fails, other treatment,

including transplacental propranolol can be considered and would be preferable to the preterm

delivery of a hydropic newborn.


1. Cuneo BF. The beginnings of long QT syndrome. Curr Opin Cardiol 2015;30:112-117.

2. Cuneo BF, Strasburger JF, Yu S, Horigome H, Hosono T, Kandori A, Wakai RT. In utero diagnosis of long QT syndrome by magnetocardiography. Circulation 2013;128:2183-2191.

3. Simpson JM, Maxwell D, Rosenthal E, Gill H. Fetal ventricular tachycardia secondary to long QT syndrome treated with maternal intravenous magnesium: case report and review of the literature. Ultrasound Obstet Gynecol 2009;34:475-480.

4. Cuneo BF, Etheridge SP, Horigome H, Sallee D, Moon-Grady A, Weng HY, Ackerman MJ, Benson DW. Arrhythmia phenotype during fetal life suggests long-QT syndrome genotype: risk stratification of perinatal long-QT syndrome. Circ Arrhythm Electrophysiol 2013;6:946-951.

5. Shimizu W, Moss AJ, Wilde AA, et al. Genotype-phenotype aspects of type 2 long QT syndrome. J Am Coll Cardiol 2009;54:2052-2062.

6. Ishikawa S, Yamada T, Kuwata T, Morikawa M, Yamada T, Matsubara S, Minakami H. Fetal presentation of long QT syndrome--evaluation of prenatal risk factors: a systematic review. Fetal Diagn Ther 2013;33:1-7.

7. Cuneo BF, Ovadia M, Strasburger JF, Zhao H, Petropulos T, Schneider J, Wakai RT. Prenatal diagnosis and in utero treatment of torsades de pointes associated with congenital long QT syndrome. Am J Cardiol 2003;91:1395-1398.

8. Davidenko JM, Cohen L, Goodrow R, Antzelevitch C. Quinidine-induced action potential prolongation, early afterdepolarizations, and triggered activity in canine Purkinje fibers. Effects of stimulation rate, potassium, and magnesium. Circulation 1989;79:674-686.

9. Chang IK, Shyu MK, Lee CN, Kau ML, Ko YH, Chow SN, Hsieh FJ. Prenatal diagnosis and treatment of fetal long QT syndrome: a case report. Prenat Diagn 2002;22:1209-1212.

Figure legends

Figure 1 Case 1. A: At 29 weeks, a fetal echocardiogram showed ventricular tachycardia (VT) with a ventricular rate of 220 beats per minute (bpm) compared with an atrial rate of 130 bpm. B: Fetal magnetocardiography (fMCG) revealed polymorphic VT. C: fMCG showed a prolonged QT interval (591 ms) during sinus rhythm.

Figure 2 Case 1. A: The infant's heart rate at the time of birth was beats per minute 56 (bpm), and he had a 2:1 atrioventricular block. B: On the 14th day of life, the ECG showed a sinus rhythm with a left bundle-branch block pattern. C: At the age of 5 months, an implantable cardioverter defibrillator was implanted.

Figure 3 Case 2. A: At 24 weeks of gestation, the initial fetal echocardiography showed fetal ventricular tachycardia with a ventricular rate of 187 beats per minute (bpm) and an atrial rate of 123 bpm. B: Fetal magnetocardiography (fMCG) revealed sustained ventricular tachycardia with a V rate of 220 bpm. C: fMCG showed a prolonged QT interval (511 ms) during transient sinus rhythm. D: At this time, the fetus also developed ascites, skin edema, and pericardial effusion as symptoms of severe hydrops.

S In severe cases of congenital LQTS, VT/TdP during fetal life can cause fetal hydrops.

S fMCG proved useful for not only diagnosing the fetal arrhythmia but monitoring the fetal heart rhythm during fetal treatment.

S Two hydropic fetuses with LQTS with ventricular arrhythmias and heart block were successfully managed in utero.


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