Just Accepted by The Journal of Maternal-Fetal & Neonatal Medicine Clinical spectrum of fetal long QT syndrome: a single-center experience A Flöck, U Herberg, U Gembruch, WM Merz doi: 10.3109/14767058.2014.967205

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

Abstract Objective: A considerable proportion of unexplained intrauterine fetal deaths are attributed to long QT syndrome (LQTS) susceptibility. Additionally, the estimated prevalence of LQTS in newborns is 1 in 2000. Still, prenatal diagnosis of LQTS is very rare. The aim of this study was to assess the frequency of prenatal diagnosis of LQTS at our institution, present the cases, compare our findings with the existing literature and propose a possible screening approach. Methods: We searched our fetal database between 2006 and 2013 for cases with suspected diagnosis of LQTS. Results: During the investigation period around 26,000 fetuses were evaluated and three cases of suspected fetal LQTS identified. Two cases of familial LQTS had no or mild intrauterine manifestation of the condition, the third fetus had a de-novo mutation with severe, early-onset disease. Conclusions: LQTS continues to be a challenging prenatal diagnosis. In fetuses who present with complex arrhythmias, a high degree of suspicion is required, and close surveillance and timely delivery in the presence of a multidisciplinary team are necessary. For asymptomatic cases or screening purposes, routine fetal heart rate registration and detailed assessment of cases with a low for gestational age baseline may be an option.

© 2014 Informa UK Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.

Clinical spectrum of fetal long QT syndrome: a single-center experience

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

Flöck A1, Herberg U2, Gembruch U1, Merz WM1 1

Department of Obstetrics and Prenatal Medicine, University Bonn Medical School, Bonn, Germany

2

Department of Pediatric Cardiology, University Bonn Medical School, Bonn, Germany

Correspondence to: PD Dr. Waltraut Maria Merz, M.Sc. Department of Obstetrics and Prenatal Medicine University Bonn Medical School Sigmund-Freud-Str. 25 53105 Bonn Germany Tel.: 0049-228-287-15942 Fax: 0049-228-287-16088 E-mail: [email protected] Abstract

Objective: A considerable proportion of unexplained intrauterine fetal deaths are attributed to long QT syndrome (LQTS) susceptibility. Additionally, the estimated prevalence of LQTS in newborns is 1 in 2000. Still, prenatal diagnosis of LQTS is very rare. The aim of this study was to assess the frequency of

1

prenatal diagnosis of LQTS at our institution, present the cases, compare our findings with the existing literature and propose a possible screening approach. Methods: We searched our fetal database between 2006 and 2013 for cases with suspected diagnosis of LQTS.

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

Results: During the investigation period around 26,000 fetuses were evaluated and three cases of suspected fetal LQTS identified. Two cases of familial LQTS had no or mild intrauterine manifestation of the condition, the third fetus had a de-novo mutation with severe, early-onset disease. Conclusions: LQTS continues to be a challenging prenatal diagnosis. In fetuses who present with complex arrhythmias, a high degree of suspicion is required, and close surveillance and timely delivery in the presence of a multidisciplinary team are necessary. For asymptomatic cases or screening purposes, routine fetal heart rate registration and detailed assessment of cases with a low for gestational age baseline may be an option.

All patients gave written consent to publish their data in anonymous form. The authors report no financial disclosures.

2

Introduction The estimated prevalence of long QT syndrome (LQTS) in European newborns is 1 in 2000 (1). Additionally, LQTS is attributed a significant role in unexplained fetal death, sudden infant death syndrome (SIDS) and sudden unexplained death of the young (SUDY) (2-6). With less than 100

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

published cases, prenatal diagnosis of LQTS is very rare (7-9). The aim of this study was to assess the frequency of prenatal manifestation of LQTS at our institution, a referral center for fetal medicine, present the cases and compare our findings with the existing literature.

Patients and Methods Patients consulting our center consist of low- and high-risk cases; they are referred either for screening purposes or for evaluation of fetal anomalies. We searched our fetal database between January 2006 and December 2013 for cases with a suspected diagnosis of LQTS.

Results During the period of investigation 25,973 second- or third-trimester fetuses were evaluated. Three cases of suspected fetal LQTS were identified, giving a frequency of 1:8,658 at our institution. Two cases of familial LQTS had no or a mild intrauterine manifestation of the condition, while the third fetus had a denovo mutation with severe, early-onset disease. Neonatal hearing screening was normal in all cases.

Cases Case 1:

3

The 32-year old primigravida was referred to our department at 20+6 weeks of gestation for fetal anomaly ultrasound. She had LQTS 1 (heterozygous mutation of KCNQ1; 1049G>T; G350V), which was also present in her brother, mother and grandmother. Investigations before pregnancy had revealed normal findings on transthoracic echocardiography (TTE) and 24-hour Holter electrocardiography (ECG). Exercise electrocardiography had shown QTc interval prolongation to 532 milliseconds (ms) at a heart

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

rate of 92 beats per minute (bpm). She was on bisoprolol 5 mg/day. In the early second trimester she reported shortness of breath after climbing stairs. Cardiac function tests (ECG, TTE) were stable. The fetal anomaly scan, including echocardiography and M mode tracing of the fetal cardiac rhythm was normal. Doppler examination of the fetal and fetoplacental circulation was unremarkable. Fortnightly controls were performed with stable findings in the mother and fetus. At 29+3 weeks of gestation, mild fetal sinus bradycardia (105 bpm) was present. Cardiotocography (CTG) (Figure 1) was normal except for the decreased baseline. Further controls were unchanged. Elective cesarean section on maternal request was performed at 39+2 weeks of gestation. An apparently healthy girl (2785 g, 8th percentile; Apgar score 9/10/10; umbilical artery pH 7.30; BE -1.0 mval/L) was delivered and admitted to our pediatric cardiology unit. Postnatal ECG confirmed LQTS (QTc interval: 510 ms), and molecular analysis confirmed inheritance of the maternal mutation. At the time of reporting the infant is one year old and doing well under oral therapy with propranolol 3 mg/day.

Case 2: The 38-year old gravida 2 para 1 was referred at 21+6 weeks of gestation for fetal echocardiography. Her past obstetric history included one emergency cesarean section for failure to progress 8 years earlier. Her medical and family history was unremarkable, and her first-born son was healthy. Fetal echocardiography revealed severe right ventricular (RV) dysfunction and pulmonary stenosis with minimal flow over the tricuspid valve and reverse flow in the ductus arteriosus. Cardiac rhythm was normal (146 bpm); a

4

triphasic blood flow pattern with reversal during atrial systole was present in the ductus venosus and umbilical vein. There were no other structural anomalies; karyotyping was declined. Fortnightly controls were performed. At 27+2 weeks of gestation periods of ventricular tachycardia (Figure 2) alternating with second-degree AV-block were present, with development of fetal nuchal edema (6.5 mm) and a thickened placenta. One week later (28+2 weeks of gestation) fetal hydrops had evolved with pericardial effusion,

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

ascites, hydrops placentae, and echogenic bowel; massive cardiomegaly secondary to RV dysfunction was present (Figure 3). Transplacental therapy with digoxin was started (positive inotropic and antiarryhthmic effect), but progressive deterioration of the fetal condition with development of pleural effusions and ventricular tachycardia necessitated delivery at the same day. A boy (1300 g, 67th percentile; Apgar score 5/6/7; umbilical artery pH 7.11; BE -6.2 mval/L) was delivered and admitted to the neonatal intensive care unit. The neonatal period was complicated by severe arrhythmias (second degree AV block, atrial flutter, Torsades de pointes-tachycardia) which required electric cardioversion. Electrocardiography had shown QTc interval prolongation to 530 ms. Treatments with adenosine, flecainide, amiodarone, mexiletine and lidocaine did not result in sustained improvement. High-dose parenteral magnesium and propranolol achieved a temporary stabilization. On day 14 a hemodynamically relevant ductus arteriosus necessitated surgical closure; additionally, a temporary intracardiac pacing system was placed, because cardiac function could not be stabilized by drug treatment. Antiarrhythmic medication other than propranolol was discontinued, but atrial pacing of 120-140 bpm only achieved a 1 : 2 conduction. Over the course of time interventional dilatation of the progressive valvular pulmonary stenosis was performed, and an epimyocardial VVI pacer was implanted. Molecular analysis revealed LQTS 2 (KCNH2; 1882G>A; G628S). The boy was discharged at the age of 4 months. Myocardial function deteriorated progressively, with development of arrhythmogenic dilatative cardiomyopathy. The VVI pacemaker was replaced by a DDD at three years of age. Cardiac decompensation secondary to influenza infection and sepsis resulted in cardiac fibrillation. After successful cardiopulmonary resuscitation the child was listed for transplantation, which was performed at four years of age. At the time of the last follow-up, the sevenyear old was stable and attended primary school.

5

Case 3: The 28-year old primigravida with an established diagnosis of LQTS 2 (KCNH2; 1838C>T; T613M) was referred at 23+3 weeks of gestation for fetal anomaly ultrasound. At the age of 16 three episodes of

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

ventricular fibrillation had occurred; an ICD-device was implanted subsequently. Investigations before pregnancy had revealed a QTc interval prolongation to 440 ms and normal findings on TTE. Exercise ECG had shown an increase of preterminal T in V4 and V6 at a heart rate of 153 bpm. She was on atenolol 32.5 mg/day. The fetal cardiac anatomy including Doppler examination of the fetal and fetoplacental circulation was normal, but complex arrhythmias were present. No firm diagnosis could be established because of extensive fetal movements. Fortnightly controls were planned. However the patient only returned at 26+5 weeks of gestation. Frequent changes between second-degree AV block (Wenckebach type) and sinus rhythm (115 bpm) had developed; otherwise, the fetus was stable. At 29+3 weeks of gestation cardiomegaly and moderate biventricular myocardial hypertrophy with intermittent sinus bradycardia (70 - 105 bpm) was present without any signs of cardiac failure. Further controls did not reveal any change in the fetal condition. The maternal cardiac condition remained stable during the entire pregnancy. At 38+3 weeks of gestation elective cesarean section was performed. An apparently healthy boy (3,725g, 78th percentile; Apgar score 8/9/10; umbilical artery pH 7.34; BE 0.8 mval/L) was delivered and referred to our pediatric cardiology unit. LQTS was confirmed by electrocardiography (QTc interval: 531 msec), and oral therapy with propranolol and magnesium was started. At the time of reporting, the child is two years old and asymptomatic under oral therapy with magnesium and propranolol.

Discussion

6

With 1 : 8,658 cases the frequency of prenatal diagnosis of LQTS at our institution is very low. This result is in accordance with the available literature (1, 8-11). At the same time, our cases represent the entire clinical spectrum of fetal LQTS and the scenarios which will bring about establishment of prenatal diagnosis, that is, symptomatic fetuses and cases with a positive family

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

history. Only few fetuses or a very small percentage of fetuses with LQTS show complex fetal arrhythmias as case 2; especially fetal ventricular tachycardia is often associated with LQTS if alternating with AV block grade 2 or grade 3. Up to now there is no established intrauterine therapy for ventricular tachycardia, the use of intravenous magnesium, lidocaine, flecainide or propranolol has been recommended, but side effects of the different medications have to be taken into consideration (12, 13). The following factors may contribute to the rarity of prenatal LQTS diagnosis: (1) Non-invasive fetal ECG and magnetocardiography are the only methods allowing a definite diagnosis; they are cumbersome and rarely available (14). QT intervals have to be corrected according to heart rate and gestational age. Additionally, in the neonatal period there is no fix cut-off level for QTc intervals, borderline values can be normal, and even with normal values LQTS may be present (15). (2) Pregnant women with LQTS may represent the mild spectrum of the disorder, since women with more severe forms of LQTS may not reach reproductive age. (3) Given the recent figure of a 1 : 2,000 prevalence in newborns (1), pregnancy in LQTS seems to proceed unremarkable in most cases. This may be a due to a lack of pro-arrhythmogenic stimuli within the uterine environment. (4) Severe fetal cases are most likely de-novo mutations that are not picked up by any screening and unlikely to undergo special surveillance. The variable time of onset additionally contributes to the low

7

detection rate (6, 16). We hypothesize that it are these cases that present either as late miscarriage, unexplained fetal death or SIDS / SUDY.

Suggested strategies for intrauterine detection of LQTS include the application of a bradycardia

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

index (17). However, the following aspects have to be taken into consideration: First, the uniqueness of fetal heart rate (FHR) assessment. FHR evaluation includes the analysis of baseline and beat to beat variability as well as the presence of accelerations or decelerations (18, 19). Determination of baseline FHR requires a 10-minute recording (20). Basal FHR decreases with advancing gestation, most probably due to a rise in vagal tone. Second, the FHR pattern is characterized by a high variability which increases with GA, most probably because of the maturation of the autonomic nervous system. These features have been established by fetal ECG (21) and Doppler ultrasound analysis (22). Magnetocardiographic investigations, allowing the measurement of cardiac time intervals, confirmed increases in waveform durations with advancing GA (23). The discrepancy between normal values for FHR in the aforementioned study and standard obstetric definitions may be a consequence of the method applied, namely, ventricular M mode waveform measurement of only five consecutive cardiac cycles. For example, in the late third trimester, fetuses increasingly show long-term accelerations that may be misinterpreted as a high baseline. Currently, the stillbirth rate in industrialized countries is approximately 4 ‰. 91% occur antenatally, and 43% of these are unexplained (24). Taking latest results from genetic autopsy in unexplained stillbirths into consideration, LQTS susceptibility may be responsible for some 9% of these (6). The prevention of one LQTS-associated stillbirth would therefore necessitate screening of 6452 pregnancies.

8

Fetal magnetocardiography can accurately measure QT interval in utero, (25), but this method is not established in routine antenatal care because of cost-intensive technology (26). For the purpose of LQTS screening gestational age-adjusted ranges for basal FHR are necessary, particularly as early, severe forms seem to occur (7). Normal ranges need to be established taking the

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

peculiarities of FHR pattern into consideration, being aware that any preselection based on the basal FHR may imply incorporation of fetuses with an idiopathically low baseline. FHR registration by cardiotocogram (CTG) is a standard antenatal procedure. Even though it may be challenging to perform at low GA, a five- to ten-minute CTG, incorporated into antenatal care, may be a possible screening strategy. The cost effectiveness of this intervention would need evaluation. In conclusion, LQTS continues to be a challenging prenatal diagnosis. In fetuses who present with ventricular tachycardia and complex arrhythmias, a high degree of suspicion is required, and close surveillance and timely delivery in the presence of a multidisciplinary team are necessary. In asymptomatic cases with or without positive family history, routine FHR registration and detailed assessment of cases with low for GA basal heart rate may be an option.

Declaration of interest statement: The authors report no declaration of interest.

9

References:

1. Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, Gabbarini F, Goulene K, Insolia R, Mannarino S, Mosca F, Nespoli L, Rimini A, Rosati E, Salice P,

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

Spazzolini C. Prevalence of the congenital long-QT syndrome. Circulation. 2009;120:1761-1767 2. Schwartz PJ, Stramba-Badiale M, Segantini A, Austoni P, Bosi G, Giorgetti R, Grancini F, Marni ED, Perticone F, Rosti D, Salice P. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med. 1998;338:1709-1714 3. Millat G, Kugener B, Chevalier P, Chahine M, Huang H, Malicier D, Rodriguez-Lafrasse C, Rousson R. Contribution of long-QT syndrome genetic variants in sudden infant death syndrome. Pediatr Cardiol. 2009;30:502-509 4. Ackerman MJ. State of postmortem genetic testing known as the cardiac channel molecular autopsy in the forensic evaluation of unexplained sudden cardiac death in the young. Pacing Clin Electrophysiol. 2009;32 Suppl 2:86-89 5. Gladding PA, Evans CA, Crawford J, Chung SK, Vaughan A, Webster D, Neas K, Love DR, Rees MI, Shelling AN, Skinner JR. Posthumous diagnosis of long QT syndrome from neonatal screening cards. Heart Rhythm. 2010;7:481-486 6. Crotti L, Tester DJ, White WM, Bartos DC, Insolia R, Besana A, Kunic JD, Will ML, Velasco EJ, Bair JJ, Ghidoni A, Cetin I, Van Dyke DL, Wick MJ, Brost B, Delisle BP, Facchinetti F, George AL, Schwartz PJ, Ackerman MJ. Long QT syndrome-associated mutations in intrauterine fetal death. JAMA. 2013;309:1473-1482

7. Horigome H, Nagashima M, Sumitomo N, Yoshinaga M, Ushinohama H, Iwamoto M, Shiono J, Ichihashi K, Hasegawa S, Yoshikawa T, Matsunaga T, Goto H, Waki K, Arima M, Takasugi H, Tanaka Y, Tauchi N, Ikoma M, Inamura N, Takahashi H, Shimizu W, Horie M. Clinical characteristics and genetic background of congenital long-QT 10

syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan. Circ Arrhythm Electrophysiol. 2010;3:10-17 8. 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 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

9. Anuwutnavin S, Wanitpongpan P, Chungsomprasong P, Soongswang J, Srisantiroj N, Wataganara T. Fetal long QT syndrome manifested as atrioventricular block and ventricular tachycardia: a case report and a review of the literature. Pediatr Cardiol. 2013;34:1955-1962 10. Greene EA, Berul CI, Donofrio MT. Prenatal diagnosis of long QT syndrome: implications for

delivery room and neonatal management. Cardiol Young. 2013;23:141-145 11. Komarlu R, Beerman L, Freeman D, Arora G. Fetal and neonatal presentation of long QT

syndrome. Pacing Clin Electrophysiol. 2012 ;35:87-90. 12.

Strasburger JF, Wakai RT. Fetal cardiac arrhythmia detection and in utero therapy. Nat Rev Cardiol. 2010 ;7:277-290.

13.

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

14. Simpson JM. Fetal arrhythmias. Ultrasound Obstet Gynecol. 2006;27:599-606. 15.

Yoshinaga M, Ushinohama H, Sato S, Tauchi N, Horigome H, Takahashi H, Sumitomo N, Kucho Y, Shiraishi H, Nomura Y, Shimizu W, Nagashima M. Electrocardiographic screening of 1-month-old infants for identifying prolonged QT intervals. Circ Arrhythm Electrophysiol. 2013;6:932-938

16. Guttmacher AE, Spong CY, Willinger M. Long QT syndrome susceptibility mutations and pregnancy loss: another piece of a still unfinished puzzle? JAMA. 2013;309:1525-1526

11

17. Mitchell JL, Cuneo BF, Etheridge SP, Horigome H, Weng HY, Benson DW. Fetal heart rate predictors of long QT syndrome. Circulation. 2012;126:2688-2695 18. FIGO News. Guidelines for the use of fetal monitoring. Int J Obstet Gynecol. 1987;25:159-167 19. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 106: Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

principles. Obstet Gynecol. 2009;114:192-202

20. Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol. 2008;112:661-666 21. Wheeler T, Murrills A. Patterns of fetal heart rate during normal pregnancy. Br J Obstet Gynaecol. 1978;85:18-27

22. Dawes GS, Houghton CR, Redman CW. Baseline in human fetal heart-rate records. Br J Obstet Gynaecol. 1982;89:270-275 23. Stinstra J, Golbach E, van Leeuwen P, Lange S, Menendez T, Moshage W, Schleussner E, Kaehler C, Horigome H, Shigemitsu S, Peters MJ. Multicentre study of fetal cardiac time intervals using magnetocardiography. BJOG. 2002 ;109:1235-1243 24. Lawn JE, Blencowe H, Pattinson R, Cousens S, Kumar R, Ibiebele I, Gardosi J, Day LT, Stanton C; Stillbirths: Where? When? Why? How to make the data count? Lancet's Stillbirths Series steering committee. Lancet. 2011 23;377:1448-1463

25. 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;128:21832191 26. Strasburger JF, Cheulkar B, Wakai RT. Magnetocardiography for fetal arrhythmias. Heart Rhythm. 2008;5:1073-1076. 12

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

Figure 1: Cardiotocography showing sinus bradycardia of approximately 105 beats per minute (case 1,

29+3 weeks of gestation)

13

Figure 2: At 27+2 weeks of gestation the pulsed-wave Doppler examination of the umbilical vein and artery demonstrated ventricular tachycardia. In the upper channel, blood flow pattern of the umbilical vein with reverse flow during atrial systole and an atrial rate of 130 bpm is shown, in the lower channel blood

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

flow pattern of the umbilical artery with heart rate of 210 bpm (case 2).

14

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Newcastle on 09/26/14 For personal use only.

Figure 3: Massive cardiomegaly secondary to right cardiac dysfunction (case 2, 28+2 weeks of gestation)

15

Clinical spectrum of fetal long QT syndrome: a single-center experience.

A considerable proportion of unexplained intrauterine fetal deaths are attributed to long QT syndrome (LQTS) susceptibility. Additionally, the estimat...
496KB Sizes 1 Downloads 6 Views