Outcome and Impact of Associated Left-Sided Cardiac Lesions in Coarctation of the Aorta Diagnosed During Fetal Life.

Significant effort has been put into the optimization of the antenatal diagnosis of coarctation of the aorta (CoA). However, although left-sided cardiac lesions are known to cluster, the necessity to intervene postnatally for other left-sided cardiac lesions has not been reported in a cohort of fetuses with suspected CoA. We report a study of all 89 fetuses with antenatally suspected and postnatally confirmed diagnosis of CoA who underwent CoA repair as the primary procedure at a single tertiary congenital heart disease center over 10 years (January 1, 2010, to December 31, 2019). Almost 1 in 5 patients (18%) had to undergo surgery and/or transcatheter intervention on additional left-sided cardiac lesions (14%) and/or reintervention on the aortic arch (12%) during follow-up to median age of 2.85 years. Freedom from intervention at 5 years was 78% (95% confidence interval [CI] 67 to 88%) if reintervention on CoA was excluded, and 72% (95% CI 60 to 82%) if this was included. Five-year survival was 95% (95% CI 90 to 100%). Furthermore, 20% of affected infants had genetic (10%) and/or extracardiac (16%) abnormalities. Our study highlights the need for comprehensive antenatal counseling, including the prognosis of primary repair of CoA and the potential development of additional left-sided cardiac lesions, which may be difficult to diagnose prenatally even in expert hands or impossible to diagnose because of the physiology of the fetal circulation.

Effect of Prenatal Laterality Disturbance and Its Accompanying Anomalies on Survival.

In this retrospective, observational study of fetuses diagnosed with a laterality disturbance we describe the findings and outcome of fetuses diagnosed between 1980 and 2017 at a tertiary fetal-pediatric cardiology unit. In addition we sought to identify features which impact on outcome. Left atrial isomerism (LAI) was diagnosed in 177 babies and right atrial isomerism (RAI) in 100. Major structural heart disease was present in all cases of RAI and 91% with LAI. Complete heart block (CHB) was present in 40% of LAI. For surviving live-born infants a biventricular circulation was feasible in 3% with RAI and 43% with LAI. The median survival for live-borns with LAI was 13 months (range 0 to 272 months) and for RAI 19 months (range 0.3 to 292 months). The median postnatal survival with CHB was 0.2 months (range 0 to 228 months) compared to 44 months with sinus rhythm (interquartile range 0 to 272 months; p <0.0001). The 5-year survival was 1980 to 1989, RAI 0%, LAI 0%; 1990 to 1999, RAI 62%, LAI 54%; 2000 to 2009, RAI 59%, LAI 53%; 2010 to 2017, RAI 67%, LAI 75% by era. The rate of intrauterine death remained. Risk factors for death/transplantation for RAI were total anomalous pulmonary venous drainage, left heart obstruction (hazard ratios 2.7, p = 0.048; 5.8, p = 0.03) and for LAI: CHB, anomalous pulmonary venous drainage and right heart obstruction (hazard ratios 11.5, 6.2, 3.8, respectively (p = 0.008, p = 0.003, p <0.001)). In conclusion, laterality disturbances represent a complex form of congenital heart disease and although survival is improved, it remains poor especially in the presence of anomalous pulmonary venous drainage, stenotic and/or atretic valves, and CHB.

Usefulness of the Prenatal Echocardiogram in Fetuses With Isolated Transposition of the Great Arteries to Predict the Need for Balloon Atrial Septostomy.

The outcome of the arterial switch operation for transposition of the great arteries (TGA) is excellent, but there is still associated preoperative mortality. Hypoxemia due to inadequate mixing of the pulmonary and systemic circulations may be implicated. Prediction of early hypoxemia by prenatal echocardiographic criteria has proved difficult. We aimed to identify prenatal echocardiographic features that may predict the need for emergency balloon atrial septostomy (BAS) in isolated TGA. Third trimester fetal echocardiograms of the last 40 cases of isolated TGA were reviewed without knowledge of the postnatal outcome. Measurements of the arterial valves, arterial duct, total septal length (TSL), and foramen ovale (FO) length were made, in addition to a subjective assessment of the atrial septum. The first postnatal echocardiogram and charts were reviewed. Comparison with 40 gestation-matched control fetuses was performed. The FO length in normal fetuses was not significantly different from those with TGA who did not require an emergency BAS but was significantly smaller in fetuses with TGA who required an emergency BAS (p = 0.01). An emergency BAS was required in 12 of 40 cases. All 3 cases with limited movement of the atrial septum required emergency BAS. A hypermobile atrial septum was observed in 10 cases and was not associated with emergency BAS (p = 0.8). The FO:TSL was significantly smaller in those who required an emergency BAS with good predictive value (area under the receiver operating characteristics curve: 0.80). The sensitivity for FO:TSL <0.5 was 99%. There was no significant difference in arterial duct, pulmonary valve, or branch pulmonary artery diameters between those cases requiring emergency BAS and those who did not. In conclusion, the likelihood of an emergency BAS is increased by FO:TSL <0.5 and a fixed appearance of the flap valve. Hypermobile and/or aneurysmal atrial septum did not indicate inadequate postnatal mixing in our group.

Prenatal diagnosis of isolated coronary artery fistulas: progression and outcome in five cases.

OBJECTIVES: The aim of this study was to describe the clinical characteristics, progression, treatment, and outcomes in isolated coronary artery fistula cases diagnosed prenatally. METHODS: We carried out a retrospective review of babies diagnosed prenatally with coronary artery fistulas between January, 2000 and December, 2013; five fetuses were included. Echocardiographic features and measurements were noted during pregnancy and after birth. Treatment and outcome were noted. RESULTS: Gestational age at initial diagnosis was between 19 and 22 weeks; four coronary artery fistulas originated from the right and one from the left circumflex coronary artery. Drainage was into the right atrium in four cases and into the left ventricle in one case. There was cardiomegaly in two cases at the initial scan. The size of the fistulas increased during pregnancy in all except one. All prenatal diagnoses were confirmed postnatally. Among all, two patients developed congestive cardiac failure soon after birth and required transcatheter closure of the coronary artery fistula, 5 and 17 days after birth, respectively; three patients remained asymptomatic, and all of them showed progressive dilation of the feeding artery and had closure of the fistula at 20 months, 4 years, and 7 years of age, respectively. During the follow-up period, which ranged 2-14 years, all the patients were alive and well. CONCLUSIONS: Coronary artery fistulas can be diagnosed accurately during fetal life. Some babies may develop congestive cardiac failure soon after birth requiring early treatment. Those treated conservatively should be kept under review as intervention may be required later.

Correlation of maternal flecainide concentrations and therapeutic effect in fetal supraventricular tachycardia.

BACKGROUND: Transplacental flecainide is an established therapy for fetal supraventricular tachycardia (SVT), but there is a paucity of data regarding the dose-response relationship. OBJECTIVE: The purpose of this study was to investigate the relationship between maternal flecainide concentrations, arrhythmia control, and adverse fetal effects in fetal SVT. METHODS: Fetuses with SVT treated with transplacental flecainide at our tertiary fetal cardiology unit between 1997 and 2012 were retrospectively studied. The maternal trough flecainide concentrations throughout treatment were collated, and clinical notes were reviewed to ascertain the response to therapy and fetal outcome. RESULTS: Thirty-three fetuses were treated at a median (range) gestation of 28 weeks (20-38 weeks). Median fetal heart rate was 250/min (range 207-316/min). One patient was lost to follow-up, and this fetus was excluded from further analysis. In total, 25 of 32 fetuses (78%) converted to sinus rhythm. Median time to conversion to sinus rhythm was 3 days (range 2-12 days). Median flecainide concentration was 460 µg/L (range 250-866 µg/L) at conversion to sinus rhythm. Flecainide concentrations were not significantly different between responders and nonresponders (P = .849). Twelve of 14 hydropic and 13 of 18 nonhydropic fetuses converted to sinus rhythm with similar flecainide concentrations (P = .316). No fetus achieved cardioversion with a maternal serum flecainide concentration <250 µg/L. No fetus died while being treated with flecainide. CONCLUSION: The clinical response to flecainide appears good, even in hydropic fetuses. Trough maternal flecainide concentrations, once therapeutic, do not predict cardioversion in the fetus with SVT. Flecainide therapy appears both safe and effective for the fetus when monitored appropriately.

Foetal congenital heart disease: obstetric management and time to first cardiac intervention in babies delivered at a tertiary centre.

OBJECTIVES: The aim of this study was to determine the timing of neonatal cardiac intervention in babies with antenatally diagnosed congenital heart disease and the impact on obstetric management. METHODS: A retrospective review of all deliveries between January, 2008 and December, 2009 was conducted in a tertiary centre with foetal and paediatric cardiology, maternal-foetal medicine, and obstetric units. All live births with antenatally detected congenital heart disease were included. Data were collected from foetal, paediatric cardiology, and maternity databases and records. Induction, delivery mode, and timing of the first cardiac intervention in the neonate were studied. RESULTS: 205 deliveries were included. Induction and elective Caesarean section rates were 51.2% (105/205) and 14.1% (29/205), respectively. The vaginal delivery rate was 56% (115/205). There was a non-significant trend towards a higher rate of vaginal delivery after spontaneous labour than after induction (75% versus 66%; p = 0.234). The rate of neonatal cardiac intervention during the initial stay was 59.5% (122/205); it was 18.5% (38/205) within 48 hours and 25.8% (53/205) within 72 hours. The median time to first intervention was 4 days (interquartile range 2-8). Babies with hypoplastic left heart syndrome (median 3, interquartile range 2-6), transposition of the great arteries (median 1, interquartile range 0-4.5), and arrhythmia (median 0.5, interquartile range 0-1) had a significantly earlier time to first intervention compared with those with other conditions (p = 0.001). CONCLUSION: Vaginal delivery can be achieved in women delivering babies with major congenital heart disease at a tertiary centre. Delivery in or near a tertiary centre is recommended for patients requiring early intervention, of which many can be identified in advance.

Prevalence of increased nuchal translucency in fetuses with congenital cardiac disease and a normal karyotype.

OBJECTIVES: Our aims were to estimate the prevalence of increased nuchal translucency in fetuses with a normal karyotype that were subsequently diagnosed with congenital cardiac disease on fetal echocardiography, and to assess whether there is a link between increased nuchal translucency and specific congenital cardiac malformations. METHODS: We reviewed all patients referred to King's College Hospital and the Evelina Children's Hospital in London for fetal echocardiography between January 1998 and December 2007. We investigated the proportion of chromosomally normal fetuses with congenitally malformed hearts in which nuchal thickness was increased, both overall and with specific defects. RESULTS: We identified 2133 fetuses with congenital cardiac disease by prenatal echocardiography. Of those, 707 were excluded due to abnormal karyotype, and 690 were excluded due to unknown karyotype. The remaining 736 were eligible for inclusion. Among 481 fetuses with documented congenital cardiac disease and normal chromosomes, making up 23% of the overall cohort, 224 had increased nuchal thickness defined as equal or greater than 2.5 millimetres, this being 0.47 of the inclusive cohort, with 95% confidence intervals from 0.42 to 0.51. These proportions were significantly higher than the expected proportion of the normal population, which was 0.05 (p < 0.001). The only diagnosis for which the proportion of fetuses with nuchal translucency measurement equal or greater than 2.5 millimetres was higher than the others was atrioventricular septal defect, with 0.62 of this cohort having abnormal values, with 95% confidence intervals from 0.47 to 0.77 (p = 0.038). CONCLUSION: We found that nearly half of prenatally diagnosed fetuses with congenitally malformed hearts, when examined ultrasonically in the first or early-second trimester, had increased nuchal thickness. We recommend, therefore, referral of all fetuses with increased nuchal translucency for fetal echocardiography.

Prediction of outcome of tricuspid valve malformations diagnosed during fetal life.

There are conflicting reports on the prenatal validity of echocardiographic indexes used to assess tricuspid valve malformations (TVM) in postnatal life. The aim of this study was to determine which echocardiographic factors are of most prognostic significance in prenatally-diagnosed TVM and to develop a clinically-based prognostic scoring system to better inform prenatal counseling. From a prospective database, 44 fetuses with isolated TVM were identified from 1995 to 2004, inclusive. Prenatal echocardiographic findings were correlated with known outcome in 43. Tricuspid valve dyplasia was diagnosed in 22, Ebstein's anomaly in 21, and unguarded tricuspid valve orifice in 1. There were 19 terminations, 9 intrauterine deaths, 5 neonatal deaths, and 10 survivors >1 month. Survival was 35% at birth and 23% at 1 month, or 63% and 42% respectively on an intention-to-treat basis. There was no significant change to termination or overall survival rates over time, but there was a significant improvement in survival for live-born babies in the second 5 years compared with the first (p = 0.02). Factors significantly associated with increased mortality included increased cardiothoracic ratio (p <0.001), Celermajer index (p <0.001), and right-left ventricular ratio (p = 0.02); reduced/absent pulmonary valve flow (p = 0.02), and retrograde duct flow (p = 0.003). These factors were combined to give a prognostic score (SAS score) with good predictive value. In conclusion, the prenatal echocardiographic factors of most prognostic significance in TVM are similar to those used postnatally. The SAS score is a useful clinical tool that may be used to inform counseling in affected pregnancies.

An echocardiographic study of diagnostic accuracy, prediction of surgical approach, and outcome for fetuses diagnosed with discordant ventriculo-arterial connections.

Our aims were to examine the diagnostic accuracy of prenatal diagnosis of concordant atrioventricular and discordant ventriculo-arterial connections, the accuracy of predictions made concerning the postnatal surgical approach, and a description of the different subtypes related to outcome. All fetuses were evaluated at a tertiary centre for fetal cardiology between January, 1994, and December, 2003. In this period, we identified congenitally malformed hearts in 1,835 fetuses, of whom 56 (3%) met the criterions of inclusion. Of the total, 30 (54%) had an intact ventricular septum, 9 (16%) had an associated ventricular septal defect, 7 (13%) had a ventricular septal defect and pulmonary stenosis, 1 (2%) had pulmonary stenosis and an intact ventricular septum, 8 (14%) had a ventricular septal defect and aortic coarctation, and 1 (2%) had coarctation of the aorta with an intact ventricular septum. All the discordant ventriculo-arterial connections were correctly identified. For associated ventricular septal defects, the diagnostic sensitivity was 96%, with specificity of 88%, positive predictive value of 85%, and negative predictive value of 97%. For aortic coarctation, the sensitivity was 100%, specificity 96%, positive predictive value 82%, and negative predictive value 100%. The prediction of the surgical approach was accurate in 41 of 48 cases (85%). For those fetuses with pulmonary stenosis and ventricular septal defect, the ratio of the diameters of the pulmonary trunk was shown to be helpful in predicting the possibility of an arterial switch as opposed to the Rastelli type of repair. Of the 49 liveborn infants, 46 were alive at 30 days (94%, with 95% confidence intervals from 83 to 99%), and 43 at one year (88%, 95% confidence intervals from 75 to 95%). Deaths were mainly related to the anatomy of the coronary arteries, and associated cardiac lesions.

Dilated cardiomyopathy presenting during fetal life.

OBJECTIVES: To describe the echocardiographic features, underlying causes, and outcome of fetuses with dilated cardiomyopathy. DESIGN: A retrospective observational study between 1983 and 2003 at a tertiary centre for fetal cardiology. PATIENTS: Affected fetuses were identified using a computerised database. We included fetuses with dilation and reduced systolic function of either the right ventricle, left ventricle, or both. We excluded fetuses with abnormal cardiac connections, arrhythmias, or stenosis of the aortic or pulmonary valves. In all, we identified 50 fetuses, born to 46 mothers. Of the fetuses, 24 had biventricular cardiomyopathy, 17 had isolated right ventricular cardiomyopathy, and 9 had isolated left ventricular cardiomyopathy. Two-thirds of the fetuses (32) were hydropic at some point during gestation. MAIN OUTCOMES: A cause of cardiomyopathy was identified in 37 cases (74 per cent). This was genetic or metabolic in 11 fetuses; infective in 11; fetal anaemia, without proven parvovirus infection, in 5; of cardiac origin in 5; and an association with renal disease in 5. In 10 cases (20 per cent), the pregnancy was terminated. Based on an intention to treat, the survival to delivery was 25 of 40 (62.5 per cent, 95 per cent confidence intervals from 46 to 77 per cent), at 28 days was 17 of 40 (42.5 per cent, 95 per cent confidence intervals from 27 to 59 per cent), and at 1 year was 15 of 40 (37.5 per cent, 95 per cent confidence intervals from 23 to 54 per cent). The overall survival of non-hydropic fetuses was 9 of 18 (50 per cent), compared to 6 of 32 (18 per cent) hydropic fetuses. CONCLUSIONS: Genetic, metabolic, infective, and cardiac diseases may present with dilated cardiomyopathy during fetal life. There is a high rate of spontaneous intra-uterine and early neonatal death. The prognosis is particularly poor for hydropic fetuses.

Neonatal transcatheter occlusion of a large coronary artery fistula with Amplatzer duct occluder.

A large fistula from the right coronary artery to the right atrium was diagnosed in a fetus at 22 weeks of gestation. Following delivery, the baby developed cardiac failure. The fistula was occluded at 3 weeks of age by transcatheter implantation of an Amplatzer duct occluder. Large coronary fistulas can be closed safely with a device even at this early age. Vigilance for ischemic events is required following implantation because of the rare possibility of thrombus extension proximally into the native coronary artery or spasm of the coronary artery.

Patterns of recurrence of congenital heart disease: an analysis of 6,640 consecutive pregnancies evaluated by detailed fetal echocardiography.

OBJECTIVES: We sought to investigate the pattern of recurrence of congenital heart disease (CHD) where there is one or more affected first-degree relative. BACKGROUND: There are little data on patterns of recurrence of different types of CHD. Analysis of a fetal series allows a high ascertainment of affected cases. METHODS: We performed an analysis of referrals for detailed fetal echocardiography to a tertiary fetal cardiology unit, where there was a first-degree family history of CHD from 1990 to the end of 1999. Data were entered prospectively on a computerized database. Recurrences were exactly concordant if CHD was identical to the index case, and concordant for the group if belonging to a similar group of CHD. RESULTS: A recurrence of CHD was seen in 178 (2.7%) of 6,640 pregnancies. The referral numbers for sibling, maternal, or paternal CHD cases were 5,151, 1,119, and 370, respectively. Exact concordance was seen in 37% of cases (range 0% to 80%), and group concordance was seen in 44%. In families where there were two or more recurrences, the exact concordance rate was 55%. Exact concordance rates were particularly high for isolated atrioventricular septal defects (4 of 5 [80%]) and laterality defects (7 of 11 [64%]). CONCLUSIONS: The concordance rates of different types of CHD vary widely. Accurate diagnosis of the index case is essential for reliable counseling on patterns of recurrence. Minor CHD in the index case does not exclude more severe disease in recurrences. There appears to be significant under-referral for fetal echocardiography in paternal CHD.

An echocardiographic study of tetralogy of Fallot in the fetus and infant.

OBJECTIVE: To document the echocardiographic features of tetralogy of Fallot during fetal and postnatal life. Correlation of echocardiographic findings with the requirement for early intervention prior to definitive repair. DESIGN: Retrospective observational study. SETTING: A tertiary fetal cardiology unit. PATIENTS: Fetuses with a diagnosis of tetralogy of Fallot identified from a prospective database between 1 January 1999 and 31 October 2002. MAIN MEASURES OF OUTCOME: Growth of aorta and pulmonary trunk during fetal and postnatal life. Doppler assessment of the great arteries both prenatally and postnatally. Clinical outcome to definitive repair. RESULTS: We identified 25 fetuses with tetralogy of Fallot, 23 having a pulmonary valvar diameter below the normal range at some point during gestation. The ratio of the diameter of the aortic to the pulmonary valve was abnormal in all cases. The pulmonary arterial Doppler velocity was within the normal range in six fetuses at presentation,and elevated in the remainder. In two fetuses, the right ventricular outflow tract was patent during fetal life, but had become atretic at birth. Both of these fetuses had reversal of flow in the arterial duct at presentation during fetal life. In 2 fetuses in whom we showed poor growth of the pulmonary trunk in late gestation, it was necessary to intervene early. The Doppler velocity across the pulmonary valve during fetal life did not differentiate between babies who required early intervention and those who were repaired electively. There was a marked increase in pulmonary arterial Doppler velocity following birth, which became more elevated with age. Of 18 liveborn infants, 17 have survived, with 2 having balloon dilation of the right ventricular outflow tract, and 3 insertion of a Blalock-Taussig shunt prior to definitive repair. CONCLUSIONS: In tetralogy of Fallot, features of pulmonary valvar hypoplasia and obstruction are evident during fetal life. Progression of obstruction in the right ventricular outflow tract was observed during fetal life as well as postnatally. Reversal of flow in the arterial duct, and failure of growth of the pulmonary trunk, predicted the need for early surgery to maintain pulmonary blood flow. Parents should be counselled about the possibility of emergency intervention being required after birth. Affected fetuses should be delivered at units with experience of managing the cyanosed newborn.

Prenatal diagnosis by echocardiogram and outcome of absent pulmonary valve syndrome.

We reported echocardiographic findings and outcomes of fetuses with absent pulmonary valve syndrome diagnosed during fetal life. Cases were identified from a prospectively acquired computerized database of 18,308 pregnancies referred to a fetal cardiology center between January 1988 and July 2000. Twenty fetuses were identified with a median gestation of 23 weeks (range 18 to 36) at presentation. In 18 cases (90%), there was an associated ventricular septal defect. Eighteen cases (90%) had branch pulmonary artery diameters above the normal range. In four cases (20%), an arterial duct was present. A chromosome 22q11 deletion was identified in 2 of 9 cases (22%) in which this deletion was sought. There were 6 terminations of pregnancy (30%), 3 intrauterine deaths (15%), 5 neonatal deaths (25%), 3 infant deaths (15%), and 3 patients who did not die (15%). Ten of the 11 "liveborn" infants required early ventilation. The outcome of absent pulmonary valve syndrome diagnosed prenatally appears poor. The high morbidity and mortality is due to both cardiac disease and associated bronchomalacia.

Coronary arterial abnormalities in pulmonary atresia with intact ventricular septum diagnosed during fetal life.

OBJECTIVES: To establish the prevalence of coronary arterial abnormalities in mid-trimester fetuses with pulmonary atresia with intact ventricular septum, and whether their presence correlates with right ventricular morphology. BACKGROUND: The presence of coronary arterial fistulas significantly alters the surgical options and prognosis for patients with pulmonary atresia with intact ventricular septum. The lesion can reliably be diagnosed using fetal echocardiography, and further definition of the prognosis is important for counselling parents. METHODS: We examined the hearts of 39 pathological specimens diagnosed during fetal life, 3 of whom died postnatally. Coronary arterial abnormalities were defined as non-connection of the left or right coronary arteries to the aorta, ostial stenosis, marked tortuosity, dilation, thickening or abnormal myocardial branching. Mild tortuosity, or myocardial bridging, were considered normal. We measured the dimensions of the tricuspid valve along with the inlet and outlet portions of the ventricles. Ebstein's malformation, tricuspid valvar dysplasia, and the presence or absence of the infundibulum, were especially noted. We examined also 12 normal hearts as controls. RESULTS: Coronary arterial abnormalities were found in 14/39 (36%). The dimensions of the right ventricle and tricuspid valves, and the gestational ages of the fetuses, were compared for these 14 with the 25 having no abnormalities using independent t-tests. The gestational ages were similar, 21.9 vs 21.1 weeks. The mean dimensions of the tricuspid valve, median z-scores, and right ventricle were smaller, 2.9 vs 7.2 mm; p < 0.002; -4.46 vs 0.23; p < 0.03; and 6.9 vs 13.7 mm; p < 0.002, for those with coronary arterial abnormalities. Ebstein's malformation, or dysplasia of the tricuspid valve, was present in 4 of 14 with, vs 15 of 25 without, coronary arterial abnormalities. A patent infundibulum was noted in 34 of 39 specimens. CONCLUSIONS: Mid-trimester fetuses with pulmonary atresia with intact ventricular septum already exhibit coronary arterial abnormalities, with a prevalence of 36%. The presence of a patent infundibulum confirms that atresia of the pulmonary valve is an acquired process. Coronary arterial abnormalities are seen in 50% of those with hypoplastic right ventricles, but less frequently in the presence of well developed ventricles. This is important information for those involved in counselling parents.