Prenatal features of ductus arteriosus-related branch pulmonary stenosis in fetal pulmonary atresia.

OBJECTIVE: Ductus arteriosus (DA)-related branch pulmonary stenosis (PS), due to ductal tissue migration into the proximal pulmonary artery (PA) ipsilateral to the DA, is common in newborns with pulmonary atresia (PAtr) and contributes significantly to their mortality and morbidity. We sought to define fetal echocardiographic predictors of DA-PS in PAtr. METHODS: This was a study of all neonates diagnosed prenatally with PAtr and a DA-dependent pulmonary circulation, with a DA that joined the underbelly of the arch, who had undergone surgical or catheter intervention in our hospital between 2009 and 2018. The postnatal echocardiograms and clinical records were reviewed to confirm the presence or absence of DA-PS based on the need for angioplasty at initial intervention and/or development of proximal PA stenosis post intervention. Fetal echocardiograms were examined for the features of DA-PS. RESULTS: Of 53 fetuses with PAtr, 34 (64%) had analyzable images, including 20/34 (59%) with and 14/34 (41%) without DA-PS. An inability to visualize the branch PAs in the same plane, largely associated with abnormal DA insertion into the ipsilateral PA (85% of cases), had sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of 75%, 100%, 100% and 74%, respectively, for the prediction of postnatal DA-PS. The mean branch PA posterior bifurcation angle was more obtuse in cases with DA-PS compared to cases without DA-PS (117° ± 17° vs 79° ± 17°, P < 0.001), and an angle of > 100°, the preoperative cut-off observed previously in affected newborns, had a sensitivity, specificity, PPV and NPV of 88%, 79%, 82% and 85%, respectively. The receiver-operating-characteristics curve revealed an angle of ≥ 105° to have a sensitivity and specificity of 88% and 93%, respectively, for prenatal prediction of DA-PS. The presence of one or both features (inability to image in the same plane and the posterior bifurcation angle of ≥ 105°) had a sensitivity, specificity, PPV and NPV of 100%, 93%, 95% and 100%, respectively. CONCLUSION: An inability to visualize the branch PAs in the same plane, associated with abnormal insertion of the DA in most cases, and/or the presence of a posterior PA bifurcation angle of ≥ 105° are predictive features of postnatal DA-PS in fetuses with PAtr. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal Pulmonary Valvuloplasty in Fetuses with Right Ventricular Outflow Tract Obstructive Disease: Experience and Outcome of the First Five Cases in China.

The current study was to report our initial experiences of fetal pulmonary valvuloplasty (FPV) for fetuses with pulmonary atresia with intact ventricular septum (PA/IVS) and critical pulmonary stenosis (CPS), including case selection, technical feasibility, and the effects of FPV on utero and postnatal outcome. Two fetuses with PA/IVS and three fetuses with CPS were enrolled between September 2016 and April 2018. All fetuses were with concomitant severe right ventricular dysplasia and growth arrest. Parameters of right cardiac development and hemodynamics, including tricuspid/mitral annulus ratio (TV/MV), right ventricle/left ventricle long-axis ratio (RV/LV), tricuspid valve inflow duration/cardiac cycle ratio (TVI/CC), degree of tricuspid regurgitation (TR), and blood flow direction of arterial duct and ductus venosus, were evaluated using echocardiogram. FPV was performed trans-abdominally under ultrasound guidance. Echocardiogram was performed post-FPV and every 2-4 weeks thereafter until delivery. The median gestational age at the time of FPV was 28 weeks. From technical perspective, pulmonary balloon valvuloplasty was successfully performed and the opening of pulmonary valve was improved in all fetuses in 2-4 weeks. However, progressive restenosis was observed in four fetuses with gestation advancing, and re-atresia occurred in two PA/IVS fetuses at 36th and 37th weeks' gestation, respectively. The growth trajectories of TV/MV, RV/LV, and TVI/CC were improved in the 1st week after FPV and then slowed down along with pulmonary valve restenosis. All fetuses were born alive and underwent postnatal interventions, including pulmonary balloon valvuloplasty in three fetuses and surgical procedures in two fetuses. During follow-up, three fetuses turned to be biventricular, one became one and a half ventricular at 1-year old, and one died of neonatal infection. Although pulmonary valve restenosis might occur as gestation advancing, FPV seems to be a safe and feasible procedure to improve the growth trajectories of right heart for fetuses with PA/IVS and CPS.

Fetal and Neonatal Circulatory Disorders in Twin to Twin Transfusion Syndrome (The Secondary Publication).

Twin to twin transfusion syndrome (TTTS) is a major complication of monochorionic diamniotic (MD) twins, and its onset is known to be associated with placental vascular anastomoses and blood flow imbalance. In a typical case of TTTS, the recipient develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis in the uterus. In contrast, the donor develops oligohydramnios and intrauterine growth restriction. Recently, the significance of the renin-angiotensin-aldosterone system (RAAS) that transfers from the donor to the recipient has attracted interest in the fetal circulation of TTTS. The donor has decreased renal blood flow due to decreased circulating blood volume. For this reason, the secretion of RAAS hormones is augmented in the fetal kidneys of the donor. In TTTS, these RAAS hormones from the donor transfer to the recipient through the anastomosed vessels. In addition to excess preload, the recipient heart is exposed to excess afterload due to systemic vasoconstriction through RAAS hormones. Commonly occurring complications in the recipient include myocardial hypertrophy, atrioventricular valve regurgitation, and pulmonary valve stenosis or pulmonary atresia. Fetoscopic laser photocoagulation (FLP) has been introduced recently because neither mortality nor neurological morbidity have been satisfactorily improved with conventional treatment. FLP is a curative method that may improve the prognosis of TTTS. In Japan, this procedure has been performed frequently, and positive neurological outcomes have been achieved.

Immediate effects and outcome of in-utero pulmonary valvuloplasty in fetuses with pulmonary atresia with intact ventricular septum or critical pulmonary stenosis.

OBJECTIVE: To assess the immediate effects of fetal pulmonary valvuloplasty on right ventricular (RV) size and function as well as in-utero RV growth and postnatal outcome. METHODS: Patients with pulmonary atresia with intact ventricular septum (PAIVS) or critical pulmonary stenosis (CPS) who underwent fetal pulmonary valvuloplasty at our center between October 2000 and July 2017 were included. Echocardiographic data obtained before and after the procedure were analyzed retrospectively (median interval after intervention, 1 (range, 1-3) days) for ventricular and valvular dimensions and ratios, RV filling time (duration of tricuspid valve (TV) inflow/cardiac cycle length), TV velocity time integral (TV-VTI) × heart rate (HR) and tricuspid regurgitation (TR) velocity. Longitudinal data were collected from only those fetuses followed up in our center. Outcome was assessed using the scoring system as described by Roman et al. for non-biventricular outcome. RESULTS: Thirty-five pulmonary valvuloplasties were performed in our institution on 23 fetuses with PAIVS (n = 15) or CPS (n = 8). Median gestational age at intervention was 28 + 4 (range, 23 + 6 to 32 + 1) weeks. No fetal death occurred. Immediately after successful intervention, RV/left ventricular length (RV/LV) ratio (P ≤ 0.0001), TV/mitral valve annular diameter (TV/MV) ratio (P ≤ 0.001), RV filling time (P ≤ 0.00001) and TV-VTI × HR (P ≤ 0.001) increased significantly and TR velocity (P ≤ 0.001) decreased significantly. In fetuses followed longitudinally to delivery (n = 5), RV/LV and TV/MV ratios improved further or remained constant until birth. Fetuses with unsuccessful intervention (n = 2) became univentricular, all others had either a biventricular (n = 15), one-and-a-half ventricular (n = 3) or still undetermined (n = 3) outcome. Five of nine fetuses with a predicted non-biventricular outcome, in which the procedure was successful, became biventricular, while two of nine had an undetermined circulation. CONCLUSION: In selected fetuses with PAIVS or CPS, in-utero pulmonary valvuloplasty led immediately to larger RV caused by reduced afterload and increased filling, thus improving the likelihood of biventricular outcome even in fetuses with a predicted non-biventricular circulation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Biventricular impact of mild to moderate fetal pulmonary valve stenosis.

OBJECTIVES: To define the pattern of fetal echocardiographic changes associated with isolated pulmonary valve stenosis (PS) and to correlate the echocardiographic findings with neonatal outcome and the need for postnatal pulmonary valvuloplasty within the first 12 months postpartum. METHODS: This was a prospective cohort study between January 2009 and October 2015 of 16 fetuses with isolated PS and 48 controls matched by gestational age at ultrasound examination (± 2 weeks) evaluated at the Fetal Cardiology Unit at BCNatal (Barcelona). Standard fetal ultrasound and comprehensive echocardiography, which included cardiovascular morphometric parameters, and systolic and diastolic functional and timing measurements, were performed in all cases. Baseline characteristics and perinatal outcome were retrieved from clinical records. Cases were followed up until 12 months of age, and admission to intensive care unit, days of hospitalization, need for prostaglandins and requirement for postnatal surgery were reviewed. Fetal PS cases were analyzed according to the need for postnatal pulmonary valvuloplasty. RESULTS: The study groups were similar in terms of baseline, fetal ultrasound and perinatal characteristics. Median gestational age at diagnosis of PS was 33.4 (range, 20.0-36.5) weeks. Most cases corresponded to mild or moderate PS; only three fetuses had reversed flow in the ductus arteriosus before delivery. Six (37.5%) newborns, including all three with reversed flow in the ductus arteriosus prenatally, required postnatal pulmonary valvuloplasty. Fetuses with PS presented with larger and more globular hearts, with increased myocardial wall thickness in the third trimester. Despite preserved right ventricular (RV) ejection fraction and systolic longitudinal motion, PS cases showed increased right cardiac output and signs of diastolic dysfunction, with higher ductus venosus pulsatility index (0.72 ± 0.32 vs 0.53 ± 0.16, P = 0.004) and tricuspid E/E' ratio (7.52 ± 3.07 vs 5.76 ± 1.79, P = 0.022). In addition, fetuses with PS displayed a compensatory increase in left ventricular (LV) radial and longitudinal motion, as shown by a higher ejection fraction (79.3 ± 8.23% vs 67.6 ± 11.3%, P = 0.003) and mitral annular-plane systolic excursion (5.94 ± 1.38 vs 5.0 ± 1.22 mm, P = 0.035). Finally, fetuses requiring postnatal pulmonary valvuloplasty showed a different pattern of echocardiographic findings from those not requiring valvuloplasty, with a significantly smaller RV and pulmonary valve diameter, reduced tricuspid annular-plane systolic excursion (5.08 ± 1.59 vs 8.07 ± 1.93 mm, P = 0.028), increased LV cardiac output (340 ± 16 vs 176 ± 44 mL/min/kg, P = 0.003) and more pronounced signs of LV diastolic dysfunction (mitral E' velocity, 5.78 ± 0.90 vs 8.16 ± 1.58 cm/s, P = 0.008). CONCLUSIONS: Fetuses with PS present with more hypertrophic, larger and more globular hearts in the third trimester of pregnancy, associated with a higher right cardiac output and impaired biventricular relaxation. In addition, signs of increased LV contraction were observed. Our data suggest that RV and LV functional parameters could be useful for predicting the need for postnatal pulmonary valvuloplasty. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Diverse outcome following early prenatal diagnosis of pulmonary stenosis.

OBJECTIVE: To assess the natural history and outcome of fetal pulmonary stenosis (PS), particularly that detected at 14-17 weeks' gestation. METHODS: In this retrospective study we searched an electronic database of women from the general Israeli population attending a private ultrasound institute (Al-Kol ultrasound institute in Haifa) for routine complete early fetal ultrasound, including all fetal systems and a fetal echocardiogram, between 2004 and 2015. Ninety-seven percent of the women were at low risk of fetal malformations, and 3% had risk factors such as maternal Type-1 diabetes mellitus, exposure during pregnancy to teratogenic drugs, or anomalies in previous pregnancies or in other family members. At presentation at 14-17 weeks of gestation, color and pulsed Doppler imaging were performed across the four cardiac valves. We identified cases in which abnormal flow was detected, leading to suspicion of PS; in these cases, a follow-up examination was carried out at 17-19 weeks and then monthly until delivery or resolution of the finding, and postnatal echocardiography was performed at birth, 4-6 weeks thereafter, and yearly afterwards. Outcome data for suspicious cases, including postnatal diagnosis and general or specific symptoms, were collected by contacting the parents via email or telephone. RESULTS: Among 24 185 early prenatal transvaginal ultrasound screening examinations, 23 cases of suspected PS were identified. They were classified into three groups, according to their ultrasound findings. In Group A (n = 8), the ultrasound screen was normal except for high flow velocity across the pulmonary valve. In six cases, this finding had resolved by 20-21 weeks of gestation and all were found to be normal at postnatal follow-up, one case underwent termination of pregnancy at 19 weeks and PS was confirmed at autopsy and one case was lost to follow-up. In Group B (n = 12), there was aliasing across the pulmonary valve. Two of these cases were normal postnatally and eight had mild-to-moderate PS; the remaining two cases developed hypoplastic right ventricle and pulmonary atresia at 19-20 weeks and the pregnancies were terminated. In Group C (n = 3) PS was associated with other anomalies; all three pregnancies were terminated. There were an additional six cases (Group D) not identified in early gestation, in which PS was late-onset. One had tricuspid regurgitation at the early screen, but was subsequently diagnosed with Ebstein's anomaly and pulmonary atresia, at 22 weeks, and was terminated. The other cases had completely normal early ultrasound screening examinations: one case had Ebstein's anomaly and PS was diagnosed at birth; four had isolated mild PS, of which one was diagnosed at 22 weeks' gestation and the other three were diagnosed postnatally, before 3 months of age. The sensitivity for detection of the ascertained cases of PS was 64% (11/17) and the specificity was > 99%. CONCLUSION: There is a diverse spectrum of presentation of fetal PS in the early mid-trimester. A possible explanation for this could be different pathophysiological pathways. Further study is needed to explain the different prenatal sonographic presentations in an unselected population. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Fetal cardiac interventions - are we ready for them?]. / Interwencyjne zabiegi kardiologiczne u plodów - czy jestesmy do nich przygotowani?

OBJECTIVE: The aim of the study was to analyze types and methods of intrauterine fetal cardiac interventions performed between June 2011 and December 2013, and to assess the perinatal management of the neonates. METHODS: The program was developed after analysis of the available literature, practical individual training in Linz, Austria, and simulation of the procedure in a dissecting-room. The rules for anesthesia in pregnant women and their fetuses were developed. The interventions were performed in fetuses with critical cardiac defects, in the operating room, under ultrasonographic control. The protocol was approved by the Local Bioethics Committee at the Centre of Postgraduate Medical Education. MATERIAL: We included fetuses with critical aortic stenosis (n=29), critical pulmonary stenosis (n=2), and closed or extremely restricted foramen ovale (n=7). Between June 2011 and December 2013, the team comprised of JD, MD and AK conducted 42 interventions in 35 fetuses, including 32 balloon aortic valvuloplasties (in 29 fetuses), 2 pulmonary valvuloplasties, 4 balloon atrial septostomies and 4 atrial septal stent placement. Three fetuses required both, aortic valvuloplasty and fenestration of the atrial septum. RESULTS: Out of the 42 procedures, 41 (97%) were technically successful. We recorded 3 cases of fetal demise associated with the intervention. We modulated the protocol of anesthesia given to pregnant women, switching from general to local anesthesia with intravenous sedation. We always provided additional fetal anesthesia with fentanyl and atracurium via the umbilical vein. CONCLUSIONS: Based on our 2.5-year experience, it seems safe to conclude that all types of fetal cardiac interventions may be successfully conducted at Polish centers. The procedures are safe for the pregnant women and improve fetal status. Most of the neonates treated prenatally were referred in good general condition to a tertiary pediatric cardiology and cardiac surgery center

[Recent developments in fetal surgery. Technical, organizational and ethical considerations]. / Développements récents de la chirurgie foetale. Aspects techniques, organisationnels et éthiques.

Progress in prenatal diagnosis has led to more frequent detection of fetal abnormalities which, if left untreated, would be fatal or cause severe disabilities despite optimal postnatal care. Intrauterine surgery is possible in selected cases. Most procedures involve microendoscopy with local or regional analgesia. Fetal analgesia is indicated for procedures that are directly invasive for the fetus. Surgical treatment of twin-to-twin transfusion is so far the only example of successful fetal therapy, as demonstrated in a randomized controlled trial. The most severe forms of congenital diaphragmatic hernia may also benefit from temporary occlusion of the fetal trachea in order to allow lung growth and prevent pulmonary hypoplasia. The future of open fetal surgery will depend partly on the results of the ongoing MOM study of intrauterine coverage of myelomeningocele. These developments also raise ethical questions, including the competence of the surgical team, and the borderline between therapeutic innovation, experimental surgery, and standard of care. The possibility of therapeutic termination should not be overlooked.

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.

Invasive intrauterine treatment of pulmonary atresia/intact ventricular septum with heart failure.

The mortality and morbidity of children with pulmonary atresia/intact ventricular septum (PA/IVS) are linked to the degree of right ventricular (RV) hypoplasia. Opening up the pulmonary valve (PV) in fetal life could result in improved growth of the RV making it amenable to biventricular repair postnatally. Successful valvulotomy of the PV was performed in a fetus with heart failure at 28 weeks. Following the procedure there was significant growth of the tricuspid valve and RV. The neonate was delivered at 38 weeks with a RV suitable for biventricular repair. In utero pulmonary valvulotomy is feasible and may change the natural history of the condition in affected fetuses with PA/IVS.

Pathogenesis of single right coronary artery and pulmonic stenosis in English Bulldogs.

English Bulldogs are the most common breed to have pulmonic stenosis. Previous studies showed that this congenital heart abnormality in Bulldogs frequently is caused by a circumpulmonary left coronary artery originating from a single right coronary artery. Fetal anasarca also occurs often in Bulldogs and might represent congestive heart failure, but the cause is unknown. To determine if fetal anasarca is associated with a coronary anomaly and pulmonic stenosis, major coronary arteries were studied in 6 bulldog puppies with fetal anasarca. Five of the puppies had normal coronary arteries, and this led to the conclusion that fetal anasarca usually is not associated with major coronary abnormalities or pulmonic stenosis. The 6th puppy had single right coronary artery with circumpulmonary left coronary artery and moderate subvalvular pulmonic stenosis. Serial section histology suggests that the underlying cause of this syndrome is malformation of the left aortic sinus (of Valsalva) and inversion of the proximal segment of the left main coronary artery.

Concurrence of supravalvular aortic stenosis and peripheral pulmonary stenosis in three generations of a family: a form of arterial dysplasia.

Isolated supravalvular aortic stenosis (SVAS) commonly is an autosomal dominant trait; it may also occur in the Williams syndrome (WS). While peripheral pulmonary stenosis (PPS) can occur in the same individual with familial isolated SVAS, concurrence of these lesions in different relatives of a family is uncommon. We describe five affected individuals in one family; three had isolated SVAS, one had isolated PPS, and one had SVAS and PPS. Based on this family and review of literature, we suggest that SVAS is a form of arterial dysplasia encompassing PPS in its spectrum. It is developmentally distinct from other left heart obstructive lesions that are hypothesized to be related to blood flow abnormalities in the developing embryo. We also conclude that the clinical disorder in this family represents one that is distinct from WS.

Severe pulmonary stenosis and interruption of the aortic arch.

A case of severe pulmonary stenosis associated with a subpulmonary ventricular septal defect and interruption of the aortic arch is described in a 5-month-old girl. This combination defies explanation by current theories of the development of obstructive abnormalities of the aortic arch secondary to reduced aortic flow during fetal life, and, to the best of our knowledge, is the first reported case with this particular association.

Pathogenesis of various forms of double outlet right ventricle in mouse fetal trisomy 13.

The pathogenesis of double outlet right ventricle with or without pulmonary infundibular atresia in mouse fetal trisomy 13 was studied at the organ level using microdissection and scanning electron microscopy. Altogether, 394 karyotyped trisomic embryos were collected between 11 days and 16 hours of gestation (presence of a vaginal plug = day 1) and 15 days of gestation at intervals of 8 hours, and at 16 days of gestation. The hearts were perfusion-fixed, microdissected, and prepared to be observed in scanning electron microscope in the following standardized orientations: frontal, right or left profile, septal and parietal halves of the right ventricle and outflow tract (conotruncus). Comparison of 276 trisomic hearts with their normal counterparts described previously has shown that: the first pathognomonic feature is the abnormal anterior position of the proximal part of the parietal outflow tract ridge or of both ridges (at 12 days and 16 hours of gestation); the abnormal anterior fusion of these ridges ("coalescence") results in a mesenchymal mass behind which is deviated the pulmonary part of the outflow tract lumen; from 14 days and 16 hours of gestation on, this lumen is either obstructed, resulting in a supravalvar stenosis of the pulmonary trunk and subsequently evolving into double outlet right ventricle with pulmonary infundibular atresia; or, in a minority of cases, this lumen is not obstructed and the heart develops into double outlet right ventricle without pulmonary infundibular atresia. The pathogenesis of these malformations differs from most of the known hypotheses based on deductions from human malformed hearts, as well as from observations of the pathogenesis of similar outflow tract malformations, such as those found in the Keeshond dog or rats treated with trimethadione.

Fetal cardiovascular cross-sectional morphology of tetralogy of Fallot in rats.

In order to clarify cross-sectional morphology of tetralogy of Fallot in the fetus, 202 rat fetuses with tetralogy of Fallot induced by maternal administration of bis-diamine were studied using cesarean section, the whole body freezing method and by photographing cross sections of the fetal heart on a freezing microtome. Some characteristic features such as large subaortic ventricular septal defects, aortic overriding over the ventricular septum, aortomitral fibrous continuity, and narrow infundibulum and pulmonary valve were found. Moreover, three subtypes were noticed. In classic tetralogy of Fallot with stenotic infundibulum, the size of the pulmonary arteries was smaller in proportion to the infundibular stenosis. In the second type with absent infundibular septum and severe valvular pulmonary stenosis, the pulmonary arteries were most hypoplastic. In the third type with absent pulmonary valve, the pulmonary arteries were dilated forming aneurysms. In the last type only, ventricles were dilated and grossly hypertrophic.

Pulmonary stenosis with intact ventricular septum: documentation of development of the lesion echocardiographically during fetal life.

We describe a case of severe pulmonary stenosis with intact interventricular septum diagnosed during fetal life at 34 weeks gestational age. An echocardiographic examination had been performed on the same fetus at 20 weeks, when no cardiac anomalies were observed. It is concluded that this form of pulmonary stenosis might be a lesion either acquired during fetal life or becoming progressively more severe in the prenatal period.

Severe pulmonary stenosis and duct dependent coarctation in a neonate. An embryological impossibility?

A baby presented in cardiac failure with cyanosis on the first day of life. Investigations demonstrated severe pulmonary valve stenosis and duct-dependent coarctation of the aorta. This combination is impossible to explain using recognised embryological theories.

The Noonan syndrome.

Twenty-one patients with Noonan syndrome are presented. Telecanthus low-set ears, epicanthus and facial asymmetry were the commoner facial stigmata. Pterygium colli, pectus excavatum-carinatum and mild physical and mental retardation were also common features. Pulmonary stenosis and patent ductus arteriosus were the most frequent cardiac anomalies. Wide QRS, left axis deviation, giant Q waves and a negative pattern in V6 were useful electrocardiographic signs. We speculate that the Noonan syndrome could be considered as a branchial arch development syndrome.

Morphological development of the pulmonary vascular bed in experimental pulmonic stenosis.

The main pulmonary trunk was banded in four fetal sheep at 63--69 days of gestation. The fetuses were killed after they had developed progressive pulmonary stenosis at 98, 123, 134 and 135 days of gestation. The right lung of each animal was perfused with glutaraldehyde and serial sections followed microscopically. The medial width/external diameter ratios for fifth generation resistance vessels were significantly less (0.13) than those from six normal control lungs (0.16, p less than 0.001). In addition, the number of resistance vessels per cm2 lung tissue in the lungs of the animals with experimental pulmonic stenosis was less than in normal controls. The altered in utero hemodynamics with severe pulmonic stenosis results in thin-walled pulmonary arterial vessels. This may be caused by an increased blood oxygen tension of the blood perfusing the pulmonary circulation via reversed flow through the ductus arteriosus, or altered pulmonary arterial pressure characteristics in the pulmonary vessels distal to the obstructed pulmonary trunk.

Response to experimental coarctation of the aorta and pulmonic stenosis in the fetal lamb.

The following conditions were surgically created in fetal lambs at the gestational ages of 80 to 90 days: (1) preductal coarctation, (2) postductal coarctation, (3) pulmonic stenosis, and (4) constriction of the ductus arteriosus. Studies performed at the time of delivery showed the following: Preductal coarctation and postductal coarctation often are associated with a dilated ductus arteriosus that remains patent. Pulmonic stenosis often results in prestenotic and poststenotic dilatation that may include the ductus arteriosus. The fetal ventricles become hypertrophied in response to the increased pressure work imposed by the distal stenoses.