Valvuloplasty in 103 fetuses with critical aortic stenosis: outcome and new predictors for postnatal circulation.

OBJECTIVES: To review our experience with fetal aortic valvuloplasty (FAV) in fetuses with critical aortic stenosis (CAS) and evolving hypoplastic left heart syndrome (eHLHS), including short- and medium-term postnatal outcome, and to refine selection criteria for FAV by identifying preprocedural predictors of biventricular (BV) outcome. METHODS: This was a retrospective review of all fetuses with CAS and eHLHS undergoing FAV at our center between December 2001 and September 2020. Echocardiograms and patient charts were analyzed for pre-FAV ventricular and valvular dimensions and hemodynamics and for postnatal procedures and outcomes. The primary endpoints were type of circulation 28 days after birth and at 1 year of age. Classification and regression-tree analysis was performed to investigate the predictive capacity of pre-FAV parameters for BV circulation at 1 year of age. RESULTS: During the study period, 103 fetuses underwent 125 FAVs at our center, of which 87.4% had a technically successful procedure. Technical success per fetus was higher in the more recent period (from 2014) than in the earlier period (96.2% (51/53) vs 78.0% (39/50); P = 0.0068). Eighty fetuses were liveborn after successful intervention and received further treatment. BV outcome at 1 year of age was achieved in 55% of liveborn patients in our cohort after successful FAV, which is significantly higher than the BV-outcome rate (23.7%) in a previously published natural history cohort fulfilling the same criteria for eHLHS (P = 0.0015). Decision-tree analysis based on the ratio of right to left ventricular (RV/LV) length combined with LV pressure (mitral valve regurgitation maximum velocity (MR-Vmax)) had a sensitivity of 96.97% and a specificity of 94.44% for predicting BV outcome without signs of pulmonary arterial hypertension at 1 year of age. The highest probability for a BV outcome was reached for fetuses with a pre-FAV RV/LV length ratio of < 1.094 (96.4%) and for those fetuses with a RV/LV length ratio ≥ 1.094 to < 1.135 combined with a MR-Vmax of ≥ 3.14 m/s (100%). CONCLUSIONS: FAV could be performed with high success rates and an acceptable risk with improving results after a learning curve. Pre-FAV RV/LV length ratio combined with LV pressure estimates were able to predict a successful BV outcome at 1 year of age with high sensitivity and specificity. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal aortic valvuloplasty may rescue fetuses with critical aortic stenosis and hydrops.

OBJECTIVE: Critical aortic stenosis (CAS) with a restrictive interatrial septum may lead to fetal congestive heart failure and hydrops, usually culminating in fetal demise if left untreated. The aim of this study was to assess the effects of fetal aortic valvuloplasty (FAV) on hemodynamics and outcome in these patients. METHODS: This was a retrospective review of fetuses with CAS and signs of hydrops that underwent FAV in our center between 2000 and 2020. Echocardiograms and patients' charts were analyzed for ventricular and valvular dimensions and for outcome. RESULTS: Hydrops was present at the time of intervention in 15 fetuses with CAS that underwent FAV at our center during the study period. All but one patient had at least one technically successful procedure. There were no procedure-related deaths, but three intrauterine deaths occurred. Twelve subjects were liveborn, of whom two died within 24 h after birth owing to persistent hydrops. Ventricular function improved and hydrops resolved within 3-4 weeks after FAV in 71.4% (10/14) of fetuses with a technically successful intervention. A biventricular outcome was achieved in 50% of the successfully treated patients. CONCLUSIONS: Fetuses with CAS and hydrops can be successfully treated with FAV. The procedure has the potential to restore sufficient fetal cardiac output, which may lead to resolution of hydrops. Surviving patients seem to be good candidates for a biventricular outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Tissue Doppler imaging in fetuses with aortic stenosis and evolving hypoplastic left heart syndrome before and after fetal aortic valvuloplasty.

OBJECTIVES: Fetal aortic valvuloplasty can improve filling and reduce afterload of the left ventricle in critical aortic stenosis. Success of an intrauterine intervention is currently measured by technical success, clinical survival and eventual postnatal biventricular physiology. In the present study we investigated the use of tissue Doppler imaging (TDI) to evaluate changes in ventricular function assessed before and after prenatal aortic valvuloplasty. METHODS: Between October 2008 and December 2012, cardiac function was assessed by TDI before and after intervention in 23 fetuses that underwent technically successful valvuloplasty for critical aortic stenosis and in which postnatal outcome was known. The measurements were transformed into gestational age-independent Z-scores where appropriate. RESULTS: Mean ± SD gestational age at intervention was 27.5 ± 3.1 weeks. Of the 23 fetuses, 14 had biventricular outcome. Before intervention all left ventricular (LV) TDI-derived parameters and mitral annular plane systolic excursion (MAPSE) were severely abnormal. It was possible to demonstrate considerably improved cardiac function after technically successful valvuloplasty. Among fetuses with postnatal biventricular outcome, TDI-derived LV myocardial peak velocity during early diastole (E') and myocardial peak velocity during systole in the ejection phase (S') significantly increased, E'/myocardial peak velocity during late diastole with atrial contraction (A') increased towards normal values, and LV transmitral-to-mitral-annular diastolic velocity ratio (E/E') and myocardial performance index (MPI') decreased but remained abnormally elevated. In addition, right ventricular A', S' and MPI' significantly improved after intervention. CONCLUSION: Technically successful fetal aortic valvuloplasty led to significantly improved myocardial performance. It was possible to use TDI to detect distinct changes in ventricular function and TDI-derived parameters correlated with a biventricular outcome after birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Maternal aspects of fetal cardiac intervention.

OBJECTIVES: Fetal cardiac interventions have the potential to alter natural disease progression and reduce morbidity and mortality in children. Although there are already encouraging data on fetal outcome, information on maternal morbidity and mortality after intervention is scarce. The aim of the present study was to assess maternal aspects, pregnancy-associated risks and adverse events in 53 intrauterine cardiac interventions. METHODS: Between October 2000 and December 2012, 53 fetal cardiac interventions were performed in 47 patients (43 aortic valve dilations in 39 patients, seven pulmonary valve dilations in six patients and three balloon atrioseptostomies in two patients). Median gestational age was 26 + 4 (range, 20 + 3 to 33 + 1) weeks. Interventions were performed by an ultrasound-guided percutaneous approach under general anesthesia. All medical records and patient charts were analyzed retrospectively. RESULTS: All women were considered to be healthy in the preoperative assessment; 39 (83%) patients continued pregnancy until term and eight of 47 patients had an intrauterine fetal death (IUFD) and were induced. Postoperative nausea was reported in 29.8% of patients and abdominal pain in 36.2% of patients on the day of surgery. Preterm contractions were observed in two patients; no preterm prelabor rupture of membranes occurred. One severe postpartum hemorrhage was observed in a patient with IUFD and subsequent induction; however, this was unrelated to the balloon valvuloplasty. No intensive care unit admission and no major anesthesia-associated complications (aspiration, anaphylactic reaction, cardiovascular collapse, damage to teeth, laryngeal damage, awareness or hypoxic brain damage) were observed. Maternal mortality was zero. A significant learning curve was observed in terms of duration of intervention. CONCLUSION: In our experience, percutaneous needle-guided fetal cardiac intervention seems to be a safe procedure for the mother. In 53 procedures no major maternal complication directly related to the intervention was observed.

Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

Intrauterine aortic valvuloplasty in fetuses with critical aortic stenosis: experience and results of 24 procedures.

OBJECTIVE: Valvuloplasty of the fetal aortic valve has the potential to prevent progression of critical aortic stenosis (AS) to hypoplastic left heart syndrome (HLHS). The aim of the study was to assess 24 aortic valvuloplasties regarding indications, success rate, procedure-related risks and outcome. METHODS: Between January 2001 and December 2009 we performed 24 aortic valvuloplasties in 23 fetuses with critical AS at a median gestational age of 26 + 4 (range, 21 + 3 to 32 + 5) weeks by a transabdominal ultrasound-guided approach. Four fetuses had hydrops as a late sign of heart failure. RESULTS: In 16/24 procedures (66.7%) corresponding to 16/23 fetuses (69.6%) the procedures were technically successful, with one intrauterine death in this group. After an initial learning curve, success rate improved to 78.6% (11 of the last 14 interventions were successful). In 10 out of the 15 (66.7%) successfully-treated and liveborn fetuses a biventricular circulation could be achieved postnatally. All four fetuses with hydrops had successful interventions, hydrops disappearing within 5 weeks. In 8/24 interventions (33.3%) the aortic valve could not be treated successfully, with intrauterine fetal death in two of these cases. In one fetus a repeat procedure was successful. All surviving fetuses with unsuccessful (n = 5) or no (n = 5) procedure performed developed HLHS until delivery. CONCLUSIONS: Fetal aortic valvuloplasty could be performed successfully in selected fetuses with critical AS and evolving HLHS, with a biventricular outcome in two thirds of the patients. Safety and success rate were dependent on patient selection and the level of experience of the whole interventional team. In fetuses with AS and hydrops, aortic valvuloplasty could reverse end-stage heart failure and hydrops and ensure fetal survival.

Effect of stenosis geometry on the Doppler-catheter gradient relation in vitro: a manifestation of pressure recovery.

OBJECTIVES: This study investigated the effect of stenosis geometry on the Doppler-catheter gradient relation. BACKGROUND: Although gradient estimation by Doppler ultrasound has been shown to be accurate in various clinical and in vitro settings, there have also been reports of substantial discrepancies between Doppler and catheter gradients. These conflicting results may be due to differences in geometry and hemodynamic characteristics of flow obstructions. METHODS: Stenoses of various geometry were simultaneously studied with continuous wave Doppler and catheter technique in a well controlled pulsatile flow model. RESULTS: Doppler and catheter gradients correlated very well regardless of stenosis geometry and site of distal catheter measurement (r = 0.98 to 0.99, SEE = 1.8 to 5.3 mm Hg). When the catheter was pulled back through the stenosis, the highest gradients were found in or close to the stenosis. When these catheter gradients were compared with Doppler gradients, the agreement between the two techniques was excellent regardless of stenosis geometry (slope 0.97; mean difference 0.6 +/- 2.0 mm Hg). However, when distal pressures were measured 10 cm downstream from the stenotic segment, the slope of the regression line, and therefore the agreement between Doppler and catheter gradients, differed for the different stenosis types (slopes from 0.98 to 1.69). In stenoses with abrupt narrowing and abrupt expansion, agreement was acceptable. Doppler gradients were only slightly greater than catheter gradients (mean difference 4.5 +/- 5.2 mm Hg). In stenoses with a gradually tapering inlet and outlet, the Doppler-catheter gradient relation was dependent on the outflow angle. Good agreement was found for an angle of 60 degrees (mean difference 0.6 +/- 1.8 mm Hg). In stenoses with a 40 degrees outflow angle, Doppler gradients exceeded the catheter gradients by 13% on average; for stenoses with a 20 degrees outflow angle, Doppler gradients exceeded catheter gradients by 46 +/- 11.4%, with differences as great as 65 mm Hg. These results were identical for stenoses gradually tapering outward to the distal tubing diameter and those with abrupt expansion after 2 cm of gradual expansion. The results were also not affected by changing the inflow angle from 20 degrees to 60 degrees. However, an abrupt narrowing instead of a tapering inlet significantly altered the Doppler-catheter gradient relation (p < 0.001); Doppler gradients exceeded the catheter gradients by 34 +/- 10% for this stenosis type. CONCLUSIONS: Doppler gradients accurately reflect the highest gradients across flow obstructions that occur in the vena contracta. However, these gradients may be significantly greater than catheter gradients that are measured farther downstream, as is usually the case in clinical catheterization studies. These discrepancies are due to pressure recovery. The magnitude of pressure recovery is highly dependent on the stenosis geometry, which therefore significantly affects the Doppler-catheter gradient relation. It is the outflow geometry that predominantly influences this relation, but the shape of the inlet may affect the results as well. Although pressure recovery occurs even in stenoses with abrupt narrowing and abrupt expansion, the phenomenon is most likely to become clinically relevant in stenoses with a gradually tapering inlet and outlet with an outflow angle < or = 20 degrees.

Doppler echocardiography of fetal ductus arteriosus constriction versus increased right ventricular output.

A prospective longitudinal study from 121 examinations of 41 normal pregnant women showed that fetal ductal flow velocities increased with gestational age. These normal data were compared with data in three groups of fetuses with altered ductal flow velocities: 22 fetuses (mean gestational age 31.3 weeks) had ductal constriction due to maternal indomethacin treatment; 10 fetuses (mean gestational age 27.9 weeks) had been exposed to terbutaline, a positive inotropic agent and 14 fetuses (mean gestational age 33.3 weeks) had hypoplastic left heart syndrome. In normal fetuses maximal systolic, mean and end-diastolic ductal flow velocities increased linearly (p less than 0.0001). The pulsatility index did not change (mean +/- 2 SD: 2.46 +/- 0.52). Fetuses with ductal constriction had higher maximal, mean and end-diastolic flow velocities and a significantly lower pulsatility index than did normal fetuses (1.25 +/- 0.76; p less than 0.0005). Six of 10 fetuses of the terbutaline group and 8 of 14 fetuses with hypoplastic left heart syndrome had increased maximal flow velocity, but normal or only mildly elevated mean flow velocity. The pulsatility index in fetuses during terbutaline therapy and with hypoplastic left heart syndrome was significantly higher than in normal fetuses (3.11 +/- 0.46 and 3.09 +/- 0.7, respectively, vs. 2.46 +/- 0.52; p less than 0.0005). Fetal ductal waveform analysis was necessary to distinguish fetal ductal constriction from increased right ventricular output. These measurements may be helpful in the diagnosis of left-sided outflow obstruction and assessment of fetal hemodynamic data.

Diagnosis, transport, and outcome in fetuses with left ventricular outflow tract obstruction.

Between March 1986 and April 1990, 22 consecutive fetuses (at gestational ages of 21 to 38 weeks) with a suspected diagnosis of critical (ductus-dependent) left ventricular outflow tract obstruction on fetal echocardiogram were referred to our center for delivery and surgical treatment. Diagnoses were hypoplastic left heart syndrome (n = 16), valvular aortic stenosis (n = 2), common atrioventricular canal with subaortic stenosis (n = 3), and single ventricle with subaortic stenosis (n = 1). Postnatal echocardiography revealed that fetal echocardiography was correct in predicting left ventricular outflow tract obstruction to be critical in all but one patient, for a positive predictive value of 96%. Of the 21 patients with true, critical left ventricular outflow tract obstruction, 17 patients underwent cardiac surgery as neonates (birth to 6 days of age, median 2 days); 13 (or 77%) survived and were discharged from the hospital. In addition, one patient underwent successful balloon aortic valvotomy for critical valvular aortic stenosis but later died of sepsis. Lethal chromosomal and congenital abnormalities should be sought and are contraindications for this approach. In utero transport of fetuses with suspected critical left ventricular outflow tract obstruction to a neonatal cardiac surgical center can result in improved neonatal condition and may improve overall survival.

BCG lymphadenitis in an HIV-infected child 9.5 years after vaccination.

Complications of Bacillus Calmette-Guerin (BCG) vaccination have been reported in immunocompetent as well as in immunocompromised individuals. Severe and/or late complications have been associated with impairment of cell-mediated immunity. A case of BCG lymphadenitis in a vertically infected HIV-positive boy 9.5 years after vaccination is presented. The vaccination was performed within the first week of life, the HIV status of the mother being unknown. When the boy was 2.5 years old, his HIV infection was diagnosed after his mother had died from AIDS. At that time his CD4 count was 739 cells/microL. In the course of the following years, his CD4 count declined steadily, until it reached a low of about 20 cells/microL at the age of 5.5 years. He was troubled with recurring respiratory infections and one incidence of severe pancreatitis. Apart from that, he was in stable condition and led a more or less normal life. At the age of 9.5 years he developed lymphadenitis in his left axilla. The node was examined via biopsy, and the appropriate tests showed an infection with Mycobacterium bovis BCG variety. The CD4 count at that time was 16 cells/microL, polymerase chain reaction showed 220,000 RNA copies/mL. There were no signs of dissemination. Antitubercular agents were administered, and an antiretroviral combination therapy was started. The patient was discharged from the hospital after approximately 2 months. After an uneventful period of 9 months, the boy, still on antitubercular medicine, exhibited a secreting fistula in his left axilla, again due to Mycobacterium bovis, BCG variety. The fistulous tissue was removed surgically, and the antitubercular treatment was given intravenously for almost 3 months before being changed to an oral application. In addition, the antiretroviral regimen was completely exchanged. The case presented illustrates that there is a risk of very late complications in HIV-infected individuals, even when they are vaccinated when they are asymptomatic newborns. Although the risk seems low, one has to be aware of the problem because timely treatment is probably essential to prevent dissemination of the infection. Late complications of BCG vaccinations are most likely to be detected in countries with high medical standards, where HIV-infected children are surviving for longer periods of time.

[Polyglandular type I autoimmune syndrome]. / Polyglanduläres Autoimmunsyndrom Typ I.

Two HLA-identical sisters have developed the full picture of type I polyglandular autoimmune syndrome over a period of 12 years. Both girls have hypoparathyroidism and Addison's disease. One of them additionally developed diabetes mellitus, hypergonadotropic hypogonadism and hypothyroidism. Autoantibodies to the adrenal, parathyroid and thyroid glands are present in both patients, as well as antinuclear antibodies. HLA associations have been described recently for the type I polyglandular autoimmune syndrome, but this could not be confirmed in the present two cases. Although we assume that the same genetic defect is present in both girls, additional factors to the genetic disposition are important for the clinical expression of the disease. The linkage of the disease-causing gene with the HLA region is not very close.

[Tubal rupture after prostaglandin instillation despite decreasing beta-HCG values]. / Tubarruptur nach Prostaglandininstillation trotz abfallender beta-HCG-Werte.

Over the past years laparoscopic surgery has become widely accepted in the treatment of tubal pregnancy and instillation of prostaglandin is well established. However, the failure rate is around 20%. This report describes a case of tubal pregnancy treated according to this procedure where the therapy initially seemed to be successful. Instillation of prostaglandin F2 alpha was followed by decreasing beta-HCG values, which continued to decrease after discharge. Thus, rupture of the operated tube on day 17 after surgery was completely unexpected.

[Zellweger syndrome, neonatal adrenoleukodystrophy or infantile Refsum's disease in a case with generalized peroxisome defect?]. / Zellweger-Syndrom, neonatale Adrenoleukodystrophie oder infantile Refsumsche Erkrankung bei einem Fall mit generalisiertem Peroxisomendefekt?

An eleven month-old boy presented clinically with craniofacial dysmorphia, severe psychomotor retardation, neurological deterioration, no response to visual and acoustic stimuli, failure to thrive, hepatomegaly and adrenal insufficiency. Specific biochemical markers for a peroxisomal deficiency disorder (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease) revealed pathological results for very long chain fatty acids, phytanic acid, pristanic acid, plasmalogen biosynthesis and catalase, thus confirming the clinical diagnosis. Comparison of clinical and biochemical findings in the patient with the characteristics of the three peroxisomal deficiency disorders showed overlapping with each of these disorders, which corresponds to the current view that these three peroxisomal disorders differ only with respect to onset and severity of the clinical manifestations, but not with regard to the biochemical defects.

[Emergencies in pediatric cardiology]. / Kinderkardiologische Notfälle.

Congenital heart defects, not recognized antenatally, may lead to emergency situation immediately after birth. Fast recognition of clinical symptoms and the use of correct diagnostic tools are life-saving under these circumstances. Principles of cardio-pulmonary resuscitation will be presented in this article as well as diagnosis and treatment of hypoxemic spells, pulmonary hypertensive crises and (usually postoperative) pericardial effusion.