Safety and feasibility pilot study of continuous low-dose maternal supplemental oxygen in fetal single ventricle heart disease.

OBJECTIVE: Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low-dose MSO in the setting of SVP. METHODS: This single-center, open-label, pilot phase-1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self-administered continuous MSO using medical-grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late-gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC). RESULTS: Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self-administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment-associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head-circumference-to-abdominal-circumference ratio Z-scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z-score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late-gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z-score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age. CONCLUSIONS: This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Treatment, not delivery, of the late preterm and term fetus with supraventricular arrhythmia.

OBJECTIVE: While in-utero treatment of sustained fetal supraventricular arrhythmia (SVA) is standard practice in the previable and preterm fetus, data are limited on best practice for late preterm (34 + 0 to 36 + 6 weeks), early term (37 + 0 to 38 + 6 weeks) and term (> 39 weeks) fetuses with SVA. We reviewed the delivery and postnatal outcomes of fetuses at ≥ 35 weeks of gestation undergoing treatment rather than immediate delivery. METHODS: This was a retrospective case series of fetuses presenting at ≥ 35 weeks of gestation with sustained SVA and treated transplacentally at six institutions between 2012 and 2022. Data were collected on gestational age at presentation and delivery, SVA diagnosis (short ventriculoatrial (VA) tachycardia, long VA tachycardia or atrial flutter), type of antiarrhythmic medication used, interval between treatment and conversion to sinus rhythm and postnatal SVA recurrence. RESULTS: Overall, 37 fetuses presented at a median gestational age of 35.7 (range, 35.0-39.7) weeks with short VA tachycardia (n = 20), long VA tachycardia (n = 7) or atrial flutter (n = 10). Four (11%) fetuses were hydropic. In-utero treatment led to restoration of sinus rhythm in 35 (95%) fetuses at a median of 2 (range, 1-17) days; this included three of the four fetuses with hydrops. Antiarrhythmic medications included flecainide (n = 11), digoxin (n = 7), sotalol (n = 11) and dual therapy (n = 8). Neonates were liveborn at 36-41 weeks via spontaneous vaginal delivery (23/37 (62%)) or Cesarean delivery (14/37 (38%)). Cesarean delivery was indicated for fetal SVA in two fetuses, atrial ectopy or sinus bradycardia in three fetuses and obstetric reasons in nine fetuses that were in sinus rhythm at the time of delivery. Twenty-one (57%) cases were treated for recurrent SVA after birth. CONCLUSION: In-utero treatment of the near term and term (≥ 35-week) SVA fetus is highly successful even in the presence of hydrops, with the majority of cases delivered vaginally closer to term, thereby avoiding unnecessary Cesarean section. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Inadvertent irreversible closure of arterial duct following therapeutic use of transplacental indomethacin in a fetus with severe Ebstein's anomaly and circular shunt.

We report on a fetal case of Ebstein's anomaly with severe tricuspid regurgitation, functional pulmonary atresia and progressive circular shunting (CS) across a widely patent ductus arteriosus (DA) and regurgitant pulmonary valve, contributing to significant systemic hypoperfusion. To mitigate the extent of CS and allow the pregnancy to continue, maternal non-steroidal anti-inflammatory drug (NSAID) therapy with indomethacin was started at 33 + 5 weeks to induce DA constriction. Rather than achieving the desired narrowing of the DA, the treatment led to its complete closure and only minimal antegrade flow across the pulmonary valve. While closure of the DA resulted in the anticipated improvement in fetal hemodynamics, at birth, the child was at risk of severe hypoxemia and its consequences due to the lack of adequate pulmonary perfusion. Reduction and eventual discontinuation of the NSAID treatment did not result in DA reopening. Our experience illustrates the risk of unintended irreversible DA closure when NSAIDs are used to treat CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

MRI characterization of hemodynamic patterns of human fetuses with cyanotic congenital heart disease.

OBJECTIVES: To characterize, using magnetic resonance imaging (MRI), the distribution of blood flow and oxygen transport in human fetuses with subtypes of congenital heart disease (CHD) that present with neonatal cyanosis. METHODS: Blood flow was measured in the major vessels of 152 late-gestation human fetuses with CHD and 40 gestational-age-matched normal fetuses, using cine phase-contrast MRI. Oxygen saturation (SaO2 ) was measured in the major vessels of 57 fetuses with CHD and 40 controls. RESULTS: Compared with controls, we found lower combined ventricular output in fetuses with single-ventricle physiology, with the lowest being observed in fetuses with severe forms of Ebstein's anomaly. Obstructive lesions of the left or right heart were associated with increased flow across the contralateral side. Pulmonary blood flow was reduced in fetuses with Ebstein's anomaly, while those with Ebstein's anomaly and tricuspid atresia had reduced umbilical flow. Flow in the superior vena cava was elevated in fetuses with transposition of the great arteries, normal in fetuses with hypoplastic left heart, tetralogy of Fallot or tricuspid atresia and reduced in fetuses with Ebstein's anomaly. Umbilical vein SaO2 was reduced in fetuses with hypoplastic left heart or tetralogy of Fallot. Ascending aorta and superior vena cava SaO2 were reduced in nearly all CHD subtypes. CONCLUSIONS: Fetuses with cyanotic CHD exhibit profound changes in the distribution of blood flow and oxygen transport, which result in changes in cerebral, pulmonary and placental blood flow and oxygenation. These alterations of fetal circulatory physiology may influence the neonatal course and help account for abnormalities of prenatal growth and development that have been described in newborns with cyanotic CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Treatment of fetal circular shunt with non-steroidal anti-inflammatory drugs.

A circular shunt (CS) is a life-threatening condition involving massive shunting of systemic arterial blood via the ductus arteriosus to the left ventricle without traversing the lungs. In the prenatal setting, it occurs mainly in fetuses with severe forms of Ebstein's anomaly (EA) owing to unrestricted ductal flow and significant pulmonary and tricuspid regurgitation. We aimed to improve the fetal hemodynamics and chances of survival of affected fetuses by inducing ductal constriction using transplacental non-steroidal anti-inflammatory drugs (NSAIDs). Following initiation of treatment between 26 and 34 weeks' gestation, three (75%) of four fetuses with EA/CS responded with sustained ductal constriction and improved hemodynamic function, which allowed continuation of pregnancy for 3-7 weeks and elective delivery. All successfully treated cases underwent neonatal surgery immediately after birth to eliminate the CS and survived. This included two neonates that underwent single-ventricle palliation surgery that required postoperative extracorporeal membrane oxygenation and hemofiltration for transient respiratory and renal failure. The one case that did not respond to treatment with NSAIDs was delivered prematurely for progressive fetal compromise and died shortly after birth. Transplacental treatment with NSAIDs represents a novel approach to controlling fetal CS, avoiding in-utero death and prolonging the pregnancy to a more advanced gestational age, thereby potentially increasing the chances of neonatal survival. This treatment should be considered and initiated at an early stage of systemic steal to prevent brain injury due to hypoperfusion. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses.

OBJECTIVE: To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject. METHODS: We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression. RESULTS: The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (ß = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (ß = 10.6, P = 0.04 and ß = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (ß = -14.7, P = 0.03). CONCLUSION: In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Minimally invasive therapy for fetal sacrococcygeal teratoma: case series and systematic review of the literature.

OBJECTIVE: Large solid sacrococcygeal teratomas (SCT) can cause high-output cardiac failure and fetal or neonatal death. The aim of this study was to describe the outcomes of minimally invasive antenatal procedures for the treatment of fetal SCT. METHODS: A case review was performed of five fetuses with a large SCT treated antenatally using minimally invasive techniques, and a systematic literature review on fetal therapy for solid SCTs was carried out. RESULTS: Five women were referred between 17 + 5 and 26 + 4 weeks' gestation for a large fetal SCT with evidence of fetal cardiac failure. Vascular flow to the tumors was interrupted by fetoscopic laser ablation (n = 1), radiofrequency ablation (RFA; n = 2) or interstitial laser ablation ± vascular coiling (n = 2). There were two intrauterine fetal deaths. The other three cases resulted in preterm labor within 10 days of surgery. One neonate died. Two survived without procedure-related complications but had long-term morbidity related to prematurity. The systematic literature review revealed 16 SCTs treated minimally invasively for (early) hydrops. Including our cases, six of 20 hydropic fetuses survived after minimally invasive therapy (30%). Survival after RFA or interstitial laser ablation was 45% (5/11). Of 12 fetuses treated for SCT without obvious hydrops and for which perinatal survival data were available, eight (67%) survived. Mean gestational age at delivery after minimally invasive therapy was 29.7 ± 4.0 weeks. Survival after open fetal surgery in hydropic fetuses was 6/11 (55%), with a mean gestational age at delivery of 29.8 ± 2.9 weeks. CONCLUSIONS: Fetal therapy can potentially improve perinatal outcomes for hydropic fetuses with a solid SCT, but is often complicated by intrauterine death and preterm birth.

Fetal cardiac function in recipient twins undergoing fetoscopic laser ablation of placental anastomoses for Stage IV twin-twin transfusion syndrome.

OBJECTIVE: Cardiac dysfunction is common in the recipient fetus of twin-twin transfusion syndrome (TTTS). In this study, we aimed to document the severity of fetal cardiac dysfunction in Stage IV TTTS (fetal hydrops) and assess evolution of cardiac function longitudinally after fetoscopic laser surgery. METHODS: We reviewed obstetric ultrasound examination data, pre- and postoperative echocardiograms and neonatal outcomes for 22 cases of Stage IV TTTS undergoing fetoscopic laser ablation of placental anastomoses between 1998 and 2011. Myocardial performance index, atrioventricular valve flow patterns, ventricular shortening fraction, ventricular hypertrophy, outflow tract obstruction and venous Doppler waveforms were assessed. RESULTS: Nineteen fetuses (86.4%) had ascites, eight (36.4%) had pleural effusions, nine (40.9%) had a pericardial effusion and 12 (54.5%) had subcutaneous edema at presentation. Preoperatively, cardiac function was grossly abnormal in all. Eight fetuses (36.4%) had functional pulmonary atresia and one (4.5%) had functional aortic atresia. Seventy-seven percent of recipient fetuses survived until birth. Postoperative echocardiographic follow-up (mean, 26 days) showed that indices of fetal cardiac function improved considerably, but never completely normalized. Six of the eight fetuses with functional pulmonary atresia (75.0%), as well as the fetus with functional aortic atresia, survived to birth. In all cases, the functional atresia resolved within 48 h of laser ablation therapy and none had structural valve anomalies at birth. All fetal effusions resolved after the laser. CONCLUSIONS: Fetoscopic laser ablation of placental anastomoses reverses cardiac dysfunction and valvulopathy, even in the most severe cases of TTTS. However, recovery takes longer than in early stage disease.

Prenatal diagnosis and outcome of absent pulmonary valve syndrome: contemporary single-center experience and review of the literature.

OBJECTIVE: To review the anomaly spectrum of prenatally detected absent pulmonary valve syndrome (APVS) and the outcome after diagnosis. Previous fetal studies reported survival rates of ≤ 25% for patients with intended postnatal care. METHODS: Clinical data and echocardiograms of 12 cases with a fetal diagnosis of APVS between 2000 and 2010 were analyzed in this retrospective single-center study. Collected parameters included: gestational age at referral, associated fetal abnormalities, cardiothoracic ratio, maximum diameters of pulmonary annulus and main and branch pulmonary arteries, ventricular dimensions and function as well as ventricular Doppler flows. Karyotyping included fluorescence in-situ hybridization (FISH) analysis for microdeletion 22q11.2. RESULTS: Median gestational age at diagnosis was 24 weeks. Three subtypes of APVS were observed: (1) with tetralogy of Fallot (TOF) and no arterial duct (n = 10; 83%); (2) isolated, with a large arterial duct (n = 1; 8%); and (3) with tricuspid atresia, right ventricular dysplasia and a restricted duct (n = 1; 8%). The cardiothoracic ratio and pulmonary artery dimensions were increased in all cases. The karyotype was abnormal in 70% of fetuses with TOF and their mortality rate was significantly higher due to pregnancy termination (n = 3) or perinatal demise (n = 2) (hazard ratio, 5; 95% CI, 0.87-28.9; P = 0.015). Of seven live births with active postnatal care, six children (86%) were alive without residual respiratory symptoms at a median follow-up of 4.7 (range, 2.1-10.6) years. CONCLUSION: Outcome after fetal diagnosis of APVS was significantly better in this study compared with those of previous fetal series, with a low mortality rate for actively managed patients.

Minimally invasive fetal therapy for hydropic lung masses: three different approaches and review of the literature.

OBJECTIVE: To report three different antenatal therapeutic approaches for fetal lung masses associated with hydrops. METHODS: Three prospectively followed cases are described, and all 30 previously published minimally invasive cases of fetal therapy for hydropic lung masses are reviewed. RESULTS: Three hydropic fetuses with large intrathoracic lung masses presented at 17, 25 and 21 weeks of gestation, respectively. An aortic feeding vessel was identified in each case and thus a bronchopulmonary sequestration (BPS) was suspected. Under ultrasound guidance, the feeding vessel was successfully occluded with interstitial laser (Case 1), radiofrequency ablation (RFA) (Case 2) and thrombogenic coil embolization (Case 3). Complete (Cases 1 and 2) or partial (Case 3) resolution of the lung mass and hydrops was observed. A healthy infant was born at term after laser therapy (Case 1), and the involved lung lobe was resected on day 2 of postnatal life. In Case 2, hydrops resolved completely following RFA, but an iatrogenic congenital diaphragmatic hernia and abdominal wall defect became apparent 4 weeks later. The neonate died from sepsis following spontaneous preterm labor at 33 weeks. In Case 3, despite technical success in complete vascular occlusion with coils, a stillbirth ensued 2 days after embolization. CONCLUSIONS: The prognosis of large microcystic or echogenic fetal chest masses associated with hydrops is dismal. This has prompted attempts at treatment by open fetal surgery, with mixed results, high risk of premature labor and consequences for future pregnancies. We have demonstrated the possibility of improved outcome following ultrasound-guided laser ablation of the systemic arterial supply. Despite technical success, RFA and coil embolization led to procedure-related complications and need further evaluation.

Non-cardiac manifestations of neonatal lupus erythematosus.

Neonatal lupus erythematosus (NLE) is characterized by the transplacental passage of maternal anti-Ro and/or anti-La antibodies and characteristic illnesses in the foetus/neonate. Most attention has focused on the most serious complication- cardiac involvement. This article will focus on non-cardiac involvement. Skin involvement (cutaneous NLE) is present in 15-25% of children with NLE. The rash of NLE tends to be photosensitive but may be present at birth or in non-sun exposed areas. It is most frequently seen around the eyes, not in the malar area, but also occurs in other parts of the body. The pathology resembles the rash of subacute cutaneous lupus erythematosus. Anti-Ro antibodies are present in >95% with the remaining mothers having anti-U1RNP antibodies only. Asymptomatic elevation of liver function tests, which may be associated with evidence of cholestasis, is seen in 10-25% of cases of NLE. Mild hepatomegaly and less commonly splenomegaly may be present. Liver involvement seen in isolation or associated with other features. The pathology resembles idiopathic neonatal giant cell hepatitis. Any haematological lineage, neutropenia and thrombocytopenia most commonly, may be affected by NLE. Haematological involvement is almost always asymptomatic. There are protean manifestations of neurologic involvement in NLE: hydrocephalus, non-specific white matter changes, calcification of the basal ganglia and a 'vasculopathy'. The most unusual feature of NLE is the radiographic finding of stippling of the epiphyses (chondrodysplasia punctata). Overall, non-cardiac involvement of NLE is more common than cardiac. The study of these manifestations may lead to new insight into how autoantibodies lead to disease.

The benefits of transplacental treatment of isolated congenital complete heart block associated with maternal anti-Ro/SSA antibodies: a review.

Isolated congenital complete atrio-ventricular block (CAVB) is associated with the transplacental passage of maternal autoantibodies directed to foetal Ro/SSA ribonucleoproteins. Their interactions most likely trigger the inflammation of the atrio-ventricular node and the myocardium in susceptible foetuses. The inflamed tissues may then heal with fibrosis that may cause heart block, endocardial fibroelastosis, and dilated cardiomyopathy. CAVB, the most common cardiac complication, typically develops between 18 and 24 gestational weeks. Untreated, the condition carries a significant mortality risk as the foetus needs to overcome the sudden drop in ventricular rate, the loss of normal atrial systolic contribution to ventricular filling, and perhaps concomitant myocardial inflammation and fibrosis. The rationale to treat a foetus at the stage of CAVB is primarily to mitigate myocardial inflammation and to augment foetal cardiac output. Maternal dexamethasone administration has been shown to improve incomplete foetal AV block, myocardial dysfunction, and cavity effusions. Beta-sympathomimetics may be useful to increase the foetal heart rate and myocardial contractility. Published data from our institution suggest an improved survival >90% if maternal high-dose dexamethasone was initiated at the time of CAVB detection and maintained during the pregnancy and if a beta-adrenergic drug was added at foetal heart rates below 55 beats/min. Despite the improvement in outcome, there is an ongoing debate about treatment-related risks. In this review, we will appraise the natural history of untreated CAVB, discuss currently available management options, and examine the results and risks of in-utero treatment of antibody-mediated CAVB.

Percutaneous ultrasound-guided stenting of the atrial septum in fetal sheep.

OBJECTIVES: Hypoplastic left heart syndrome (HLHS) with a restricitive foramen ovale is associated with high mortality related to fetal left atrial hypertension. Fetal atrial balloon septoplasty has largely failed to achieve adequate decompression due to the small size of the holes produced. We attempted to produce larger atrial communications by stenting the atrial septum in fetal sheep using a minimally invasive technique. METHODS: We used a percutaneous, ultrasound-guided transpulmonary or transhepatic approach to attempt deployment of coronary stents (2-5 mm in diameter and 13-23 mm in length) in the atrial septum primum of 10 normal fetal sheep. RESULTS: Coronary stents were deployed in eight of the 10 fetal sheep (119-139 days' gestation). The transhepatic route was unsuccessful (n = 2). Transpulmonary implantation was only possible in prone fetuses, so three initially supine fetuses underwent external version. Small coronary stents (2.0-2.5 mm in diameter) were deployed rapidly without complication via an 18G needle (n = 4). Larger coronary stents (5 mm in diameter) were delivered through a 4F sheath, but a right pleural effusion occurred in three of the four cases, related to inferior vena cava injury by the balloon. One stent dislodged from a floppy septum. Another was partially occluded within a week by endocardial cells. CONCLUSIONS: Percutaneous ultrasound-guided deployment of coronary stents into the septum primum is feasible without laparotomy or uterine exteriorization in fetal sheep. Partial luminal occlusion by rapid proliferation of endocardial cells is a concern.

Heart sounds at home: feasibility of an ambulatory fetal heart rhythm surveillance program for anti-SSA-positive pregnancies.

OBJECTIVE: Fetuses exposed to anti-SSA (Sjögren's) antibodies are at risk of developing irreversible complete atrioventricular block (CAVB), resulting in death or permanent cardiac pacing. Anti-inflammatory treatment during the transition period from normal heart rhythm (fetal heart rhythm (FHR)) to CAVB (emergent CAVB) can restore sinus rhythm, but detection of emergent CAVB is challenging, because it can develop in ⩽24 h. We tested the feasibility of a new technique that relies on home FHR monitoring by the mother, to surveil for emergent CAVB. STUDY DESIGN: We recruited anti-SSA-positive mothers at 16 to 18 weeks gestation (baseline) from 8 centers and instructed them to monitor FHR two times a day until 26 weeks, using a Doppler device at home. FHR was also surveilled by weekly or every other week fetal echo. If FHR was irregular, the mother underwent additional fetal echo. We compared maternal stress/anxiety before and after monitoring. Postnatally, infants underwent a 12-lead electrocardiogram. RESULTS: Among 133 recruited, 125 (94%) enrolled. Among those enrolled, 96% completed the study. Reasons for withdrawal (n=5) were as follows: termination of pregnancy, monitoring too time consuming or moved away. During home monitoring, 9 (7.5%) mothers detected irregular FHR diagnosed by fetal echo as normal (false positive, n=2) or benign atrial arrhythmia (n=7). No CAVB was undetected or developed after monitoring. Questionnaire analysis indicated mothers felt comforted by the experience and would monitor again in future pregnancies. CONCLUSION: These data suggest ambulatory FHR surveillance of anti-SSA-positive pregnancies is feasible, has a low false positive rate and is empowering to mothers.

Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.

BACKGROUND: Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. METHODS AND RESULTS: A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05). CONCLUSIONS: In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Role of ischemia and infarction in late right ventricular dysfunction after atrial repair of transposition of the great arteries.

OBJECTIVES: This study was conducted to assess whether myocardial ischemia and/or infarction are involved in the pathogenesis of late right ventricular dysfunction in adult survivors of atrial baffle repair for transposition of the great arteries in infancy. BACKGROUND: The medium-term success of intraatrial baffle repair for transposition of the great arteries is good, with many patients surviving into adult life, but prognosis can be limited by progressive right ventricular dysfunction. We hypothesized that ongoing myocardial ischemia and/or infarction are important factors in the pathogenesis of this complication. Radionuclide techniques offer an opportunity to study both myocardial perfusion and concomitant ventricular wall motion. METHODS: Dipyridamole sestamibi single-photon emission computed tomography followed by rest sestamibi single-photon emission computed tomography was used to assess right ventricular myocardial perfusion, wall motion, wall thickening and ejection fraction in 22 adolescents/young adults who had undergone atrial baffle repair for simple transposition of the great arteries at median 6.7 (range 0.5 to 54) months of age. The patients were aged 10 to 25 (median 15.5) years; 19 in New York Heart Association class I, 2 in class II and 1 in class III. All were in a regular cardiac rhythm during the studies. The right ventricular tomographic images were examined in three parallel and two orthogonal planes, analyzed in 12 segments. RESULTS: Perfusion defects were evident in all patients in at least one segment, in either the rest or stress images. Twelve patients (55%) demonstrated fixed defects only, nine (41%) had fixed and reversible defects and one (4.5%) had reversible defects only. Concomitant wall-thickening abnormalities occurred in 83% of segments with fixed perfusion defects, mirrored by a reduction in wall motion in 91% of segments analyzed. Right ventricular ejection fraction was correlated with age (R = 0.62; p = 0.002), and with wall-thickening abnormalities (R = 0.60; p < 0.005). CONCLUSIONS: Reversible and fixed perfusion defects with concordant regional wall motion abnormalities occur in the right (systemic) ventricle 10 to 20 years after Mustard repair for transposition of the great arteries; this may be important in the pathogenesis of late right ventricular dysfunction in this group.