Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

Prenatal care in the era of economic collapse.

OBJECTIVES: To describe the effect of economic collapse on prenatal care. METHODS: This is an observational study aiming to depict the changes that occur in prenatal care in the case of an economic collapse. Biochemical screening and ultrasound examinations, as well as medical emigration and private-public sector activity, are discussed. RESULTS: Starting October 2019, Lebanon experienced significant and unprecedented economic degradation leading to 81% degradation of the local currency, 85% inflation, and socio-economic suffering, and the situation is currently still deteriorating. The impact on the medical infrastructure has been global and hit all areas. The crisis is multifaceted, varied in the way it played out across public and private sectors, and did not affect them equally. Some were better prepared than others to cope with severe fiscal pressure mainly through the support of non-governmental organizations. All aspects of prenatal care are affected by the crisis. CONCLUSIONS: Given the multiple strains on the Lebanese health care system today, the plight of antenatal care providers needs assistance to ensure adequate follow-up of pregnancies.

Normal values of cardiac axis (CA) measurements in healthy fetuses during the first trimester screening ultrasound.

OBJECTIVES: To report the normal fetal cardiac axis (CA) values at the time of the first trimester screening ultrasound. METHODS: Standardized images and measurement of the CA were obtained from 100 healthy fetuses between 11+0 and 13+6 weeks of gestation along with the nucal thichkness (NT), Crown-rump length (CRL) and other measurements. We excluded cases with abnormal NT, later diagnosis of abnormalities, and suspected fetal cardiopathy during the pregnancy follow-up. Data analysis was performed after all the patients delivered and cardiopathy was excluded. RESULTS: CA was measurable in all the cases. Higher CRL was associated with a decrease in the CA. The mean ± SD embryonic/fetal CA was 48±5,2°, ranging from 39 to 60°, The 2.5 percentile was defined at 40° and the 97.5 percentile at 59°. The Pearson test resulted in a significant correlation between CA and CRL with a coefficient R of 70% and p-value <0.01. CONCLUSIONS: CA tends to decrease at the 11 to 13+6 gestational ages. We defined 2.5 and 97.5% curves for the normal values of CA in our Middle Eastern population. A larger study will be required to differentiate normal and abnormal values for the early detection of heart abnormalities.

Transcatheter closure of congenital Gerbode-type ventricular septal defect using the new multifunctional occluder device.

The KONAR-Multifunctional™ VSD Occluder (MFO) (Lifetech) is one of the most recent additions to the armamentarium of transcatheter therapies. The device offers superior technical features and experienced interventionists having been using it in risky and complex anatomies. Herein, we report the first use of the MFO device to close a congenital Gerbode-type perimembranous ventricular septal defect in an 18-year-old girl. The device was retrogradely implanted into proper position under ultrasound and fluoroscopic guidance. Immediate and 12-month-follow-up confirmed successful outcomes with complete shunt closure and resolution of tricuspid regurgitation.

Percutaneous closure of restrictive-type perimembranous ventricular septal defect using the new KONAR multifunctional occluder: Midterm outcomes of the first middle-eastern experience.

OBJECTIVES: To evaluate the safety, efficiency, and midterm outcomes of transcatheter perimembranous ventricular septal defect (pmVSD) closure using the new KONAR-MF™ VSD occluder. BACKGROUND: Off-label percutaneous pmVSD closure is a well-established procedure with promising results. Yet, interventionists are still searching for the ideal device. METHODS: Between June 2018 and March 2019, 20 patients with hemodynamically significant but restrictive-type pmVSD underwent an attempted transcatheter closure using the new KONAR-MF™. All implantations were performed retrogradely under general anesthesia, transoesophageal echocardiography, and fluoroscopic guidance. Prospective follow-up using transthoracic echocardiography and electrocardiogram was done until August 2019. RESULTS: The median age was 6.4 years (8 months to 43.4 years), and the median body weight was 17.3 (9-74) kg. The mean defect size on the left ventricular aspect was 11.7 ± 2.8 mm. All devices were successfully and rapidly implanted. One device embolized in the pulmonary artery, 24 hr after implantation and was percutaneously retrieved with no complication. Over a mean follow-up period of 8.2 ± 3.0 months, complete closure was achieved in 84.2% of patients. One new onset of mild aortic regurgitation was detected before discharge and remained stable. Tricuspid valve regurgitation, complete heart block, major complication, and death were not observed. CONCLUSIONS: Transcatheter pmVSD closure using the KONAR-MF™ can be successfully performed in adult and pediatric patients. It is a safe and promising device, designed to provide high conformability to septal defects with a lower risk of heart block. Retrograde implantation allows procedural flexibility, efficient deliverability, and control of valvular interferences.

Ductal stenting to improve pulmonary blood flow in pulmonary atresia with intact ventricular septum and critical pulmonary stenosis after balloon valvuloplasty.

OBJECTIVE: To assess the feasibility, safety, and efficiency of ductal stenting in pulmonary atresia with intact ventricular septum or critical pulmonary stenosis after balloon pulmonary valvuloplasty. BACKGROUND: Ductal stenting in pulmonary atresia with intact ventricular septum is a re-emerging and promising technique. There is little data available on its outcomes after establishing prograde pulmonary blood flow. METHODS: We retrospectively reviewed all neonates with pulmonary atresia with intact ventricular septum or critical pulmonary stenosis who underwent ductal stenting after balloon valvuloplasty. Ductal stenting was performed either in the same setting (group A) or a few days later after balloon valvuloplasty (group B). We compared the two groups. RESULTS: Eighteen coronary stents were transvenously delivered and successfully deployed in 18 newborns. There was no procedure-related mortality. The median hospital stay post-intervention was 6 days with a mean discharge oxygen saturation of 94%. Group A had a shorter overall hospital stay with a shorter overall time of irradiation but with a longer overall procedural time. On a follow-up of 18 months, no re-intervention for stent failure or overflow was undertaken. The median stent patency based on echocardiography was 12 months. CONCLUSION: Stenting the arterial duct in pulmonary atresia with intact ventricular septum or critical pulmonary stenosis is a feasible, safe, and efficient technique. It avoids surgery or long hospital stay with prostaglandin infusion. The minimal 6 months stent longevity provides a period of time long enough to decide whether the right ventricular diastolic function is normalised or Glenn surgery is still needed.

Prenatal diagnosis of ectopia cordis in a twin fetus.

We report images of the 7th case worldwide of a twin fetus with a complete isolated ectopia cordis in a dichorionic diamniotic twin gestation. There is no consanguinity, family history of abnormalities, IVF, or first trimester medication. The diagnosis of this isolated anomaly was done at 23 weeks in one fetus, while the other had normal morphology; the pregnancy was complicated by preterm labor and a cesarean delivery followed at 34 weeks. The affected baby weighed 1800 g and had an outcome complicated by episodes of desaturation and deceased at day 8. Parents did not wish either in utero termination of pregnancy or postnatal surgery for reintegration in the thorax and chose instead palliative care.

[The percutaneous treatment of pulmonary atresia with intact ventricular septum]. / Traitement percutané de l'atrésie pulmonaire à septum interventriculaire intact.

OBJECTIVE: Describe a mechanical method of perforation-dilatation of the pulmonary valve in pulmonary atresia with intact interventricular septum (PA-IVS), with or without stenting the patent ductus arteriosus (PDA) and medium-term results. METHOD: Since 2007, all patients with PA-IVS and a right ventricle adequate for biventricular repair, benefited from a transcatheter attempt to perforate-dilate the valve with or without stenting the PDA, and were included in this retrospective study. TECHNIQUE: A catheter was percutaneously introduced through the femoral vein and positionned in front of the atretic pulmonary valve. A lasso catheter was introduced through the femoral artery to the other side of the pulmonary valve. The tip of a rigid guidewire was then pushed through the atretic valve and taken with the lasso, creating a loop that allowed for balloon valvuloplasty. If the child remained ductal dependant following PGE1 withdrawal, a stent is placed in the ductus arteriosus. RESULTS: Five patients were included in this series. Four patients were successfully dilated, and two patients necessitated stents. The procedure had to be interrupted in one patient. FOLLOW-UP: One patient with a patent stent was operated at the age of one year and died in the postoperative period. The other patient with a stent is now 16 months old with a patent stent and an oxygen saturation of 98%. The two remaining patients without stent are now 3- and 18-month-old with oxygen saturation of 85% and 96% respectively. CONCLUSION: The percutaneous treatment of PA-IVS is feasible and avoids early high risk surgery. Stenting the ductus arteriosus may replace a Blalock shunt. However, the prognosis is still related to the severity of the anomaly.

Unusual Findings in Down's Syndrome: Hand Agenesis and Hypospadias.

A baby with Down syndrome presented initial findings at the first-trimester ultrasound of increased nuchal thickness and unilateral hand agenesis. During follow-up, other elements were found mainly hypospadias. This report emphasizes through prenatal and postnatal imaging the phenotypic variability of Down syndrome babies.

Fetal supraventricular tachycardia and maternal COVID-19 vaccination: is there any relationship?

Fetal supraventricular tachycardia accounts for 60-80% of the fetal tachyarrhythmias with prevalence ranging from 1/1000 to 1/25 000 pregnancies. It may be secondary to fetal anomalies or maternal factors. By reviewing the literature, there is no previous article that reports fetal arrhythmia after maternal vaccination. We present herein two cases of fetal supraventricular tachycardia following the administration of the Pfizer-BioNTech COVID-19 vaccine during pregnancy. Continued safety monitoring and more longitudinal follow-up are needed to evaluate the fetal impact after maternal COVID-19 vaccination.

Characteristics and outcome in prenatally diagnosed vascular aorta-umbilical vein malformation.

Congenital arteriovenous fistulas involving the abdominal aorta are very rare. We report an unusual presentation involving the umbilical vein and characterized by the occurrence of a postnatal thrombosis and a favorable outcome.Synopsis: Fetal abdominal arteriovenous fistulas are rare involve branches from the aorta and can lead to umbilical vein thrombosis.

Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.

The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.

Role of first-trimester sonography in the diagnosis of aneuploidy and structural fetal anomalies.

OBJECTIVE: We sought to determine the sensitivity of the first-trimester scan in the early diagnosis of aneuploidy and structural fetal anomalies in an unselected low-risk population. METHODS: This was a retrospective chart review of all patients having first-trimester scans between 2002 and 2009. At our center, a survey of fetal anatomy is performed at the time of nuchal translucency assessment at 11 weeks to 13 weeks 6 days. A second-trimester scan is done at 20 to 23 weeks and a third-trimester scan at 32 to 35 weeks. Isolated sonographic findings of choroid plexus cysts and echogenic intracardiac foci were excluded. Lethal anomalies and those requiring immediate surgical intervention at birth were considered major structural anomalies. All scans were performed by a single sonologist certified by the Fetal Medicine Foundation. All neonates were examined at birth by a pediatrician. RESULTS: Our study included 1370 fetuses. Six cases of aneuploidy (0.4%) were detected. The first-trimester scan detected 5 of 6 cases of aneuploidy (83%), confirmed by karyotype. There were 36 cases of structural fetal anomalies (2.6%); 20 (1.5%) were major anomalies. The first-trimester scan detected 16 of 36 (44%); 20 (56%) were identified by second- or third-trimester scans. The first-trimester scan detection rate for major structural anomalies was 14 of 20 (70%). The 5 that were missed by the first-trimester scan were detected by a second-trimester scan. CONCLUSIONS: Our study emphasizes the importance of the first-trimester scan in the early detection of aneuploidy and structural fetal anomalies. In this small unselected low-risk population, the first-trimester scan detected 83% of aneuploidies and 70% of major structural anomalies. Our results are comparable to previously published studies from other centers and further exemplify the invaluable role of the first-trimester scan in the early detection of aneuploidy and structural anomalies in an unselected low-risk population.

Role of ultrasonography in early gestation in the diagnosis of congenital heart defects.

OBJECTIVE: The purpose of this series was to determine the sensitivity of ultrasonography in early gestation (UEG) using nuchal translucency (NT) and the 4-chamber view (4CV) in the early diagnosis of congenital heart defects (CHDs). METHODS: This was a retrospective chart review of all patients presenting for UEG between 2002 and 2009. At our center, a survey of fetal anatomy is performed at the time of the NT assessment at 11 weeks to 13 weeks 6 days. A second-trimester scan (STS) is done at 20 to 23 weeks and a third-trimester scan at 32 to 35 weeks. Suspected cases of CHDs were evaluated by a pediatric cardiologist. All neonates were examined at birth by a pediatrician, and when clinically indicated, fetal echocardiography was performed. RESULTS: A total of 1370 fetuses were scanned. Congenital heart defects were identified in 8 (0.6%). Nuchal translucency was above the 95th percentile for gestational age (GA) in 6 of 8, and the 4CV was abnormal in 6 of 8. Ultrasonography in early gestation detected 75% fetuses with CHDs, and 25% were detected by an STS. CONCLUSIONS: Our study emphasizes the importance of UEG in the detection of CHDs. In this small unselected low-risk population, UEG detected 75% of CHDs. Nuchal translucency was above the 95th percentile for GA, the 4CV was abnormal, or both in all 8 cases with CHDs.

Ventricular Tachycardia in an Infant Without Congenital Anomaly: A Case Report.

Ventricular tachycardia (VT) is a serious form of arrhythmia that can be life-threatening; that's why diagnosis and treatment are very important in order to avoid serious complications. We are reporting this case of VT which is a rare entity, especially, in healthy infants. This infant, without cardiac pathology known from birth, presented with poor food intake and grunting with hepatomegaly on clinical examination, and a heartbeat at 200/ min. The electrocardiogram (ECG) showed wide QRS complex tachycardia, and the echocardiogram showed a dilated and hypokinetic cardiomyopathy. The clinical signs and chest X-ray changes were consistent with mild cardiac failure. This presentation makes the diagnosis challenging, therefore, it is important to take a good history of the case with a complete clinical exam to achieve the correct diagnosis, and to avoid potential complications. VT of an infant may be benign but should not be diagnosed as such before eliminating serious causes.

The Amplatzer Duct Occluder II: a new device for percutaneous ductus arteriosus closure.

OBJECTIVE: Study the new Amplatzer Duct Occluder II (ADO II). Limitations were encountered with the preexisting devices in nonconical ducts, large ducts, or in small infants. These include failure, residual shunts, protrusion, migration, and vascular damage. METHODS: Between June 2008 and March 2009, 20 consecutive patients were enrolled. In cases where different devices were applicable, we favored the use of the ADO II to maximize our experience with this device and prove its superiority. No coils were required in these 20 patients. RESULTS: There were 15 females and 5 males (median age 2 years). ADO II group (n = 16): Immediate complete closure in 75% of the patients, rising to 93.7% at 24 hours. A residual shunt persisted at 3 months in one child. Aortic narrowing from device protrusion was noted in two type E ducts, without any significant gradient, however. ADO I group (n = 4): In two adolescents and in one adult patient, the duct was successfully closed. In a 2-year-old patient with a 6.6 mm type B duct, the ADO I totally obstructed the aortic flow and was retrieved before releasing. The child was sent for surgery. CONCLUSION: Even though we did not compare the ADO II to other devices, we feel that it has the capacity to substitute most of the coils, and some of the original ADO I indications. Arterial access was sufficient in most patients, but venous delivery is advised in small infants with large or long ducts, to avoid aortic protrusion and residual shunts.

Absence of cardiac siderosis by MRI T2* despite transfusion burden, hepatic and serum iron overload in Lebanese patients with sickle cell disease.

BACKGROUND: The use of magnetic resonance imaging (MRI) to detect organ-specific iron overload is becoming increasingly common. Although hepatic iron overload has been recognized in patients with sickle cell disease (SCD), cardiac iron deposition has only been examined in a few reports. METHODS: This was a cross-sectional study of 23 patients with SCD. Patient charts were reviewed and data collected for drug use, total lifetime transfusions (TLT), transfusion rate (TR), status of the spleen, and comorbid illnesses or infections. Blood samples were obtained for assessment of hemoglobin, serum ferritin, non-transferrin-bound iron (NTBI), and liver enzyme levels. Doppler echocardiography was performed to detect pulmonary hypertension (PHT) and assess left ventricular ejection fraction. Cardiac iron levels were measured by MRI T2*. Direct determination of liver iron concentration (LIC) was performed using R2 MRI. In this study, cardiac T2* >20 ms was considered normal. RESULTS: The mean age was 24.4 +/- 9.7 yr, with a male to female ratio of 15:8. A total of 9 (49.9%) patients were splenectomized. The mean TR was 14.1 +/- 13.2 Units/yr, and the mean hemoglobin level was 9.0 g/dL. PHT was detected in 6 (27.3%) patients, but none had evidence of heart failure. The mean serum ferritin, LIC, and NTBI levels were 997.7 ng/mL, 4.6 mg Fe/g dw, and 1.1 +/- 2.2, respectively. TR was a much better predictor of iron burden (LIC, ferritin, NTBI) than TLT. In fact, TR less than 10 Units/yr did not produce significant iron overload reflecting spontaneous losses as high as 0.11 mg/kg/d. None of the patients had evidence of cardiac iron overload (mean cardiac T2* = 37.3 +/- 6.2 ms; range: 21.9-46.8 ms). There was also no statistically significant correlation between cardiac T2* values and any of the study variables. CONCLUSION: Our study demonstrates that TR is a stronger predictor of iron overload than TLT. It also confirms cardiac sparing in patients with SCD, even in subjects with significant transfusion burden, systemic and hepatic iron overload.

Device Closure of Perimembranous Ventricular Septal Defect: Choosing Between Amplatzer Occluders.

Background: Off-label device closure of perimembranous ventricular septal defect (pmVSD) is well reported in the literature with encouraging results. However, technical challenges may be encountered. Objectives: To evaluate and compare feasibility, technical aspects, procedural outcomes, and mid-term follow-up of pmVSD closure using Amplatzer™ occluders. Patients and Methods: From July 2015 to July 2018, patients in whom pmVSD closure was attempted using an Amplatzer occluder were retrospectively identified from our institution's database. Device selection was made according to the defect anatomy that was obtained via ventriculography and trans-esophageal echocardiography. Follow-up evaluations were done at discharge, then at 1, 3, 6, and 12 months and yearly thereafter with transthoracic echocardiography and electrocardiogram. Results: In total, 8 Amplatzer Duct Occluder (ADO), 27 ADO II, and 17 Amplatzer Muscular VSD Occluder (AMO) were used in 51 patients with a mean age of 7.4 ± 6.9 years and a mean weight of 25.4 ± 19.8 kg. Implantation was successful in 50/51 patients (98.0%). There was no procedure related mortality. One ADO accidentally embolized to the aorta after release and was surgically recaptured from the iliac artery. All ADO II were delivered retrogradely with the least amount of time (p = 0.002) and the lowest radiation exposure (p < 0.001). Minor valvular disturbances occurred in 8/49 patients (16.3%), including five tricuspid regurgitation (three with ADOII and two with AMO) and three trivial aortic regurgitations (two with ADO and one with ADOII). On a median follow-up of 194 days (range, 60-895 days), no surgical device removal was necessary. At 6 months of follow-up, trivial residual shunt was present in 5/49 patients (10.2%), among which none occurred with ADO. One complete atrioventricular block was detected 18 months after ADO implantation and required permanent pacing. Conclusions: Transcatheter closure of PmVSD using Amplatzer occluders is feasible, safe and efficacious in properly selected patients. The major key factor behind high procedural success rate is proper device selection. ADOII is remarkably superior in terms of device softness, flexibility and faster implantation process. Yet, its use is limited to small defects with particular anatomy.

Catheter closure of a recanalized vertical vein after repair of total anomalous pulmonary venous connection.

The vertical vein is sometimes left open in repair of total anomalous pulmonary venous connection. It usually closes later but can remain patent leading to a significant shunt. We describe a recanalized vertical vein in a 7-year-old having undergone repair in infancy. It was closed using an Amplatzer device.