Impact of concomitant complex cardiac anatomy in nonsyndromic patients with complete atrioventricular septal defect.

OBJECTIVE: We studied a cohort of patients with nonsyndromic complete atrioventricular septal defect with and without concomitant complex cardiac anatomy and compared the outcomes after surgical repair. METHODS: Between 1993 and 2018, 62 nonsyndromic patients underwent complete atrioventricular septal defect repair. Sixteen patients (26%) had complex complete atrioventricular septal defect with variables representing concomitant cardiac anatomic complexity: tetralogy of Fallot, double outlet right ventricle, total anomalous pulmonary venous return, concomitant aortic arch reconstruction, multiple ventricular septal defects, staged repair of coarctation of the aorta, and a persisting left superior vena cava. The mean follow-up was 12.7 ± 7.9 years. Baseline variables were retrospectively evaluated and analyzed using univariable logistic regression. Survival was studied using Kaplan-Meier estimates, and group comparisons were performed using the log-rank test. A competing-risk analysis estimated the risk of reoperation with death as the competing event. A Gray's test was used to test equality of the cumulative incidence curves between groups. RESULTS: The perioperative mortality was 3.2% (2/62). Actuarial survival was 100% versus 66.7% ± 14.9% at 10 years in the noncomplex and complex groups, respectively (P < .01). There was no significant difference in the overall reoperation rate between the noncomplex group (7/46; 15%) and the complex group (4/16; 25%) (odds ratio, 1.86; 95% confidence interval, 0.46-7.45; P = .30). The competing-risk analysis demonstrated no significant difference in reoperation between the groups (P = .28). CONCLUSIONS: Our data show that nonsyndromic patients without complex cardiac anatomy have a good long-term survival and an acceptable risk of reoperation similar to contemporary outcomes for patients with complete atrioventricular septal defect with trisomy 21. However, the corresponding group of nonsyndromic patients with concomitant complex cardiac lesions are still a high-risk population, especially regarding mortality.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.

Perinatal and infant outcome of fetuses with prenatally diagnosed hyperechogenic kidneys.

OBJECTIVE: Hyperechogenic kidneys are a relatively rare antenatal finding, which can generate significant parental anxiety due to uncertain prognosis. We report on the perinatal and infant outcomes of a large cohort of fetuses with antenatally diagnosed hyperechogenic kidneys. METHODS: This was a retrospective analysis of all cases diagnosed prenatally with hyperechogenic kidneys between 2002 and 2017 in a large tertiary fetal medicine unit. Hyperechogenicity was defined as kidney parenchyma with greater echogenicity than that of the liver. Pregnancy, pathological and postnatal outcomes were collected from hospital and general practitioner records up to 1 year of age. Abnormal renal outcome was defined as elevated creatinine beyond 6 months of age, hypertension requiring medication or major kidney surgery, such as nephrectomy. Severe abnormal renal outcome was defined as the need for dialysis or kidney transplant at any stage. RESULTS: Three-hundred and sixteen fetuses with hyperechogenic kidneys were identified at a mean gestational age of 21 (range, 13-37) weeks. The majority of cases (97%) had bilateral hyperechogenic kidneys. In the 265 cases with available follow-up data, other associated renal tract abnormalities were identified prenatally in 36%, concomitant extrarenal structural abnormalities in 39% and abnormal karyotype in 15% of cases. Of the 316 included cases, 139 did not survive, including 105 terminations of pregnancy, five intrauterine deaths and 29 early neonatal deaths. Only 4.3% (6/139) of these fetuses had isolated hyperechogenic kidneys while 28.1% (39/139) had associated multiple renal tract abnormalities alongside hyperechogenic kidneys and over two-thirds (67.6%; 94/139) had concomitant extrarenal abnormalities. Of the 177 cases that survived beyond 1 month of age, outcome data were available in 126. Of these, based on the antenatal findings, 60 (47.6%) cases had isolated hyperechogenic kidneys, 56 (44.4%) had associated renal structural abnormalities and 10 (7.9%) had additional extrarenal abnormalities. Considering renal outcome alone, kidney function was abnormal in 13 (21.7%), 10 (17.9%) and 0 (0%) infants in these three groups, respectively, although concurrent pathology clearly affected global outcome in the more complex cases. Neonatal mortality of 1.6% was observed in the isolated renal hyperechogenicity group. The presence of oligohydramnios or abnormal renal volume was not associated significantly with abnormal renal function (odds ratio (OR), 2.32 (99% CI, 0.54-10.02) and OR, 0.74 (99% CI, 0.21-2.59), respectively) in this group. CONCLUSIONS: Hyperechogenic kidneys are often complicated by associated renal tract and extrarenal abnormalities, aberrant karyotype and genetic disease, and these factors have a greater effect on overall outcome than does kidney echogenicity. The renal outcome of fetuses with isolated hyperechogenic kidneys is good generally, with over 70% of cases having normal renal function postpartum. Importantly, for prognostic counseling, all of the fetuses in this non-selected series with isolated hyperechogenic kidneys and normal amniotic fluid levels had normal renal outcome in infancy. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The Correlation Between Severity of Postoperative Hypocalcemia and Perioperative Mortality in Chromosome 22q11.2 Microdeletion (22q11DS) Patient After Cardiac-Correction Surgery: A Retrospective Analysis.

OBJECTIVES: The aim of our study was to elucidate the association between severity of postoperative hypocalcemia and the prognosis of the patients with 22q11DS. METHODS: Data retrospectively were collected from 23 children with 22q11DS who underwent cardiac correction surgery. Area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio were calculated to determine the tendency of perioperative mortality rate, according to the minimum levels of serum calcium and the duration of hypocalcemia. A novel risk assessment system for perioperative mortality was established according to these valid parameters. RESULTS: The death group had lower minimum levels of serum calcium and longer duration of hypocalcemia. The AUC of minimum levels of serum calcium was 0.912 (95% CI: 0.753-1; P = .003) and qualified its high accuracy for perioperative mortality. The AUC of duration of hypocalcemia was 0.804 (95% CI: 0.561-1; P = .03) and qualified its moderate accuracy. The tendency analyses also indicated the correlation between these two parameters and perioperative mortality. Based on the cut-off values from ROC analysis, a novel risk assessment system for perioperative mortality was established according to these two parameters. The patients with the lowest serum calcium level <0.885 mmol/L or duration of the hypocalcemia > 90.33 hours would be sorted into a high-risk group; others were divided into a low-risk group. The diagnostic odds ratio for this assessment system was 143(95% CI: 5.13-3982.52). No significant difference was found with regard to patient age, weight, preoperative serum total calcium, cardiopulmonary bypass (CPB) time, and aortic cross-clamp time between the high- and low-risk groups. CONCLUSIONS: The minimum levels of serum calcium and duration of hypocalcemia were valid predictors for preoperative mortality of 22q11DS patients.

Sudden death in epilepsy and ectopic neurohypophysis in Joubert syndrome 23 diagnosed using SNVs/indels and structural variants pipelines on WGS data: a case report.

BACKGROUND: Joubert syndrome (JBTS) is a genetically heterogeneous group of neurodevelopmental syndromes caused by primary cilia dysfunction. Usually the neurological presentation starts with abnormal neonatal breathing followed by muscular hypotonia, psychomotor delay, and cerebellar ataxia. Cerebral MRI shows mid- and hindbrain anomalies including the molar tooth sign. We report a male patient with atypical presentation of Joubert syndrome type 23, thus expanding the phenotype. CASE PRESENTATION: Clinical features were consistent with JBTS already from infancy, yet the syndrome was not suspected before cerebral MRI later in childhood showed the characteristic molar tooth sign and ectopic neurohypophysis. From age 11 years seizures developed and after few years became increasingly difficult to treat, also related to inadequate compliance to therapy. He died at 23 years of sudden unexpected death in epilepsy (SUDEP). The genetic diagnosis remained elusive for many years, despite extensive genetic testing. We reached the genetic diagnosis by performing whole genome sequencing of the family trio and analyzing the data with the combination of one analysis pipeline for single nucleotide variants (SNVs)/indels and one for structural variants (SVs). This lead to the identification of the most common variant detected in patients with JBTS23 (OMIM# 616490), rs534542684, in compound heterozygosity with a 8.3 kb deletion in KIAA0586, not previously reported. CONCLUSIONS: We describe for the first time ectopic neurohypophysis and SUDEP in JBTS23, expanding the phenotype of this condition and raising the attention on the possible severity of the epilepsy in this disease. We also highlight the diagnostic power of WGS, which efficiently detects SNVs/indels and in addition allows the identification of SVs.

An inducible intestinal epithelial cell-specific NHE3 knockout mouse model mimicking congenital sodium diarrhea.

The sodium-hydrogen exchanger isoform 3 (NHE3, SLC9A3) is abundantly expressed in the gastrointestinal tract and is proposed to play essential roles in Na+ and fluid absorption as well as acid-base homeostasis. Mutations in the SLC9A3 gene can cause congenital sodium diarrhea (CSD). However, understanding the precise role of intestinal NHE3 has been severely hampered due to the lack of a suitable animal model. To navigate this problem and better understand the role of intestinal NHE3, we generated a tamoxifen-inducible intestinal epithelial cell-specific NHE3 knockout mouse model (NHE3IEC-KO). Before tamoxifen administration, the phenotype and blood parameters of NHE3IEC-KO were unremarkable compared with control mice. After tamoxifen administration, NHE3IEC-KO mice have undetectable levels of NHE3 in the intestine. NHE3IEC-KO mice develop watery, alkaline diarrhea in combination with a swollen small intestine, cecum and colon. The persistent diarrhea results in higher fluid intake. After 3 weeks, NHE3IEC-KO mice show a ∼25% mortality rate. The contribution of intestinal NHE3 to acid-base and Na+ homeostasis under normal conditions becomes evident in NHE3IEC-KO mice that have metabolic acidosis, lower blood bicarbonate levels, hyponatremia and hyperkalemia associated with drastically elevated plasma aldosterone levels. These results demonstrate that intestinal NHE3 has a significant contribution to acid-base, Na+ and volume homeostasis, and lack of intestinal NHE3 has consequences on intestinal structural integrity. This mouse model mimics and explains the phenotype of individuals with CSD carrying SLC9A3 mutations.

Does prenatal counseling for pregnancies complicated by multiple fetal abnormalities concord with postnatal outcomes?

OBJECTIVE: In pregnancies complicated by multiple fetal abnormalities, our objective was to determine the degree of concordance between prenatal prognosis and postnatal outcomes. METHOD: Retrospective cohort study of pregnancies with multiple fetal abnormalities referred to the Fetal Concerns Center of Wisconsin (FCCW) from 2015 to 2018. We reviewed records for anomalies, given prognostic severity, and postnatal outcomes. Prognostic severity was categorized as "likely mortality," "severe impairment," "moderate," and "mild" based on predetermined criteria. RESULTS: In 85 pregnancies with multiple fetal abnormalities, 48% were given a prognosis of "likely mortality," and 19% were given a prognosis of "severe impairment." In pregnancies that were continued after being counseled as "likely mortality," this outcome was concordant in all but one case, despite medical interventions. In pregnancies counseled as "severe impairment," the more common outcome was mortality or severe impairment in 88% of cases and survival with severe impairment in 33% of cases. Postnatal outcomes were concordant with prenatal severity in 68% of the cases, more severe in 20% of the cases, and less severe in fewer than 5% of cases. CONCLUSION: Prenatal predictions about severe outcomes are usually true in pregnancies complicated by multiple abnormalities. In cases of outcome discordance, outcomes tend to be more severe than predicted.

Diagnosis and treatment of abnormal left coronary artery originating from the pulmonary artery: A single-center experience.

OBJECTIVE: We aimed to review symptoms, findings, surgical treatment options, short- and mid-term outcomes, and reoperation rate of patients diagnosed with of left coronary artery from the pulmonary artery (ALCAPA) of an anomalous origin in our institution. METHODS: From May 2000 to March 2018, 33 patients who had left coronary artery originating from the pulmonary artery were retrospectively examined. The clinical features of patients, diagnostic tools and their efficacy, outcomes of surgical repair, and problems during follow-up were evaluated. RESULTS: Thirty-three patients (22 females, 11 males) were included in the study. At the time of surgery, the median age and weight of patients were 6 months (minimum/maximum, 1-166 months) and 6.5 kg (minimum/maximum, 3-38.5 kg), respectively. The mean follow-up was 5±3.5 years (range, 1-16 years). Dyspnea, tachypnea, diaphoresis, prolonged feeding time, and developmental delay were common presenting signs and symptoms. It was determined that all the patients who were diagnosed at another center reached our center for surgical treatment within 1 month. Twenty-three (69.7%) patients had pathologic Q wave with anterior and/or anterolateral myocardial infarction signs on an electrocardiogram (ECG), whereas 22 (66.6%) patients had ST-T segment changes. Twenty-one (63.6%) patients had cardiomegaly on the telecardiogram. A reimplantation surgery was performed to 22 patients and 10 patients underwent the Takeuchi procedure. In addition to ALCAPA repair, 5 patients needed mitral valve plasty. Atrial septal defect (ASD) and ventricular septal defect (VSD) were closed in one patient, and Tetralogy of Fallot was totally corrected in another. At discharge, there was a significant improvement in left ventricular (LV) systolic functions. At the last visit, all patients had normal LV systolic functions except four who had mild dysfunction. The mean follow-up of the four patients was 2.8 years. In the early postoperative period, complications were seen in 10 patients. Five patients died in the early postoperative period, while one patient died 9 months after the ALCAPA surgery because of low cardiac output syndrome that developed after mitral repair. CONCLUSION: Patients with ALCAPA commonly present with congestive heart failure symptoms. When the diagnosis is confirmed in these patients, surgical treatment should not be delayed. The availability of surgical center and surgery outcomes for ALCAPA diagnosed patients are comparable with other countries, but the delay in the diagnosis of disease is still a problem in our country.

Nitric Oxide in Pulmonary Hypoplasia: Results from the European iNO Registry.

OBJECTIVES: The aim of this work was to describe treatment response and outcome data for preterm infants with pulmonary hypoplasia treated with inhaled nitric oxide (iNO). We hypothesised that an acute oxygenation response to iNO would be associated with survival. DESIGN: A retrospective observational study design was used to identify cases of pulmonary hypoplasia in preterm infants <34 weeks' gestation reported to the European iNO Registry. Demographic and clinical data were collected including oxygenation and echocardiographic parameters. The primary outcome was acute oxygenation response defined as a reduction in fractional inspired oxygen of >0.15. Outcome data included chronic lung disease (CLD) and death. RESULTS: Seventy-two infants with pulmonary hypoplasia were treated with iNO during a 10-year period (2007-2016). In total, 30/69 (43%) of the infants showed a significant improvement in oxygenation and were categorised as "responders." Thirty-one treated infants died, and 19 survivors developed CLD. Although there were no differences in demographics and baseline cardiorespiratory parameters between responders and non-responders, an acute response was significantly associated with survival. Neither pulmonary hypertension nor PPHN (persistent pulmonary hypertension of the newborn) physiology predicted the acute response to iNO or survival. CONCLUSION: Although the acute oxygenation response to iNO therapy in pulmonary hypoplasia is comparable to other respiratory disorders in preterm infants, mortality in this group remains very high. An acute response is associated with survival and suggests that a short therapeutic trial of iNO therapy is warranted in this population. This study underscores the value of registries in evaluating therapies for rare neonatal disorders, although their limitations must be recognised.

Predictors of in-hospital mortality in newborn conjoined twins.

BACKGROUND: Conjoined twins are rare developmental anomalies. There is a paucity of literature other than case reports and small case series. The aim of this study was to examine national outcomes and identify predictors of mortality in newborn conjoined twins. METHODS: We reviewed data on newborn conjoined twins from the Kids' Inpatient Database (1997-2012). RESULTS: A total of 240 patients were identified for a nationally weighted incidence of 1 per 100,000 live births. The majority of conjoined twins were female (n = 190 [81%]). The most commonly associated anomalies were cardiac (n = 87 [36%]), gastrointestinal (n = 41 [17%]), and abdominal wall (n = 32 [13%]) defects. Fifty-six (23%) patients underwent operative procedures, including 28 (12%) neonatal separation surgeries. The overall mortality rate was 61%; most deaths occurred within 24 hours (99 of 146 [68%]) to 48 hours (129 of 146 [88%]) after birth. Mortality was higher in female compared with male children (66% vs 38%, P = .025), premature compared with full-term children (72% vs 44%, P = .007), and in children with extremely low birth weight (95% vs 59%, P = .002). Congenital diaphragmatic hernias were seen in 15 (6%) patients and were uniformly fatal (100% vs 58%, P = .029). Mortality was highest in hospitals not designated as children's hospitals (72%) compared with children's hospitals (44%) (P = .007). CONCLUSION: Conjoined twins are rare anomalies who are susceptible to extremely high perinatal mortality, especially in female children, those who are premature, or those who have low birth weight. These data support caring for these complex patients at hospitals equipped to care for this fragile population.

Rastelli Operation for D-Transposition of the Great Arteries, Ventricular Septal Defect, and Pulmonary Stenosis.

OBJECTIVES: Our preferred approach for the surgical treatment of patients with D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis has been the Rastelli operation. We herein evaluate our 30-year experience with this procedure. METHODS: Clinical records for patients who underwent the Rastelli operation between 1988 and 2017 at our institution were retrospectively reviewed. Primary outcomes included freedom from death or cardiac transplantation and freedom from conduit reintervention. RESULTS: Forty-seven patients met inclusion criteria. Mean follow-up was 11.7 ± 6.8 years. Forty-three (91.5%) patients received a palliative systemic-to-pulmonary artery shunt and/or atrial septostomy prior to the Rastelli procedure. Five (10.6%) patients required ventricular septal defect enlargement at the time of the Rastelli procedure. The overall mean right ventricle-to-pulmonary artery conduit size was 17.0 mm. Mortalities included one early and three late deaths. Freedom from death or cardiac transplantation was 93% and 84% at 5 and 25 years, respectively. Seven patients required pacemaker placement, two immediately postoperatively and five late. Freedom from conduit replacement was 85% and 25% at 5 and 15 years, respectively. Seven (14.9%) patients required a second conduit intervention. Forty-one (87.2%) patients were New York Heart Association class I or II at the most recent follow-up. CONCLUSIONS: The Rastelli operation for D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis offers excellent mid- to long-term survival. The need for conduit replacement remains the most common indication for reintervention, and further study of the optimal choice of conduit will be useful.

Surgical outcome after complete repair of tetralogy of Fallot with absent pulmonary valve: comparison between bovine jugular vein-valved conduit and monocusp-valve patch.

BACKGROUND: The prognosis of tetralogy of Fallot with absent pulmonary valve (TOF/APV) without operation is poor. We evaluated the surgical outcome of TOF/APV in a single center. METHODS: Twenty-two TOF/APV patients underwent complete surgical correction in our hospital. Right ventricular outflow tract reconstruction was performed using bovine jugular vein (BJV)-valved conduit implantation (n = 10), homograft-valved conduit implantation (n = 2), or monocusp-valve patch (n = 10). Health-related quality of life (QOL) was evaluated during follow-up. RESULTS: The overall survival at 5 and 10 years was 86.4 ± 7.3% (confidence interval 69.4-97.2%). The survival rates were significantly different between patients with and without bronchial stenosis (40 and 100%, P = 0.0003, log-rank test). The survival of patients aged > 6 months was higher than those ≤ 6 months (100 vs. 40%, P = 0.0003, log-rank test). Patients with BJV-valved conduits had higher systolic gradients from the right ventricle to the pulmonary artery (RV-PA) compared to those with monocusp-valve patches. BJV-valved conduit implantation was a risk factor for post-operative pulmonary-valve stenosis. The QOL score for patients with BJV-valved conduits was lower than those with monocusp-valve patches (P < 0.05). No reoperation was performed during follow-up. CONCLUSIONS: Bronchial stenosis and lower age (≤ 6 months) were the main factors influencing post-operative survival. The use of a BJV-valved conduit was a main reason for RV-PA restenosis; thus, the use of a BJV-valved conduit may increase the need for repeat intervention and decrease the post-operative quality of life.

Midterm Echocardiographic Assessment of Right Ventricular Function After Midline Unifocalization.

BACKGROUND: Patients with an open ventricular septal defect (VSD) after repair of pulmonary atresia (PA), VSD, and major aortopulmonary collaterals (MAPCAs) are the most vulnerable subgroup. We analyzed the impact of concomitant versus delayed VSD closure on survival and intermediate-term right ventricular (RV) function. METHODS: Between October 1996 and February 2017, 96 patients underwent a pulmonary flow study-aided repair of PA/VSD/MAPCAs. For patients who underwent either concomitant or delayed intracardiac repair, echocardiographic RV systolic function was retrospectively calculated to assess (1) RV fractional area change (RVFAC) and (2) two-dimensional RV longitudinal strain (RVLS) of the free wall of the right ventricle. QLAB cardiac analysis software version 10.3 (Philips Medical Systems, Andover, MA) was used for analysis. RESULTS: A total of 64 patients underwent concomitant VSD closure at the time of unifocalization, and 16 patients underwent delayed VSD closure at a median of 2.3 years (range: 3 days to 7.4 years). At a median follow-up of 8.1 years (range: 0.1 to 19.5 years) for the concomitant repair group versus 7.4 years (range: 0.01 to 15.3 years) for the delayed repair group, no differences in RVFAC and RVLS were observed (RVFAC: 41.0% ± 6.2% versus 41.2% ± 7.6%, p = 0.91; RVLS: -18.7 ± 4.3 versus -18.9 ± 4.0, p = 0.87). CONCLUSIONS: Patients (83%) with PA/VSD/MAPCAs underwent complete repair at intermediate-term follow-up with preserved RV function. Delayed VSD closure was accomplished in 50% of the patients initially deemed unsuitable for repair. Delayed VSD closure did not affect survival and did not portend impaired RV systolic function.

Single Ventricle and Total Anomalous Pulmonary Venous Connection: Implications of Prenatal Diagnosis.

BACKGROUND: Single ventricle (SV) patients with total anomalous pulmonary venous connection (TAPVC) are at high risk. Given the limited published data available, we examined outcomes and the implications of a prenatal diagnosis of SV/TAPVC. METHODS: A single-center, retrospective review was performed in neonates with SV/TAPVC from 1998 to 2014, identified through institutional databases. Patient demographic, perioperative, and follow-up data were collected. RESULTS: Thirty-four eligible infants with SV/TAPVC were identified (mean birth weight: 3.0 kg). The TAPVC types were supracardiac (59%), infracardiac (21%), mixed (12%), and cardiac (9%). Heterotaxy syndrome was present in 25 (74%) infants. A prenatal diagnosis of SV was made in 26 (76%) infants, with TAPVC identified in 12 (35%). Seventeen (50%) had obstructed TAPVC within the first 48 hours of life; 7 of these patients had obstructed TAPVC identified prenatally. There were two preoperative deaths. Overall survival for the cohort was 65% at 1 year and 50% at 3 years. Survival in the obstructed group was significantly worse compared to the unobstructed group (47% vs 81% at 1 year; 27% vs 73% at 3 years, P = .01). Obstructed TAPVC and a prenatal prediction of obstructed TAPVC were significantly associated with postoperative mortality ( P = .01 and .03, respectively). CONCLUSIONS: Patients with SV/TAPVC remain a high-risk group, with obstructed TAPVC a significant risk factor for mortality. Prenatal diagnosis of TAPVC in SV patients is challenging, but given those with obstructed TAPVC are especially at high risk, improved prenatal diagnostic techniques in this group may enhance counseling/delivery planning.

Genetic and Extracardiac Anomalies Are Associated With Inferior Single Ventricle Palliation Outcomes.

BACKGROUND: We examined the effect of genetic syndromes and extracardiac (GS/EC) anomalies on single-ventricle (SV) palliation with focus on hospital and interstage death and progression toward subsequent palliation stages. METHODS: First-stage palliation was performed in 530 neonates with SV: Norwood in 284 (53%), shunt in 173 (33%), and band in 73 (14%). Outcomes were compared between those with GS/EC anomalies (121 [23%]) and without GS/EC anomalies (409 [77%]). Regression analyses were adjusted for other risk factors (age, sex, prematurity, weight, SV anomaly, and first-stage palliation operation). RESULTS: GS/EC anomalies varied among SV defects (range, 3% for double-inlet left ventricle to 100% for atrial isomerism). Patients with GS/EC anomalies required significantly longer durations of mechanical ventilation and intensive care unit and hospital stay. Although patients had comparable rates of extracorporeal membrane oxygenation (13% vs 11%, p = 0.552) and unplanned reoperation (16% vs 11%, p = 0.189), hospital mortality was higher in patients with GS/EC anomalies (24% vs 12%, p = 0.0008). After discharge, patients with GS/EC anomalies had higher interstage death, with lower progression to Glenn (60% vs 77%, p = 0.002) and lower 10-year survival (56% vs 76%, p < 0.001). After adjustment for other risk factors, GS/EC anomalies significantly affected survival in almost all subgroups of patients. CONCLUSIONS: The presence of GS/EC anomalies varies among SV anomalies and is associated with additional risk factors such as prematurity and low weight. After adjusting for other risk factors, GS/EC anomalies are associated with prolonged recovery after first-stage palliation and increased hospital and interstage death, with subsequently fewer patients progressing toward Glenn shunt. The increased death risk in those patients is highest in the first 6 months and persists for 2 to 3 years after first-stage palliation, suggesting the need for more vigilant monitoring and outpatient care in these high-risk patients.

Repair of Ductus or Hemi-Truncus to One Lung and Major Aortopulmonary Collaterals to the Other Lung.

BACKGROUND: There are patients born with pulmonary atresia and a ductus arteriosus or hemi-truncus to one lung and major aortopulmonary collateral arteries (MAPCAs) to the contralateral lung. The purpose of this study was to review our surgical results for this relatively rare subset of patients. METHODS: This was a retrospective review of 35 patients with ductus/hemi-truncus in association with pulmonary atresia with ventricular septal defect and MAPCAs. Our surgical algorithm is bifurcated into two strategies: (1) patients with "favorable" MAPCAs are candidates for single stage complete repair, and (2) patients with "unfavorable" MAPCAs undergo a staged approach. The median age at surgery was 3 months (range, 1 to 7 months), and the mean number of MAPCAs was 3.1 ± 1.3. RESULTS: Twenty patients underwent a single stage complete repair. All 20 of these patients are alive with a right ventricle to aortic pressure ratio of 0.34 ± 0.07. The distribution of pulmonary blood flow by lung perfusion scan was 44% to the right and 56% to the left lung. Fifteen patients underwent a staged approach, including unifocalization of the MAPCAs to a central shunt. There were 2 interim deaths. Twelve patients have undergone complete repair with a right ventricle to aortic pressure ratio of 0.38 ± 0.07. There was 1 late death after complete repair. The distribution of pulmonary blood flow was 39% to the right and 61% to the left lung. CONCLUSIONS: The data demonstrate that 32 of 35 patients with ductus/hemi-truncus and MAPCAs ultimately achieved complete repair with relatively low pulmonary artery pressures.

Significance of Intraoperative Revision During Arterial Switch Operation in the Current Era.

BACKGROUND: Arterial switch operation (ASO) is a relatively safe operation nowadays. We hypothesize that intraoperative revision for coronary malperfusion still plays an important role during ASO in the current era. METHODS: From January 2005 to May 2016, 244 patients underwent ASO. Medical records were reviewed and the details of intraoperative revision were described. Morbidity and mortality were compared in patients with/without intraoperative revision. Factors related to the need for intraoperative revision were analyzed. RESULTS: Seventeen (7%) patients needed intraoperative revision. As a technique for intraoperative revision, revision of a coronary button was performed in eight patients and revision of the main pulmonary artery anastomosis to relieve compression on the coronary artery was performed in five patients. Factors related to intraoperative revision were body weight at surgery ( P = .051), eccentric position of the coronary ostium ( P = .01), single coronary artery system ( P = .03), and intramural coronary artery ( P = .003). The commonest coronary artery origin and branching pattern was not protective against the need for intraoperative revision ( P = .43). Discharge mortality was 2% overall: 2 of 17 with intraoperative revision versus 3 of 238 without it ( P = .04). Patients who underwent intraoperative revision had longer postoperative hospitalization ( P = .003). CONCLUSION: The need for intraoperative revision was related to eccentric coronary ostium, single coronary artery, and intramural coronary artery. Although the need for intraoperative revision correlated with higher mortality and morbidity, prompt intraoperative revision also likely contributed to our good results after ASO.

Characteristics and outcomes of children with ductal-dependent congenital heart disease and esophageal atresia/tracheoesophageal fistula: A multi-institutional analysis.

BACKGROUND: Extracardiac birth defects are associated with worse outcomes in congenital heart disease (CHD). The impact of esophageal atresia/trachea-esophageal fistula (EA/TEF) on outcomes after surgery for ductal-dependent CHD is unknown. METHODS: Retrospective matched cohort study using the Pediatric Health Information System database from 07/2004 to 06/2015. Hospitalizations with ductal-dependent CHD and EA/TEF, undergoing CHD surgery were included as cases. Admissions with ductal-dependent CHD without EA/TEF were matched 3:1 for age at admission and Risk Adjustment for Congenital Heart Surgery-1 classification. Comparisons were performed using generalized estimating equations. RESULTS: There were 124 cases and 372 controls. Cases included 32 (25.8%) low-risk, 86 (69.3%) intermediate-risk, and 6 (4.8%) high-risk patients. Cases had more females compared to controls (53.2% vs 41.1%, P = .022). Cases were more likely to be premature (28.2% vs 13.7%, P = .001) and low birth weight (29.8% vs 11.8%, P < .001). Cases had a similar frequency of Down syndrome, and DiGeorge/Velocardiofacial syndrome, but a higher frequency of anorectal malformations (4.3% vs 2.4%, P < .001) and renal anomalies (27.4% vs 9.9%, P < .001) than controls. Cases had a higher mortality on univariate (22.0% vs 8.4%, P < .001) and multivariable analysis (odds ratio 2.45, 95%, confidence interval 1.34 - 4.49). Prematurity also was significantly associated with mortality on multivariable analysis. Cases had a longer duration of mechanical ventilation, longer hospital duration of stay, and higher total cost than controls (all P < .001). CONCLUSION: In children with ductal-dependent CHD, EA/TEF is associated with increased morbidity, mortality and resource utilization. A majority of patients undergo EA/TEF repair prior to congenital heart disease surgery. (Surgery 2017;160:XXX-XXX.).

Primary versus Staged Closure of Exomphalos Major: Cardiac Anomalies Do Not Affect Outcome.

AIM: The objective of the study is to describe management of exomphalos major and investigate the effect of congenital cardiac anomalies. METHODS: A single-center retrospective review (with audit approval) was performed of neonates with exomphalos major (fascial defect ≥ 5cm ± liver herniation) between 2004 and 2014.Demographic and operative data were collected and outcomes compared between infants who had primary or staged closure. Data, median (range), were analyzed appropriately. RESULTS: A total of 22 patients were included, 20 with liver herniation and 1 with pentalogy of Cantrell. Gestational age was 38 (30-40) weeks, birth weight 2.7 (1.4-4.6) kg, and 13 (60%) were male. Two were managed conservatively due to severe comorbidities, 5 underwent primary closure, and 15 had application of Prolene (Ethicon Inc) mesh silo and serial reduction. Five died, including two managed conservatively, none primarily of the exomphalos. Survivors were followed up for 38 months (2-71). Cardiac anomalies were present in 20 (91%) patients: 8 had minor and 12 major anomalies. Twelve (55%) patients had other anomalies. Primary closure was associated with shorter length of stay (13 vs. 85 days, p = 0.02), but infants had similar lengths of intensive care stay, duration of parenteral feeds, and time to full feeds. Infants with cardiac anomalies had shorter times to full closure (28 vs. 62 days, p = 0.03), but other outcomes were similar. CONCLUSION: Infants whose defect can be closed primarily have a shorter length of stay, but other outcomes are similar. Infants with more significant abdominovisceral disproportion are managed with staged closure; the presence of major cardiac anomalies does not affect surgical outcome.

Complicated Gastroschisis Is Associated with Greater Intestinal Morbidity than Gastroschisis or Intestinal Atresia Alone.

AIM: The study aimed to compare outcomes and intestinal morbidity among complicated gastroschisis, isolated gastroschisis, and intestinal atresia. METHODS: In this retrospective observational single institution study, outcomes and intestinal morbidity were compared among gastroschisis complicated by intestinal atresia or perinatal bowel perforation, isolated gastroschisis, and isolated intestinal atresia. We included two cohorts; the first cohort included 68 consecutive patients with complicated gastroschisis (n = 9), isolated gastroschisis (n = 34), and intestinal atresia (n = 25) managed in our center. The second cohort included 20 patients (12 referred) with intestinal failure due to these underlying etiologies managed by our intestinal rehabilitation team. RESULTS: Patients with complicated gastroschisis had a significantly longer need for mechanical ventilation, primary hospital stay, and duration of parenteral nutrition (PN) and developed intestinal failure more often compared with other groups (p < 0.05 for all). Reoperations for surgical complications were also more frequent in patients with complicated gastroschisis (p < 0.05). Among those, who developed intestinal failure, autologous intestinal reconstruction (AIR) surgery was performed in 11 patients with comparable frequency in all groups. Repeated AIR surgery for bowel re-dilatation was required in 3/3 patients with complicated gastroschisis and 0/8 with isolated gastroschisis or intestinal atresia (p = 0.004). CONCLUSION: Complicated gastroschisis is associated with markedly increased intestinal morbidity, reflected by prolonged duration of PN, more frequent reoperations for intestinal complications, and bowel re-dilatation after AIR surgery, when compared with patients with isolated gastroschisis or intestinal atresia.