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Aim Cystic ovarian masses in children may be physiological or neoplastic. It is mandatory that suspected neoplastic lesions are resected without tumour spillage. However, a large midline incision is cosmetically unappealing incision to young women. Here we describe our experience of using controlled drainage without spillage that allows a cosmetic pfannenstiel approach without compromising oncological principles. Method All girls treated with large ovarian cystic masses since 2008 in our centre were identified and data was collected prospectively. A small pfannenstiel incision was performed followed by peritoneal washings; tissue glue was used to stick an Opsite™ dressing to the cyst surface and fluid drained so there was no leakage back into the patient. Once aspirated the cyst was delivered and an ovarian preserving cystectomy was performed where possible. Results Twenty-three girls (median age 14.5 years (8.1 to 16.5 years) were included. Pre-operative MRI scan showed a complex lesions with median volume of 1169 ml (range 252–7077 ml). At surgery 22/23 cysts were intact and removed without spillage. Histology: mature teratoma (11), serous cyst (3), mucinous cyst adenocarcinoma (2), mucinous cystadenoma (5), Sertoli-Leydig tumour, sclerosing stromal tumour. One girl with pre-operative rupture of a mucinous adenocarcinoma subsequently died. Ovarian sparing cystectomy was performed in 17/23 girls. All other patients are well without evidence of recurrence. Conclusion This is the largest series in children and adolescents using controlled drainage of cystic ovarian tumours. Though there were a range of diagnoses we have shown that these can be removed safely with a cosmetic pfannenstiel approach while following oncological principles.

Individuals with single-ventricle congenital heart disease who are palliated to a Fontan circulation are at risk for heart failure and liver disease, with recurrent ascites being a potentially debilitating cause of late morbidity. Although ascites associated with heart failure or liver failure is usually characterized by a high serum-ascites albumin gradient (SAAG), we have observed multiple instances of ascites in Fontan patients with low SAAG, suggesting an inflammatory process. We present three cases in which recalcitrant ascites severely and adversely impacted the quality of life and describe our initial experience with intraperitoneal corticosteroids in this setting.

PURPOSE In a large cohort of 373 pediatric patients with Marfan syndrome (MFS) with a severe cardiovascular phenotype, we explored the proportion of patients with MFS with a pathogenic FBN1 variant and analyzed whether the type/location of FBN1 variants was associated with specific clinical characteristics and response to treatment. Patients were recruited on the basis of the following criteria: aortic root z-score > 3, age 6 months to 25 years, no prior or planned surgery, and aortic root diameter < 5 cm. METHODS Targeted resequencing and deletion/duplication testing of FBN1 and related genes were performed. RESULTS We identified (likely) pathogenic FBN1 variants in 91% of patients. Ectopia lentis was more frequent in patients with dominant-negative (DN) variants (61%) than in those with haploinsufficient variants (27%). For DN FBN1 variants, the prevalence of ectopia lentis was highest in the N-terminal region (84%) and lowest in the C-terminal region (17%). The association with a more severe cardiovascular phenotype was not restricted to DN variants in the neonatal FBN1 region (exon 25-33) but was also seen in the variants in exons 26 to 49. No difference in the therapeutic response was detected between genotypes. CONCLUSION Important novel genotype-phenotype associations involving both cardiovascular and extra-cardiovascular manifestations were identified, and existing ones were confirmed. These findings have implications for prognostic counseling of families with MFS.

Background Valve-sparing aortic root replacement (VSARR) is an increasingly popular alternative to traditional aortic root replacement for aortic root aneurysm disease with a normal aortic valve. We evaluated the early and midterm outcomes of VSARR—reimplantation technique (VSARR-RT) done at a single institution over a decade. Materials and Methods We performed a retrospective study of all patients who underwent VSARR-RT between January 2004 and July 2014. Results A total of 85 patients underwent VSARR-RT. Median time to latest echocardiographic follow-up was 4 years (range: 15–72 months). Total observation time was 491 patient years. Mean age was 44.6 ± 14.3 years, and 13 (15%) were women. Thirty-nine (46%) patients had a connective tissue disorder and 6 (7%) had a bicuspid aortic valve. Thirty-three (39%) patients underwent concomitant procedures, including coronary artery bypass grafting (n = 9, 11%), mitral valve repair (n = 8, 9%), and aortic hemi-arch replacement (n = 7, 8%). There were no operative deaths or in-house mortality and no postoperative strokes. Kaplan-Meier analysis demonstrated survival of 99% (95% confidence interval [CI]: 97–100%) at 2 years and 98% (95% CI: 97–100%) at 8 years. Freedom from reoperation was 95.8% (95% CI: 91.2–100%) at 8 years. Freedom from endocarditis was 100% at 8 years. At the last echocardiographic follow-up, 95% of patients were free of severe aortic regurgitation (AR) and 82% free of moderate AR. Of the four patients who had severe AR, three underwent reoperations and received prosthetic valves and one is being clinically monitored. Conclusion This study reports early and midterm outcomes after VSARR-RT at our institution, including those patients who underwent a VSARR-RT procedure combined with other procedures. Further follow-up remains necessary to determine long-term outcomes.

Bicuspid aortic valve aortopathy is defined by dilation of the aortic root (AoRt) and/or ascending aorta (AsAo), and increases risk for aortic aneurysm and dissection. The effects of medical prophylaxis on aortic growth rates in moderate to severe bicuspid aortopathy have not yet been evaluated. This was a single-center retrospective study of young patients (1 day to 29 years) with bicuspid aortopathy (AoRt or AsAo z-score ≥ 4 SD, or absolute dimension ≥ 4 cm), treated with either losartan or atenolol. Maximal diameters and BSA-adjusted z-scores obtained from serial echocardiograms were utilized in a mixed linear effects regression model. The primary outcome was the annual rate of change in AoRt and AsAo z-scores during treatment, compared with before treatment. The mean ages (years) at treatment initiation were 14.2 ± 5.1 (losartan; n = 27) and 15.2 ± 4.9 (atenolol; n = 18). Median treatment duration (years) was 3.1 (IQR 2.4, 6.0) for losartan, and 3.7 (IQR 1.4, 6.6) for atenolol. Treatment was associated with decreases in AoRt and AsAo z-scores (SD/year), for both losartan and atenolol (pre- vs post-treatment): losartan/AoRt: +0.06 ± 0.02 vs -0.14 ± 0.03, p0.001; losartan/AsAo: +0.20 ± 0.03 vs -0.09 ± 0.05, p0.001; atenolol/AoRt: +0.07 ± 0.03 vs -0.02 ± 0.04, p = 0.04; atenolol/AsAo: +0.21 ± 0.04 vs -0.06 ± 0.06, p0.001. Treatment was also associated with decreases in absolute growth rates (cm/year) for all comparisons (p ≤ 0.02). Medical prophylaxis reduced proximal aortic growth rates in young patients with at least moderate and progressive bicuspid aortopathy.

Midaortic syndrome (MAS) is a rare cause of severe childhood hypertension characterized by narrowing of the abdominal aorta in children and is associated with extensive vascular disease. It may occur as part of a genetic syndrome, such as neurofibromatosis, or as consequence of a pathological inflammatory disease. However, most cases are considered idiopathic. We hypothesized that in a high percentage of these patients, a monogenic cause of disease may be detected by evaluating whole exome sequencing data for mutations in 1 of 38 candidate genes previously described to cause vasculopathy. We studied a cohort of 36 individuals from 35 different families with MAS by exome sequencing. In 15 of 35 families (42.9%), we detected likely causal dominant mutations. In 15 of 35 (42.9%) families with MAS, whole exome sequencing revealed a mutation in one of the genes previously associated with vascular disease ( NF1 , JAG1 , ELN , GATA6 , and RNF213 ). Ten of the 15 mutations have not previously been reported. This is the first report of ELN , RNF213 , or GATA6 mutations in individuals with MAS. Mutations were detected in NF1 (6/15 families), JAG1 (4/15 families), ELN (3/15 families), and one family each for GATA6 and RNF213 . Eight individuals had syndromic disease and 7 individuals had isolated MAS. Whole exome sequencing can provide conclusive molecular genetic diagnosis in a high fraction of individuals with syndromic or isolated MAS. Establishing an etiologic diagnosis may reveal genotype/phenotype correlations for MAS in the future and should, therefore, be performed routinely in MAS.

Aortic stiffness measured by cardiac magnetic resonance (CMR) in connective tissue disorder (CTD) patients has been previously shown to be abnormal and to be associated with adverse aortic outcomes. The rate of increase in aortic stiffness with normal aging has been previously described. However, longitudinal changes in aortic stiffness have not been characterized in CTD patients. We examined longitudinal changes in CMR-derived aortic stiffness in children and young adults with CTDs. A retrospective analysis of 50 children and young adults (median age, 20 years; range, 0.2 to 49; 40% 18 years old) with a CTD, and with at least 2 CMR examinations (total 152 examinations) over a median duration of 3.9 (1 to 13.2) years was performed. Aortic stiffness measures (strain, distensibility, and β stiffness index) were calculated on each examination at the aortic root (AoR), ascending aorta, and descending aorta. Longitudinal changes in parameters were analyzed using linear mixed-effects models. Aortic strain and distensibility decreased with age, whereas the β stiffness index increased at all aortic segments. The average rates of decline in distensibility (x10

Background/Purpose The success rate of early thoracoscopic debridement (TD) for childhood empyema was reviewed in light of the increasing reported incidence of empyema associated with pulmonary necrosis (PN). Methods Data were collected from 106 patients who underwent thoracoscopic intervention from 2010 to 2016. Twenty additional patients with severe PN/Bronchopleural Fistula (BPF) were not suitable for TD requiring thoracotomy and Serratus anterior digitation flap. Results 106 patients with a median age of 4 years (IQR 2–6 years) were considered for TD as primary intervention of which 3 needed conversion to thoracotomy. TD alone was successful in 93/106 however, 10 patients required subsequent minithoracotomy for PN/BPF (managed with Serratus anterior digitation flap). Counting conversions as failure, the overall success rate of TD was 88%. No statistical difference was demonstrable in success rate compared to our previous series (93% (106/114) vs 88% (93/106)). Conclusions Primary TD in pediatric empyema is associated with an excellent outcome achieving adequate drainage and full expansion of the lung. The majority of failures in our series were attributable to PN/BPF, requiring thoracotomy and Serratus anterior digitation flap. This is likely a consequence of the increasing incidence of necrotizing pneumonia. Level of evidence Level IV.

Objective To evaluate the outcomes of various surgical approaches in the treatment of renovascular hypertension and midaortic syndrome (MAS) in children. Methods We performed a retrospective medical record review of patients who had undergone surgery for renovascular hypertension from 2010 to 2018 at our center under the care of a multidisciplinary team. The operative interventions included mesenteric artery growth improves circulation (MAGIC), tissue expander-stimulated lengthening of arteries (TESLA), aortic bypass using polytetrafluorethylene, renal artery reimplantation, and autotransplantation. The MAGIC procedure uses the meandering mesenteric artery as a free conduit for aortic bypass. The TESLA procedure is based on lengthening the normal distal aorta and iliac arteries by gradual filling of a retroaortic tissue expander for several weeks, followed by resection of the stenotic aorta and subsequent primary reconstruction. Results A total of 39 patients were identified, 10 with isolated renal artery stenosis, 26 with MAS, and 3 with systemic inflammatory vasculitis. The median age at presentation and surgery was 6.4 years (range, 0-16.3 years) and 9.3 years (range, 0-9.2 years), respectively. The MAS-associated syndromes included neurofibromatosis type 1 (15.4%) and Williams syndrome (5.1%), although most cases were idiopathic. At surgery, 33.3% had had stage 1 hypertension (HTN), 53.8% stage 2 HTN, and 12.8% normal blood pressure with a median of three antihypertensive medications. Follow-up of 37 patients at a median of 2.5 years demonstrated normal blood pressure in 86.1%, stage 1 HTN in 8.3%, and stage 2 HTN in 5.6%, with a median of one antihypertensive medication for the entire cohort. Conclusions The patterns of vascular involvement leading to renovascular hypertension in children are variable and complex, requiring thoughtful multidisciplinary planning and surgical decision-making. The MAGIC and TESLA procedures provide feasible approaches for aortic bypass and reconstruction using autologous tissues and will result in normalization of blood pressure in 85% of children 2.5 years after surgery.

Objective The short- and mid-term outcomes of endovascular aortic aneurysm repair have made it a standard treatment of abdominal aortic aneurysms. However, newer generation devices have yet to demonstrate improved long-term rates for complications, reinterventions, and survival. The TREO stent graft is a latest generation device and was evaluated for approval in the United States. Methods In a multicenter, nonrandomized, investigational device exemption clinical trial, we assessed the safety and effectiveness of the TREO device, with core laboratory assessment of the imaging studies and an independent adjudication of safety. The primary effectiveness endpoint was successful aneurysm treatment at 1 year. The primary safety endpoint was the incidence of major adverse events (MAE) at 30 days. Results A total of 150 patients (132 men; 88.0%) with infrarenal abdominal aortic (87.3%) or aortoiliac (12.7%) aneurysms were enrolled. The data were normally distributed. The mean age was 71.7 ± 7.4 years. The MAE incidence at 30 days was 0.7%. One subject experienced two MAE: myocardial infarction and procedural blood loss of 1000 mL. The proportion of successful aneurysm treatment at 1 year was 93.1%. Longer term follow-up continues, with no aneurysm-related mortality at the latest follow-up. At 3 years, the cumulative all-cause mortality and incidence of type I and type III endoleaks was 10.7% (n = 16), 2.7% (n = 4), and 0% (n = 0), respectively. In addition, aneurysm sac shrinkage >5 mm at 3 years had occurred in 54.3% of patients, and 9.3% had required a secondary intervention (n = 14). Conclusions The safety and effectiveness of endovascular repair of abdominal aneurysms with TREO were demonstrated, with 93.1% successful aneurysm treatment at 1 year and aneurysm sac shrinkage >5 mm at 3 years in 54.3% of patients. Long-term follow-up continues to determine whether these favorable outcomes will be sustained.

Background Hepatic fibrosis is highly prevalent in individuals with Fontan circulation. FibroSure (LabCorp, Burlington, NC) and hyaluronic acid (HA) have been validated for assessment of hepatic fibrosis in several forms of liver disease. We sought to determine whether these tests could identify Fontan patients with advanced hepatic fibrosis or cirrhosis. Methods Subjects who had liver biopsy and FibroSure or HA testing within 6 months of biopsy were identified from the Alliance for Adult Research in Congenital Cardiology Fontan Liver Health study. Biopsy specimens were scored for degree of sinusoidal and portal fibrosis on a 3- and 5-point scale, respectively. Histologic findings were correlated with FibroSure and HA results. Results The study included 27 subjects. Median age was 26.8 years (range, 17.4–59.8 years), and the median time since the Fontan surgery was 20.4 years (range, 12.0–31.3 years). FibroSure scores were elevated (>0.21) in 21 of 23 subjects (91%), and the scores for 3 (13%) suggested cirrhosis (>0.74). HA suggested cirrhosis (>46 ng/mL) in 3 of 17 subjects (18%). One subject died during the collection period. Eleven of 26 subjects (42%) had 4/5 or 5/5 portal fibrosis, consistent with cirrhosis; 17 (63%) had 3/3 sinusoidal fibrosis involving >66% of sinusoids. The FibroSure score and HA levels did not correlate with the degree of hepatic fibrosis and did not predict cirrhosis. Conclusions Abnormal biomarkers of hepatic fibrosis and specimen-proven hepatic fibrosis are common in adults with Fontan circulation. However, FibroSure and HA do not accurately predict the degree of histologic hepatic fibrosis. Further studies are needed to guide strategies for surveillance of liver disease in this population.

Aim A small proportion of infants with oesophageal atresia (OA) are thought to have a proximal tracheoesophageal fistula (TOF). Failure to recognize these can hamper mobilization of the upper pouch and lead to life-threatening episodes of aspiration once oral feeding starts. We reviewed our experience of upper pouch fistulae to identify characteristic features of proximal TOF. Methods A retrospective review of TOF/OA patient notes and bronchoscopy photographs and videos, identified from our database from 01/01/2006 to 12/31/2015, was performed. Results Eight (6.1%) infants were identified (M:F 5:3) from a total population of 131 newly diagnosed TOF/OA infants during the period. Their median gestational age was 33 (range 28–39) weeks, and median birth weight was 1647g (range 1100–3400g). Five were initially diagnosed with pure OA and 3 with a distal TOF. All patients underwent rigid bronchoscopy at the initial surgery but only one proximal fistula was identified. The 7 missed proximal fistulae were subsequently found either during on-table oesophagograms for gap assessment (n=2), at the time of thoracotomy when mobilizing the upper pouch (n=3), or during subsequent bronchoscopy for symptoms post OA repair (n=2). Two patients needed a further operation to divide the fistula. Review of the bronchoscopy videos identified four characteristic differences between upper and lower pouch fistulae. Proximal fistulae are found just distal to the vocal cords, are very small, often no more than a pit, do not open and close with ventilation, and are best identified by insufflation of the esophagus. Conclusion Upper pouch fistulae are relatively easy to miss because of different characteristics compared with H-type or distal fistulae that have not previously been mentioned in the literature. Level of evidence: level IV.

Background Glomerular filtration rate is a key physiologic variable with a central role in clinical decision making and a strong association with prognosis in diverse populations. Reduced estimated glomerular filtration rate (eGFR) is common among adults with congenital heart disease (ACHD). Methods We conducted a prospective cohort study of outpatient ACHD ≥18 years old seen in 2012-2017. Creatinine and cystatin C were measured; eGFR was calculated using either the creatinine or cystatin C Chronic Kidney Disease–Epidemiology Collaboration equation (CKD-EPICr and CKD-EPICysC, respectively). Survival analysis was performed to define the relationship between eGFR and both all-cause mortality and a composite outcome of death or nonelective cardiovascular hospitalization. Results Our cohort included 911 ACHD (39 ± 14 years old, 49% female). Mean CKD-EPICr and CKD-EPICysC were similar (101 ± 20 vs 100 ± 23 mL/min/1.73 m2), but CKD-EPICr estimates were higher for patients with a Fontan circulation (n = 131, +10 ± 19 mL/min/1.73 m2). After mean follow-up of 659 days, 128 patients (14.1%) experienced the composite outcome and 31 (3.4%) died. CKD-EPICysC more strongly predicted all-cause mortality (eGFR 90 mL/min/1.73 m2: CKD-EPICysC unadjusted HR = 20.2 [95% CI 7.6-53.1], C-statistic = 0.797; CKD-EPICr unadjusted HR = 4.6 [1.7-12.7], C-statistic = 0.620). CKD-EPICysC independently predicted the composite outcome, whereas CKD-EPICr did not (CKD-EPICysC adjusted HR = 3.0 [1.7-5.3]; CKD-EPICr adjusted HR = 1.5 [0.8-3.1]). Patients reclassified to a lower eGFR category by CKD-EPICysC, compared with CKD-EPICr, were at increased risk for the composite outcome (HR = 2.9 [2.0-4.3], P Conclusions Cystatin C–based eGFR more strongly predicts clinical events than creatinine-based eGFR in ACHD. Creatinine-based methods appear particularly questionable in the Fontan circulation.

Introduction Mortality for neonates requiring surgery for serious pathology such as NEC, remains high. Damage control surgery (DCS) has evolved as an operative strategy in battlefield trauma that sacrifices the completeness of the initial surgery to address the deadly triad of acidosis, hypothermia and coagulopathy. This approach is now used routinely in sick adults with nontrauma surgical emergencies. Here we describe our experience of using DCS in neonates. Method Neonates undergoing DCS at our hospital from 1/8/2010 to 30/11/17 had data collected prospectively. Results 27 neonates (median age 21 days; gestation 29 weeks; weight 1200 g; M:F 18:9) underwent DCS. Diagnosis (NEC 23, volvulus 2, meconium peritonitis 1, spontaneous perforation 1). Preoperative physiology: median temperature 35.5 °C, lactate 3.7, Activated prothrombin time 49; on a median of 1 inotrope (range 0 to 4); 19 had surgery on the intensive care unit. Surgery involved resection of dead bowel with the ends ligated and the abdomen left open. Operation took 38 min (26–80 min) and crew-resource management techniques were used to optimize efficiency. Second look occurred at 48 h (24–108 h) when the physiology had normalized. There were a total of 32 anastomoses in 18 patients with one leak; 3 patients had stomas for distal rectal disease. Overall mortality was 15% (4/27) or 18% in the NEC group (4/23). Conclusion Though techniques such as “clip and drop” exist, they have not been routinely incorporated into an operative strategy for sick neonates based on physiological derangement. The two benefits from our DCS approach were a low mortality and an avoidance of stomas. This approach deserves more investigation to see whether it is as effective in babies and children with nontrauma associated abdominal catastrophes as it is in adults. Type of study Case controlled study. Level of evidence Level III.

Red cell distribution width (RDW), a measure of variability in red cell size, predicts adverse outcomes in acquired causes of heart failure. We examined the relation of RDW and outcomes in adults with congenital heart disease. We performed a prospective cohort study on 696 ambulatory patients ≥18years old enrolled in the Boston Adult Congenital Heart Disease Biobank between 2012 and 2016 (mean age 38.7 ± 13.5 years; 49.9% women). The combined outcome was all-cause mortality or nonelective cardiovascular hospitalization. Most patients had moderately or severely complex congenital heart disease (42.5% and 38.5%, respectively). Mean RDW was 14.0 ± 1.3%. RDW15% was present in 81 patients (11.6%). After median 767days of follow-up, 115 patients sustained the primary combined outcome, including 31 who died. Higher RDW predicted both the combined outcome (hazard ratio [HR] for RDW15% = 4.5, 95% confidence interval [CI] 3.0 to 6.6; HR per + 1SD RDW = 1.8, 95% CI 1.6 to 2.0, both p0.0001) and death alone (HR for RDW15% = 7.1, 95% CI 3.5 to 14.4; HR per + 1SD RDW = 1.8, 95% CI 1.6 to 2.0, both p0.0001). RDW remained an independent predictor of the combined outcome after adjusting for age, cyanosis, congenital heart disease complexity, ventricular systolic function, New York Heart Association functional class, hemoglobin concentration, mean corpuscular volume, high-sensitivity C-reactive protein and estimated glomerular filtration rate (HR per + 1SD RDW = 1.5, 95% CI 1.2 to 1.9, p0.0001). RDW also remained an independent predictor of mortality alone after adjustment for age plus each variable individually. In conclusion, elevated RDW is an independent predictor of all-cause mortality or nonelective cardiovascular hospitalization in adults with congenital heart disease. This simple clinical biomarker identifies increased risk for adverse events even among patients with preserved functional status.

Marfan syndrome is a genetic disorder of connective tissue with principal manifestations in the cardiovascular, ocular, and skeletal systems. Cardiovascular disease, mainly progressive aortic root dilation and aortic dissection, is the leading cause of morbidity and mortality. The primary aims of this report were to examine the evidence related to medical therapy for Marfan syndrome, including recently completed randomized clinical trials on the efficacy of β-blockers and angiotensin II receptor blockers for the prophylactic treatment of aortic enlargement in Marfan syndrome, and to provide recommendations for medical therapy on the basis of available evidence. Medical therapy for Marfan syndrome should be individualized according to patient tolerance and risk factors such as age, aortic size, and family history of aortic dissection. The Pediatric Heart Network trial showed that atenolol and losartan each reduced the rate of aortic dilation. All patients with known or suspected Marfan syndrome and aortic root dilation should receive medical therapy with adequate doses of either β-blocker or angiotensin receptor blocker. The Pediatric Heart Network trial also showed that atenolol and losartan are more effective at reduction of aortic root z score in younger subjects, which suggests that medical therapy should be prescribed even in the youngest children with aortic dilation. For patients with Marfan syndrome without aortic dilation, the available evidence is less clear. If aortic dilation is severe and/or progressive, therapy with a combination of β-blocker and angiotensin receptor blocker should be considered, although trial results are mixed with respect to the efficacy of combination therapy vs monotherapy.

Background The Fontan operation redirects venous blood flow directly to the pulmonary circulation in subjects with single ventricle anatomy. Congestive hepatopathy and cirrhosis have been described in subjects with Fontan circulation, but the prevalence of and predictors for liver disease remain unknown. Methods We performed a retrospective study of liver histopathology in Fontan subjects who had liver biopsy or autopsy. All specimens were graded using a pre-determined protocol. Additional data were collected through chart review. Among 68 subjects, specimens were obtained at a median age of 23.2 years (range 5.0 to 52.7 years). Median time since Fontan was 18.1 years (range 1.2 to 32.7 years). Results Centrilobular fibrosis was seen in every specimen, with 41.2% showing Grade 4 centrilobular fibrosis. Portal fibrosis was seen in 82.3% of specimens, with 14.7% showing cirrhosis. Megamitochondria were seen in 58.8% of specimens. Centrilobular fibrosis grade was greater in those with a dominant left or right ventricle than in those with a combined right and left systemic ventricle (p = 0.008). Portal fibrosis grade correlated with alkaline phosphatase (p = 0.04) and mode of biopsy (p = 0.02). Neither centrilobular fibrosis nor portal fibrosis grade was predictive of transplant-free survival or overall survival. Conclusions Individuals with Fontan physiology have a high prevalence of hepatic fibrosis. Signs and symptoms of liver disease did not predict histopathologic findings. Few risk factors for advanced disease were identified. Histopathology findings did not predict transplant-free survival. The role of liver biopsy in this population remains uncertain.

Foregut duplication cysts originate from the foetal foregut and can be oesophageal duplications or bronchogenic cyst. The majority of patients are diagnosed antenatally and are asymptomatic at birth. A postnatal CT scan will confirm the diagnosis. All foregut duplications should be removed as they will eventually cause symptoms. If the patient is asymptomatic, thoracic cysts are best excised thoracoscopically.

Latent transforming growth factor binding proteins (LTBP) are a family of extracellular matrix glycoproteins that play an important role in the regulation of transforming growth factor beta (TGF-s) activation. Dysregulation of the TGF-s pathway has been implicated in the pathogenesis of inherited disorders predisposing to thoracic aortic aneurysms syndromes (TAAS) including Marfan syndrome (MFS; FBN1) and Loeys-Dietz syndrome (LDS; TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3). While these syndromes have distinct clinical criteria, they share clinical features including aortic root dilation and musculoskeletal findings. LTBP1 is a component of the TGF-s pathway that binds to fibrillin-1 in the extracellular matrix rendering TGF-s inactive. We describe a three-generation family case series with a heterozygous ∼5.1 Mb novel contiguous gene deletion of chromosome 2p22.3-p22.2 involving 11 genes, including LTBP1. The deletion has been identified in the proband, father and grandfather, who all have a phenotype consistent with a TAAS. Findings include thoracic aortic dilation, ptosis, malar hypoplasia, high arched palate, retrognathia, pes planus, hindfoot deformity, obstructive sleep apnea, and low truncal tone during childhood with joint laxity that progressed to reduced joint mobility over time. While the three affected individuals did not meet criteria for either MFS or LDS, they shared features of both. Although the deletion includes 11 genes, given the relationship between LTBP1, TGF-s, and fibrillin-1, LTBP1 stands out as one of the possible candidate genes for the clinical syndrome observed in this family. More studies are necessary to evaluate the potential role of LTBP1 in the pathophysiology of TAAS.

Although consensus guidelines on the management of cardiovascular disease in pregnancy reserve cesarean delivery for obstetric indications, there is a paucity of data to support this approach.The objective of the study was to compare cardiovascular and obstetric morbidity in women with cardiovascular disease according to the plan for vaginal birth or cesarean delivery.We assembled a prospective cohort of women delivering at an academic tertiary care center with a protocolized multidisciplinary approach to management of cardiovascular disease between September 2011 and December 2016. Our practice is to encourage vaginal birth in women with cardiovascular disease unless there is an obstetric indication for cesarean delivery. We allow women attempting vaginal birth a trial of Valsalva in the second stage with the ability to provide operative vaginal delivery if pushing leads to changes in hemodynamics or symptoms. Women were classified according to planned mode of delivery: either vaginal birth or cesarean delivery. We then used univariate analysis to compare adverse outcomes according to planned mode of delivery. The primary composite cardiac outcome of interest included sustained arrhythmia, heart failure, cardiac arrest, cerebral vascular accident, need for cardiac surgery or intervention, or death. Secondary obstetric and neonatal outcomes were also considered.We included 276 consenting women with congenital heart disease (68.5%), arrhythmias (11.2%), connective tissue disease (9.1%), cardiomyopathy (8.0%), valvular disease (1.4%), or vascular heart disease (1.8%) at or beyond 24 weeks' gestation. Seventy-six percent (n = 210) planned vaginal birth and 24% (n = 66) planned cesarean delivery. Women planning vaginal birth had lower rates of left ventricular outflow tract obstruction, multiparity, and preterm delivery. All women attempting vaginal birth were allowed Valsalva. Among planned vaginal deliveries 86.2% (n = 181) were successful, with a 9.5% operative vaginal delivery rate. Five women underwent operative vaginal delivery for the indication of cardiovascular disease without another obstetric indication at the discretion of the delivering provider. Four of these patients tolerated trials of Valsalva ranging from 15 to 75 minutes prior to delivery. Adverse cardiac outcomes were similar between planned vaginal birth and cesarean delivery groups (4.3% vs 3.0%, P = 1.00). Rates of postpartum hemorrhage (1.9% vs 10.6%, P.01) and transfusion (1.9% vs 9.1%, P = .01) were lower in the planned vaginal birth group. There were no differences in adverse cardiac, obstetric, or neonatal outcomes in the cohort overall or the subset of women with high-risk cardiovascular disease or a high burden of obstetric comorbidity.These findings suggest that cesarean delivery does not reduce adverse cardiovascular outcomes and lend support to a planned vaginal birth for the majority of women with cardiovascular disease including those with high-risk disease.

The aim of this study was to assess the effectiveness of Manuka honey ointment and dressings in the conservative management of exomphalos major (EM).A retrospective review of five patients with EM who underwent non-operative management with Manuka honey ointments and dressings was carried out to assess the time to complete epithelialisation, time to full feeds, hospital stay, adverse effects, complications and outcome.The skin epithelialisation over the EM sac was achieved in a median of 63 days (48-119). The median time to full enteral feed was 13 days (3-29). The median hospital stay was 66 days (21-121). No adverse effects were noted related to Manuka honey. Three patients had pulmonary hypoplasia requiring prolonged hospitalization; one of those died with respiratory complications at home after achieving complete epithelialisation. The follow-up was a median 16 months (6-22). Two patients did not require repair of the ventral hernia. One patient had ventral hernia repair at 16 months with excellent cosmesis. The remaining patient is awaiting repair.This is the first description of the use of medicated Manuka honey ointment and impregnated dressings in the conservative management of EM. This treatment is safe, efficacious and promotes wound healing with favorable outcome.

We hypothesized that cystatin C estimated glomerular filtration rate (eGFR) would be superior to creatinine eGFR for predicting clinical events in adults with congenital heart disease (ACHD). We measured creatinine & cystatin C in outpatients ≥18 yo with CHD. eGFR was calculated using the Chronic

Background Transient elastography (TE) offers a noninvasive correlate with the degree of hepatic fibrosis. However, factors other than fibrosis affect liver stiffness. We sought to determine whether hepatic congestion related to hemodynamics in Fontan circulation influences liver stiffness measurement (LSM) assessed by TE. Methods We studied 45 subjects with Fontan circulation undergoing cardiac catheterization with or without simultaneous liver biopsy. Subjects underwent TE within 5 days before catheterization. Clinical history, hemodynamic and biopsy data, and hepatic biomarkers were collected. Five subjects who had previously undergone liver biopsy and TE were also included. Results Median age was 13.1 years (range 2.4–57.8); median time since Fontan was 9.9 years (range 0.1–32.5). No subject had known hepatitis C. Mean LSM for the entire cohort was 21.4 ± 10.8 kPa. Univariate regression analysis using LSM as a continuous outcome variable shows significant correlations with age (R = 0.35, P = .01), time since Fontan (R = 0.41, P = .003), Fontan pressure (R = 0.31, P = .04), cardiac index (R = 0.33, P = .03), pulmonary vascular resistance (R = 0.34, P = .03), systemic arterial oxygen saturation (R = 0.31, P = .04), and platelet count (R = 0.29, P = .05). On multiple regression analysis, Fontan pressure (β = 0.901, P = .03) and cardiac index (β = 2.703, P = .02) were significant predictors of LSM with overall model R2 = 0.206. Univariate analysis shows LSM to be associated with more severe centrilobular fibrosis (P = .05). Conclusions Higher LSM is associated with unfavorable Fontan hemodynamics and advanced centrilobular hepatic fibrosis. TE may be a useful tool for identifying Fontan patients who warrant invasive testing.

Objectif: Determiner la prevalence de la dysfonction de la valve aortique, de la dilatation de l'aorte proximale et des interventions au niveau de la valve aortique et de l'aorte ascendante chez les adultes avec une coarctation de l'aorte. Contexte: La dysfonction de la valve aortique et la dilatation de l'aorte proximale sont rares chez les enfants et les adolescents avec une coarctation de l'aorte. A long terme, les adultes pourraient etre plus a risque de developper ce type de pathologie. Methode: Nous avons retrospectivement passe en revue tous les adultes avec une coarctation de l'aorte corrigee ou pas suivis au « Boston Children's Hospital » entre 2004 et 2010. Resultats: 216 adultes (56 % d'hommes) avec une coarctation ont ete identifies. L'âge median a la derniere evaluation etait de 28 (de 18 a 75) ans. Une bicuspidie aortique etait presente dans 66% des cas. Au dernier controle, 3% avaient une stenose aortique moderee ou severe et 4% avaient une insuffisance aortique moderee a severe. Une dilatation de la racine de l'aorte ou de l'aorte ascendante etait presente dans 28%, respectivement 42% des patients. Une dilatation au moins moderee de la racine de l'aorte ou de l'aorte ascendante (score Z > 4) etait presente dans 8%, respectivement 14%. Les patients avec une bicuspidie aortique etaient plus sujets a avoir une dilatation au moins moderee de la racine de l'aorte ou de l'aorte ascendante compares a ceux sans bicuspidie (20% contre 0%; p

Background: Adults with congenital heart disease (ACHD) comprise a growing, increasingly complex population. The Boston Adult Congenital Heart Disease Biobank is a program for the collection and storage of biospecimens to provide a sustainable resource for scientific biomarker investigation in ACHD. Methods: We describe a protocol to collect, process, and store biospecimens for ACHD or associated diagnoses developed based on existing literature and consultation with cardiovascular biomarker epidemiologists. The protocol involves collecting urine and ∼48.5 mL of blood. A subset of the blood and urine undergoes immediate clinically relevant testing. The remaining biospecimens are processed soon after collection and stored at −80°C as aliquots of ethylenediaminetetraacetic acid (EDTA) and lithium heparin plasma, serum, red cell and buffy coat pellet, and urine supernatant. Including tubes with diverse anticoagulant and clot accelerator contents will enable flexible downstream use. Demographic and clinical data are entered into a database; data on biospecimen collection, processing, and storage are managed by an enterprise laboratory information management system. Results: Since implementation in 2012, we have enrolled more than 650 unique participants (aged 18-80 years, 53.3% women); the Biobank contains over 11,000 biospecimen aliquots. The most common primary CHD diagnoses are single ventricle status-post Fontan procedure (18.8%), repaired tetralogy of Fallot with pulmonary stenosis or atresia (17.6%), and left-sided obstructive lesions (17.5%). Conclusions: We describe the design and implementation of biospecimen collection, handling, and storage protocols with multiple levels of quality assurance. These protocols are feasible and reflect the size and goals of the Boston ACHD Biobank.

Marfan syndrome is a multi-system connective tissue disorder, with primary involvement of the cardiovascular, ocular and skeletal systems. This autosomal heritable disease is mainly attributable to a defect in the FBN1 gene. Until 2010, the clinical diagnosis of Marfan syndrome was based on the Ghent criteria of 1996. Recently, the Ghent criteria have been revised. The revised guidelines of 2010 place more emphasis on aortic root dilatation, ectopia lentis and FBN1 mutation testing in the diagnostic assessment of Marfan syndrome. Although the revised Ghent criteria of 2010 are easier to apply, they do raise some issues that need to be addressed. In addition to adjustments in the diagnosis of Marfan syndrome, there is progress in the understanding of the pathophysiology in Marfan syndrome, leading to new treatment strategies. Losartan, an angiotensin II receptor type 1 blocker, has been shown to inhibit transforming growth factor beta signal transduction and thereby prevent aortic root aneurysms in a mouse model of Marfan syndrome. This article will provide a critical appraisal of the revised Ghent nosology in 2010 and will highlight future perspectives regarding the treatment of Marfan syndrome.

Purpose Surgical management of bronchopleural (B-P) fistula associated with thoracic empyema and necrotizing pneumonia is challenging. We evaluated the treatment and outcome of early surgical intervention with limited decortication and insertion of a serratus anterior muscle digitation flap. Methods A retrospective review during a 10-year period of children with empyema and B-P fistula secondary to necrotizing pneumonia was performed. During this period, 335 children with empyema were admitted, of which 20 developed a B-P fistula. All underwent a thoracotomy with insertion of a serratus anterior muscle digitation flap. Results Prethoracotomy chest computed tomographic scan was performed to define the pathologic characteristic. Streptococcus pneumoniae was identified by pus culture (n = 6) and by polymerase chain reaction (n = 4). The median postoperative time with pyrexia after surgical intervention was 2 days (range, 1-3 days). The median period of thoracostomy drain was 7 days (range, 5-15 days). Length of hospital stay was 21 days (range, 7-43 days). This parenchyma-preserving technique was able to control the B-P fistula successfully in all cases. No reintervention was necessary in any case. Respiratory symptoms and radiology improved in all children on follow-up, except for 3 who required oral antibiotics for subsequent chest infections. Conclusion Early surgical intervention with insertion of a serratus anterior muscle digitation flap is effective and safe and avoids morbidity associated with conservative management and necrotic lung resection surgery.

Background The aorta in patients with bicuspid aortic valve (BAV) is larger and grows more rapidly than in patients with tricommissural aortic valve. Young patients with BAV can have significant aortic dilation that places them at risk for morbidity and mortality. Objective The aims of this study were to determine the rate of growth of the aorta in young patients with BAV and to identify predictors of significant dilation and rapid aortic growth. Methods 333 patients were randomly selected from an inception cohort of 1192 patients with BAV identified between 1986 and 1999. Results Median age at the most recent study was 13.5 (0–30) years, 74% were male. Moderate/severe (Z>4) aortic root and ascending aortic dilation was present in 14/333 (5%) and 53/333 (16%) of patients, respectively. In longitudinal follow-up, only a minimal change in aortic Z-score was noted. Predictors of moderate/severe aortic root dilation included moderate/severe aortic regurgitation, absence of moderate/severe aortic stenosis and fusion of the right and left coronary leaflets. Predictors of moderate/severe ascending aortic dilation included moderate/severe aortic regurgitation and absence of aortic coarctation. Conclusion Moderate/severe dilation of the ascending aorta is common in young patients with BAV, but moderate/severe dilation of the aortic root is less common. The Z-scores for both remained relatively constant over time even in patients with significant dilation, implying that young children with moderate/severe aortic dilation may be at the highest risk for dilation-related complications as adults.

Background— Arterial tortuosity is described as a common and distinctive feature of Loeys-Dietz syndrome (LDS), yet reports on arterial tortuosity are based on qualitative observations and none have investigated an association between tortuosity and cardiovascular outcomes in LDS or other connective tissue disorders. Methods and Results— We performed a retrospective analysis of 90 patients ≤50 years of age with Marfan syndrome, LDS, Ehlers-Danlos syndrome, or nonspecific connective tissue disorder who underwent thoracic contrast-enhanced magnetic resonance angiography. Controls (n=30) underwent magnetic resonance imaging to exclude arrhythmogenic right ventricular dysplasia. Using a volume-rendered angiogram, vertebral arteries were measured along the curvature of the vessel (actual length) and linearly (straight length), and distance factor was calculated: [(actual/straight length−1)×100]. Each subject's maximum distance factor was designated the Vertebral Tortuosity Index (VTI). The VTI was compared among diagnostic groups and among patients with cardiac surgery, dissection, and death. Median age at magnetic resonance imaging was 19.6 years (range 0.2 to 50.1). VTI interrater reliability was excellent (intraclass correlation coefficient =0.987). The VTI was higher in Marfan syndrome (n=57, median 26; interquartile range 10 to 49) and LDS (n=13, median 58; interquartile range 18 to 92) compared with controls (median 4.5; interquartile range 3 to 6; P P =0.002). Vertebral tortuosity index ≥50 was associated with earlier age at dissection and death compared with VTI P =0.001 versus P Conclusion— Arterial tortuosity measured by magnetic resonance angiography is a reproducible marker of adverse cardiovascular outcomes in connective tissue disorders.

The primary causes of morbidity and mortality in Marfan syndrome (MFS) are related to complications of aortic root (AR) dilatation. We investigated whether AR size in childhood predicts aortic events (surgery or dissection) in adulthood. Retrospective analysis of MFS patients by revised Ghent

The vascular smooth muscle cell (SMC)-specific isoform of alpha-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. Sequencing of DNA from patients with nonfamilial TAAD and from premature-onset CAD patients independently identified ACTA2 mutations in these patients and premature onset strokes in family members with ACTA2 mutations. Vascular pathology and analysis of explanted SMCs and myofibroblasts from patients harboring ACTA2 suggested that increased proliferation of SMCs contributed to occlusive diseases. These results indicate that heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD. These data demonstrate that diffuse vascular diseases resulting from either occluded or enlarged arteries can be caused by mutations in a single gene and have direct implications for clinical management and research on familial vascular diseases.

We thank Murakami et al for their interest in our article.1 They propose that the aortic dilatation observed in patients with connective tissue disorders is a compensatory response to increased aortic stiffness to preserve coronary blood flow. Although our study was not designed to test this interesting hypothesis, we agree that future investigations designed specifically to address this theory are warranted. Weismann et al question the use of aortic strain in our study and suggest that its relationship with adverse aortic outcomes may be driven by aortic size alone. However, their comments fail to take into account that, in addition to aortic size, several other factors …

Primary spontaneous pneumothorax (PSP) is managed in accordance with the adult British Thoracic Society (BTS) guidelines due to lack of paediatric evidence and consensus. We aim to highlight the differences and provide a best practice surgical management strategy for PSP based on experience of two major paediatric surgical centres. Retrospective review of PSP management and outcomes from two UK Tertiary Paediatric hospitals between 2004 and 2015. Fifty children with 55 PSP (5 bilateral) were referred to our Thoracic Surgical Services after initial management: 53 % of the needle aspirations failed. Nine children (20 %) were associated with visible bullae on the initial chest X-ray. Forty-nine children were assessed with computed tomography scan (CT). Apical emphysematous-like changes (ELC) were identified in 37 children (75 %). Ten children had also bullae in the asymptomatic contralateral lungs (20 %). In two children (4 %), CT demonstrated other lung lesions: a tumour of the left main bronchus in one child; a multi-cystic lesion of the right middle lobe in keeping with a congenital lung malformation in another child. Contralateral asymptomatic ELC were detected in 20 % of the children: of those 40 % developed pneumothorax within 6 months. Best surgical management was thoracoscopic staple bullectomy and pleurectomy with 11 % risk of recurrence. Histology confirmed ELC in 100 % of the apical lung wedge resections even in those apexes apparently normal at the time of thoracoscopy. Our experience suggests that adult BTS guidelines are not applicable to children with large PSP. Needle aspiration is ineffective. We advocate early referral to a Paediatric Thoracic Service. We suggest early chest CT scan to identify ELC, for counselling regarding contralateral asymptomatic ELC and to rule out secondary pathological conditions causing pneumothorax. In rare instance if bulla is visible on presenting chest X-ray, thoracoscopy could be offered as primary option.

We conducted a randomized, double-blind trial of losartan (100 mg QD) versus atenolol (50 mg QD) for 6 months in adults with Marfan syndrome. Carotid-femoral pulse wave velocity (PWV), central augmentation index (AIx), aortic diameter and left ventricular (LV) function were assessed with arterial tonometry and echocardiography. Thirty-four subjects (18 female; median age 35 years, IQR 27, 45) were randomized. Central systolic and diastolic blood pressure decreased comparably with atenolol and losartan ( p = 0.64 and 0.31, respectively); heart rate decreased with atenolol ( p = 0.02), but not with losartan. PWV decreased in patients treated with atenolol (–1.15 ± 1.68 m/s; p = 0.01), but not in those treated with losartan (–0.22 ± 0.59 m/s; p = 0.15; between-group difference p = 0.04). In contrast, AIx decreased in the losartan group (–9.6 ± 8.6%; p < 0.001) but not in the atenolol group (0.9 ± 6.2%, p = 0.57; between-group difference p < 0.001). There was no significant change in aortic diameters or LV ejection fraction in either treatment group. In adults with Marfan syndrome, 6 months of treatment with atenolol improves PWV, whereas losartan reduces the AIx. By improving vascular stiffness via distinct mechanisms of action, there is physiologic value to considering the use of both medications in individuals with Marfan syndrome.

Context: Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL). Objective: The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL. Design/Setting/Participants: We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000–2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes. Results: In study 1, we identified 20 PHEO-PGL cases, of which 18 had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1–57 y). Cases were young at diagnosis (median 31.5 y, range 15–57 y) and 7 of 18 had multiple tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of such syndromes. In study 2, hospitalized CCHD patients had an increased likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6–13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD had no increased risk (odds ratio 0.9, P = .48). Conclusions: There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to hypoxic stress, common genetic or developmental factors, or some combination requires further investigation.

Background— Aortic diameter is an imperfect predictor of aortic complications in connective tissue disorders (CTDs). Novel indicators of vascular phenotype severity such as aortic stiffness and vertebral tortuosity index have been proposed. We assessed the relation between aortic stiffness by cardiac MRI, surgical root replacement, and rates of aortic root dilation in children and young adults with CTDs. Methods and Results— Retrospective analysis of cardiac MRI data on children and young adults with a CTD was performed to derive aortic stiffness measures (strain, distensibility, and β-stiffness index) at the aortic root, ascending aorta, and descending aorta. Vertebral tortuosity index was calculated as previously described. Rate of aortic root dilation before cardiac MRI was calculated as change in echocardiographic aortic root diameter z score per year. In 83 CTD patients (median age, 24 years; range, 1–55; 17% z score, –1.93 (range, –8.7 to 1.3; P P =0.05) and higher vertebral tortuosity index ( P =0.01) were independently associated with aortic root replacement. Lower ascending aorta strain ( P =0.02) was associated with a higher rate of aortic root dilation. Conclusions— Higher aortic stiffness is associated with higher rates of surgical aortic replacement and aortic root dilation in children and young adults with CTDs.

Transient elastography (TE) offers a noninvasive correlate with the degree of hepatic fibrosis. However, factors other than fibrosis affect liver stiffness. We sought to determine whether hepatic congestion related to hemodynamics in Fontan circulation influences liver stiffness measurement (LSM) assessed by TE.We studied 45 subjects with Fontan circulation undergoing cardiac catheterization with or without simultaneous liver biopsy. Subjects underwent TE within 5 days before catheterization. Clinical history, hemodynamic and biopsy data, and hepatic biomarkers were collected. Five subjects who had previously undergone liver biopsy and TE were also included.Median age was 13.1 years (range 2.4-57.8); median time since Fontan was 9.9 years (range 0.1-32.5). No subject had known hepatitis C. Mean LSM for the entire cohort was 21.4 ± 10.8 kPa. Univariate regression analysis using LSM as a continuous outcome variable shows significant correlations with age (R = 0.35, P = .01), time since Fontan (R = 0.41, P = .003), Fontan pressure (R = 0.31, P = .04), cardiac index (R = 0.33, P = .03), pulmonary vascular resistance (R = 0.34, P = .03), systemic arterial oxygen saturation (R = 0.31, P = .04), and platelet count (R = 0.29, P = .05). On multiple regression analysis, Fontan pressure (β = 0.901, P = .03) and cardiac index (β = 2.703, P = .02) were significant predictors of LSM with overall model R(2) = 0.206. Univariate analysis shows LSM to be associated with more severe centrilobular fibrosis (P = .05).Higher LSM is associated with unfavorable Fontan hemodynamics and advanced centrilobular hepatic fibrosis. TE may be a useful tool for identifying Fontan patients who warrant invasive testing.

To determine the prevalence of aortic valve dysfunction, aortic dilation, and aortic valve and ascending aortic intervention in adults with coarctation of the aorta (CoA).Aortic valve dysfunction and aortic dilation are rare among children and adolescents with CoA. With longer follow-up, adults may be more likely to have progressive disease.We retrospectively reviewed all adults with CoA, repaired or unrepaired, seen at our center between 2004 and 2010.Two hundred sixteen adults (56.0% male) with CoA were identified. Median age at last evaluation was 28.3 (range 18.0 to 75.3) years. Bicuspid aortic valve (BAV) was present in 65.7%. At last follow-up, 3.2% had moderate or severe aortic stenosis, and 3.7% had moderate or severe aortic regurgitation. Dilation of the aortic root or ascending aorta was present in 28.0% and 41.6% of patients, respectively. Moderate or severe aortic root or ascending aortic dilation (z-score4) was present in 8.2% and 13.7%, respectively. Patients with BAV were more likely to have moderate or severe ascending aortic dilation compared with those without BAV (19.5% vs. 0%; P0.001). Age was associated with ascending aortic dilation (P = 0.04). At most recent follow-up, 5.6% had undergone aortic valve intervention, and 3.2% had aortic root or ascending aortic replacement.In adults with CoA, significant aortic valve dysfunction and interventions during early adulthood were uncommon. However, aortic dilation was prevalent, especially of the ascending aorta, in patients with BAV.

Objective The Fontan operation is a staged palliation for complex congenital heart disease and single ventricle physiology. Perioperative survivors of the Fontan operation experience long-term cardiac complications, including death. Liver and renal dysfunction are reported in these patients and have a direct effect on morbidity and mortality. This study aims to investigate whether the Model for End-stage Liver Disease eXcluding INR score (function of creatinine and total bilirubin, MELD-XI) predicts risk for cardiac mortality or transplantation in patients with Fontan circulation. Design and setting Retrospective, single-centre study. Time of first evaluation was the time of the earliest available MELD-XI score measurement, and follow-up was terminated by a cardiac event or by the last clinical evaluation. Patients Patients surviving after Fontan surgery and evaluated at Boston Children9s Hospital between 1993 and 2008. Main outcome measure Composite endpoint of sudden death, death from congestive heart failure or cardiac transplantation. Results The MELD-XI score was calculated as MELD-XI=11.76(log e creatinine)+5.112(log e total bilirubin)+9.44. Ninety-six patients were included (52 male, median age 26 years). After a mean follow-up period of 5.7 years, 18 patients (19%) experienced the composite end point. Baseline MELD-XI score was independently and directly related to the incidence of the composite endpoint (HR for high MELD-XI score group of 7.76, 95% CI 2.05 to 29.33, p=0.008). Conclusions Fontan patients with a higher MELD-XI score have shorter freedom from sudden cardiac death, death from congestive heart failure and cardiac transplantation.