Short- and intermediate-term survival after extracorporeal membrane oxygenation in children with cardiac disease

ObjectivesIn children with cardiac disease, common indications for extracorporeal membrane oxygenation (ECMO) include refractory cardiopulmonary resuscitation (E-CPR), failure to separate from cardiopulmonary bypass (OR-ECMO), and low cardiac output syndrome (LCOS-ECMO). Despite established acceptance, ECMO outcomes are suboptimal with a survival between 38% and 55%. We evaluated factors associated with significantly increased survival in cardiac patients requiring ECMO.MethodsWe conducted a retrospective investigation of consecutive patients undergoing ECMO between 2006 and 2010. Demographic, pre-ECMO, ECMO, and post-ECMO parameters were analyzed. Neurologic outcomes were assessed with the pediatric overall performance category scale at the latest follow-up.ResultsThere were 3524 admissions, 95 (3%) of which necessitated ECMO; 40 (42%) E-CPR, 31 (33%) OR-ECMO, and 24 (25%) LCOS-ECMO. The overall hospital survival was 73%. The within-groups hospital survival was 75% in E-CPR, 77% OR-ECMO and 62% LCOS-ECMO. In the multivariable logistic regression analysis, chromosomal anomalies (odds ratio [OR], 8; 95% confidence interval [CI], 2-35), single ventricle (OR ,6; 95% CI, 3-33), multiple ECMO runs (OR, 15; 95% CI, 4-42), higher 24-hour ECMO flows (OR, 8; 95% CI, 4-22), decreased lung compliance (OR, 5; 95% CI, 2-16), and need for plasma exchange (OR, 5; 95% CI, 3-18) were all significant factors associated with mortality. From the univariate analysis, a common parameter associated with mortality within all groups was intracranial hemorrhage. At 1.9 years (0.9, 2.9) of follow-up, 66% were still alive, and 89% of survivors had normal function or only mild neurodevelopmental disability.ConclusionsECMO was successfully used in children with cardiac disease with 73% and 66% short- and intermediate-term survival, respectively. The majority of the survivors had normal function or only a minimal neurodevelopmental deficit

A Novel Restorative Pulmonary Valve Conduit : early Outcomes of Two Clinical Trials

Objectives: We report the first use of a biorestorative valved conduit (Xeltis pulmonary valve-XPV) in children. Based on early follow-up data the valve design was modified; we report on the comparative performance of the two designs at 12 months post-implantation. Methods: Twelve children (six male) median age 5 (2 to 12) years and weight 17 (10 to 43) kg, had implantation of the first XPV valve design (XPV-1, group 1; 16 mm (n = 5), and 18mm (n = 7). All had had previous surgery. Based on XPV performance at 12 months, the leaflet design was modified and an additional six children (five male) with complex malformations, median age 5 (3 to 9) years, and weight 21 (14 to 29) kg underwent implantation of the new XPV (XPV-2, group 2; 18 mm in all). For both subgroups, the 12 month clinical and echocardiographic outcomes were compared. Results: All patients in both groups have completed 12 months of follow-up. All are in NYHA functional class I. Seventeen of the 18 conduits have shown no evidence of progressive stenosis, dilation or aneurysm formation. Residual gradients of >40 mm Hg were observed in three patients in group 1 due to kinking of the conduit (n = 1), and peripheral stenosis of the branch pulmonary arteries (n = 2). In group 2, one patient developed rapidly progressive stenosis of the proximal conduit anastomosis, requiring conduit replacement. Five patients in group 1 developed severe pulmonary valve regurgitation (PI) due to prolapse of valve leaflet. In contrast, only one patient in group 2 developed more than mild PI at 12 months, which was not related to leaflet prolapse. Conclusions: The XPV, a biorestorative valved conduit, demonstrated promising early clinical outcomes in humans with 17 of 18 patients being free of reintervention at 1 year. Early onset PI seen in the XPV-1 version seems to have been corrected in the XPV-2, which has led to the approval of an FDA clinical trial

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals

Total Artificial Heart as Rescue Therapy for Primary Graft Failure in an Infant

An infant unable to be weaned from cardiopulmonary bypass after orthotopic heart transplantation was cannulated for extracorporeal membrane oxygenation. During the next 3 days, allograft failure and intracardiac thrombosis necessitated cardiectomy. To provide acute mechanical circulatory support, artificial atrial chambers were constructed with Gore-Tex conduits and PediMag centrifugal pumps were connected to each by Berlin Heart EXCOR cannulae. The PediMag pumps were subsequently exchanged for 10-mL Berlin Heart EXCOR pumps. After 60 days of support by total artificial heart, the patient was bridged successfully to a second heart transplant

Right ventricular outflow tract reconstruction with bicuspid valved polytetrafluoroethylene conduit.

BACKGROUND: In general, all conduits available for right ventricular outflow tract (RVOT) reconstruction eventually become stenotic or insufficient. Owing to the lack of an ideal conduit and with the hope of reducing the incidence of reoperations, we have developed and utilized a bicuspid valved polytetrafluoroethylene (PTFE) conduit for the reconstruction of the RVOT. The purpose of this study was to review our early experience with this conduit. METHODS: From October 2008 to September 2009, we have implanted bicuspid valved PTFE conduits in 18 patients with a median age of 1.7 years (range 6 days to 16 years). Their diagnoses include tetralogy of Fallot with pulmonary atresia in 8, truncus arteriosus in 6, congenital aortic stenosis in 2, transposition of great arteries in 1, and interrupted aortic arch with a ventricular septal defect in 1. In 16 patients, a complete biventricular repair was performed. In another 2 cases, the conduit was used for palliative RVOT reconstruction. The conduit sizes varied from 10 mm to 24 mm in diameter. Three-dimensional flow fields obtained from computational fluid dynamics studies were utilized in the conduit design process. RESULTS: There was no surgical mortality or reinterventions associated with the PTFE conduit placement in our series. At the time of discharge, none of the patients had any echocardiographic findings consistent with significant conduit stenosis or insufficiency. During the follow-up period of 6.2 ± 3.9 months, all patients were alive and only 3 had more than mild pulmonary insufficiency. CONCLUSIONS: Our bicuspid valved PTFE conduit has an acceptable early performance, with a low incidence of valve insufficiency and no conduit stenosis. Certainly, longer follow-up is necessary to fully assess its long-term benefits.</p

Neurodevelopmental Outcomes after Pediatric Cardiac ECMO Support

Purpose: To characterize the neurodevelopmental outcomes and identify factors associated with poor outcomes in pediatric patients undergoing cardiac extracorporeal membrane oxygenation (ECMO). Methods: Five year retrospective review, including demographics, cardiac lesion and surgical complexity, reason for ECMO, ECMO complications, and neurodevelopmental status at discharge and latest follow-up. Neurodevelopmental status was determined through the Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scales.Results: Overall ECMO survival was 73% at hospital discharge and 66% a t the latest follow-up. Most patients underwent CPR (43%), and the majority (53%) had a significant disease complexity (Aristotle=4). Complications occurred in 42% of the ECMO runs, of which 12% were intracranial injuries. At hospital discharge, 75% of patients had normal to mild disability, improving to 81% at 2 years follow-up. At hospital discharge, moderate to severe disability was associated with CPR, plasma exchange or intracranial insults. After discharge, 23% showed improvement in neurologic status and 4% showed deterioration. Cerebral infarction was the only parameter associated with deterioration at the later follow-up stage.Conclusions: ECMO was successfully used in children with cardiac disease with 73% and 66% short and long-term survival respectively. Majority of the survivors had normal to mild neurodevelopmental disability and a significant portion showed neurologic improvement by the latest follow-up. Nevertheless, despite the grossly favorable outcomes standardized comprehensive neuropsychological testing is of paramount importance in all these patients

Feasibility of laparoscopic Nissen fundoplication after pediatric lung or heart-lung transplantation: Should this be the standard?

Background: Five-year graft survival in the pediatric lung transplant (LTxp) population is less than 50%, with obliterative bronchiolitis (OB) the leading cause of death at 1, 3, and 5 years post-transplant. Bronchiolitis obliterans syndrome (BOS), defined using spirometry values, is the clinical surrogate for the histological diagnosis of obliterative bronchiolitis. Surgical correction of documented gastroesophageal reflux disease (GERD) has been proposed as a means to potentially delay the onset of BOS and prolong allograft survival in adults before or after lung transplantation but only one such study exists in children. We have examined the safety and possible benefits of laparoscopic antireflux surgery in pediatric patients following lung (LTxp) and heart-lung transplantation (HLTxp). Methods: An Institutional Review Board (IRB)-approved retrospective chart review was performed to evaluate the outcomes and complications of laparoscopic antireflux surgery in pediatric lung and heart-lung transplant patients. Spirometry data were collected for BOS staging using BOS criteria for children. Results: Twenty-five lung and heart-lung transplants were performed between January 2003 and July 2009. Eleven transplant recipients, including six double-lung and five heart-lung (HLTxp), with a median age of 11.7 years (range 5.1-18.4 years), underwent a total of 12 laparoscopic Nissen fundoplications at a median of 427 days after transplant (range 51-2310 days). GERD was determined based upon clinical impression, pH probe study, gastric emptying study, and/or esophagram in all patients. Three patients already had a gastrostomy tube in place and two had one placed at the time of fundoplication. There were no conversions to open surgery, 30-day readmissions, or 30-day mortalities. Complications included one exploratory laparoscopy for free air 6 days after laparoscopic Nissen fundoplication for a gastric perforation that had spontaneously sealed. Another patient required a revision laparoscopic Nissen 822 days following the initial fundoplication for a paraesophageal hernia and recurrent GERD. The average length of hospital stay was 4.4 ± 1.7 days. Nine of the 12 fundoplications were performed in patients with baseline spirometry values prior to fundoplication and who could also complete spirometry reliably. One of these nine operations was associated with improvement in BOS stage 6 months after fundoplication; seven were associated with no change in BOS stage; and one was associated with a decline in BOS stage. Conclusion: It is feasible to perform laparoscopic Nissen fundoplication in pediatric lung and heart-lung transplant recipients without mortality or significant morbidity for the treatment of GERD. The real effect on pulmonary function cannot be assessed due to our small sample size and lack of reproducible spirometry in our younger patients. Additional studies are needed to elucidate the relationship between antireflux surgery and the potential for improving pulmonary allograft function and survival in children which has been previously observed in adult patients. © 2010 Springer Science+Business Media, LLC