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BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (

OBJECTIVE: Pulmonary artery reconstruction during comprehensive stage 2 (CS2) procedure can be challenging. Since 2017, we have employed preemptive left pulmonary artery (LPA) stenting. We hypothesized that LPA stenting promotes adequate growth and without compromising Fontan candidacy. Herewith, we report our midterm results. METHODS: From 2002 to 2020, 159 patients underwent CS2. Patients were divided as follows: no stent (n = 122; Group 1) and perioperative LPA stent (n = 37; Group 2). Group 2 was subdivided according to unplanned stent (n = 17; Group 2a) or preemptive stent (n = 20; Group 2b). Relevant perioperative data was reviewed. Nonparametric statistics were utilized. RESULTS: Median age and weight at surgery and hospital length of stay after CS2 did not differ between groups. Median cardiopulmonary bypass and crossclamp times were significantly greater in Group 1 (265 vs 243 minutes [P = .021] and 46 vs 26 minutes [P = .008]). In-hospital mortality was similar between Groups 1 and 2 (9.0% vs 18.9%, respectively [P = .1348]). Group 2b demonstrated a superior survival compared to Group 2a (P = .0335) but not Group 1 (P > .9999). Preemptive stenting significantly increased median hilar LPA diameter at CS2 exit angiogram compared with no stenting (P

Minimal data exist about the incidence and risk factors for arch intervention after comprehensive stage II (CSII). Goal of this study was to document incidence of arch interventions after CSII and determine if any differences existed between those who underwent an arch intervention (aiCSII) versus those did not have an intervention. Single-center retrospective chart review of all hypoplastic left heart syndrome patients who underwent a CSII between 6/1/2005 and 2/1/2020 was performed. Univariate analysis was conducted in addition to principal components analysis (PCA). One hundred patients were evaluated. Sixteen patients underwent 24 arch interventions. Age at initial arch reintervention was 1.3 ± 1.2 years (median 1.0 years, range 0.5-2.2 years). Univariate analysis showed that the aiCSII group were more likely to be female, to have had a retrograde arch intervention post-hybrid procedure, and to be younger at time of CSII. On echocardiograms, aiCSII group had significantly higher pre-CSII patent ductus arteriosus velocities, arch velocities on their 1st post-operative and discharge study post-CSII, and arch velocities pre-Fontan. Gradients were higher in the aiCSII via pre-Fontan catheterization. With PCA, echocardiographic and catheterization data remained significantly associated with aiCSII versus those who did not undergo an arch intervention (OR = 4.5 (1.9, 19.8), p = 0.008). Incidence of arch intervention post-CSII was 16%. Echocardiographic arch velocities during the CSII hospitalization were the strongest predictors for subsequent aortic arch interventions. Further studies are needed to determine any modifiable variables that may reduce the incidence of arch interventions.

BACKGROUND The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 ( n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease , and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin . Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events , including major bleeding, were reduced in the PSS group. CONCLUSIONS The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Background: Tricuspid valve (TV) and right ventricular (RV) function are major determinants of morbidity and mortality in patients with hypoplastic left heart syndrome (HLHS). We sought to retrospectively evaluate these parameters throughout the hybrid palliation strategy. Methods: From 2002 to 2018, 203 patients with HLHS and variants presented for hybrid stage I (HS1). Echocardiographic evaluation of tricuspid regurgitation (TR) and RV function was assessed at multiple time points. Clinical outcomes including tricuspid valvuloplasty, transplantation, and death were reviewed. Results: The most prevalent HLHS subtype was aortic atresia/mitral atresia. The presence of significant TR and/or RV dysfunction was 14.78% and 9.36%, respectively, at the time of initial HS1. There were 185 survivors following HS1 (91.13%, n = 185/203), while 147 patients underwent comprehensive stage II or bidirectional Glenn shunt (72.41%, n = 147/203). Tricuspid valvuloplasty was undertaken in nine patients (4.86%, n = 9/185). Ultimately, 100 patients underwent the Fontan procedure. The odds of development of significant TR and/or RV dysfunction were not statistically different throughout the stages of palliation (TR: odds ratio [OR] = 0.14-0.25, P = .5260; RV dysfunction: OR = 0.02-0.13, P = .3992). However, the risk of death and/or transplant was 2.5- to 3.8-fold when either were present alone or in combination (TR: OR = 2.58, P = .0356; RV dysfunction: OR = 3.84, P = .0262). Transplant-free survival at 15 years was 44.8%. Conclusion: Following hybrid palliation for HLHS, the majority of survivors have normal RV and TV functions. Tricuspid valvuloplasty was required in few patients. Once significant TR and/or RV dysfunction ensues, there is a two- to three-fold risk of death and/or transplant.

Mitral valve replacement (MVR) in children under 2 years is associated with significant morbidity and mortality. Decellularized porcine intestinal submucosa is a commercially available formulation of an extracellular matrix (ECM) with an indication for cardiac tissue repair. The present study reports our experience using ECM cylinder valves in patients for MVR. A retrospective review of patients under 2 years who underwent ECM custom-made cylinder mitral valve (ECM-MV) replacement was performed. Clinical, demographic, operative and post-operative follow-up data, including serial echocardiographic data are presented. Eight patients (age 5.6 ± 1.6 months; weight: 6.0 ± 1.1 kg) were identified who underwent ECM-MVR. There was one in-hospital death and no major neurological events. Six patients underwent replacement of their cylinder valve with either a Melody valve inside the ECM-MVR (n = 3), a mechanical valve (n = 2), or a decellularized bovine pericardial cylinder valve (n = 1). The mean time to replacement surgery was 8.4 ± 2.6 months after ECM-MV. The indications for replacement of ECM-MV included mitral stenosis/regurgitation (n = 4) or dehiscence (n = 2). One remaining patient is 24 months from ECM-MV, with trivial regurgitation and no stenosis. Mitral valve creation using ECM is an option for MVR in pediatrics, avoiding anticoagulation, and provides a suitable construct for later placement of a Melody valve, extending surgical and non-surgical options. However, the durability of the native ECM-MV in the mitral position is concerning considering the high re-intervention rate in a relatively short time period. Further studies are needed to determine the longer-term outcomes of this valve in this complex patient population.

BACKGROUND The HeartMate 3 ventricular assist device (VAD) is a newer centrifugal continuous-flow VAD used for bridge-to-transplant and destination therapy in adults. However, there is limited experience regarding its use in children and adults with complex congenital heart disease (CHD). METHODS The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a multicenter learning network comprised of pediatric hospitals implanting VADs in children and adults with complex CHD. We examined the outcomes of patients undergoing HeartMate 3 implantation at an ACTION center between December 2017 and September 2019. RESULTS The HeartMate 3 was implanted in 35 patients at 9 ACTION centers, with a median age of 15.7 (8.8–47.3) years, median weight of 65.7 (19.1–114.1) kg, and median body surface area (BSA) of 1.74 (0.78–2.36) m2. Of the cohort, 14 patients (40%) weighed CONCLUSIONS Use of the HeartMate 3 in ACTION centers was associated with a low incidence of mortality and adverse events. Patients as small as 19 kg (BSA 0.78 m2) were successfully implanted and supported, indicating that this device may be appropriate for older children and small adults.

Left ventricular noncompaction cardiomyopathy (LVNC) is a rare form of heritable cardiomyopathy with wide genotypic variability, numerous phenotypic variations, and a wide spectrum of clinical disease from asymptomatic to end stage heart failure. Here, we present a case of a 2-year-old boy who presented to their pediatrician with a cough as a first clinical sign of heart failure, rapidly progressing to severe heart failure. He was found to have mixed LVNC with a restrictive phenotype, a rare phenotype of this form of cardiomyopathy. Eventually, the patient was supported via mechanical circulation with a Berlin Heart EXCOR® ventricular assist device as bridge to successful cardiac transplantation. Genetic testing for inherited cardiomyopathies found a mutation in MYH7 (Arg369Gln), known to be associated with various forms of cardiomyopathy, but has not been reported in restrictive LVNC.

Introduction: Minimal data exist about the incidence and risk factors for arch intervention after Comprehensive Stage II (CSII). Goal of this study was to document incidence of arch interventions after CSII and determine if any differences existed between those that underwent an arch intervention (aiCSII) versus those did not have an intervention. Methods: Retrospective chart review of all hypoplastic left heart syndrome patients that underwent a CSII between 6/1/2005 through 2/1/2020 was performed. Univariate analysis was conducted in addition to principal components analysis (PCA). Results: One hundred patients were evaluated. Sixteen patients underwent 24 arch interventions. Age at initial arch reintervention was 1.3 + 1.2 years (median 1.0 years, range 0.5 - 2.2 years). Univariate analysis showed that the aiCSII group were more likely to be female, to have had a retrograde arch intervention post-hybrid procedure, and to be younger at time of CSII. On echocardiograms, aiCSII group had significantly higher pre-CSII patent ductus arteriosus velocities, arch velocities on their 1 st post-operative and discharge study post-CSII, and arch velocities pre-Fontan. Gradients were higher in the aiCSII via pre-Fontan catheterization. With PCA, echocardiographic and catheterization data remained significantly associated with aiCSII versus those that did not undergo an arch intervention (OR = 4.5 (1.9, 19.8), p < 0.01). Mortality was not associated with arch intervention. Conclusions: Incidence of arch intervention post-CSII was 16%. Echocardiographic arch gradients during the CSII hospitalization were the strongest predictors for subsequent aortic arch interventions. Further studies are needed to determine any modifiable variables that may reduce the incidence of arch interventions.

Infective endocarditis (IE) is an uncommon disease in children that, when present, is accompanied by significant morbidity and mortality. The presence of congenital heart disease often complicates management. The aim of the present study is to describe the characteristics and outcomes of children undergoing surgery for IE.A retrospective chart review from 2004 to 2020 was conducted to identify consecutive patients younger than age 20 years with IE undergoing surgery.A total of 94 patients with IE were identified, of whom 47 underwent surgery at a median age of 16.7 years. Thirty-one patients (65.95%) had congenital heart disease. Vegetation and embolic phenomena occurred in 41 and 29 patients (87.23% and 61.7%), respectively, with the brain as most common location (57.1%). Native valve involvement had a greater tendency to embolize (P .001). Staphylococcus spp was the most common organism (49%). The mitral valve was the most affected (31.9%). Seven (14.9%) patients had multivalvar involvement and valve replacement was the most common procedure performed (37 patients; 78.7%). There were 3 operative deaths (6.4%). Median length of hospital stay was 21 days. Risk factors for prolonged hospital stay were time to surgery in days (P .001) and native valvar involvement (P = .05). Five patients (10.6%) had postoperative recurrent IE. Survival at 1 and 5 years was 93.6% and 89.4%, respectively.Children with IE can undergo surgery with acceptable results. The morbidity, but not mortality, is driven by embolic complications. Staphylococcus spp and native valve involvement are significant risk factors. VIDEO ABSTRACT.

AIMS Cylinder mitral valve construct (cMVC) is new technique for replacing the mitral valve compared to more traditional mitral valve replacement (MVR) procedures. Goal of this study was to describe echocardiographic changes over time in patients undergoing a cMVC. Secondary goal was to compare echocardiographic changes in patients that underwent a cMVC to a group of patients that underwent a MVR. METHODS Retrospective analysis of patients undergoing a cMVC was performed. Demographics, discharge echocardiogram, and recent echocardiogram vales were evaluated. Age matched patients undergoing a MVR were assessed. Discharge and recent echocardiographic parameters were compared within the cMVC group. cMVC and MVR values were compared between groups. RESULTS Five cMVC patients were studied. Age at surgery for the cMVC was 4.3 ± 4.2 years (median 2.2, .8-10.3 years). Time interval from hospital discharge echocardiogram to the most recent echocardiogram was 1.2 ± .7 years (median 1.0, .6-2.0 years). Mean mitral valve gradient significantly increased over time (3.6 ± 3.0 mm Hg vs 7.6 ± 2.9 mm Hg). There were significant improvements in left ventricular diameters, systolic sphericity index, shortening fraction, and ejection fraction over time. There were no significant differences in demographics, discharge echocardiogram values, and follow up echocardiogram values between the cMVC and MVR groups. CONCLUSION In conclusion, echocardiographic indices of left ventricular function improved over time in patients undergoing cMVC. In addition, there were no significant differences between cMVC and MVR patients in echocardiographic values. Studies with a larger patient sample with longer follow up are needed to determine if cMVC continues to have comparable echocardiographic results to MVR.

While clinical status at the time of ventricular assist device (VAD) implant can negatively affect outcomes, it is unclear if early improvement after implant can have a positive effect. Therefore, the objectives of this study were to describe the clinical status of pediatric patients supported with a VAD and determine the impact of clinical status on the 1-month follow-up form on survival and ability to discharge. This was a retrospective analysis of data collected prospectively by the Pediatric Interagency Registry for Mechanical Circulatory Support Registry (Pedimacs) Registry. The Pedimacs database was queried for patients implanted between September 19, 2012, and September 30, 2019, who were alive on VAD support at 1-month postimplant on either a paracorporeal pulsatile or intracorporeal continuous device. Four factors on the 1-month follow-up were the focus of this study: mechanical ventilation, supplemental nutritional support, inotropic support, and ambulatory status. These factors were regarded as present if detected between 1-week and 1-month postimplant and were analyzed to determine their impact on survival following 1 month of VAD support and on successful discharge from hospital in patients with implantable continuous-flow devices. The eligible study cohort consisted of 414 patients with a mean age of 9.6 ± 6.2 years, weight of 40.8 ± 32.3 kg with the majority being male (56.7%) and having cardiomyopathy (68%). An isolated left ventricular assist device (LVAD) was the most common implant (85.5%). At implant, 40% were ventilated, 57% required nutritional support, 93% were on inotropes, and 58% were nonambulating. On the 1-month postimplant form, there were significant improvements in all four categories (14% ventilator support, 46% nutritional support, 53% on inotropes, and 25% nonambulating). However, there was no significant early change in the percentage of patients requiring supplemental nutrition in the paracorporeal pulsatile devices (88% vs. 82%; p = 0.2). Presence of these clinical parameters in early follow-up postimplant had a significant negative impact on survival and on the ability of patients with continuous-flow devices to be discharged. Presence of four specific clinical parameters early after VAD placement is associated with worse overall survival and an inability to discharge patients on VAD support. Ongoing work is needed for optimization of patients before implant and aggressive rehabilitation after implant to help improve long-term outcomes.

Button batteries (BBs) are found in many households and are a source of esophageal foreign body in the pediatric population. Upon ingestion, significant caustic injury can occur within 2 hours leading to tissue damage and severe, potentially fatal sequelae. Aortoesophageal fistula (AEF) is a rare complication that nearly always results in mortality. We report a rare case of a toddler who developed an AEF after BB ingestion and survived following staged aortic repair. There should be a high index of suspicion for this complication with the history of BB ingestion and presence of hematemesis, hemoptysis, or melena.

Introduction: A dilated main pulmonary artery (MPA) seen in congenital heart disease (CHD) or pulmonary arterial hypertension (PAH) is a rare cause of angina due to left main coronary artery (LMCA) compression. Case: A 49 year old male with no prior cardiac history presented with substernal chest pain. He reported exercise intolerance for several years. On exam he had an oxygen saturation of 85%, loud P2, fixed split second heart sound and ejection click. Electrocardiogram showed right ventricular (RV) hypertrophy and no significant ST changes. Laboratory data revealed a negative troponin. An enlarged main and right pulmonary artery (RPA) (Figure 1A) was seen on computed tomography (CT) chest angiography for pulmonary embolism (CTPE) and on echocardiography he had a severely dilated RV with decreased function (Figure 1B,1C). Cardiac catheterization showed a step up in saturations from 56 to 71%, Qp:Qs of 1.5 mean MPA pressure of 53 mmHg, pulmonary capillary wedge pressure of 11mmHg and pulmonary vascular resistance (PVR) of 7WU. A slit-like narrowing of LMCA ostium was seen on coronary angiography and intravascular ultrasound (Figure 1D). He was diagnosed with a sinus venosus defect, anomalous right upper pulmonary venous drainage and suspicion for extrinsic compression of LMCA by the dilated RPA that was confirmed on cardiac CT (Figure 1E-I). He was started on triple therapy for PAH with a significant reduction in PA pressures (mean 36 mmHg and PVR 2.1 WU). Percutaneous stenting of the LMCA was deferred and he underwent successful sinus venosus defect repair with a 5mm fenestrated patch, baffling of the anomalous pulmonary veins and a 32 mm interposition graft in the MPA with reduction plasty of MPA/RPA. Conclusion: This is an unusual presentation of unrepaired CHD with angina due to a compressed LMCA from a dilated pulmonary artery. Treatment of the underlying PAH as well as repair of the defect including reduction plasty of the MPA is a consideration for symptomatic relief.

Background: Curcumin is a polyphenol extracted from the turmeric plant which may have anti-inflammatory properties. We hypothesized that curcumin pretreatment would result in a reduction in inflammatory markers in a large animal model of extracorporeal support. Methods: A total of seven samples were obtained from three swine treated with curcumin and 16 samples were obtained from six swine in the control group (procedure terminated in two swine before last sample could be obtained). Results: Samples for interleukin (IL)-8 and IL-1b had concentrations below the limit of detection at all points and were discarded from further analysis. IL-6, tumor necrosis factor (TNF)-alpha, and intercellular adhesion molecule (ICAM)-1 concentrations were lower in curcumin pretreated animals when compared to control animals. This decrease was statistically significant for TNF-alpha, and ICAM-1. Conclusions: This project may provide information for the development of a translational study in humans as we noted that curcumin pretreatment in a large animal model of cardiopulmonary bypass (CPB) and extracorporeal support resulted in a decrease in TNF-alpha and ICAM-1 expression compared to control animals. Cardiol Res. 2018;9(1):7-10 doi: https://doi.org/10.14740/cr677w

Objective Adults with congenital heart disease may require heart transplantation for end-stage heart failure. Whereas heart transplantation potentially allows adults with congenital heart disease to resume their usual activities, employment outcomes in this population are unknown. Therefore, we investigated the prevalence and predictors of work participation after heart transplantation for congenital heart disease. Design Retrospective review of a prospective registry. Setting United Network for Organ Sharing registry of transplant recipients in the United States. Patients Adult recipients of first-time heart transplantation with a primary diagnosis of congenital heart disease, performed between 2004 and 2015. Interventions None. Outcome measures Employment status reported by transplant centers at required follow-up intervals up to 5 y posttransplant. Results Among 470 patients included in the analysis (mean follow-up: 5 ± 3 y), 127 (27%) worked after transplant, 69 (15%) died before beginning or returning to work, and 274 (58%) survived until censoring, but did not participate in paid work. Multivariable competing-risks regression analysis examined characteristics associated with posttransplant employment, accounting for mortality as a competing outcome. In descriptive and multivariable analysis, pretransplant work participation was associated with a greater likelihood of posttransplant employment, while the use of Medicaid insurance at the time of transplant was associated with a significantly lower likelihood of working after transplant (subhazard ratio compared to private insurance: 0.55; 95% confidence interval: 0.32, 0.95; P = .032). Conclusions Employment was rare after heart transplantation for congenital heart disease, and was significantly less common than in the broader population of adults with congenital heart disease. Differences in return to work were primarily related to pretransplant employment and the use of public insurance, rather than clinical characteristics.

Heparin-induced thrombocytopenia (HIT) can cause life-threatening complications following the administration of heparin. Discontinuation of all sources of heparin exposure and the use of alternative agents for anticoagulation are necessary when HIT is suspected or diagnosed. We present the successful use of bivalirudin anticoagulation in an adolescent patient during cardiopulmonary bypass who underwent both placement of a left ventricular assist device and subsequent heart transplantation within a 36-hour period. The pathophysiology and diagnosis of HIT are reviewed, previous reports of the use of direct thrombin inhibitors for cardiac surgery are presented, and potential dosing regimens for bivalirudin are discussed.

Young adult heart transplantation (HTx) recipients experience high mortality risk attributed to increased nonadherence to immunosuppressive medication in this age window. This study sought to test whether a high-risk age window in HTx recipients persisted in the absence of reported nonadherence.Heart transplantation recipients aged 2 to 40 years, transplanted between October 1999 and January 2007, were identified in the United Network for Organ Sharing database. Multivariable survival analysis was used to estimate influences of age at transplantation and attained posttransplant age on mortality hazard among patients stratified by center report of nonadherence to immunosuppression that compromised recovery.Three thousand eighty-one HTx recipients were included, with univariate analysis demonstrating peak hazards of mortality and reported nonadherence among 567 patients transplanted between ages 17 and 24 years. Multivariable analysis adjusting for reported nonadherence demonstrated lower mortality among patients transplanted at younger (hazards ratio, 0.813; 95% confidence interval, 0.663-0.997; P = 0.047) or older (hazards ratio, 0.835; 95% confidence interval, 0.701-0.994; P = 0.042) ages. Peak mortality hazard at ages 17 to 24 years was confirmed in the subgroup of patients with no nonadherence reported during follow-up. This result was replicated using attained age after HTx as the time metric, with younger and older ages predicting improved survival in the absence of reported nonadherence.Late adolescence and young adulthood coincide with greater mortality hazard and greater chances of nonadherence to immunosuppressive medication after HTx, but the elevation of mortality hazard in this age range persists in the absence of reported nonadherence. Other causes of the high-risk age window for post-HTx mortality should be demonstrated to identify opportunities for intervention.

Background: Patients with dilated cardiomyopathy often have progressive heart failure with systolic dysfunction, ventricular remodeling and clinical decompensation heralded by elevations of filling...

Outcomes for extracorporeal membrane oxygenation (ECMO) have been described for patients with single ventricle physiology (SVP) undergoing cavopulmonary connection (Glenn procedure). An alternative surgical pathway for patients with SVP consists of an initial hybrid procedure followed by a comprehensive Stage II procedure. No data exist describing the outcomes of patients requiring ECMO after the comprehensive Stage II procedure. The goal of this study is to describe the outcomes for patients who required ECMO after the comprehensive Stage II procedure. Data from the Extracorporeal Life Support Organization (ELSO) registry from 2001 to 2015 for children undergoing the comprehensive Stage II procedure older than 3 months of age were retrospectively analyzed. Demographics and ECMO characteristics were recorded. A total of six children required ECMO support after the comprehensive Stage II procedure (2 males, 4 females). Four patients had the diagnosis of hypoplastic left heart syndrome and two patients had the diagnosis of an unbalanced atrioventricular septal defect. Bypass time was 242.8 ± 110.9 min and cross-clamp time was 91.2 ± 46.2 min for the surgical procedure. Weight was 5.8 ± 1.3 kg and age was 150.2 + 37.9 days at time of ECMO. ECMO duration was 276.0 ± 218.1 h. Complications during the ECMO run included hemorrhage in four patients (67%), renal dysfunction in two patients (33%), and neurologic injury in two patients (33%). Four patients (67%) were discharged alive after ECMO decannulation. Despite being a much more extensive surgical procedure, the morbidity and mortality after ECMO in patients undergoing the comprehensive Stage II procedure are similar to those in patients undergoing the Glenn procedure. If needed, ECMO support is reasonable for patients after the comprehensive Stage II procedure.

Transplant center expertise improves survival after heart transplant (HTx) but it is unknown whether center expertise ameliorates risk associated with mechanical circulatory support (MCS) bridge to transplantation. This study investigated whether center HTx volume reduced survival disparities among pediatric HTx patients bridged with extracorporeal membrane oxygenation (ECMO), left ventricular assist device (LVAD), or no MCS. Patients ≤18 years of age receiving first-time HTx between 2005 and 2015 were identified in the United Network of Organ Sharing registry. Center volume was the total number of HTx during the study period, classified into tertiles. The primary outcome was 1 year post-transplant survival, and MCS type was interacted with center volume in Cox proportional hazards regression. The study cohort included 4131 patients, of whom 719 were supported with LVAD and 230 with ECMO. In small centers (≤133 HTx over study period), patients bridged with ECMO had increased post-transplant mortality hazard compared to patients bridged with LVAD (HR 0.29, 95% CI 0.12, 0.71; p = 0.006) and patients with no MCS (HR 0.33, 95% CI 0.19, 0.57; p < 0.001). Interactions of MCS type with medium or large center volume were not statistically significant, and the same differences in survival by MCS type were observed in medium- or large-volume centers (136–208 or ≥214 HTx over the study period). Post-HTx survival disadvantage of pediatric patients bridged with ECMO persisted regardless of transplant program volume. The role of institutional ECMO expertise outside the transplant setting for improving outcomes of ECMO bridge to HTx should be explored.

Mitral valve construction using decellularized bovine pericardium is a new procedure. A 10-month-old infant with neonatal Marfan syndrome underwent mitral valve replacement due to severe mitral regurgitation with a cylinder valve constructed from decellularized bovine pericardium. Nineteen months postoperatively the patient is clinically well with trivial mitral regurgitation, mild stenosis, and without need for anticoagulation.

Background Research on induction immunosuppression in patients undergoing combined heart-lung transplantation (HLTx) is limited. Methods The United Network for Organ Sharing database was queried from 2000 to 2013 to examine the influence of induction immunosuppression for combined HLTx in adult (≥18 years) and adolescent (≥12 and

Background Pre-lung transplant (LTx) panel reactive antibody (PRA) levels are associated with adverse outcomes in adult LTx recipients, but their impact in pediatric LTx recipients is unknown. Methods The United Network for Organ Sharing registry was queried from 2004 to 2013 to compare survival between pediatric LTx recipients with PRA class I and II levels = 0 versus > 0. Results Overall, 333 pediatric LTx recipients had data on class I or II PRA and were included in the analysis. Univariate analysis demonstrated that PRA > 0 was not associated with survival benefit for class I (hazard ratio [HR] = 0.985; 95% confidence interval [CI]: 0.623, 1.555; p = 0.947) or class II (HR = 1.080; 95% CI: 0.657, 1.774; p = 0.762) PRA. Multivariate Cox models confirmed no significant association with mortality hazard for both class I (HR = 1.230; 95% CI: 0.641, 2.363; p = 0.533) and class II (HR = 0.847; 95% CI: 0.359, 1.997; p = 0.704) PRA. Multivariate logistic regression models identified no association between class I or class II and acute rejection within 3 years of LTx. Conclusions Pretransplant class I and II PRA levels > 0 were not associated with mortality or acute rejection in pediatric LTx recipients.

Mitral valve construction using extracellular matrix (ECM) is a relatively new procedure. In this case, a 15-month-old boy with a history of severe mitral valve regurgitation secondary to endocarditis underwent mitral valve surgery. Mitral valve repair was not possible, and thus, a 17 mm extracellular matrix cylinder valve (ECM-CV) was constructed for valve replacement. The ECM-CV is clearly imaged using echocardiography, especially three-dimensional imaging, that helped define valve function. As the use of ECM for valve construction increases, echocardiography will play an essential role in evaluating the function and mechanics of these novel valves.

BACKGROUND The reported ventricular assist device (VAD) experience in the pediatric congenital heart disease (CHD) population is limited. We sought to describe contemporary use and outcomes of VADs in children with CHD and compare these outcomes to those of non-CHD children. METHODS Patients enrolled in the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) between September 19, 2012 through June 30, 2017 were included. CHD was classified as biventricular vs single ventricle (Stages 1, 2, or 3). Outcomes were compared between groups and multivariable analysis was used to identify factors associated with mortality on the device. RESULTS Among the 471 patients enrolled, 108 (24%) had CHD (45 biventricular and 63 single ventricle). CHD patients were younger (5.7 ± 5.7 years vs 9.8 ± 6.5 years; p < 0.0001) and smaller (0.8 ± 0.5 m2 vs 1.2 ± 0.7 m2; p < 0.0001) compared with non-CHD patients. CHD patients were more likely to receive a paracorporeal continuous-flow VAD (36.1% vs 12.9%; p < 0.0001) and less likely to receive an implantable continuous-flow VAD (27.8% vs 55.0%; p < 0.0001) compared with non-CHD patients. After 6 months on a VAD, CHD patients had higher mortality (36.4% vs 12.1%) and a lower transplantation rate (29.1% vs 59.9%) than non-CHD patients (p < 0.0001). In the multivariable analysis, CHD was the factor most strongly associated with mortality on VAD (hazard ratio [HR] = 2.9; p < 0.0001), whereas the factors implantable continuous-flow device and high-volume center were protective (HR = 0.3, p < 0.0001, and HR = 0.6, respectively; p = 0.02). CONCLUSIONS VAD use in children with CHD is associated with increased mortality and decreased transplant rates compared to children without CHD. For the subgroup of children with CHD who received implantable continuous-flow VADs, survival rates were higher and comparable to those of children without CHD. Increased experience correlated with better survival in pediatric VADs.

Purpose We sought to describe the off-label use to date of an intracorporeal, centrifugal, continuous flow ventricular assist device (cfVAD) characterized by a magnetically levitated impeller in US pediatric cardiac centers, in order to further inform device selection quality improvement initiatives. Methods Members of the ACTION (Advanced Cardiac Therapies Improving Outcomes Network) collaborative whose centers implanted ≥1 intracorporeal magnetically levitated cfVAD were identified. Centers submitted de-identified data on each implant through 10/21/18. Results are reported as count (percentage) or median (range) for summary statistics. Results Fourteen implants occurred at 6 centers; the number of implants per center was 1 - 4. Thirteen patients (93%) had dilated cardiomyopathy (DCM); one patient (7%) had congenital heart disease (CHD) with a Fontan circulation. Of the DCM patients, 3 had neuromuscular disease (2 with Duchenne and 1 with Becker muscular dystrophy). Device strategy included bridge to transplant in 8/14 (57%), bridge to candidacy in 4/14 (29%), and destination therapy in 2/14 (14%). Median age at implant was 15 y (12 y - 24 y), with median weight 70 kg (31 kg - 118 kg) and median body surface area (BSA) 1.8 m2 (1.3 m2 - 2.4 m2). Most patients (10/14, 71%) were INTERMACS category 2 at implant; 3/14 (21%) were category 3 and 1/14 (7%) was category 4. No biVADs were placed. Median support time was 32 d (5 d - 315 d). To date, 5/14 (36%) patients were discharged, 1/14 (7%) underwent heart transplantation, and 1/14 (7%) died on VAD support; the remainder are hospitalized with the device in place. For discharged patients, median hospital length of stay after implant was 26 d (12 d - 37 d). There were no episodes of stroke or pump thrombosis. Conclusion The intracorporeal, centrifugal, magnetically levitated cfVAD is a newer device being used with increasing frequency in the pediatric and CHD population. Utilization of the device has largely been limited to older, larger children with DCM. This preliminary data will contribute to our understanding of device selection in order to improve outcomes.

Graphical abstract, Highlights • Adult congenital patients with tetralogy of Fallot require life long follow-up. • Early left ventricular dysfunction in repaired tetralogy of Fallot warrants evaluation. • Multimodality imaging should be used when unusual echocardiography findings are present.

Objective To quantify outcomes of infants ( Study design MEDLINE (PubMed), Scopus, and Web of Science were searched through February 1, 2017, with no language restrictions. Publications including infants diagnosed with primary PVS, defined as the absence of preceding intervention(s), were considered. The study was performed according to Meta-analysis of Observational Studies in Epidemiology guidelines, the Systematic Reviews, and Meta-Analysis checklist, and registered prospectively. The quality of selected reports was critically examined. Data extraction was independently performed by multiple observers with outcomes agreed upon a priori. Data were pooled using an inverse variance heterogeneity model with incidence of mortality the primary outcome of interest. Results Forty-eight studies of 185 infants were included. Studies were highly diverse with regards to the participants, interventions, and outcomes reported. The median (range) age at diagnosis was 5.0 (0.1-11.6) months. Pooled mortality was 58.5% (95% CI 49.8%-67.0%, I2 = 21.4%). We observed greater mortality incidence among infants with 3 or 4 vein stenoses than in those with 1 or 2 vein stenoses (83.3% vs 36.1%; P Conclusions Studies of primary PVS during infancy are highly variable in their methodological quality and estimates of clinical outcomes; therefore, estimates of prognosis remain uncertain. Multicenter, interdisciplinary collaborations, including alignment of key outcome measurements, are needed to answer questions beyond the scope of available data.

SummaryBackground The transfusion of blood products in the setting of uncontrolled bleeding is unquestionably lifesaving. However, in many instances, the decision to transfuse is based on physician gestalt rather than medical evidence. When indications for transfusion are unclear, the benefits of blood products must be balanced against their significant risks and associated costs. As our institution is a referral center for patients of Jehovah's Witness faith, this population has pushed our development of techniques to achieve the goal of bloodless surgery. Our practices in caring for this population have become our standard practice for managing all patients undergoing congenital cardiac surgery. Objectives To evaluate our success in minimizing the use of blood products during pediatric cardiac surgery. Methods After IRB approval, we retrospectively reviewed all patients who underwent cardiac surgery utilizing cardiopulmonary bypass (CPB), for biventricular repair procedures. The study was conducted at a single institution (Nationwide Children's Hospital (NCH)) during the period: January 1, 2013 and December 31, 2013. Results A total of 209 patients were included. Overall, 81 patients (38.8%) and 81 of 136 (59.6%) weighing more than 6 kg received no blood products (bloodless) during their entire hospital stay. Bloodless surgery was most successful in patients weighing more than 18 kg, followed by patients weighing 6–18 kg. All 73 patients who weighed

A number of materials have been used for the repair of congenital heart disease. However, an ideal material is yet to be discovered. Decellularized extracellular matrix from porcine small intestinal submucosa (CorMatrix) has been developed and commercialized as a biological tissue substitute. This has been used for valvuloplasty, sepal defect repair, or angioplasty as a patch. In this study, we demonstrate our preliminary experience using CorMatrix as a tube graft. A retrospective review of 13 patients who underwent cardiac surgery using CorMatrix as an interposition graft was performed (10 patients for central pulmonary artery reconstruction in comprehensive stage II surgery for hypoplastic left-sided heart syndrome and 3 patients for aortic arch reconstruction in interrupted aortic arch). At a mean follow-up of 9.7 months, 8 of 10 patients who underwent central pulmonary artery reconstruction using CorMatrix tube showed progressive significant stenosis. One patient underwent replacement of the CorMatrix tube with a homograft because of severe stenosis after the placement of a stent. All 3 patients who had aortic arch reconstruction with the CorMatrix tube demonstrated no stenosis, no dilatation, and no aneurysm formation. Although angioplasty using CorMatrix as an interposition tube vascular graft demonstrated no adverse event in the aortic position in short term, a high rate of intimal hyperplasia formation with significant stenosis was found in the low-pressure small-diameter system. Longer follow-up is required to assess the growth potential of the arterial conduit. CorMatrix may not be the ideal material as conduit in the low-pressure small-diameter system to provide long-term durable outcomes.

Direct mechanical ventricular actuation (DMVA) exerts direct cardiac compression/decompression and does not require blood contact. The safety and effects of DMVA support in chronically dysfunctional beating hearts in vivo have not been established. This study evaluated hemodynamics and load-independent systolic/diastolic cardiac function before/after acute support (2 hours) using DMVA in small hearts with induced chronic failure. Chronic heart failure was created in seven small dogs (15 ± 2 kg) via either serial coronary microembolizations or right-ventricular overdrive pacing. Dogs were instrumented to measure cardiac output, hemodynamic pressures, left ventricular volumes for pressure-volume analysis via preload reduction. Temporary cardiac support using a DMVA device was instituted for 2 hours. Hemodynamic and mechanical assessments, including dobutamine dose-responses, were compared both before and after support. Hemodynamic indices were preserved with support. Both left-ventricular systolic and diastolic function were improved postsupport, as the slopes of the preload-recruitable stroke work (+29 ± 7%, p < 0.05) and the end-diastolic pressure-volume relationship (EDPVR: -28 ± 9%, p < 0.05) improved post-DMVA support. Diastolic/systolic myocardial reserve, as assessed by responsiveness to dobutamine challenges, was preserved after DMVA support. Short-term DMVA support can safely and effectively sustain hemodynamics, whereas triggering favorable effects on cardiac function in the setting of chronic heart failure. In particular, DMVA support preserved load-independent diastolic function and reserve.

Rationale: The objective of this autopsy study was to determine whether gastrointestinal angiodysplasia develops during continuous-flow left ventricular assist device (LVAD) support. Objective: LVAD support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support itself may cause angiodysplasia. The relationship to abnormal vWF metabolism is unknown. We tested the hypothesis that abnormal gastrointestinal vascularity develops during continuous-flow LVAD support. Methods and Results: Small bowel was obtained from deceased humans, cows, and sheep supported with a continuous-flow LVAD (n=9 LVAD, n=11 control). Transmural sections of jejunum were stained with fluorescein isothiocyanate–conjugated isolectin-B4 for endothelium to demarcate vascular structures and quantify intestinal vascularity. Paired plasma samples were obtained from humans before LVAD implantation and during LVAD support (n=41). vWF multimers and degradation fragments were quantified with agarose and polyacrylamide gel electrophoresis and immunoblotting. Abnormal vascular architecture was observed in the submucosa of the jejunum of human patients, cows, and sheep supported with a continuous-flow LVAD. Intestinal vascularity was significantly higher after LVAD support versus controls (5.2±1.0% versus 2.1±0.4%, P =0.004). LVAD support caused significant degradation of high–molecular-weight vWF multimers (–9±1%, P P P Conclusions: Abnormal intestinal vascular architecture and LVAD-associated vWF degradation were consistent findings in multiple species supported with a continuous-flow LVAD. These are the first direct evidence that LVAD support causes gastrointestinal angiodysplasia. Pathologic vWF metabolism may be a mechanistic link between LVAD support, abnormal angiogenesis, gastrointestinal angiodysplasia, and bleeding.

Extracorporeal membrane oxygenation (ECMO) is an accepted treatment modality for life support refractory to conventional efforts in neonates with complex congenital heart lesions. Cannulation for ECMO can be accomplished by venovenous (VV) access where patients receive primarily respiratory support or venoarterial (VA) access which provides complete cardiopulmonary support. VV ECMO delivered by a single-vessel cannulation with a dual-chamber venous cannula allows for respiratory support while the patient remains dependent upon intrinsic cardiac function to support hemodynamics. We present a case of support of a newborn with single ventricle physiology and intraparenchymal near-atresia of the pulmonary veins using VV ECMO.

Background Healthcare-associated infections are a major focus for quality improvement in hospitals today. Surgical site infections (SSIs), a postoperative complication in cardiac surgery, are associated with increased morbidity, mortality, hospital length of stay, and financial burden. Methods A recent increase in cardiothoracic surgery SSIs (CT-SSIs) at our institution instigated a multidisciplinary team to explore infection prevention, bundle element compliance, and to identify interventions to reduce the CT-SSI rate. Key interventions included preoperative screening and decolonization of methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus with repeated intranasal applications of mupirocin, universal skin prep with chlorhexidine for all patients, and additional antibiotic dosing upon initiating cardiopulmonary bypass. Results In 2014, the CT-SSI rate at our institution was 1.9/100 cases, which increased during the "intervention period" to 3.6 infections/100 cases in 2015 (16 total infections). Postinterventions, the CT-SSI rate decreased to 0.3 infections/100 cases (2 total infections), which was significantly lower than our baseline before the spike in infection rate. Conclusions A comprehensive interdisciplinary approach with multiple interventions was successful in significantly reducing the CT-SSI rate in cardiothoracic surgery at a tertiary care pediatric hospital.

Congenital heart disease (CHD) is the most common birth defect with treatment known to consume considerable resources. As the delivery model in healthcare shifts from volume to a value based system, pressure exists to improve quality while reducing cost. Reduction in length of stay (LOS) is

Mechanical mitral valve replacement in the pediatric population is associated with significant morbidity and mortality. Decullularized porcine intestinal submucosa is a commercially available formulation of an extracellular matrix (ECM) that has an indication for cardiac tissue repair. Cylinder

Venous aneurysms are rare clinical entities, particularly in children, and their presentation and natural history often depend on the anatomical location and underlying etiology. We present a single case of a 12-year-old girl who presented with a palpable right supraclavicular mass. Imaging evaluation with CT, conventional venography, MRI and sonography revealed a large fusiform subclavian vein aneurysm with an unusual, mass-like fibrofatty component incorporated into the vessel wall. The girl ultimately required complete resection of the right subclavian vein with placement of a synthetic interposition graft. This case provides a radiology/pathology correlation of an entity that has not previously been described as well as an example of the utility of multiple imaging modalities to aid diagnosis and preoperative planning.

Extracorporeal membrane oxygenation (ECMO) is an established therapy for primary graft dysfunction (PGD) in adults after lung transplant, while venovenous (VV) ECMO is an evolving therapy that can bridge patients to lung transplantation. This report describes a case of relatively quick improvement of grade 3 PGD, based on the PaO2/FIO2 (P/F) ratio, in a 17-year-old patient with cystic fibrosis who was bridged to lung transplantation with ambulatory VV ECMO and then received support with VV ECMO as a protective strategy during the initial phases of PGD after lung transplantation.

We report the SAR around a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. 2-Aminophenethyl analogs demonstrate excellent potency but moderate kinase selectivity, while 2-aminobenzyl analogs that fill the Ala571 subpocket exhibit good inhibition activity and excellent kinase selectivity.

A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring.

We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall.

(Echocardiography 2014;31:E264–E266)Key words: CorMatrix, tricuspid valve, extracellular matrix graft, bioprosthetic valve, echocardiogra-phy, three-dimensional echocardiographyA 26-year-old woman with the diagnosis of adysplastic tricuspid valve was referred for surgicalcorrection due to increasing frequency of dysp-nea on exertion and presyncopal symptoms.Preoperative transthoracic echocardiogram doc-umented severely dilated right-sided chambersand severe tricuspid regurgitation (movie clipS1). The patient was clear that if a repair wasunsuccessful, she did not want a mechanicalvalve replacement.In the operating room, preoperative trans-esophageal echocardiography (TEE) (Vivid I, GEHealthcare, Wauwatosa, WI, USA) again demon-strated severe tricuspid regurgitation (movie clipS2). Initial attempts at repair with closure of mul-tiple leaflet fenestrations as part of performing amodified cone repair and then additionallydownsizing the annulus with a 36-mm tricuspidvalve annuloplasty ring were attempted but ulti-mately failed due to abnormal anterior leafletattachment to the dilated right ventricular (RV)free wall. A custom-made 34-mm extracellularmatrix cylinder valve (ECM-CV; CorMatrix Car-diovascular, Roswell, GA, USA) was used forreplacement. The cylinder valve was constructedfrom a single sheet of ECM fashioned into a cylin-der with a valve height of 1.5 times that of thediameter. It was sewn in circumferentially at theannulus and tacked with pledgeted suture to theRV septum, the RV free wall (there was no ante-rior papillary muscle and the moderator bandwas too remote) and the true posterior papillarymuscle. TEE showed no tricuspid regurgitation inone view (movie clip S3, Fig. 1) and moderateregurgitation in another view (movie clip S4,Fig. 2). Thus, the mechanism of regurgitationwas not entirely clear. Three-dimensional (3D)images clearly showed the mechanism ofregurgitation was through a central coaptationpoint and not due to another mechanism (movie

A 16-year-old male patient underwent bilateral pulmonary embolectomy complicated by reperfusion injury and acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation support using a bicaval double-lumen catheter. A unique hemodynamic profile developed consistent with tamponade but without an associated decrease in venovenous extracorporeal membrane oxygenation pump flow, improved venovenous extracorporeal membrane oxygenation circuit preload, and decreased recirculation. The use of newer bicaval double-lumen catheters can result in old problems presenting in new ways and require clinicians to be ever vigilant.