Aortic growth after arch reconstruction with patch augmentation: a 2-decade experience.

OBJECTIVES: Optimal aortic sizing during aortic arch reconstruction remains unknown. Negative effects of arch under- or oversizing are well-published. We aimed to characterize longitudinal aortic growth after patch-augmented arch reconstruction to identify the initial reconstructed arch size that results in normal mid-term arch dimensions. METHODS: Single-centre, retrospective review of infants undergoing Damus-Kaye-Stansel (DKS) or non-DKS patch-augmented aortic arch reconstruction between 2000 and 2021. Ascending aorta, proximal and distal transverse arch, aortic isthmus (AIsth) and descending aorta dimensions were measured in postoperative echocardiograms (<3 months from index operation) and cross-sectional imaging (>12 months). Longitudinal changes to aortic dimensions and z-scores were analysed. Secondary outcomes included reintervention, valve and ventricular function, mortality and transplantation. RESULTS: Fifty-four patients (16 DKS, 38 non-DKS) were included. At 6.3 [2.2, 12.0]-year follow-up, all aortic segments grew significantly in both groups, while z-scores remained unchanged except for non-DKS proximal and distal transverse arch z-scores, which significantly increased (P < 0.05 each). When stratified by initial postoperative z-score (z < -1, -1 ≤ z ≤ 1, z > 1), non-DKS patients with initial AIsth z-score <-1 had a final z-score significantly smaller than both the targeted z-score zero (P = 0.014) and final z-score in a group with initial postoperative z-score ±1 (P = 0.009). Valve and ventricular function remained stable. Eighteen patients required reintervention, 1 died and 1 underwent transplant. CONCLUSIONS: Over mid-term follow-up, aortic growth after arch reconstruction with patch augmentation was proportional when repaired to normal z-score dimensions, aside from proximal transverse arch, which disproportionately dilated. AIsth undersizing prevailed mid-term and trended towards a higher reintervention rate. Initial reconstruction between z-score 0 and +1 resulted in maintenance of that z-score size at mid-term follow-up. Overall, it is crucial to achieve targeted aortic sizing at index operation to maintain appropriate aortic dimensions over time and reduce reintervention risk with specific focus on the AIsth.

Staged ventricular recruitment and biventricular conversion following single-ventricle palliation in unbalanced atrioventricular canal defects.

Objective: Restoration of biventricular circulation is an alternative management strategy in unbalanced atrioventricular canal defects (uAVCDs), especially in patients with risk factors for single-ventricle palliation (SVP) failure. When ventricular volume is inadequate for biventricular circulation, recruitment procedures may accommodate its growth. In this study, we review our uAVCD experience with biventricular conversion (BIVC) after prior SVP. Methods: This is a single-institution, retrospective cohort study of uAVCD patients who underwent BIVC after SVP, with staged recruitment (staged) or primary BIVC (direct) between 2003 to 2018. Mortality, unplanned reinterventions, imaging, and catheterization data were analyzed. Results: Sixty-five patients underwent BIVC from SVP (17 stage 1, 42 bidirectional Glenn, and 6 Fontan). Decision for conversion was based on poor SVP candidacy (n = 43) or 2 adequately sized ventricles (n = 22). Of the 65 patients, 20 patients underwent recruitment before conversion. The staged group had more severe ventricular hypoplasia than the direct group, reflected in prestaging end-diastolic volume z scores (-4.0 vs -2.6; P < .01), which significantly improved after recruitment (-4.0 to -1.8; P < .01). Median follow-up time was 1.0 years. Survival and recatheterizations were similar between both groups (hazard ratio, 0.9; 95% CI, 0.2-3.7; P = .95 and hazard ratio, 1.9; 95% CI, 0.9-4.1; P = .09), but more reoperations occurred with staged approach (hazard ratio, 3.1; 95% CI, 1.3-7.1; P = .01). Conclusions: Biventricular conversion from SVP is an alternative strategy to manage uAVCD, particularly when risk factors for SVP failure are present. Severe forms of uAVCDs can be converted with staged BIVC with acceptable mortality, albeit increased reinterventions, when primary BIVC is not possible.

Exploratory Use of Glycoprotein IIb/IIIa Inhibition in Prevention of Blalock-Taussig Shunt Thrombosis.

OBJECTIVES: Morbidity and mortality related to modified Blalock-Taussig shunt (mBTTS) thrombosis remain a significant risk. Platelet inhibition following mBTTS may reduce this risk. However, oral antiplatelet agents have variable absorption following surgery. We determine risk factors for mBTTS thrombosis and hypothesize that IV glycoprotein IIb/IIIa inhibitor (tirofiban) as a bridge to oral aspirin reduces the rate of shunt thrombosis in the immediate postoperative period. End points within the 14-day follow-up period include mBTTS thrombosis, overall thrombosis, bleeding, length of stay, and mortality. DESIGN: Retrospective, Institutional Review Board-approved cohort study. SETTING: Single-center cardiac ICU. PATIENTS: Patients under the age of 18 who had an mBTTS placed within the study period of January 2008 to December 2018 were included. INTERVENTIONS: Patients were divided into two groups: standard of care (SOC) anticoagulation alone and SOC with tirofiban as a bridge to oral aspirin. MEASUREMENTS AND MAIN RESULTS: Freedom from mBTTS thrombosis was estimated using the Kaplan-Meier method. A multivariable predictive model using the four most significant risk factors was developed using logistic regression. A total of 272 patients were included: 36 subjects in the SOC/tirofiban group and 236 in the SOC group. Shunt thrombosis occurred in 26 (11%) SOC group with zero in SOC/tirofiban group ( p = 0.03). The median time to thrombosis was 0 days (range, 0-12 d). The area under the curve for the predictive model (anticoagulation group, history of coagulopathy, intraoperative shunt clipping, and shunt size/weight ratio) is 0.790 ( p < 0.001). Prevalence of bleeding and mortality was not significantly different between the groups. CONCLUSIONS: Highest risk for shunt thrombosis following mBTTS occurs within the first few days after surgical procedure. Tirofiban is a safe addition to SOC and may be an effective strategy to prevent early mBTTS thrombosis.

Restriction of Atrial Septal Defect Leads to Growth of Hypoplastic Ventricle in Patients with Borderline Right or Left Heart.

Patients with borderline hypoplastic right or left ventricle and VSD may be candidates for either single ventricle palliation or staged ventricular recruitment (SVR) followed by eventual biventricular conversion. Components of SVR include restriction of atrial septal defects (ASD) without ventricular septal defects (VSD) closure and addition of accessory pulmonary blood flow. This study evaluated the impact of ASD restriction on ventricular growth and function. We retrospectively reviewed patients with borderline ventricular hypoplasia and VSD who underwent a staged ventricular recruitment (SVR) procedure from 2012 to June 2019. Pre- and post-recruitment MRI and echocardiogram data were compared and analyzed. We excluded cases in which we intentionally restricted VSD with simultaneous ASD restriction. Forty-six patients (41 with right-dominant ventricle, 25 with risk factors for Fontan procedure) underwent SVR at a median age of 15.1 months' (interquartile range (IQR), 7.2-37.2 months'). The median indexed ventricular end-diastolic volume, end-systolic volume, and stroke volume according to cardiac MRI significantly increased at median 11.0 months' (IQR:7.8~14.1 months') after recruitment. Among them, except 2 operative mortalities after SVR, 26 patients underwent bi-ventricular repair (56.5% including one and a half ventricle repair) at a median of 8.0 months' (IQR: 6.2-12.2 months') after recruitment. Fifteen patients await biventricular completion, and 3 patients underwent single ventricle palliation. Pulmonary blood flow (Qp) tended to increase after recruitment regardless of type of pulmonary blood flow modification without statistical significance. Six patients died at a median duration of 6.5 months' (IQR: 2.9-11.7) after SVR; 3 patients died after biventricular completion, 2 after recruitment, and 1 after returning to single ventricle palliation. All of them were considered poor Fontan candidates due to severe atrioventricular valve regurgitation, pulmonary hypertension, pulmonary vein stenosis, or airway stenosis. Restriction of the atrial septum leads to the growth of hypoplastic ventricle in patients with ventricular septal defects who undergo SVR regardless of the preoperative characteristics, and eventual biventricular repair can be performed in a subgroup of these patients. Future work is necessary to optimize timing of SVR and method of accessory pulmonary blood flow.

Patch augmentation of small ascending aorta during stage I procedure reduces the risk of morbidity and mortality.

OBJECTIVES: Hypoplastic left heart syndrome (HLHS) with aortic atresia (AA) patients are prone to coronary insufficiency due to a small ascending aorta. Prophylactic patch augmentation of the small ascending aorta during the stage I procedure (S1P) may reduce the risk of coronary insufficiency as marked by ventricular dysfunction, need for extracorporeal membrane oxygenator (ECMO) support or mortality. METHODS: Retrospective analysis of patients with HLHS with AA who underwent an S1P was completed. Baseline ascending aorta size, right ventricular (RV) function and outcome variables of transplant-free survival, ECMO support after the stage 1 operation and RV function at the time of the bidirectional Glenn and latest follow-up were collected. RESULTS: Between January 2010 and April 2020, 11 patients underwent prophylactic ascending aorta augmentation at the time of the S1P as a planned portion of the procedure. A total of 125 patients underwent S1P during this period as a comparison. Overall survival was 100% for the augmented group and 74% for the control group (P = 0.66). A composite end point of transplant-free survival, no post-S1P ECMO and less than moderate RV dysfunction was created. At the time of BDG, this composite end point was 100% for the augmented group and 61.8% for the control group (P = 0.008) and at most recent follow-up was 100% for the augmented group and 59.3% for control (P = 0.007). Eight patients required a rescue procedure for the clinical evidence of coronary insufficiency following S1P that included ascending aorta patch augmentation or stent placement. When comparing these rescue versus prophylactic ascending aortic augmentations, there were also differences in the composite outcome 100% for augmented and 60% for rescue (P = 0.009) and at the time of most recent follow-up 100% for augmented and 50% for rescue (P = 0.029). CONCLUSIONS: Prophylactic patch augmentation of the ascending aorta in HLHS patients with AA may reduce the risk of mortality, ECMO and reduced RV function. Patients not initially undergoing augmentation but then requiring a rescue procedure have particularly poor outcomes. Patch augmentation for smaller ascending aortic diameters should be considered and further clinical experience may help delineate aorta diameter threshold for augmentation.

Biventricular conversion after Fontan completion: A preliminary experience.

OBJECTIVE: To assess the feasibility and outcomes of biventricular conversion following takedown of Fontan circulation. METHODS: Retrospective analysis of patients who had takedown of Fontan circulation and conversion to biventricular circulation at a single center from September 2007 to April 2020. Failing Fontan physiology was defined as Fontan circulation pressure >15 mm Hg and/or the presence of associated complications. RESULTS: Biventricular conversion was performed in 23 patients at a median age of 10.0 (7.5-13.0) years. Indications included failing Fontan physiology in 15 (65%) and elective takedown in 8 (35%) patients. A subset of patients (n = 6) underwent procedures for staged recruitment of the nondominant ventricle before conversion. Median z score of end-diastolic volume of borderline ventricle before takedown was -2.3 (-3.3, -1.3). Hypoplastic left heart syndrome (P < .01) and sub-/aortic stenosis (P < .01) were more common in these patients. Biventricular conversion with or without staged ventricular recruitment led to a significant increase in indexed end-diastolic volume (P < .01), indexed end-systolic volume (P < .01), and ventricular mass (P < .01) of the nondominant ventricle (14 right, 9 left ventricle). There were 5 (22%) deaths (1 [4%] early death). All who underwent elective biventricular conversion survived, whereas 2-year survival rate for patients with a failing Fontan circulation was 72.7% (95% confidence interval, 37%-90%). The overall, 3-year reoperation-free survival was 86.7% (95% confidence interval, 56%-96%). Left dominant atrioventricular canal defect (P < .01) and early era of biventricular conversion (P = .02) were significant predictors for mortality. CONCLUSIONS: A primary as well as a staged biventricular conversion is feasible in patients who have had previous Fontan procedure. Although this provides an alternative to transplantation in patients with failing Fontan, outcomes are worse in those with failing Fontan compared with elective takedown of Fontan circulation. Optimal timing needs further evaluation.

Management of Congenitally Corrected Transposition of the Great Arteries With Intact Ventricular Septum: Anatomic Repair or Palliative Treatment?

[Figure: see text].

Super Glenn for staged biventricular repair: impact on left ventricular growth?

OBJECTIVES: The Super Glenn procedure involves targeted increased in blood flow to left sided heart structures with fenestrated atrial septation. The objective of this study was to examine the outcomes of patients who had this procedure as a part of biventricular staging and specifically evaluate the effect on dimensions of left heart structures. METHODS: Data for patients who had this procedure between 2005 and 2019 were retrospectively identified. RESULTS: Thirty-seven patients were identified. Most common diagnosis was hypoplastic left heart syndrome in 40% (n = 15). On echocardiography, the median mitral valve z score was -2.26. On cardiac magnetic resonance imaging, median indexed left ventricular end-diastolic volume was 31.5 ml/m2 and mitral/tricuspid inflow ratio was 0.35. The median age at Super Glenn was 2.3 years (interquartile range 1.5-3.6) while median weight was 12 kg (interquartile range 9.8-14). There were no early/hospital deaths. The median intensive care unit length of stay was 4 days, and median hospital length of stay was 10 days. Median follow-up for the entire cohort was 3 years (range 15 days to 13.2 years). There was a statistically significant increase in indexed left ventricular dimensions. There were 5 deaths (14%). Three patients (8%) underwent heart transplant. Freedom from death/transplant was 79% at 5 years. Seven patients (19%) needed a reoperation. Twenty-three patients (62%) underwent biventricular conversion after a median of 11.3 months after Super Glenn. CONCLUSIONS: The Super Glenn procedure achieves consistent increase in left ventricular dimensions. This may be a useful strategy to help achieve a successful biventricular circulation in patients with borderline left ventricle. The superiority/non-inferiority of this approach over the conventional Fontan pathway is unclear.

Human endothelial colony-forming cells provide trophic support for pluripotent stem cell-derived cardiomyocytes via distinctively high expression of neuregulin-1.

The search for a source of endothelial cells (ECs) with translational therapeutic potential remains crucial in regenerative medicine. Human blood-derived endothelial colony-forming cells (ECFCs) represent a promising source of autologous ECs due to their robust capacity to form vascular networks in vivo and their easy accessibility from peripheral blood. However, whether ECFCs have distinct characteristics with translational value compared to other ECs remains unclear. Here, we show that vascular networks generated with human ECFCs exhibited robust paracrine support for human pluripotent stem cell-derived cardiomyocytes (iCMs), significantly improving protection against drug-induced cardiac injury and enhancing engraftment at ectopic (subcutaneous) and orthotopic (cardiac) sites. In contrast, iCM support was notably absent in grafts with vessels lined by mature-ECs. This differential trophic ability was due to a unique high constitutive expression of the cardioprotective growth factor neuregulin-1 (NRG1). ECFCs, but not mature-ECs, were capable of actively releasing NRG1, which, in turn, reduced apoptosis and increased the proliferation of iCMs via the PI3K/Akt signaling pathway. Transcriptional silencing of NRG1 abrogated these cardioprotective effects. Our study suggests that ECFCs are uniquely suited to support human iCMs, making these progenitor cells ideal for cardiovascular regenerative medicine.

Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury.

OBJECTIVES: To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI). METHODS: A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control). RESULTS: Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO-defined as freedom from ECMO reinstitution within 1 week after initial separation-was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (-23.0%; range, -20.0% to -28.8%) compared with the Control group (-16.8%; range, -13.0% to -18.4%) (P = .03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P = .04) CONCLUSIONS: In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI.

Platelet Inhibition With IV Glycoprotein IIb/IIIa Inhibitor to Prevent Thrombosis in Pediatric Patients Undergoing Aortopulmonary Shunting.

OBJECTIVES: Shunt thrombosis, a potential complication of aortopulmonary shunting, is associated with high mortality. Commonly used oral antiplatelet drugs such as aspirin demonstrate variable absorption and inconsistent antiplatelet effect in critically ill patients early after surgery. IV glycoprotein IIb/IIIa inhibitors are antiplatelet agents with rapid and reproducible effect that may be beneficial as a bridge to oral therapy. DESIGN: Retrospective review of pediatric patients undergoing treatment with IV tirofiban. Discarded blood samples were used to determine pharmacokinetic parameters. SETTING: Pediatric cardiac ICU at a single institution. PATIENTS: Fifty-two pediatric patients (< 18 yr) undergoing surgical aortopulmonary shunt procedure who received tirofiban infusion as a bridge to oral aspirin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were shunt thrombosis and bleeding events, whereas secondary outcomes included measurement of platelet inhibition by thromboelastography with platelet mapping and pharmacokinetic analysis (performed in a subset of 15 patients). Shunt thrombosis occurred in two of 52 patients (3.9%) after prophylaxis treatment with tirofiban; both thrombosis events occurred after discontinuation of the drug. One patient (1.9%) experienced bleeding complication during the infusion. A tirofiban bolus of 10 µg/kg and infusion of 0.15 µg/kg/min resulted in significantly increased platelet inhibition via adenosine diphosphate pathway (median 66% [43-96] pre-tirofiban compared with 97% [92-99%] at 2 hr; p < 0.05). Half-life of tirofiban in plasma was 142 ± 1.5 minutes, and the average steady-state concentration was 112 ± 62 ng/mL. Age and serum creatinine were significant covariates associated with systemic clearance. Dosing simulations were generated based upon one compartment model. CONCLUSIONS: IV glycoprotein IIb/IIIa inhibitor as a bridge to oral antiplatelet therapy is safe in pediatric patients after aortopulmonary shunting. Dosing considerations should include both age and renal function. Randomized trials are warranted to establish efficacy compared with current anticoagulation practices.

Intraoperative localization of cardiac conduction tissue regions using real-time fibre-optic confocal microscopy: first in human trial.

OBJECTIVES: The aim of this study was to evaluate the feasibility and safety of fibre-optic confocal microscopy (FCM) using fluorescein sodium dye for the intraoperative location of conduction tissue regions during paediatric heart surgery. METHODS: The pilot study included 6 patients undergoing elective surgery for the closure of isolated secundum atrial septal defect aged 30 days to 21 years. FCM imaging was integrated within the normal intraoperative protocol for atrial septal defect repair. Fluorescein sodium dye was applied on the arrested heart. FCM images were acquired at the atrioventricular node region, sinus node region and right ventricle (RV). Total imaging time was limited to 3 min. Any adverse events related to the study were recorded and analysed. Subjects received standard postoperative care. Trained reviewers (n = 9) classified, de-identified and randomized FCM images (n = 60) recorded from the patients as presenting striated, reticulated or indistinguishable microstructures. The reliability of reviewer agreement was assessed using Fleiss' kappa. RESULTS: The FCM imaging instruments were integrated effectively into the cardiac surgery operating room. All adverse events found in the study were deemed expected and not related to FCM imaging. Reticulated myocardial microstructures were found during FCM imaging at atrioventricular node and sinus node regions, while striated microstructures were observed in RV. Reliability of agreement of reviewers classifying the FCM images was high (Fleiss' kappa: 0.822). CONCLUSIONS: FCM using fluorescein sodium dye was found to be safe for use during paediatric heart surgery. The study demonstrates the potential for FCM to be effective in identifying conduction tissue regions during congenital heart surgery. CLINICAL TRIAL REGISTRATION NUMBER: NCT03189134.

Do patients with anomalous origin of the left coronary artery benefit from an early repair of the mitral valve?

OBJECTIVES: The aim of this study was to determine mid-term outcomes of patients with anomalous origin of the left coronary artery from the pulmonary artery undergoing coronary repair only (group A) or simultaneous mitral valve repair (group B). METHODS: Patients with anomalous origin of the left coronary artery from the pulmonary artery who underwent surgery from 2000 to 2017 were reviewed. Mitral regurgitation (MR) grade (none, mild, moderate, severe), left ventricular (LV) function [ejection fraction (EF): <40%, 40-50%, >50%] and LV Z-scores (long axis) were assessed preoperatively and at last visit. Outcomes were compared within/between the groups using the Wilcoxon signed-rank test. RESULTS: Of 58 patients (67% women; median age 4.4 months), 39 patients were in group A (67%) and 19 patients in group B (33%). The median hospital stay (11 days, interquartile range 5-18) and average follow-up time (2.6 ± 0.5 years) did not differ significantly between the groups (P > 0.05). Four patients in group A (10.3%) underwent mitral valve reintervention. The median MR grade differed significantly between the groups preoperatively (2 vs 3, P < 0.001) but not at the last visit (2 vs 2, P = 0.88); both groups improved significantly (P = 0.021, P < 0.001). EF grade (<40%, 40-50%, >50%) did not differ significantly between the groups at baseline (group A: 38%/23%/38% vs group B: 58%/10%/32%, P = 0.32) or at last visit (group A: 18%/15%/67% vs group B: 26%/16%/58%, P = 0.75); both groups improved significantly (P = 0.004, P = 0.014). The mean LV Z-scores for groups A and B were 3.1 ± 0.5 and 4.5 ± 0.6 before surgery (P < 0.05) and 1.5 ± 0.3 and 2.7 ± 0.6 at last visit (P = 0.77). CONCLUSIONS: The repair of anomalous origin of the left coronary artery from the pulmonary artery is associated with improvement in MR, EF and LV dimensions. However, in cases of ≥moderate MR, the risk of mitral valve reintervention may be higher in patients undergoing coronary transfer only.

Repair of double outlet right ventricle: Midterm outcomes.

OBJECTIVE: Double outlet right ventricle (DORV) is a complex cardiac malformation with many anatomic variations and various approaches for surgical repair. This study aimed to describe the clinical outcomes of biventricular (BiV) repair for DORV. METHODS: Patients with DORV, who underwent BiV repair between January 2000 and December 2017 were retrospectively reviewed. Group 1 underwent primary BiV repair, whereas group 2 underwent staged BiV repair over a series of operations. The decision to pursue staged approach included complexity of intracardiac anatomy, age of the patient, and the size and function of the ventricles and the atrioventricular valves. Time-dependent surgical reintervention for LVOTO and mortality were evaluated using Kaplan-Meier survival analysis. RESULTS: A total of 238 patients with DORV underwent BiV repair at a median age of 6.2 months (range, 1.1 month-27.5 years) (158 in group 1, 80 in group 2). Twenty-two patients (7.8%) required surgical reintervention within 30 days of BiV repair. Overall survival at 5 years was 89.0%. Freedom from LVOTO reoperation at 5 years was 84%. Primary outcomes were not significantly different between groups. CAVC repair and right ventricle to pulmonary artery conduit at BiV repair were associated with higher surgical reintervention (hazard ratio, 2.9 and 1.75, respectively). CONCLUSIONS: Patients with DORV and complex anatomy may undergo staged BiV repair with acceptable outcomes. Although LVOTO is a potential complication in these patients, the rate of surgical reintervention for LVOTO does not differ significantly from patients undergoing primary BiV repair.

High-dose heparin is associated with higher bleeding and thrombosis rates in pediatric patients following cardiac surgery.

OBJECTIVE: To determine the association between unfractionated heparin (UFH) dose and the rate of postoperative bleeding and thrombosis events in pediatric cardiac patients. We tested the hypothesis that high-dose UFH is associated with higher rates of bleeding and thrombosis. METHODS: This is a retrospective review of pediatric patients admitted to the cardiac intensive care unit following cardiac surgery between November 2016 and December 2017. Peripheral venous thrombosis was excluded from analysis. Bleeding was defined as spontaneous bleeding remote from procedural manipulation. Postoperative UFH dosing strategy was categorized into 3 groups: no UFH, low-dose UFH (<15 U/kg/h) and high-dose UFH (≥15 U/kg/h). Statistical analysis was performed using multivariable logistic regression. RESULTS: We observed 966 consecutive patients (median age, 1.37 years; interquartile range, 0.27-5.50 years) during their stay in the cardiac intensive care unit. There were 94 patients (10%) with bleeding and 52 patients (5%) with thrombosis during follow-up. Patients receiving high-dose UFH experienced significantly more bleeding (odds ratio, 2.35; 95% confidence interval, 1.45-3.95) and thrombosis events (odds ratio, 3.65; 95% confidence interval, 1.81-7.38) compared with patients receiving low-dose UFH. The odds of bleeding (odds ratio, 0.81; 95% confidence interval, 0.45-1.47) and thrombosis (odds ratio, 0.59; 95% confidence interval, 0.26-1.35) were similar in the low-dose UFH and no-UFH groups. CONCLUSIONS: Bleeding remote from immediate postsurgical bleeding occurs uncommonly in pediatric patients following cardiac surgery. Anticoagulation with high-dose UFH is associated with higher bleeding rates as well as higher thrombosis rates. Indications for high-dose UFH should be carefully considered to reduce the rate of bleeding in this population.

Evaluation of Placental Mesenchymal Stem Cell Sheets for Myocardial Repair and Regeneration.

IMPACT STATEMENT: This work explores placental tissue as a cell source for fabrication of tissue-engineered surgical patches for myocardial repair of congenital heart defects. This study demonstrates promising findings for the clinically driven evaluation of the cell source as defined by potential cardiac benefit, compatibility, cell source availability, and implant deliverability. It documents methods for the isolation of mesenchymal stem cells from human placental amnion and chorion tissues, characterization of these cells, and eventual cell sheet growth that can be leveraged going forward for patch fabrication. It establishes support to continue pursuing the placenta as a valuable cell source for myocardial repair.

Surgical Atrioventricular Valve Replacement With Melody Valve in Infants and Children.

Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes <15 mm. Based on successful experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, the prosthesis has been modified for surgical valve replacement in pediatric patients with atrioventricular dysfunction with the intention of subsequent valve expansion in the catheterization laboratory as the child grows. Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9-24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P<0.001) with no significant increase in grade of regurgitation. Twelve months after implantation, cumulative incidence analysis indicated that 55% of the patients would be expected to be free from death, heart transplantation, structural valve deterioration, or valve replacement. Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.

Staged ventricular recruitment in patients with borderline ventricles and large ventricular septal defects.

OBJECTIVES: Patients with borderline ventricles and ventricular septal defects (VSDs) who have previously undergone single ventricle palliation might be candidates for staged ventricular recruitment with the ultimate goal of biventricular conversion. This study aimed to determine the effect of atrial septal defect (ASD) restriction without VSD closure on ventricular growth in patients with borderline right or left ventricles and VSDs. METHODS: Patients with borderline ventricles and VSD who underwent a staged ventricular recruitment procedure with strategies to increase blood flow through hypoplastic ventricle via ASD restriction without VSD closure after single ventricle palliation were retrospectively reviewed. Pre- and postrecruitment ventricular volumes were compared using Wilcoxon signed rank test. RESULTS: A total of 21 patients underwent staged ventricular recruitment via ASD restriction without VSD closure at median age of 20.0 months (interquartile range [IQR], 8.0-52.5 months). At a median of 9.0 months (IQR, 8.0-11.8 months) after the recruitment procedure, there were increases in the median indexed ventricular diastolic volume (31.7 mL/m2 [IQR, 24.5-37.1] to 48.5 mL/m2 [IQR, 38.4-58.0; P < .01]), median indexed systolic volume (13.3 mL/m2 [IQR, 9.7-18.7] to 19.5 mL/m2 [IQR, 16.8-29.7]; P < .01), and the median indexed stroke volume (18.4 mL/m2 [IQR, 14.8-21.1] to 28.1 mL/m2 [IQR, 21.3-31.8]; P < .01). Biventricular conversion was ultimately performed in 14 (67%). Two patients died after biventricular conversion. CONCLUSIONS: Staged ventricular recruitment via ASD restriction without VSD closure is associated with growth of the hypoplastic ventricle. In patients who are deemed high-risk for single ventricle, this approach might facilitate eventual biventricular conversion. Further studies are needed to identify optimal candidates for this approach.

Flow Preservation of Umbilical Vein for Autologous Shunt and Cardiovascular Reconstruction.

BACKGROUND: Synthetic graft materials are commonly used for shunts and cardiovascular reconstruction in neonates, but are prone to thrombosis and scarring. The umbilical vein is a potential source of autologous, endothelialized tissue for neonatal shunts and tissue reconstruction, but requires preservation before implantation. METHODS: Umbilical cords were collected in UW solution with antibiotics at 4°C until dissection. Umbilical vein segments were tested for burst pressure before and after 2 weeks of preservation. Umbilical veins segments were preserved under static or flow conditions at 4°C in UW solution with 5% human plasma lysate for 7 days. Veins were evaluated with histopathology, scanning electron microscopy, and platelet adhesion testing. RESULTS: Umbilical veins have no difference in burst pressure at harvest (n = 16) compared with 2 weeks of preservation (n = 11; 431 ± 229 versus 438 ± 244 mm Hg). After 1 week, static and flow-preserved veins showed viability of the vessel segments with endothelium staining positive for CD31, von Willebrand factor, and endothelial nitric oxide synthase. Scanning electron microscopy demonstrated preservation of normal endothelial morphology and flow alignment in the flow-preserved samples compared with cobblestone endothelial appearance and some endothelial cell loss in the static samples. Static samples had significantly more platelet adhesion than flow-preserved samples did. CONCLUSIONS: Umbilical veins have adequate burst strength to function at neonatal systemic pressures. Preservation under flow conditions demonstrated normal endothelial and overall vascular morphology with less platelet adhesion compared with static samples. Preserved autologous umbilical veins are potential source for endothelialized shunts or cardiovascular repair tissue for neonates.

Host non-inflammatory neutrophils mediate the engraftment of bioengineered vascular networks.

Notwithstanding remarkable progress in vascular network engineering, implanted bioengineered microvessels largely fail to form anastomoses with the host vasculature. Here, we demonstrate that implants containing assembled human vascular networks (A-Grafts) fail to engraft due to their inability to engage non-inflammatory host neutrophils upon implantation into mice. In contrast, unassembled vascular cells (U-Grafts) readily engage alternatively polarized neutrophils, which in turn serve as indispensable mediators of vascular assembly and anastomosis. The depletion of host neutrophils abrogated vascularization in U-Grafts, whereas an adoptive transfer of neutrophils fully restored vascularization in myeloid-depleted mice. Neutrophil engagement was regulated by secreted factors and was progressively silenced as the vasculature matured. Exogenous addition of factors from U-Grafts reengaged neutrophils and enhanced revascularization in A-Grafts, a process that was recapitulated by blocking Notch signaling. Our data suggest that the pro-vascularization potential of neutrophils can be harnessed to improve the engraftment of bioengineered tissues.