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Objective The Norwood neoaortic arch biomechanical properties are abnormal due to reduced vessel wall compliance and abnormal geometry. Others have previously described neoaortic geometric distortion by the degree of diameter reduction (tapering) and associated this with mismatched ventricular-neoaortic coupling, abnormal flow hemodynamic parameters, and worse patient outcome. Our purposes were to investigate the influence of neoaortic tapering (ie, diameter reduction) on flow-mediated viscous energy loss (EL') in post-Norwood palliated hypoplastic left heart syndrome patients, and correlate flow-geometry with single ventricle power generation. Methods Twenty-six palliated hypoplastic left heart syndrome patients underwent comprehensive cardiac evaluation with 4-dimensional-flow magnetic resonance imaging. Patients were grouped into high- (group H, n = 13) and low- (group L, n = 13) degree neoaortic tapering using the median cutoff value of neoaortic diameter variance. EL' was calculated along standardized segments using 4-dimensional-flow magnetic resonance imaging. Flow-mediated power loss as a percentage of total power generated by the single ventricle was determined. Results Group H had a higher prevalence of abnormal recirculating flow in the neoaorta and elevated neoaortic EL' in the ascending aorta (1.0 vs 0.6 mW; P = .004). Group H EL' was increased across the entire thoracic aorta (2.6 vs 1.3 mW; P = .002) and accounted for 0.7% of generated ventricular power versus 0.3% in group L (P = .024). EL' directly correlated with the degree of ascending aortic dilation (R = 0.49; P = .012). Conclusions Patients with high degree neoaortic tapering have more perturbed flow through the neoaorta and increased EL'. Flow-mediated energy loss due to abnormal flow represents irreversibly wasted power generated by the single right ventricle. In patients with high-degree neoaortic tapering, EL' was more than 2-fold greater than low-degree tapering patients. These data suggest that oversizing the Norwood neoaortic reconstruction should be avoided and that patients with distorted neoaortic geometry may warrant increased surveillance for single-ventricle deterioration.

BACKGROUND The atretic connection between the left fourth and sixth aortic arches is a rare congenital cardiac anomaly with controversial debates on its origin. This anatomy has been previously reported with additional cardiac anomalies of maldevelopment. AIMS We present the successful surgical management of a 3-month-old female with Cornelia de Lange syndrome and coarctation of the aorta in the setting of this unique collateral channel. MATERIALS & METHODS We review the beneficial utility and novelty of three-dimensional computed tomography angiography for this anatomic lesion while also discussing the importance of multidisciplinary preoperative planning in the coordinated management of this arch anomaly and potential concomitant comorbid conditions. RESULTS The presented surgical case demonstrates the successful reconstruction of the aortic arch by coarctectomy with extended end-to-end anastomosis by a left posterolateral thoracotomy in a patient with a collateral arch channel and a hemodynamically significant aortic coarctation. CONCLUSION Atretic connection between the left fourth and sixth aortic arches remains a rare congenital anomaly and may occur in the setting of an aortic coarctation. Unclear arch anatomy and indeterminant proximal aortic sizing on echocardiogram should prompt cross-sectional imaging with computed tomography angiography to guide surgical technique selection for aortic arch reconstruction when a collateral arch channel or unique branching pattern is suspected.

Evaluate the use of coronary CTA as an initial assessment for determining Right Ventricle Dependent Coronary Circulation (RVDCC) in neonates with Pulmonary Atresia with Intact Ventricular Septum (PA IVS). Retrospective review of cases with coronary CTA and compare with available catheter angiography, pathology, surgical reports, and outcomes from Mar 2015 to May 2022. In our cohort of 16 patients, 3 were positive for RVDCC, confirmed by pathologic evaluation, and there was concordance for presence or absence of RVDCC with catheter angiography in 5 patients (4 negatives for RVDCC, 1 positive). Clinical follow up for the 8 patients that underwent RV decompression had no clinical evidence of myocardial ischemia. Our findings suggest that coronary CTA is reliable as first-line imaging for determination of RVDCC in neonates with PA IVS. These findings, if supported by further prospective study, may reserve invasive coronary angiography for cases with diagnostic uncertainty or at the time of necessary transcatheter interventions.

Cardiac tumors remain rare in children with benign pathologies predominating. Indications for surgical management often result from compromised ventricular chamber size, biventricular outflow tract obstruction, impaired ventricular function, or the presence of medically refractory dysrhythmias. We present a case of a six-month-old infant with two intracardiac fibromas originating in the interventricular septum. The fibromas were causing significant biventricular outflow obstruction. The patient successfully underwent tumor resection on cardiopulmonary bypass The literature on pediatric cardiac tumors is reviewed. Multi-disciplinary medical planning is necessary for successful anesthetic and surgical treatment of this high-risk patient population.

Surgical site infections (SSI) following congenital heart surgery (CHS) remain a significant source of morbidity. Delayed sternal closure (DSC) is often required to minimize the potential for hemodynamic instability. The purpose of this study was to determine the incidence of SSI among patients undergoing DSC versus primary chest closure (PCC) and to define a potential inflection point for increased risk of SSI as a function of open chest duration (OCD).A retrospective review of our institutional Society of Thoracic Surgeons dataset is to identify patients undergoing CHS at our institution between 2015 and 2020. Incidences of SSI were compared between DSC and PCC patients. DSC patients were evaluated to determine the association of OCD and the incidence of SSI.2582 operations were performed at our institution between 2015 and 2020, including 195 DSC and 2387 PCC cases. The incidence of SSI within the cohort was 1.8% (47/2,582). DSC patients had significantly higher incidences of SSI (17/195, 8.7%) than PCC patients (30/2387, 1.3%, p 0.001). Further, patients with an OCD of four or more days had a significantly higher incidence of SSI (11/62, 17.7%, p = 0.006) than patients with an OCD less than 4 days (6/115, 5.3%).The incidence of SSI following CHS is higher in DSC patients compared to PCC patients. Prolonged OCD of 4 days or more significantly increases the risk of SSI and represents a potentially modifiable risk factor for SSI predisposition. These data support dedicated, daily post-operative assessment of candidacy for chest closure to minimize the risk of SSI.

Background Elevated systemic afterload in patients with Fontan circulation may lead to impaired single ventricular function. Wave intensity analysis (WIA) enables evaluation of compression and expansion waves traveling through vasculature. We aimed to investigate the unfavorable wave propagation causing excessive afterload may be an important contributor to the overall single ventricle function and to the limited functional capacity in this patient population. Methods Patients with hypoplastic left heart syndrome (HLHS) (n = 25), single left ventricle (SLV) (n = 24), and normal controls (n = 10) underwent phase-contrast MRI based WIA analysis evaluated in the ascending aorta. Forward compression wave (FCW) representing dP/dt, backward compression wave (BCW) reflecting vascular stiffness, and forward decompression wave (FDW) representing LV relaxation were recorded and indexed to each other. Results FCW was lowest in HLHS patients (1098 mm5/s), and higher in the SLV group (1457 mm5/s), and controls (6457 mm5/s) (P Conclusions Patients with HLHS and SLV have unfavorable aortic WIA patterns with increased BCW/FCW ratio indicating increased systemic afterload due to retrograde compression waves. Reduced FCW and systolic MRI indices correlated with peak VO2 suggesting that abnormal systolic wave propagation may play a role in exercise intolerance for Fontan patients.

In this manuscript, we review the diagnosis, causes, and management of cardiac thrombosis in children with congenital and acquired heart disease. Indications for invasive management and surgery are discussed. The differential diagnostic considerations and management of cardiac thromboses will be reviewed, including those that occur as a consequence of repair and palliation of congenital heart disease. The definition of venous thromboembolism has recently been expanded to include thromboses within both the right and left heart chambers. Direct thrombin inhibitors (DTIs) and direct oral anticoagulants (DOACs) are emerging as treatment alternatives to the heparins and vitamin K antagonists for the management of thrombosis in pediatric heart disease. Thrombosis within the heart occurs as a consequence of abnormalities and alterations in blood flow resulting in stasis and turbulence. Children with acquired and congenital heart disease carry a number of risk factors in Virchow’s triad. Thrombosis can occur throughout any part of the cardiovascular system in congenital heart disease and after surgery for repair or palliation of defects.

The Fontan circulation is characterized as a nonpulsatile flow propagation without a pressure-generating ventricle. However, flow through the Fontan circulation still exhibits oscillatory waves as a result of pressure changes generated by the systemic single ventricle. Identification of discrete flow patterns through the Fontan circuit may be important to understand single ventricle performance. Ninety-seven patients with Fontan circulation underwent phase-contrast MRI of the right pulmonary artery, yielding subject-specific flow waveforms. Principal component (PC) analysis was performed on preprocessed flow waveforms. Principal components were then correlated with standard MRI indices of function, volume, and aortopulmonary collateral flow. The first principal component (PC) described systolic versus diastolic-dominant flow through the Fontan circulation, accounting for 31.3% of the variance in all waveforms. The first PC correlated with end-diastolic volume ( R = 0.34, P = 0.001), and end-systolic volume ( R = 0.30, P = 0.003), cardiac index ( R = 0.51, P < 0.001), and the amount of aortopulmonary collateral flow ( R = 0.25, P = 0.027)—lower ventricular volumes and a smaller volume of collateral flow—were associated with diastolic-dominant cavopulmonary flow. The second PC accounted for 19.5% of variance and described late diastolic acceleration versus deceleration and correlated with ejection fraction—diastolic deceleration was associated with higher ejection fraction. Principal components describing the diastolic flow variations in pulmonary arteries are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to preserved ventricular volume and function, respectively. NEW & NOTEWORTHY The exact physiological significance of flow oscillations of phasic and temporal flow variations in Fontan circulation is unknown. With the use of principal component analysis, we discovered that flow variations in the right pulmonary artery of Fontan patients are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to more ideal ventricular volume and systolic function, respectively.

The purpose of this review is to provide a concise discussion regarding surgical management of infants born pre-term and/or of low birth weight with congenital heart disease (CHD). The following provides a summary of current available experiential data and treatment paradigms that remain in evolution for this high-risk subset of infants. The composite of these findings supports center- and patient-specific decision-making to define the optimal timing and technique utilized for the palliation and definitive surgical treatment of CHD across a spectrum of severity. The following establishes that infants born both pre-term and of low birth weight represent a high-risk surgical cohort with CHD. Despite this increased risk of both morbidity and mortality following surgical palliation or definitive anatomic correction, advancements in prenatal diagnostics, in postnatal resuscitation, and in the conduct of complex neonatal surgery and cardiopulmonary bypass now enable early intervention with improved outcomes and favorable long-term risk of need for re-intervention. Infants of low birth weight and those born pre-term represent a high-risk subset of patients with CHD. Advancements in both surgical technique and the advent of interventional therapies have introduced important considerations that have enabled earlier treatment in a subset of carefully selected patients. Further prospective, well-controlled data are needed to better define the multi-system effects of early surgical intervention in this high-risk patient population.

Aortopathy is a recognized comorbidity of Tetralogy of Fallot (TOF). Aortic flow in children with repaired TOF is abnormal despite normal aortic valve anatomy and early surgical repair that results in aortic size normalization. The purpose of this study was to investigate the flow hemodynamics inside the left ventricle (LV) of children with repaired TOF using 4D-Flow MRI derived vorticity. Vorticity is the spatial derivative of flow velocity and is sensitive to anatomic and geometric variations. Vorticity was calculated inside the LV of children with repaired TOF having normal aortic size (n = 14) and normal controls (n = 10) during systolic ejection phase. All subjects underwent comprehensive biventricular analysis including the MRI based feature-tracking based LV strain analysis and mechanical dyssynchrony. Right ventricular (RV) volumetric indices along with LV mechanical indices were correlated with LV vorticity. All TOF patients had supraphysiologic helical flow in the ascending aorta. The generated peak systolic vorticity integrated over the LV volume was elevated in TOF group compared to control (median: 1344 vs. 858 s−1, P

In this study, the mechanical properties of concrete mixtures containing different cementitious combinations and two aggregate systems were investigated under plastic and drying conditions....

This cohort study investigates the association between the COVID-19 pandemic and waiting list times among pediatric heart transplant recipients in the US.

OBJECTIVES Aortopathy in tetralogy of Fallot (TOF) is characterized by increased aortic stiffness, dilation and reduced left ventricular (LV) function. Repair in infancy normalizes aortic dimensions in early childhood. Our prior work demonstrated that early TOF repair does not normalize aortic compliance and that abnormal ascending aortic flow patterns are prevalent. The objectives of this study were to: (i) determine whether proximal aortic flow-mediated viscous energy loss (EL′) is elevated in patients with early TOF repair compared with healthy controls, and (ii) determine whether the degree of EL′ is associated with LV function. METHODS Forty-one patients post TOF repair with normalized aortic size and 15 healthy controls underwent 4-dimenisonal-flow magnetic resonance imaging flow analysis and EL′ assessment. Correlations between EL′, aortic size, and LV function were assessed. RESULTS The TOF group had increased peak systolic thoracic aorta EL′ (3.8 vs 1.5 mW, P = 0.004) and increased averaged EL′ throughout the cardiac cycle (1.2 vs 0.5 mW, P = 0.003). Peak and mean systolic EL′ in the ascending aorta was increased 2-fold in the TOF group compared with control (peak: 2.0 vs 0.9 mW, P = 0.007). Peak EL′ measured along the entire thoracic aortic length correlated with LV ejection fraction (R = −0.45, P = 0.009), indexed LV end-systolic volume (R = −0.40, P = 0.010), and right ventricular end-systolic volume (R = −0.37, P = 0.034). CONCLUSIONS Patients with repaired TOF exhibit abnormal aortic flow associated with increased EL′ in the thoracic aorta. The magnitude of EL′ is associated with LV function and volumes. Increased aortic EL′ in TOF is likely due to inherently abnormal LV outflow geometry and or right ventricular interaction. Reduced aortic flow efficiency in TOF increases cardiac work and may be an important factor in long-term cardiac performance.

Apert syndrome is a form of acrocephalosyndactyly involving craniosynostosis, syndactyly, and less commonly tracheal cartilaginous sleeve (TCS), a potential cause of tracheal stenosis. Slide tracheoplasty is performed in children with tracheal stenosis. No reports exist for its application in stenosis related to TCS. We present a case in which slide tracheoplasty was utilized for expansion of long segment tracheal stenosis due to TCS in a newborn with Apert syndrome. Using this technique, a safe and durable airway was achieved without tracheostomy.

Objective This study used cardiac magnetic resonance imaging to evaluate flow characteristics and ventricular hemodynamics for children with single right (hypoplastic left heart syndrome) and single left (hypoplastic right heart syndrome) systemic ventricle anatomy after Fontan palliation compared with normal biventricular controls. Methods Twenty children with single ventricle anatomy (hypoplastic left heart syndrome, n = 10; hypoplastic right heart syndrome, n = 10) underwent standardized 4-dimensional flow cardiac magnetic resonance and were compared with age-matched controls (n = 10). End-diastolic volume was partitioned into 4 defined components of variable kinetic energy (direct flow, retained inflow, delayed ejection, and residual volume) and compared between groups. Further, volumetric and functional parameters as defined by cardiac magnetic resonance were evaluated. Results Children with hypoplastic left heart syndrome had significantly increased indexed end-diastolic and end-systolic volumes compared with both hypoplastic right heart syndrome and control groups. Flow component analysis demonstrated diastolic inefficiency in both hypoplastic left heart syndrome and hypoplastic right heart syndrome groups compared with controls as defined by decreased direct flow and increased residual volumes. Decreased direct flow correlated with decreased ejection fraction and increased end-diastolic and end-systolic volume indices. Increased residual volume correlated with decreased ejection fraction and increased end-systolic volume index. Conclusions Fontan-palliated patients with single ventricle physiology (hypoplastic left heart syndrome and hypoplastic right heart syndrome) demonstrate altered and inefficient flow patterns in the systemic ventricle as defined by 4-dimensional flow cardiac magnetic resonance compared with normal biventricular controls. Decreased direct flow and increased residual volume indicate that diastolic ventricular dysfunction is prevalent after Fontan palliation. This study provides a foundation for future predictive modeling and cardiac magnetic resonance flow diagnostic studies in this high-risk patient population.

Introduction: Heart failure (HF) remains a leading cause of death and indication for transplant in single ventricle congenital heart disease (SV). However, little is known regarding the molecular mechanisms leading to HF in SV. The purpose of this study was to characterize mitochondrial function in the myocardium of failing (SVHF) and non-failing (SVNF) SV patients compared to biventricular NF controls (BVNF). Furthermore, we investigated the effect of ex vivo treatment with the phosphodiesterase-5 inhibitor (PDE5i) sildenafil on mitochondrial function. Methods: Freshly explanted ventricular tissue was saponin permeabilized and mitochondrial oxygen consumption was measured sequentially throughout the electron transport system using SUbstrate-Inhibitor-Titration (“SUIT”) protocols and an Oroboros O2k high resolution respirometer. Permeabilized ventricular tissue was treated for 40 min with sildenafil [1μM] prior to measurement of oxygen consumption. A Western blot for PDE5 was performed in isolated mitochondrial proteins from SVHF subjects ± PDE5i. Results: Compared to BVNF (n=15) and SVNF (n=6), SVHF (n=8) hearts have decreased function of Complex I and Complex I and II (A, B), and decreased maximal respiration (C), all of which improve with acute ex vivo treatment with sildenafil in SVHF (SVHF+PDE5i, n=6). Importantly, mitochondrial function is impaired in BVNF+PDE5i (n=5) and SVNF+PDE5i hearts (n=5) (A-C, one-way Anova p Conclusions: Our results indicate that mitochondrial function is impaired in SVHF, PDE5 protein is expressed in SVHF mitochondria, and PDE5i improves mitochondrial function in SVHF, but may be detrimental to mitochondrial function in SVNF and BVNF. Together these data suggest that mitochondrial PDE5 is a potential therapeutic target, but that indiscriminate use of PDE5i in SV patients may not be advisable.

Background The purpose of this study was to determine whether aortic biomechanical properties are abnormal in children with repaired truncus arteriosus (TA) and to concurrently evaluate left ventricular (LV) function post-repair utilizing a novel platform for regional ventricular function. Methods Cardiac magnetic resonance (CMR) studies from 26 children (mean age: 15.6 ± 7.2 years) post-TA repair were compared with 20 normal controls (mean age: 14.7 ± 2.6 years). Parameters of aortic stiffness (pulse wave velocity and relative area change) were measured. Flow hemodynamic metrics (aortic regurgitant fraction, peak systolic flow, and peak systolic velocity) and LV function (volumetric data, ejection fraction, regional wall strain) were also compared. Results Ascending aortic pulse wave velocity was elevated and relative area change was decreased in TA patients compared with controls. Patients post-TA repair demonstrated elevated end diastolic and end systolic volumes in addition to decreased regional wall strain and increased mechanical dyssynchrony. LV functional changes were independent of aortic biomechanical properties. Conclusions Children with repaired TA have increased ascending aortic stiffness and altered LV function as measured by CMR imaging. Longitudinal studies and advanced CMR assessments are warranted to better determine the long-term potential for late aortic complications and to optimize both the medical and surgical management of these patients after TA repair.

Background Calcium accumulation and fibrotic activities are principal mechanisms for calcific aortic valve disease (CAVD). Active complement products are observed in human stenotic aortic valves. Runt-related transcription factor 2 (Runx-2) is involved in tissue calcification. We hypothesized that complement upregulates Runx-2 to induce profibrogenic change in human aortic valve interstitial cells (AVICs). Methods AVICs were isolated from 6 normal and 6 CAVD donor valves. Cells were treated with complement cocktails. Profibrogenic activities and associated signaling molecules were analyzed by Western blot assay and collagen staining. Results Complement time and dose dependently enhanced profibrogenic activities in AVICs, and complement exposure also induced total collagen deposition in AVICs. Complement-induced profibrogenic responses were associated with increased Runx-2 expression and phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). Genetic silencing of Runx-2 decreased both matrix metalloproteinase 9 (MMP-9) and collagen I levels. Pharmacological inhibition of ERK1/2 decreased complement-mediated MMP-9, collagen I, and Runx-2 expression as well as total collagen deposition in human AVICs. Further, treating AVICs with heat-deactivated complement resulted in reduced MMP-9, collagen I, and Runx-2 levels compared with active complement treatment. Conclusions Complement induced profibrogenic activities in AVICs by activation of ERK1/2–mediated Runx-2 signaling pathways. This study demonstrates a potential role for complement-mediated CAVD pathogenesis, establishing a possible therapeutic target to limit CAVD progression.

Background Control of postoperative hypertension is central to the care of infants and children after cardiac operations. Continuous pharmacologic delivery affords the advantage of rapid onset and ease of titration. Although well established in older children and adults, calcium channel blockers are routinely avoided in children aged younger than 1 year secondary to concerns of safety and efficacy in the setting of sarcoplasmic reticulum development. Thus, the purpose of this study was to review a single-institution experience with nicardipine, a selective calcium channel blocker, in pediatric patients after cardiac operations. Methods Children undergoing cardiac operations at the University of Virginia from 2010 to 2015 were retrospectively reviewed after selection based on receipt of nicardipine for blood pressure management in the postoperative period. Demographic, operative, laboratory, and postoperative data were collected for adverse effect analysis and outcomes comparisons between infants aged younger than 6 months (group 1) and older than 6 months (group 2). Results During the study period, 68 children (group 1: n = 33 [48%]; group 2: n = 35 [52%]) received nicardipine after cardiac operations (0.5 to 1 μg · kg –1 · min –1 ). Nicardipine was initiated at a mean of 6.6 ± 13.1 hours postoperatively in group 1 and 5.4 ± 7.8 hours in group 2. Nine patients (13%) demonstrated clinically significant hypotension necessitating dosing titration with no statistically significant differences between groups. No major adverse events occurred following nicardipine administration. Conclusions Nicardipine is well tolerated after cardiac operations in children irrespective of age or underlying pathology. Thus, nicardipine should be considered as safe and effective in children of all ages for control of hypertension after cardiac operations.

The primary shortcoming of traditional four-step models is that they cannot capture derived travel demand behaviors. However, travel demand modeling (TDM) is an essential input for urban transportation planning. TDM needs to be highly precise and accurate by integrating the accurate base year estimation along with suitable alternatives. Currently, activity-based models (ABMs) have been developed mostly for large metropolitan planning organizations (MPO), whereas smaller/medium-sized MPOs typically lack these models. The main reason for this disparity in ABM development is the complexity of the models and the cost and data requirements needed. We posit however that smaller MPOs could develop ABMs from traditional travel surveys. Therefore, the specific aim of this paper is to develop a probabilistic home-based destination activity trip generation model considering travel time behavior. Results show that the developed model can significantly capture the actual number of trip generations.

Coarctation of the aorta is a common form of congenital heart disease. Presentation, evaluation, and treatment of coarctation of the aorta is different in neonates and infants compared with older children. Neonates may present in shock and require prostaglandin E1 to maintain ductal patentcy until the time of surgical repair. Older children usually present with upper extremity hypertension or murmur. The approach to surgical repair of coarctation in neonates and infants depends on the presence or absence of concomitant defects and the degree of associated arch hypoplasia. For older children, robust collaterals and limited mobility of the aorta may mandate patch repair, interposition graft, or bypass of the coarctation segment. Percutaneous techniques, including angioplasty and stent placement, are often viable options for older children and adolescents with native or recurrent coarctation. Surgical and interventional outcomes have improved over time. Reliable repair may be anticipated with a very low rate of morbidity and mortality, although lifetime follow-up is recommended.

Background Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs. Methods C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs. Results Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix. Conclusions These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of donor lungs. The therapeutic benefits of EVs are in part mediated through anti-inflammatory promoting mechanisms via attenuation of immune cell activation as well as prevention of endothelial barrier integrity to prevent lung edema. Therefore, MSC-derived EVs offer a potential therapeutic strategy to treat post-transplant IR injury as well as rehabilitation of DCD lungs.

The purpose of this study was to evaluate the usefulness of chest radiography in the direction of postbronchoscopy clinical therapy. From 2001 to 2011, 368 rigid bronchoscopies were performed at a single institution in 221 children. Indications for bronchoscopy, concomitant bronchoscopic procedures, and results of postoperative chest radiography were evaluated. Rigid bronchoscopy was performed in children at a median age of 2.21 years (range, two days to 20 years). Chest radiography was performed at the discretion of the primary surgeon after 275 (74.7%) procedures. Malpositioning of the endotracheal or tracheostomy tube occurred in 1.5 per cent (n = three of 203) of ventilated patients postbronchoscopy. Pneumothorax occurred in 0.5 per cent (n = two of 368) of children and followed laser degranulation (n = one of 117 [0.9%]) and removal of an aspirated foreign body (n = one of 80 [1.3%]). Neither child required tube thoracostomy. Three children necessitated intraoperative tube thoracostomy placement for symptomatic pneumothoraces before radiographic assessment. No children sustained postprocedural complications in the absence of postbronchoscopy radiography. Postbronchoscopy chest radiography in the absence of defined symptomatology is not associated with a change in the postprocedural treatment course, suggesting selective application may be appropriate after at-risk bronchoscopic interventions. Such practice will limit the future cost and radiation exposure associated with this common procedure.

Background and Aim of Study The purpose of this study was to examine whether blood product utilization, one-year cell-mediated rejection rates, and mid-term survival significantly differ for ventricular assist device (VAD patients compared to non-VAD (NVAD) patients following cardiac transplantation. Methods From July 2004 to August 2011, 79 patients underwent cardiac transplantation at a single institution. Following exclusion of patients bridged to transplantation with VADs other than the HeartMate II® LVAD (n = 10), patients were stratified by VAD presence at transplantation: VAD patients (n = 35, age: 54.0 [48.0–59.0] years) vs. NVAD patients (n = 34, age: 52.5 [42.8–59.3] years). The primary outcomes of interest were blood product transfusion requirements, one-year cell-mediated rejection rates, and mid-term survival post-transplantation. Results Preoperative patient characteristics were similar for VAD and NVAD patients. NVAD patients presented with higher median preoperative creatinine levels compared to VAD patients (1.3 [1.1–1.6] vs. 1.1 [0.9–1.4], p = 0.004). VAD patients accrued higher intraoperative transfusion of all blood products (all p ≤ 0.001) compared to NVAD patients. The incidence of clinically significant cell-mediated rejection within the first posttransplant year was higher in VAD compared to NVAD patients (66.7% vs. 33.3%, p = 0.02). During a median follow-up period of 3.2 (2.0, 6.3) years, VAD patients demonstrated an increased postoperative mortality that did not reach statistical significance (20.0% vs. 8.8%, p = 0.20). Conclusions During the initial era as a bridge to transplantation, the HeartMate II® LVAD significantly increased blood product utilization and one-year cell-mediated rejection rates for cardiac transplantation. Further study is warranted to optimize anticoagulation strategies and to define causal relationships between these factors for the current era of cardiac transplantation. doi: 10.1111/jocs.12474 (J Card Surg 2015;30:194–200)

Cardiac surgical reexploration is necessary in approximately 5% of all patients. However, the impact of routine, planned reexploration performed in the intensive care unit (ICU) remains poorly defined. This study evaluated postoperative outcomes after cardiac reexplorations to determine the safety and efficacy of a planned approach in the ICU.All patients undergoing ICU cardiac reexplorations (2000 to2011) at a single institution were stratified according to a routine, planned ICU approach to reexploration (planned) versus unplanned ICU or operating room reexploration. Patient risk and outcomes were compared by univariate and multivariate analyses.8,151 total patients underwent cardiac operations, including 267 (3.2%) reexplorations (planned ICU=75% and unplanned ICU=18%). Among planned ICU reexplorations, 38% of patients had an identifiable surgical bleeding source, and 60% underwent reexploration less than 12 hours after the index procedure. Unplanned ICU reexplorations had a higher Society of Thoracic Surgeons (STS) predicted mortality (5% vs 3%, p0.001) and incurred higher observed mortality (37% vs 6%, p0.001) and morbidity. Sternal wound infections were rare and were similar between groups (p=0.81). Furthermore, upon STS mortality risk adjustment, unplanned ICU reexplorations were associated with significantly increased odds of mortality (OR=26.6 [7.1, 99.7], p0.001) compared with planned ICU reexplorations.Planned reexploration in the ICU is a safe procedure with acceptable mortality and morbidity and low infection rates. Unplanned reexplorations, however, increase postoperative risk and are associated with high mortality and morbidity. These data argue for coordinated, routine approaches to planned ICU reexploration to avoid delay in treatment for postoperative hemorrhage.

The purpose of this study was to examine risk-adjusted associations between race and gender on postoperative morbidity, mortality, and resource utilization in pediatric surgical patients within the United States.101,083 pediatric surgical patients were evaluated using the U.S. national KID Inpatient Database (2003 and 2006): appendectomy (81.2%), pyloromyotomy (9.8%), intussusception (6.2%), decortication (1.9%), congenital diaphragmatic hernia repair (0.7%), and colonic resection for Hirschsprung's disease (0.2%). Patients were stratified according to gender (male: 63.1%, n=63,783) and race: white (n=58,711), Hispanic (n=26,118), black (n=9,103), Asian (n=1,582), Native American (n=474), and other (n=5,096). Multivariable logistic regression modeling was utilized to evaluate risk-adjusted associations between race, gender, and outcomes.After risk adjustment, race was independently associated with in-hospital death (p=0.02), with an increased risk for black children. Gender was not associated with mortality (p=0.77). Postoperative morbidity was significantly associated with gender (p0.001) and race (p=0.01). Gender (p=0.003) and race (p0.001) were further associated with increased hospital length of stay. Importantly, these results were dependent on operation type.Race and gender significantly affect postoperative outcomes following pediatric surgery. Black patients are at disproportionate risk for postoperative mortality, while black and Hispanic patients have increased morbidity and hospital resource utilization. While gender does not affect mortality, gender is a determinant of both postoperative morbidity and increased resource utilization.

Background Fibrocytes are integral in the development of fibroproliferative disease. The CXCL12/CXCR4 chemokine axis has been shown to play a central role in fibrocyte migration and the development of bronchiolitis obliterans (BO) after lung transplantation. Inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin has been shown to decrease expression of both CXCR4 and its receptor agonist CXCL12. Thus, we hypothesized that rapamycin treatment would decrease fibrocyte trafficking into tracheal allografts and prevent BO. Methods A total alloantigenic mismatch murine heterotopic tracheal transplant (HTT) model of BO was used. Animals were either treated with rapamycin or dimethyl sulfoxide (DMSO) for 14 days after tracheal transplantation. Fibrocyte levels were assessed by flow cytometry, and allograft neutrophil, CD3 + T-cell, macrophage, and smooth muscle actin (SMA) levels were assessed by immunohistochemistry. Tracheal luminal obliteration was assessed on hematoxylin and eosin (H&E) stains. Results Compared with DMSO-treated controls, rapamycin-treated mice showed a significant decrease in fibrocyte levels in tracheal allografts. Fibrocyte levels in recipient blood showed a similar pattern, although it was not statistically significant. Furthermore, animals treated with rapamycin showed a significant decrease in tracheal allograft luminal obliteration compared with controls. Based on immunohistochemical analyses, populations of α-SMA–positive (α-SMA + ) cells, neutrophils, CD3 + T cells, and macrophages were all decreased in rapamycin-treated allografts versus DMSO controls. Conclusions Rapamycin effectively reduces recruitment of fibrocytes into tracheal allografts and mitigates development of tracheal luminal fibrosis. Further studies are needed to determine the cellular and molecular mechanisms that mediate the protective effect of rapamycin against BO.

Current healthcare reform efforts have highlighted the potential impact of insurance status on patient outcomes. The influence of primary payer status (PPS) within the pediatric surgical patient population remains unknown. The purpose of this study was to examine risk-adjusted associations between PPS and postoperative mortality, morbidity, and resource utilization in pediatric surgical patients within the United States.A weighted total of 153,333 pediatric surgical patients were evaluated using the national Kids' Inpatient Database (2003 and 2006): appendectomy, intussusception, decortication, pyloromyotomy, congenital diaphragmatic hernia repair, and colonic resection for Hirschsprung's disease. Patients were stratified according to PPS: Medicare (n=180), Medicaid (n=51,862), uninsured (n=12,539), and private insurance (n=88,753). Multivariable hierarchical regression modeling was utilized to evaluate risk-adjusted associations between PPS and outcomes.Overall median patient age was 12 years, operations were primarily non-elective (92.4%), and appendectomies accounted for the highest proportion of cases (81.3%). After adjustment for patient, hospital, and operation-related factors, PPS was independently associated with in-hospital death (p0.0001) and postoperative complications (p0.02), with increased risk for Medicaid and uninsured populations. Moreover, Medicaid PPS was also associated with greater adjusted lengths of stay and total hospital charges (p0.0001). Importantly, these results were dependent on operation type.Primary payer status is associated with risk-adjusted postoperative mortality, morbidity, and resource utilization among pediatric surgical patients. Uninsured patients are at increased risk for postoperative mortality while Medicaid patients accrue greater morbidity, hospital lengths of stay, and total charges. These results highlight a complex interaction between socioeconomic and patient-related factors, and primary payer status should be considered in the preoperative risk stratification of pediatric patients.

Ischemia-reperfusion (IR) injury after lung transplantation, which affects both short- and long-term allograft survival, involves activation of NADPH oxidase 2 (NOX2) and activation of invariant natural killer T (iNKT) cells to produce IL-17. Adenosine A2A receptor (A2AR) agonists are known to potently attenuate lung IR injury and IL-17 production. However, mechanisms for iNKT cell activation after IR and A2AR agonist-mediated protection remain unclear.We tested the hypothesis that NOX2 mediates IL-17 production by iNKT cells after IR and that A2AR agonism prevents IR injury by blocking NOX2 activation in iNKT cells.An in vivo murine hilar ligation model of IR injury was used, in which left lungs underwent 1 hour of ischemia and 2 hours of reperfusion.Adoptive transfer of iNKT cells from p47(phox-/-) or NOX2(-/-) mice to Jα18(-/-) (iNKT cell-deficient) mice significantly attenuated lung IR injury and IL-17 production. Treatment with an A2AR agonist attenuated IR injury and IL-17 production in wild-type (WT) mice and in Jα18(-/-) mice reconstituted with WT, but not A2AR(-/-), iNKT cells. Furthermore, the A2AR agonist prevented IL-17 production by murine and human iNKT cells after acute hypoxia-reoxygenation by blocking p47(phox) phosphorylation, a critical step for NOX2 activation.NOX2 plays a key role in inducing iNKT cell-mediated IL-17 production and subsequent lung injury after IR. A primary mechanism for A2AR agonist-mediated protection entails inhibition of NOX2 in iNKT cells. Therefore, agonism of A2ARs on iNKT cells may be a novel therapeutic strategy to prevent primary graft dysfunction after lung transplantation.

Pulmonary valve disease ranges from physiologic pulmonic flow murmurs to significant stenosis that result in changes to the structure and function of the native valve. Inherent to each pathophysiologic change at the pulmonic valve is a predisposing structural or congenital condition. An understanding of the underlying etiology for pulmonary valve disease guides multidisciplinary decision-making regarding the approach and timing for surgical replacement or reconstruction. The following chapter describes pulmonary valve embryology and structure, predisposing congenital conditions for pulmonary valve disease, postoperative anatomic considerations, and reviews imaging modalities utilized in the characterization of pulmonary valve disease. This discussion provides a framework for the brief description of surgical approaches to repair.

Objectives Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non–heart-beating donor lungs. Methods Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia–reperfusion injury. Results The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. Conclusions Uncontrolled non–heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.

Mitral valve (MV) disease is often accompanied by concomitant tricuspid valve (TV) disease. This study determined the influence of performing TV procedures in the setting of MV operations within a multiinstitutional patient population.From 2001 to 2008, 5,495 MV operations were performed at 17 different statewide centers. Of these, 5,062 patients (age, 63.4 ± 13.0 years) underwent an MV operation and 433 (age, 64.0 ± 14.2 years) underwent combined MV and TV (MV+TV) operations. The influence of concomitant TV procedures on operative death and the composite incidence of major complications was assessed by univariate and multivariate analyses.Patients undergoing MV+TV were more commonly women (62.7% vs 45.5%, p0.001), had higher rates of heart failure (73.7% vs 50.9%, p0.001), and more frequently underwent reoperations (17.1% vs 7.4%, p0.001) compared with MV patients. Other patient characteristics, including preoperative endocarditis (8.5% vs 8.2%, p = 0.78), were similar between groups. MV replacement (63.5%) was more common than repair (36.5%, p0.001) in MV+TV operations, and MV+TV operations incurred longer median cardiopulmonary bypass times (181 vs 149 minutes, p0.001). Unadjusted operative mortality (6.0% vs 10.4%, p = 0.001) and postoperative complications were higher after MV+TV compared with MV. More important, risk adjustment showed performance of concomitant TV procedures was an independent predictor of operative death (odds ratio, 1.50; p = 0.03) and major complications (odds ratio, 1.39; p = 0.004).A concomitant TV operation is a proxy for more advanced valve disease. Compared with MV operations alone, simultaneous MV+TV operations are associated with elevated morbidity and death, even after risk adjustment. This elevated risk should be considered during preoperative patient risk stratification.