Regional Arch Measurements Differ Between Imaging Modalities in Infants With Aortic Coarctation.

BACKGROUND: Aortic arch measurements provide a framework for surgical decision-making in neonatal aortic coarctation, specifically in the determination of approach for arch repair by lateral thoracotomy vs median sternotomy. The purpose of this study was to evaluate our experience with transthoracic echocardiography (TTE) and computed tomography angiography (CTA) in the preoperative evaluation of infants with aortic coarctation, specifically comparing arch dimensions as a function of imaging modality. METHODS: Imaging data were reviewed for all infants undergoing surgical repair of aortic coarctation at our institution from 2012 to 2022. Infants with both TTE and CTA evaluations were included. Aortic measurements were compared at predefined anatomic regions including ascending aorta, proximal arch, distal arch, and isthmus. RESULTS: During the study period, 372 infants underwent surgical coarctation repair; 72 (19.4%) infants had TTE and CTA arch evaluations preoperatively. Significant discrepancies between imaging modalities were defined by poor correlation coefficients and absolute measurement differences and were most prominent in the proximal aortic arch (R2 = 0.23 [-4.4 to 3.2 mm]) and isthmus regions (R2 = 0.11 [-4.2 to 1.7 mm]). Improved correlation was demonstrated in the ascending aorta (R2 = 0.63) and distal aortic arch (R2 = 0.54). CONCLUSIONS: Significant variability exists between TTE- and CTA-derived aortic measurements in infants with coarctation, with proximal arch measurements demonstrating the poorest correlation. This anatomic location represents a commonly used arch region for the determination of approach for repair of neonatal aortic coarctation. Thus, these findings have important implications for current preoperative surgical decision-making paradigms and future prospective study to minimize the risk of residual or recurrent arch obstruction.

Two-Stage Biventricular Repair of Complex Aortic Atresia.

We describe the successful 2-stage treatment of an infant with double-outlet right ventricle, aortic valve atresia, normally related great vessels, muscular outlet ventricular septal defect, and ductal arch origin of the cephalic vessels using a hybrid ductal stent and branch pulmonary artery banding followed by a comprehensive Yasui-type biventricular repair.

Open Chest Duration Following Congenital Cardiac Surgery Increases Risk for Surgical Site Infection.

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.

Computed Tomographic Angiography Provides Reliable Coronary Artery Evaluation in Infants With Pulmonary Atresia Intact Ventricular Septum.

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.

Multi-Disciplinary Management and Surgical Resection of Intracardiac Fibromas Causing Bilateral Ventricular Outflow Tract Obstructions in an Infant.

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.

Diastolic inflow is associated with inefficient ventricular flow dynamics in Fontan patients.

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.

Slide Tracheoplasty for Tracheal Cartilaginous Sleeve in a Patient With Apert Syndrome.

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 used for the expansion of long segment tracheal stenosis owing to TCS in a newborn with Apert syndrome. Using this technique, a safe and durable airway was achieved without tracheostomy.

High-degree Norwood neoaortic tapering is associated with abnormal flow conduction and elevated flow-mediated energy loss.

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.

Increased Aortic Stiffness and Left Ventricular Dysfunction Exist After Truncus Arteriosus Repair.

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.

Abnormal aortic flow conduction is associated with increased viscous energy loss in patients with repaired tetralogy of Fallot.

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.

Use of Nicardipine After Cardiac Operations Is Safe in Children Regardless of Age.

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.

Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death.

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.

NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A2A Receptor to Inhibit Lung Ischemia-Reperfusion Injury.

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Ex Vivo Perfusion With Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs After Circulatory Death.

BACKGROUND: Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs before transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. METHODS: Mice underwent euthanasia and 60 minutes warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 minutes). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 minutes (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP + ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. RESULTS: Ex vivo lung perfusion significantly improved lung function versus CSP, which was further, significantly improved by EVLP + ATL1223. Lung edema, cytokines, and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP + ATL1223. Gene array analysis revealed differential expression of 1594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6, and IL-17 signaling. Several pathways were uniquely regulated by EVLP + ATL1223 including the downregulation of genes involved in IL-1 signaling, such as ADCY9, ECSIT, IRAK1, MAPK12, and TOLLIP. CONCLUSIONS: Ex vivo lung perfusion modulates proinflammatory genes and reduces pulmonary dysfunction, edema, and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs.

Sphingosine-1-phosphate receptor 1 agonism attenuates lung ischemia-reperfusion injury.

Outcomes for lung transplantation are the worst of any solid organ, and ischemia-reperfusion injury (IRI) limits both short- and long-term outcomes. Presently no therapeutic agents are available to prevent IRI. Sphingosine 1-phosphate (S1P) modulates immune function through binding to a set of G protein-coupled receptors (S1PR1-5). Although S1P has been shown to attenuate lung IRI, the S1P receptors responsible for protection have not been defined. The present study tests the hypothesis that protection from lung IRI is primarily mediated through S1PR1 activation. Mice were treated with either vehicle, FTY720 (a nonselective S1P receptor agonist), or VPC01091 (a selective S1PR1 agonist and S1PR3 antagonist) before left lung IR. Function, vascular permeability, cytokine expression, neutrophil infiltration, and myeloperoxidase levels were measured in lungs. After IR, both FTY720 and VPC01091 significantly improved lung function (reduced pulmonary artery pressure and increased pulmonary compliance) vs. vehicle control. In addition, FTY720 and VPC01091 significantly reduced vascular permeability, expression of proinflammatory cytokines (IL-6, IL-17, IL-12/IL-23 p40, CC chemokine ligand-2, and TNF-α), myeloperoxidase levels, and neutrophil infiltration compared with control. No significant differences were observed between VPC01091 and FTY720 treatment groups. VPC01091 did not significantly affect elevated invariant natural killer T cell infiltration after IR, and administration of an S1PR1 antagonist reversed VPC01091-mediated protection after IR. In conclusion, VPC01091 and FTY720 provide comparable protection from lung injury and dysfunction after IR. These findings suggest that S1P-mediated protection from IRI is mediated by S1PR1 activation, independent of S1PR3, and that selective S1PR1 agonists may provide a novel therapeutic strategy to prevent lung IRI.

Chest radiography does not alter the treatment course for children after rigid bronchoscopy.

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.

Ventricular assist devices and increased blood product utilization for cardiac transplantation.

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.

Planned cardiac reexploration in the intensive care unit is a safe procedure.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%, p<0.001) and incurred higher observed mortality (37% vs 6%, p<0.001) 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], p<0.001) compared with planned ICU reexplorations. CONCLUSIONS: 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.

Inhibition of interleukin-1ß decreases aneurysm formation and progression in a novel model of thoracic aortic aneurysms.

BACKGROUND: Thoracic aortic aneurysms (TAAs) are common, but experimental TAA models are limited and the role of interleukin-1ß (IL-1ß) is undetermined. METHODS AND RESULTS: IL-1ß protein was measured in human TAAs and control aortas, and IL-1ß protein was increased ≈20-fold in human TAAs. To develop an experimental model of TAAs, 8- to 10-week-old male C57Bl/6 mice (wild type [WT]) underwent thoracotomy with application of periadventitial elastase (WT TAA) or saline (WT control; n=30 per group). Elastase treatment to thoracic aortas resulted in progressive dilation until day 14 with maximal dilation of 99.6±24.7% compared with 14.4±8.2% for WT saline control (P<0.0001). WT TAAs demonstrated elastin fragmentation, smooth muscle cell loss, macrophage infiltration, and increased IL-1ß expression. Next, TAAs were induced in mice deficient of IL-1ß (IL-1ß knockout) or IL-1 receptor (IL-1R knockout; n=10 each). Genetic deletion of IL-1ß and IL-1R significantly decreased thoracic aortic dilation (IL-1ß knockout=54.2±16.8% and IL-1R knockout=62.6±17.2% versus WT TAA=104.7±23.8%; P<0.001for both). IL-1ß knockout and IL-1R knockout aortas demonstrated preserved elastin and smooth muscle cells with fewer inflammatory cells. Correspondingly, IL-1ß and IL-1R knockout aortas had decreased inflammatory cytokine and matrix metalloproteinase 9 expression. Separately, WT mice pretreated with either IL-1R antagonist anakinra (100 mg/kg per day) or vehicle alone (control) underwent elastase treatment. Pretreatment of WT mice with anakinra attenuated TAA formation (control: 99.2±15.5% versus anakinra: 68.3±19.2%; P<0.005). Finally, to investigate treatment of small TAAs, WT mice were treated with anakinra 3 days after TAA induction. Anakinra treatment in WT mice with small TAAs reduced aortic dilation on day 14 (control treatment: 89.1±18.6% versus anakinra treatment: 59.7±25.7%; P=0.01). CONCLUSIONS: Periadventitial application of elastase to murine thoracic aortas reproducibly produced aneurysms with molecular and histological features consistent with TAA disease. Genetic and pharmacological inhibition of IL-1ß decreased TAA formation and progression, indicating that IL-1ß may be a potential target for TAA treatment.