Social Determinants of Health and Outcomes After Pediatric Ventricular Assist Device Implantation.

BACKGROUND: Limited research exists on the influence of social determinants of health (SDOH) on outcomes in pediatric patients with advanced heart failure receiving mechanical circulatory support. METHODS: Linkage of the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) and Society of Thoracic Surgeon's Congenital Heart Surgery Database (STS-CHSD) identified pediatric patients who underwent ventricular assist device (VAD) implantation from 2012 to 2022 with available residential zip codes. Utilizing the available zip codes, each patient was assigned a Childhood Opportunity Index (COI) score. Level of childhood opportunity, race, and insurance type were used as proxies for SDOH. Major outcomes included death, transplant, alive with device, and recovery. Secondary outcomes were adverse events. Statistical analyses were performed using the Kaplan-Meier survival, competing risk analyses, and multivariable Cox proportional hazards model. RESULTS: Three hundred seventeen patients were included in the study. Childhood opportunity level and insurance status did not significantly impact morbidity or mortality after VAD implantation. White race was associated with reduced 1-year survival (71% in White vs. 87% in non-White patients, p = 0.05) and increased risk of pump thrombosis (p = 0.02). CONCLUSION: Childhood opportunity level and insurance status were not linked to morbidity and mortality in pediatric patients after VAD implantation. Notably, White race was associated with higher mortality rates. The study underscores the importance of considering SDOH in evaluating advanced therapies for pediatric heart failure and emphasizes the need for accurate socioeconomic data collection in future studies and national registries.

Impact of donor-recipient age-difference in adolescent heart transplantation.

INTRODUCTION: The relationship between donor age and adolescent heart transplant outcomes remains incompletely understood. We aimed to explore the effect of donor-recipient age difference on survival after adolescent heart transplantation. METHODS: The United Network for Organ Sharing database was used to identify 2,855 adolescents aged 10-17 years undergoing isolated primary heart transplantation from 1/1/2000 to 12/31/2022. The primary outcome was 10-year post-transplant survival. Multivariable Cox regression identified predictors of mortality after adjusting for donor and recipient characteristics. A restricted cubic spline assessed the non-linear association between donor-recipient age-difference and the adjusted relative mortality hazard. RESULTS: The median donor-recipient age-difference was +3 (range -13 to +47) years, and 17.7% (n = 504) of recipients had an age- difference > 10 years. Recipients with an age-difference > 10 years had a less favorable pre-transplant profile, including a higher incidence of priority status 1A (81.6%, n = 411 vs. 73.6%, n = 1730; p = .01). The 10-year survival rate was 54.6% (95% confidence interval (CI) 48.8- 60.4) among recipients with a donor-recipient age-difference > 10 years and 66.9% (95% CI: 64.4-69.4) among those with an age-difference ≤10 years. An age-difference > 10 years was an independent predictor of mortality (hazard ratio 1.43, 95% CI: 1.18-1.72, p < .001). Spline analysis demonstrated that the adjusted mortality hazard increased with increasingly positive donor-recipient age-difference and became significantly higher at an age-difference of 11 years. CONCLUSION: A donor-recipient age-difference > 11 years is independently associated with higher long-term mortality after adolescent heart transplantation. This finding may help inform acceptable donor selection practice for adolescent heart transplant candidates.

Lower extremity complications in children following femoral cannulation for extracorporeal membrane oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation cannulation strategies vary between adults and children. Femoral approach is common in adults and extremity morbidity is well-documented. Aside from limb ischemia, complications in children are theorized and have yet to be studied. This study aims to comprehensively evaluate implications of pediatric femoral cannulation. METHODS: This is a single-center retrospective review of children <21 years, undergoing femoral venoarterial (VA) or venovenous (VV) cannulation between 2015 and 2022. The primary outcome was incidence of lower extremity complications on ECMO (groin hematoma/hemorrhage, vascular thrombosis, North-South syndrome, compartment syndrome, limb loss). Secondary outcome was incidence of post-decannulation extremity complications (pseudoaneurysm, surgical site infection, vascular thrombosis, motor/sensory deficits). RESULTS: 29 children were cannulated via femoral approach. Most required VA support (89%). Common sites were right femoral artery (70.8%) and right femoral vein (56%). 18 patients (75%) had distal reperfusion cannulas (DPC) placed. Short-term lower extremity complication rate was 59%, most frequently groin hematoma/hemorrhage (30%) and North-South syndrome (19%). Compartment syndrome occurred in 3 patients (11%), though none suffered digit/limb loss. There were no significant differences in complications between cannulation approach (open vs percutaneous) or vessel laterality (ipsilateral vs contralateral). Of those decannulated (n = 15), median ECMO duration was 8 days. Following decannulation, 20% suffered pseudoaneurysm. Ten (63%) experienced ipsilateral motor weakness which resolved in 50% of patients at 1-month follow-up; 20% suffered sensory deficits all resolving by discharge. CONCLUSION: Approximately one third of children who underwent femoral cannulation suffered groin hematoma/hemorrhage and nearly 20% experienced North-South syndrome. Following decannulation, most had extremity weakness while sensory deficits were rarer. This marked risk of extremity morbidity prompts proactive inpatient monitoring and close surveillance after discharge.

Advanced Therapies for Severe Tracheobronchomalacia: A Review of the Use of 3D-Printed, Patient-Specific, Externally Implanted, Bioresorbable Airway Splints.

Tracheobronchomalacia is a condition of dynamic collapse of the trachea and mainstem bronchi. The clinical significance of tracheobronchomalacia depends on its severity. Mild cases may be medically managed with limited symptomology, while severe cases require advanced therapies, lengthy hospital stays, and carry significant morbidity and mortality. Current therapies for severe tracheobronchomalacia include tracheostomy with prolonged mechanical ventilation, aortopexy, tracheobronchopexy, and intraluminal metallic, silicone, or bioresorbable stents. Three-dimensional (3D)-printed, patient-specific, bioresorbable airway splinting is a novel treatment option that is undergoing investigation in a cohort of critically ill children with severe tracheobronchomalacia. At the time of our last review of our data, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. The median follow-up was 8.5 months. There were 12 long-term survivors, and all but one lived at home. This article discusses the details of our institution's development and use of 3D-printed, patient-specific, bioresorbable splints for treatment of severe tracheobronchomalacia in the pediatric population.

Smartphone-based app for evaluating cardiothoracic residents: Feasibility and engagement.

PURPOSE: Timely and high-quality feedback is important in cardiothoracic (CT) surgery education. Feedback on operative proficiency is an area for improvement in CT surgery programs. Traditional evaluations significantly lag behind operative interactions. We hypothesized that use of the System for Improving and Measuring Procedural Learning (SIMPL) app would improve operative feedback for trainees. METHODS: Use of SIMPL was evaluated from December 2018 to January, 2021 within an academic CT surgery training program. Ratings include level of supervision, complexity of the operation, and trainee performance. Completion was limited to 72 h after the operation. Descriptive statistics of the users and ratings are presented. RESULTS: Over 28 months, 816 evaluations were completed, and of these, 495 had a rating from both the faculty and trainee. There were 19 trainees representing post-graduate years 1-8 and 19 faculty members who received or submitted at least one evaluation over the study period. The number of evaluations for each trainee ranged from 1 to 166 and from 1 to 81 for each of the faculty. The response rate for faculty ranged from 0% to 100%. "Active help" was the most common type of supervision (50.7% by the faculty, 60.4% from the trainees). CONCLUSIONS: Use of SIMPL within a CT surgery training program was feasible and engagement was observed from both trainees and faculty. SIMPL provided trainees with timely, concise feedback on operative performance. Further work will focus on correlating SIMPL ratings with pre-existing assessments of performance.

Mechanical Thrombectomy Improves Outcome for Large Vessel Occlusion Stroke after Cardiac Surgery.

BACKGROUND: Stroke is a feared complication of cardiac surgery. Modern clot-retrieval techniques provide effective treatment for large vessel occlusion (LVO) strokes. The purpose of this study was to 1) report the incidence of LVO stroke after cardiac surgery at a large academic center, and 2) describe outcomes of postoperative LVO strokes. METHODS: All patients experiencing stroke within 30 days after undergoing cardiac surgery at a single center in 2014-2018 were reviewed. LVOs were identified through review of imaging and medical records, and their characteristics and clinical courses were examined. RESULTS: Over the study period, 7,112 cardiac surgeries, including endovascular procedures, were performed. Acute ischemic stroke within 30 days after surgery was noted in 163 patients (2.3%). Among those with a stroke, 51/163 (31.3%) had a CTA or MRA, and 15/163 (9.2%) presented with LVO stroke. For all stroke patients, the median time from surgery to stroke was 2 days (interquartile range, IQR, 0-6 days), and for patients with LVO, the median time from surgery to stroke was 4 days (IQR 0-6 days). The overall rate of postoperative LVO was 0.2% (95% CI 0.1-0.4%), though only 6/15 received thrombectomy. LVO patients receiving thrombectomy were significantly more likely to return to independent living compared to those managed medically (n = 4/6, 66.6% for mechanical thrombectomy vs. n = 0/9, 0% for medical management, P = .01). Of the 9 patients who did not get thrombectomy, 6 may currently be candidates for thrombectomy given new expanded treatment windows. CONCLUSIONS: The rate of LVO after cardiac surgery is low, though substantially elevated above the general population, and the majority do not receive thrombectomy currently. Patients receiving thrombectomy had improved neurologic outcomes compared to patients managed medically. Optimized postoperative care may increase the rate of LVO recognition, and cardiac surgery patients and their caregivers should be aware of this effective therapy.

Deletion of cysteine-cysteine receptor 7 promotes fibrotic injury in experimental post-thrombotic vein wall remodeling.

OBJECTIVE: Deep vein thrombosis (VT) can result in vein wall injury, which clinically manifests as post-thrombotic syndrome. Postinjury fibrosis may be modulated in part through cellular cysteine-cysteine receptor 7 (CCR7)-mediated events. We tested the hypothesis that late vein wall fibrotic remodeling is dependent on CCR7. APPROACH AND RESULTS: CCR7(-/-) and C57BL/6 wild-type mice had inferior vena cava VT induced by nonstasis or stasis mechanisms. In both models, VT size was largest at day 1 and trended down by day 21, and CCR7(+) cells peaked at day 8 in wild-type mice. No significant differences in VT resolution were found in CCR7(-/-) as compared with wild type in either model. In the nonstasis VT model, vein wall changes consistent with fibrotic injury were evidenced by significant increases in collagen I, III, matrix metalloproteinase 2, and transforming growth factor-ß gene expression, increases in α-smooth muscle actin and fibroblast specific protein-1 antigen, and total collagen at 8 days. Correspondingly, SM22α and fibroblast specific protein-1, but not DDR2(+) cells, were increased at 8 days. Early wild-type thrombus exposure inhibited profibrotic gene expression in CCR7(-/-) in ex vivo vein wall culture. Bone marrow chimera experiments further showed that circulating CCR7(+) leukocytes partially rescued midterm profibrotic changes in CCR7(-/-) mice. In human histological sections of chronic thrombosed femoral veins, CCR7(+) cells were present in the fibrotic areas. CONCLUSIONS: Post-thrombotic vein wall remodeling is impaired in CCR7(-/-) mice, with a profibrotic phenotype, is dependent on the thrombotic mechanism, and is mediated by circulating CCR7(+) cells. Unlike other postinjury fibrotic responses, CCR7(+) signaling may be important for positive vein wall remodeling after VT.

Open and endovascular repair of the nontraumatic isolated aortic arch aneurysm.

OBJECTIVE: Repair of isolated aortic arch aneurysms (nontraumatic) by either open (OAR) or endovascular (TEVAR) methods is associated with need for hypothermic circulatory arrest, complex debranching procedures, or use of marginal proximal landing zones. This study evaluates outcomes for treatment of this cohort. METHODS: Of 2153 patients undergoing arch repair (1993-2013), 137 (mean age, 60 years) were treated with isolated arch resection for nontraumatic aneurysms. Treatment was by open (n = 93), hybrid (n = 11), or TEVAR (n = 33) methods, with the last two approaches reserved for poor OAR candidates. Treatment was predominantly for saccular (n = 53) or fusiform (n = 30) aneurysms or dissection (n = 15). Rupture was present in 15%. Prior aortic repair was performed in the ascending (n = 30), arch (n = 40), descending (n = 24), or abdominal (n = 9) aorta. Propensity score adjustment was performed for multivariable analysis to account for baseline differences in patient groups as well as treatment selection bias. RESULTS: Early mortality was seen in nine patients (7%). Morbidity included stroke (n = 9), paraplegia (n = 1), and need for dialysis (n = 5) or tracheostomy (n = 10). A composite outcome of death and stroke was independently predicted by advancing age (P = .055) and performance of a hybrid procedure (P = .012). The 15-year survival was 59%, with late mortality predicted by increasing age, presence of peripheral vascular disease, and perioperative stroke (all P < .05). The 10-year freedom from aortic rupture or reintervention was 75% and was higher after OAR (2-year OAR, 94% vs TEVAR or hybrid, 78%; P = .018). After propensity-adjusted Cox regression analysis, both prior abdominal aortic aneurysmectomy (P = .017) and an endovascular or hybrid procedure (P = .001) independently predicted late aortic rupture or need for reintervention. CONCLUSIONS: Isolated arch repair remains a high-risk procedure occurring frequently in the reoperative setting. Despite being performed in a higher risk group, endovascular strategies yielded similar outcomes but with an increased risk for aorta-related complications. These data support ongoing efforts to develop branched endografts specifically tailored for arch disease to potentially reduce morbidity related to currently available approaches.

Hybrid Interventions in Congenital Heart Disease: A Review of Current Practice and Rationale for Use.

BACKGROUND: Hybrid interventions have become a common option in the management for a variety of patients with congenital heart disease. In this review, we discuss the data that have driven decision making about hybrid interventions to date. METHODS: The existing literature on various hybrid approaches was reviewed and summarized. In addition, the key tenants to creating a successful hybrid program within a congenital heart center are elucidated. RESULTS: Hybrid strategies for single-ventricle patients, pulmonary atresia with intact ventricular septum, branch pulmonary artery stenosis, and muscular ventricular septal defect closure have important benefits and limitations compared with traditional approaches. CONCLUSION: A growing body of evidence supports the use of hybrid interventions in congenital heart disease. But important questions remain regarding improved survival and other long-term outcomes, such as neurocognition, that might impact widespread adoption as a primary treatment strategy.

Hypoplastic Left Heart Syndrome with Mitral Stenosis and Aortic Atresia-Echocardiographic Findings and Early Outcomes.

BACKGROUND: Mitral stenosis/aortic atresia (MS/AA) has been reported as a high-risk variant of hypoplastic left heart syndrome (HLHS), potentially related to ventriculocoronary connections (VCCs) or endocardial fibroelastosis (EFE) and myocardial hypoperfusion. We aimed to identify echocardiographic and clinical factors associated with early death or transplant in this group. METHODS: Patients with HLHS MS/AA treated at our center between 2000 and 2020 were included. Pre-stage I palliation echocardiograms were reviewed. Certain imaging factors, such as determination of VCC, EFE, and measurement of tricuspid annular plane systolic excursion were measured from retrospective review of preoperative images; others were derived from clinical reports. Groups were compared according to primary outcome of death or transplant prior to stage II palliation. RESULTS: Of 141 patients included, 39 (27.7%) experienced a primary outcome. Ventriculocoronary connections were identified in 103 (73.0%) patients and EFE in 95 (67.4%) patients. Among imaging variables, smaller ascending aorta size (median, 2.2 [interquartile range (IQR) 1.7-2.8] vs 2.6 [2.2-3.4] mm, P = .01) was associated with primary outcome. There was similar frequency of VCC (74.4% vs 72.5%, P = .83), EFE (59.0% vs 72.5%, P = .19), moderate or greater tricuspid regurgitation (5.1% vs 5.9%, P = 1.00), and similar right ventricular systolic function (indexed tricuspid annular plane systolic excursion 32.5 ± 7.3 vs 31.4 ± 7.2 mm/m2, P = .47) in the primary outcome group compared to other patients. Clinical factors associated with primary outcome included lower birth weight (mean, 2.8 ± SD 0.8 vs 3.3 ± 0.5 kg, P = .0003), gestational age <37 weeks (31.6% vs 4.9%, P < .0001), longer cardiopulmonary bypass time (median, 112 [IQR, 93-162] vs 82 [71-119] minutes, P = .001), longer intensive care unit length of stay (median, 19 [IQR, 10-30] vs 10 [7-15] days, P = .001), and extracorporeal membrane oxygenation following stage I palliation (43.6% vs 8.8%, P < .0001). Presence of VCCs and EFE was not associated with death or transplant after controlling for birth weight and era of stage I palliation. CONCLUSIONS: In one of the largest reported single-center cohorts of HLHS MS/AA, there were few pre-stage I palliation imaging characteristics associated with primary outcome. Imaging findings evaluated in this study, including the presence of VCC and/or EFE as determined using highly sensitive echocardiogram criteria, should not preclude intervention, although impact on long-term outcomes requires further evaluation.

Determinants of survival following heart transplantation in adults with congenital heart disease.

BACKGROUND: Adult patients surviving with congenital heart disease (ACHD) is growing. We examine the factors associated with heart transplant outcomes in this challenging population with complex anatomy requiring redo-surgeries. METHODS: We reviewed the United Network for Organ Sharing-Standard Transplant Analysis and Research database and analyzed 35,952 heart transplants from January 1st, 2000, to September 30th, 2018. We compared transplant characteristics for ischemic cardiomyopathy (ICM) (n = 14,236), nonischemic cardiomyopathy (NICM) (n = 20,676), and ACHD (n = 1040). Mean follow-up was 6.20 ± 4.84 years. Kaplan-Meier survival curves and Cox-proportional hazards analysis were used to analyze survival data. RESULTS: Multivariable analysis confirmed that ACHD was associated greater in-hospital death compared to ICM (HR = 0.54, P < 0.001) and NICM (HR = 0.46, P < 0.001). Notable factors associated with increased mortality were history of cerebrovascular disease (HR = 1.11, P = 0.026), prior history of malignancy (HR = 1.12, P = 0.006), pre-transplant biventricular support (HR = 1.12, P = 0.069), postoperative stroke (HR = 1.47, P < 0.001) and postoperative dialysis (HR = 1.71, P < 0.001). ACHD transplants had a longer donor heart ischemic time (P < 0.001) and trend towards more deaths from primary graft dysfunction (P = 0.07). In-hospital deaths were more likely with ACHD and use of mechanical support such as use of right ventricular assist device (HR = 2.20, P = 0.049), biventricular support (HR = 1.62, P < 0.001) and extracorporeal membrane oxygenation (HR = 2.36, P < 0.001). Conditional survival after censoring hospital deaths was significantly higher in ACHD (P < 0.001). CONCLUSION: Heart transplant in ACHD is associated with a higher post-operative mortality given anatomical complexity but a better long-term conditional survival. Normothermic donor heart perfusion may improve outcomes in the ACHD population by reducing the impact of longer ischemic times.

The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling.

BACKGROUND: Vein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP2 contributes to vein wall remodeling after VT is unknown. METHODS: Stasis VT was produced by ligation of the inferior vena cava and tissue was harvested at 2, 8, and 21 days in MMP2 -/- and genetic wild type (WT) mice. Tissue analysis by immunohistochemistry, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and zymography was performed. RESULTS: Thrombus resolution was less at 8 days in MMP2 -/- compared with WT, evidenced by a 51% increase in VT size (P < .01), and threefold fewer von Willebrand's factor positive channels (P < .05). In MMP2 -/- mice, the main phenotypic fibrotic differences occurred at 8 days post-VT, with significantly less vein wall collagen content (P = .013), fourfold lower procollagen III gene expression (P < .01), but no difference in procollagen I compared with WT. Decreased inflammation in MMP2 -/- vein walls was suggested by ∼ threefold reduced TNFα and IL-1ß at 2 days and 8 days post-VT (P < .05). A fourfold increase in vein wall monocytes (P = .03) with threefold decreased apoptosis (P < .05), but no difference in cellular proliferation at 8 days was found in MMP2 -/- compared with WT. As increased compensatory MMP9 activity was observed in the MMP2 -/-mice, MMP2/9 double null mice had thrombus induced with VT harvest at 8 days. Consistently, twofold larger VT, a threefold decrease in vein wall collagen, and a threefold increase in monocytes were found (all P < .05). Similar findings were observed in MMP9 -/- mice administered an exogenous MMP2 inhibitor. CONCLUSIONS: In stasis VT, deletion of MMP2 was associated with less midterm vein wall fibrosis and inflammation, despite an increase in monocytes. Consideration that VT resolution was impaired with MMP2 (and MMP2/9) deletion suggests direct inhibition will likely also require anticoagulant therapy.

Considerations of valvular heart disease in children with ventricular assist devices.

Ventricular assist devices have become a valuable tool in the treatment of heart failure in children. The use of ventricular assist devices has decreased mortality in children with end-stage heart failure awaiting transplant. It is not uncommon for children with end-stage heart failure associated with cardiomyopathy or congenital heart disease to have significant systemic semilunar and atrioventricular valve regurgitation, which can impact the efficiency and efficacy of hemodynamic support provided by a ventricular assist device. Therefore, implanting clinicians should carefully assess for valve abnormalities that may need repair and impact device selection and cannulation strategy to effectively support this diverse population. The purpose of this review is to provide an overview of this important and relevant topic and to discuss strategies for managing these patients.

Contemporary Outcomes of Tracheostomy in Patients With Single Ventricle Heart Lesions.

OBJECTIVES: Approximately 0.2% to 2.7% of children with congenital heart disease require a tracheostomy after cardiac surgery with the majority having single ventricle (SV) type heart lesions. Tracheostomy in SV patients is reported to be associated with high mortality. We hypothesized that short- and long-term survival of patients with SV heart disease would vary according to tracheostomy indication. METHODS: This is a single center, 20-year, retrospective review of all patients with SV heart disease who underwent tracheostomy. Demographic, cardiac anatomy, surgical, intensive care unit, and hospital course data were collected. The primary outcome was survival following tracheostomy. Secondary outcome was the completion of staged palliation to Fontan. RESULTS: In total, 25 patients with SV heart disease who underwent tracheostomy were included. Indications for tracheostomy included one or more of the following: tracheobronchomalacia (n = 8), vocal cord paralysis (n = 7), tracheal/subglottic stenosis (n = 6), primary respiratory insufficiency (n = 4), diaphragm paralysis (n = 3), suboptimal hemodynamics (n = 2), and other upper airway issues (n = 1). Survival at six months, one year, five years, and ten years was 76%, 68%, 63%, and 49%, respectively. Most patients completed Fontan palliation (64%). Patients who underwent tracheostomy for suboptimal hemodynamics and/or respiratory insufficiency had a higher mortality risk compared to those with indications of upper airway obstruction or diaphragm paralysis (hazard ratio 4.1, 95% confidence interval 1.2-13.7; P = .02). CONCLUSIONS: Mortality risk varies according to tracheostomy indication in patients with SV heart disease. Tracheostomy may allow staged surgical palliation to proceed with acceptable risk if it was indicated for anatomic or functional airway dysfunction.

Long-term impact of anatomic subtype in hypoplastic left heart syndrome after Fontan completion.

BACKGROUND: Aortic atresia (AA)/mitral stenosis (MS) is a well-known risk factor for survival after Norwood; however, the effect of anatomical subtypes in those who survive surgical palliation is unknown. METHODS: We performed a retrospective single-center study of patients with classic hypoplastic left heart syndrome (HLHS) who underwent Fontan at our center between August 1989 and July 2017. Clinical outcomes, as well as ventricular and atrioventricular-valve (AVV) function, were determined for each patient, and the effects of HLHS subtype were estimated using multivariable statistical analyses. RESULTS: We included 418 patients with HLHS (AA/mitral atresia [MA] 153, AA/MS 100, aortic stenosis [AS]/MS 154, and AS/MA 11). The median follow-up period was 8.6 (interquartile range, 2.9-15.8) years. Overall transplant-free survival, cumulative incidence of AVV failure, and ventricular failure, which were defined by moderate dysfunction or greater or the necessity of surgical interventions, were 70.1%, 35.9%, and 17.9% at 20 years, respectively. Of the 3 major subtypes, AA/MS was associated with lower survival rate (AA/MA 74.6% vs AS/MS 79.1% vs AA/MS 56.1% at 17 years, P = .04). The subanalysis between AA/MA and AA/MS revealed AA/MS tended to have a greater rate of ventricular failure without a significant difference of AVV failure (AA/MA 11.2% vs AA/MS 26.2% at 17 years, P = .053). CONCLUSIONS: The survival risk of the anatomic subtype AA/MS persisted long term after Fontan completion and was likely due to a greater rate of single ventricle rather than AVV failure. These findings suggest that the abnormal pressure overload condition of the hypoplastic left ventricle created by AA/MS has a detrimental effect on single right ventricle function.

Unicuspid Aortic Valve With Severe Aortic Stenosis and Progressive Heart Failure During Pregnancy.

A 39-year-old gravida 7 para 6 woman with unicuspid aortic valve and severe symptomatic stenosis was admitted to the hospital at 15 weeks gestation. We describe maternal cardiovascular complications and their implication on obstetric and fetal care. We also describe our multidisciplinary approach to caring for this complex patient.

The role of urokinase plasminogen activator and plasmin activator inhibitor-1 on vein wall remodeling in experimental deep vein thrombosis.

OBJECTIVE: Deep vein thrombosis (DVT) resolution instigates an inflammatory response, resulting in vessel wall damage and scarring. Urokinase-plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), are integral components of the fibrinolytic system, essential for venous thrombosis (VT) resolution. This study determined the vein wall response when exposed to increased and decreased plasmin activity. METHODS: A mouse inferior vena cava (IVC) ligation model in uPA -/- or PAI-1 -/- and their genetic wild types (B6/SvEv and C57/BL6, respectively) was used to create stasis thrombi, with tissue harvest at either 8 or 21 days. Tissue analysis included gene expression of vascular smooth muscle cells (alpha smooth muscle actin [αSMA], SM22) and endothelial marker (CD31), by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, matrix metalloproteinase (MMP)-2 and -9 activity by zymography, and vein wall collagen by picro-Sirius red histologic analysis. A P < .05 was considered significant. RESULTS: Thrombi were significantly larger in both 8-day and 21-day uPA -/- as compared with wild type (WT) and were significantly smaller in both 8-day and 21-day PAI-1 -/- as compared with WT. Correspondingly, 8-day plasmin levels were reduced in half in uPA -/- and increased three-fold in PAI-1 -/- when compared with respective WT thrombi (P < .05; n = 5-6). The endothelial marker CD31 was elevated two-fold in PAI-1 -/- mice at 8 days, but reduced 2.5-fold at 21 days in uPA -/- as compared with WT (P = .02; n = 5-6), suggesting less endothelial preservation. Vein wall vascular smooth muscle cell (VSMC) gene expression showed that 8-day and 21-day PAI-1 -/- mice had 2.3- and 3.8-fold more SM22 and 1.8- and 2.3-fold more αSMA expression than respective WT (P < .05; n = 5-7), as well as 1.8-fold increased αSMA (+) cells (P ≤ .05; n = 3-5). No significant difference in MMP-2 or -9 activity was found in the PAI-1 -/- mice compared with WT, while 5.4-fold more MMP-9 was present in 21-day WT than 21-day uPA -/- (P = .03; n = 5). Lastly, collagen was ∼two-fold greater at 8 days in PAI-1 -/- IVC as compared with WT (P = .03; n = 6) with no differences observed in uPA -/- mice. CONCLUSIONS: In stasis DVT, plasmin activity is critical for thrombus resolution. Divergent vein wall responses occur with gain or loss of plasmin activity, and despite smaller VT, greater vein wall fibrosis was associated with lack of PAI-1.

Toll-like receptor 9 signaling is critical for early experimental deep vein thrombosis resolution.

OBJECTIVE: Toll-like receptors (TLR) bridge innate immunity and host responses, including inflammation. Sterile inflammation such as a venous thrombus (Vt) may involve TLR signaling, including TLR9. METHODS AND RESULTS: TLR9 signaling on thrombus resolution was investigated using a mouse model of stasis Vt. Vt were significantly larger in TLR9-/- mice compared with wild-type (WT) at 2 and 8 days, despite a 2-fold increase in thrombus polymorphonucleic neutrophils at 2 days and monocytes at 8 days, whereas thrombus collagen and neovascularization was 55% and 37% less, respectively, at 8 days. Coincidently, decreased fibrinogen and increased thrombin-antithrombin complex were observed in TLR9-/- mouse thrombi. Vein wall interferon-α, interleukin-1α, and interleukin-2 were significantly reduced in TLR9-/- mice compared with WT. Thrombus cell death pathway markers were not significantly altered at 2 days, but caspase-1 was reduced in TLR9-/- thrombi at 8 days. MyD88 confers TLR9 intracellular signaling, but MyD88-/- mice had Vt resolution similar to that of WT. However, inhibition of the NOTCH ligand δ-like 4 was associated with larger Vt. Finally, stimulation with a TLR9 agonist was associated with smaller Vt. CONCLUSIONS: TLR9 signaling is integral for early and mid-Vt resolution through modulation of sterile inflammation, maintaining a TH1 milieu, and effects on the thrombosis pathway.

Portrayal of organ donation and transplantation on American primetime television.

Recently, both living and deceased organ donation rates have hit a plateau, despite increases in need for viable organs. One approach to improve donation rate is public education and policy; thus, it is necessary to understand the information the public is receiving regarding organ donation. We hypothesized that primetime medical dramas portray organ donation and transplantation in a negative manner. We compiled data on all primetime medical drama episodes with transplant themes from November 2008 through June 2010 and assessed depictions of organ donors and transplant candidates. Positive and negative thematic elements surrounding the process and individuals involved were also identified. One hundred and fifty-five million and 145 million households watched episodes containing any negative message and any positive message, respectively. Episodes containing only negative messages had over twice the household viewership per episode compared to episodes containing only positive messages (8.4 million vs. 4.1 million, p = 0.01). Widespread exposure to these representations may reinforce public misconceptions of transplantation. The transplant community should consider the popularity of medical dramas as an opportunity to impact the perception of organ donation and transplantation for millions of Americans.