National experience with pediatric surgical aortic valve repair: A Pediatric Health Information System analysis.

OBJECTIVE: To characterize national experience with surgical aortic valve repair in pediatric patients. METHODS: Patients in the Pediatric Health Information System database aged 17 years or younger with International Statistical Classification of Diseases and Related Health Problems codes for open aortic valve repair from 2003 to 2022 were included (n = 5582). Outcomes of reintervention during index admission (repeat repair, n = 54; replacement, n = 48; and endovascular intervention, n = 1), readmission (n = 2176), and in-hospital mortality (n = 178) were compared. A logistic regression was performed for in-hospital mortality. RESULTS: One-quarter (26%) of patients were infants. The majority (61%) were boys. Heart failure was present in 16% of patients, congenital heart disease in 73%, and rheumatic disease in 4%. Valve disease was insufficiency in 22% of patients, stenosis in 29%, and mixed in 15%. The highest quartile of centers by volume (median, 101 cases; interquartile range, 55-155 cases) performed half (n = 2768) of cases. Infants had the highest prevalence of reintervention (3%; P < .001), readmission (53%; P < .001), and in-hospital mortality (10%; P < .001). Previously hospitalized patients (median, 6 days; interquartile range, 4-13 days) were at higher risk for reintervention (4%; P < .001), readmission (55%; P < .001), and in-hospital mortality (11%; P < .001), as were patients with heart failure (reintervention [6%; P < .001], readmission [42%; P = .050], and in-hospital mortality [10%; P < .001]). Stenosis was associated with reduced reintervention (1%; P < .001) and readmission (35%; P = .002). The median number of readmissions was 1 (range, 0-6) and time to readmission was 28 days (interquartile range, 7-125 days). A regression of in-hospital mortality identified heart failure (odds ratio, 3.05; 95% CI, 1.59-5.49), inpatient status (odds ratio, 2.40; 95% CI, 1.19-4.82), and infancy (odds ratio, 5.70; 95% CI, 2.60-12.46) as significant. CONCLUSIONS: The Pediatric Health Information System cohort demonstrated success with aortic valve repair; however, early mortality remains high in infants, hospitalized patients, and patients with heart failure.

The majority of pediatric Fontan patients have excellent post-transplant survival.

OBJECTIVE: Many pediatric Fontan patients require heart transplant, but this cohort is understudied given the difficulty in identifying these patients in national registries. We sought to characterize survival post-transplant in a large cohort of pediatric patients undergoing the Fontan. METHODS: The United Network for Organ Sharing and Pediatric Health Information System were used to identify Fontan heart transplant recipients aged less than 18 years (n = 241) between 2005 and 2022. Decompensation was defined as the presence of extracorporeal membrane oxygenation, ventilation, hepatic/renal dysfunction, paralytics, or total parenteral nutrition at transplant. RESULTS: Median age at transplant was 9 (interquartile range, 5-12) years. Median waitlist time was 107 (37-229) days. Median volume across 32 center was 8 (3-11) cases. Approximately half (n = 107, 45%) of recipients had 1A/1 initial listing status. Sixty-four patients (28%) were functionally impaired at transplant, 10 patients (4%) were ventilated, and 18 patients (8%) had ventricular assist device support. Fifty-nine patients (25%) had hepatic dysfunction, and 15 patients (6%) had renal dysfunction. Twenty-one patients (9%) were dependent on total parenteral nutrition. Median postoperative stay was 24 (14-46) days, and in-hospital mortality was 7%. Kaplan-Meier analysis showed 1- and 5-year survivals of 89% (95% CI, 85-94) and 74% (95% CI, 81-86), respectively. Kaplan-Meier of Fontan patients without decompensation (n = 154) at transplant demonstrated 1- and 5-year survivals of 93% (95% CI, 88-97) and 88% (95% CI, 82-94), respectively. In-hospital mortality was higher in decompensated patients (11% vs 4%, P = .023). Multivariable analysis showed that decompensation predicted worse post-transplant survival (hazard ratio, 2.47; 95% CI, 1.16-5.22; P = .018), whereas older age at transplant predicted superior post-transplant survival (hazard ratio, 0.89/year; 95% CI, 0.80-0.98; P = .019). CONCLUSIONS: Pediatric Fontan post-transplant outcomes are promising, although early mortality remains high. For nondecompensated pediatric patients at transplant without end-organ disease (>63% of cohort), early mortality is circumvented and post-transplant survival is excellent and similar to all pediatric transplantation.

Factor XII promotes the thromboinflammatory response in a rat model of venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Factor XII (FXII) is a multifunctional protease capable of activating thrombotic and inflammatory pathways. FXII has been linked to thrombosis in extracorporeal membrane oxygenation (ECMO), but the role of FXII in ECMO-induced inflammatory complications has not been studied. We used novel gene-targeted FXII- deficient rats to evaluate the role of FXII in ECMO-induced thromboinflammation. METHODS: FXII-deficient (FXII-/-) Sprague-Dawley rats were generated using CRISPR/Cas9. A minimally invasive venoarterial (VA) ECMO model was used to compare wild-type (WT) and FXII-/- rats in 2 separate experimental cohorts: rats placed on ECMO without pharmacologic anticoagulation and rats anticoagulated with argatroban. Rats were maintained on ECMO for 1 hour or until circuit failure occurred. Comparisons were made with unchallenged rats and rats that underwent a sham surgical procedure without ECMO. RESULTS: FXII-/- rats were maintained on ECMO without pharmacologic anticoagulation with low resistance throughout the 1-hour experiment. In contrast, WT rats placed on ECMO without anticoagulation developed thrombotic circuit failure within 10 minutes. Argatroban provided a means to maintain WT and FXII-/- rats on ECMO for the 1-hour time frame without thrombotic complications. Analyses of these rats demonstrated that ECMO resulted in increased neutrophil migration into the liver that was significantly blunted by FXII deficiency. ECMO also resulted in increases in high molecular weight kininogen cleavage and complement activation that were abrogated by genetic deletion of FXII. CONCLUSIONS: FXII initiates hemostatic system activation and key inflammatory sequelae in ECMO, suggesting that therapies targeting FXII could limit both thromboembolism and inopportune inflammatory complications in this setting.

Hand-Constructed CorMatrix Tubular Valve Used for Tricuspid Valve Replacement in Neonate With Congenital Tricuspid Dysplasia: Five-Year Follow-Up.

Tricuspid valve (TV) dysplasia is a rare congenital defect that, in severe cases, can cause heart failure necessitating surgical correction. TV replacement options are limited in neonates since few commercial valves are available and the rates of failure and postoperative mortality are high. The authors report a neonate with TV dysplasia who underwent replacement with a hand-constructed tube valve using small intestinal submucosal extracellular matrix, which functioned well for >5 years.

Exogenous nitric oxide delivery protects against cardiopulmonary bypass-associated acute kidney injury: Histologic and serologic evidence from an ovine model.

OBJECTIVE: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. METHODS: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. RESULTS: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). CONCLUSIONS: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

A Murine Model of Veno-Arterial Extracorporeal Membrane Oxygenation.

The mechanisms driving the pathologic state created by extracorporeal membrane oxygenation (ECMO) remain poorly defined. We developed the first complete blood-primed murine model of veno-arterial ECMO capable of maintaining oxygenation and perfusion, allowing molecular studies that are unavailable in larger animal models. Fifteen C57BL/6 mice underwent ECMO by cannulating the left common carotid artery and the right external jugular vein. The mean arterial pressure was measured through cannulation of the femoral artery. The blood-primed circuit functioned well. Hemodynamic parameters remained stable and blood gas analyses showed adequate oxygenation of the animals during ECMO over a 1-hour timeframe. A significant increase in plasma-free hemoglobin was observed following ECMO, likely secondary to hemolysis within the miniaturized circuit components. Paralleling clinical data, ECMO resulted in a significant increase in plasma levels of multiple proinflammatory cytokines as well as evidence of early signs of kidney and liver dysfunction. These results demonstrate that this novel, miniature blood-primed ECMO circuit represents a functional murine model of ECMO that will provide unique opportunities for further studies to expand our knowledge of ECMO-related pathologies using the wealth of available genetic, pharmacological, and biochemical murine reagents not available for other species.

Pediatric heart transplantation: The past, the present, and the future.

Heart transplantation (HTx) has a storied past, with origins dating back to the early twentieth century and the first pediatric orthotopic heart transplant performed in 1967 on a neonate with Ebstein abnormality. Today, approximately 500 pediatric HTx are performed annually, with survival times now measured in decades rather than days or weeks. In large part, advances in immunosuppression, critical care, dedicated transplant teams and mechanical circulatory support have paved the way for improvements in waitlist mortality and post-transplant survival, with future directions including the development of intracorporeal ventricular assist devices (VADs) for small children, expanding/standardizing donor criteria, and xenotransplantation.