Serum Protein Changes in Pediatric Sepsis Patients Identified With an Aptamer-Based Multiplexed Proteomic Approach.

OBJECTIVES: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death and disability among children worldwide. Identifying sepsis in pediatric patients is difficult and can lead to treatment delay. Our objective was to assess the host proteomic response to infection utilizing an aptamer-based multiplexed proteomics approach to identify novel serum protein changes that might help distinguish between pediatric sepsis and infection-negative systemic inflammation and hence can potentially improve sensitivity and specificity of the diagnosis of sepsis over current clinical criteria approaches. DESIGN: Retrospective, observational cohort study. SETTING: PICU and cardiac ICU, Seattle Children's Hospital, Seattle, WA. PATIENTS: A cohort of 40 children with clinically overt sepsis and 30 children immediately postcardiopulmonary bypass surgery (infection-negative systemic inflammation control subjects) was recruited. Children with sepsis had a confirmed or suspected infection, two or more systemic inflammatory response syndrome criteria, and at least cardiovascular and/or pulmonary organ dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum samples from 35 of the sepsis and 28 of the bypass surgery subjects were available for screening with an aptamer-based proteomic platform that measures 1,305 proteins to search for large-scale serum protein expression pattern changes in sepsis. A total of 111 proteins were significantly differentially expressed between the sepsis and control groups, using the linear models for microarray data (linear modeling) and Boruta (decision trees) R packages, with 55 being previously identified in sepsis patients. Weighted gene correlation network analysis helped identify 76 proteins that correlated highly with clinical sepsis traits, 27 of which had not been previously reported in sepsis. CONCLUSIONS: The serum protein changes identified with the aptamer-based multiplexed proteomics approach used in this study can be useful to distinguish between sepsis and noninfectious systemic inflammation.

Multimodality and multiterritory vascular imaging in a toddler with acquired, complex, and unusual aortic arch anatomy.

A 20-month-old otherwise well child with no cardiac history presented for evaluation of a recent onset cardiac murmur. His initial examination revealed significant right carotid bruit along with a transthoracic echocardiogram (ECHO) concerning for severe transverse arch hypoplasia with unusual appearance and left ventricular hypertrophy with preserved function. This report demonstrates the utility of various modalities including echo, CT, and MRI to assess vascular structures in different vascular territories in a challenging patient who underwent a satisfactory arch repair with unexpected pathology findings.

A tale of two cases of pulmonary arteriovenous malformation: How they fared after cardiac transplantation.

BACKGROUND: In single ventricle patients, aortopulmonary collaterals (APCs) and pulmonary arteriovenous malformations (PAVMs) following superior cavopulmonary shunt (CPS) can complicate orthotopic heart transplant (OHT) by cyanosis and hemoptysis. Although PAVMs can regress with the restoration of hepatic venous flow to the pulmonary circulation, the effects of hypoxemia on the "unconditioned" allograft are not known. CASES: Two patients with significant PAVMs after CPS were cyanotic following OHT. One patient with predominantly unilateral left PAVMs had arterial saturation levels less than 70% despite pulmonary vasodilators and ventilation. A custom flow restrictor-covered stent was deployed in the pulmonary artery of the affected side, redirecting the blood flow to the contralateral lung, immediately improving cyanosis. When the PAVMs regressed, the flow restrictor stent was dilated to eliminate the constriction. The second patient with PAVMs had cyanosis and severe hemoptysis from APCs post-OHT. The APCs required an extensive coil embolization, while the cyanosis responded to oxygen and pulmonary vasodilators. Both recipients did well with gradual resolution of PAVMs within 8 months. CONCLUSIONS: Despite cyanosis from right-to-left intrapulmonary shunting, allograft function recovered. Novel transcatheter interventions can play a role in patients with significant APCs or PAVM following cardiac transplantation.

Hybrid stage 1 palliation as a bridge to cardiac transplantation in patients with high-risk single ventricle physiology.

BACKGROUND: The hybrid stage 1 palliation for hypoplastic left heart syndrome (HLHS) was first described in 1993 as a bridge to heart transplant for HLHS. There are limited data on this strategy as primary heart transplantation for HLHS has become less common. METHODS: This is an observational, single-center study comparing pre- and post-transplant outcomes of patients listed for transplant following hybrid palliation with those following surgical stage 1 palliation. RESULTS: From 2004 to 2017, 21 patients underwent hybrid palliation as a bridge to heart transplant and 28 patients were listed for transplant following surgical stage 1 palliation or aortic arch repair and pulmonary artery band placement. Premature birth and the presence of genetic or anatomic abnormalities were more common in the hybrid group. Need for extracorporeal membrane oxygenation (ECMO) support and ventricular dysfunction was more common in the surgical group. There was a trend toward shorter waitlist times in the surgical cohort (36 days vs 70 days, P = 0.06). There was no difference in waitlist mortality (19% vs 21%, P = 0.61). Survival at 1 and 5 years post-transplant was similar for the hybrid and surgical cohorts (5-year survival, 80% vs 85%, P = 0.94, respectively). There was no difference in the number of post-transplant interventions. CONCLUSIONS: Although the hybrid patients represented a higher risk cohort and demonstrated longer wait times, the waitlist and post-transplant mortality was equivalent between the two groups. For high-risk patients, the hybrid palliation as a bridge to transplant appears to be a reasonable strategy.

Diagnostic Accuracy of a Host Gene Expression Signature That Discriminates Clinical Severe Sepsis Syndrome and Infection-Negative Systemic Inflammation Among Critically Ill Children.

OBJECTIVES: SeptiCyte Lab (Immunexpress, Seattle, WA), a molecular signature measuring the relative expression levels of four host messenger RNAs, was developed to discriminate critically ill adults with infection-positive versus infection-negative systemic inflammation. The objective was to assess the performance of Septicyte Lab in critically ill pediatric patients. DESIGN: Prospective observational study. SETTING: Pediatric and Cardiac ICUs, Seattle Children's Hospital, Seattle, WA. PATIENTS: A cohort of 40 children with clinically overt severe sepsis syndrome and 30 children immediately postcardiopulmonary bypass surgery was recruited. The clinically overt severe sepsis syndrome children had confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), two or more systemic inflammatory response syndrome criteria (including temperature and leukocyte criteria), and at least cardiovascular ± pulmonary organ dysfunction. INTERVENTIONS: None (observational study only). MEASUREMENTS AND MAIN RESULTS: Next-generation RNA sequencing was conducted on PAXgene blood RNA samples, successfully for 35 of 40 (87.5%) of the clinically overt severe sepsis syndrome patients and 29 of 30 (96.7%) of the postcardiopulmonary bypass patients. Forty patient samples (~ 60% of cohort) were reanalyzed by reverse transcription-quantitative polymerase chain reaction, to check for concordance with next-generation sequencing results. Postcardiopulmonary bypass versus clinically overt severe sepsis syndrome descriptors included the following: age, 7.3 ± 5.5 versus 9.0 ± 6.6 years; gender, 41% versus 49% male; Pediatric Risk of Mortality, version III, 7.0 ± 4.6 versus 8.7 ± 6.4; Pediatric Logistic Organ Dysfunction, version II, 5.1 ± 2.2 versus 4.8 ± 2.8. SeptiCyte Lab strongly differentiated postcardiopulmonary bypass and clinically overt severe sepsis syndrome patients by receiver operating characteristic curve analysis, with an area-under-curve value of 0.99 (95% CI, 0.96-1.00). Equivalent performance was found using reverse transcription-quantitative polymerase chain reaction. There was no significant correlation between the score produced by the SeptiCyte Lab test and measures of illness severity, immune compromise, or microbial culture status. CONCLUSIONS: SeptiCyte Lab is able to discriminate clearly between clinically well-defined and homogeneous postcardiopulmonary bypass and clinically overt severe sepsis syndrome groups in children. A broader investigation among children with more heterogeneous inflammation-associated diagnoses and care settings is warranted.

Impact of donor-recipient sex match on long-term survival after heart transplantation in children: An analysis of 5797 pediatric heart transplants.

The effect of donor-recipient sex matching on long-term survival in pediatric heart transplantation is not well known. Adult data have shown worse survival when male recipients receive a sex-mismatched heart, with conflicting results in female recipients. We analyzed 5795 heart transplant recipients ≤ 18 yr in the Scientific Registry of Transplant Recipients (1990-2012). Recipients were stratified based on donor and recipient sex, creating four groups: MM (N = 1888), FM (N = 1384), FF (N = 1082), and MF (N = 1441). Males receiving sex-matched donor hearts had increased unadjusted allograft survival at five yr (73.2 vs. 71%, p = 0.01). However, this survival advantage disappeared with longer follow-up and when adjusted for additional risk factors by multivariable Cox regression analysis. In contrast, for females, receiving a sex-mismatched heart was associated with an 18% higher risk of allograft loss over time compared to receiving a sex-matched heart (HR 1.18, 95% CI: 1.00-1.38) and a 26% higher risk compared to sex-matched male recipients (HR 1.26, 95% CI: 1.10-1.45). Females who receive a heart from a male donor appear to have a distinct long-term survival disadvantage compared to all other groups.

Complete atrioventricular septal defect with absent or diminutive primum component: Incidence, anatomic characteristics, and outcomes.

BACKGROUND: Repair of complete atrioventricular septal defect with absent or diminutive primum defect is challenging because of atrial septal malposition and abnormal anatomy of the left atrioventricular valve. We sought to define the incidence, anatomy, and surgical outcomes of this entity. METHODS: We identified all patients in our institutional database presenting for complete atrioventricular septal defect repair from 2006 to 2018. Operative reports and echocardiograms were reviewed to determine the presence and size of the primum defect, atrioventricular valve anatomy, degree of atrioventricular valve regurgitation, repair method, and complications, including reoperation for atrioventricular valve regurgitation. Functionally univentricular patients and those receiving repair at an outside institution were excluded. RESULTS: Of 183 patients with complete atrioventricular septal defect, absent/diminutive primum defect occurred in 16 patients (8.7%; 10 absent, 6 diminutive). Six patients (38%) had leftward malposition of the atrium septum on the common atrioventricular valve. The rate of reoperation for left atrioventricular valve regurgitation was 31% (3 early, 2 late), for which preoperative predictors included leftward malposition of the atrial septum onto the common atrioventricular valve (4/6 patients with malposition required reoperation, P = .036, Fisher exact test). One patient exhibiting this risk factor died. The overall rate of moderate or greater left atrioventricular valve regurgitation on the most recent postoperative echocardiogram was 13% (2/16 patients; median follow-up, 141 days; range, 3-2236 days). CONCLUSIONS: Complete atrioventricular septal defect with absent or diminutive primum defect is a unique variant of complete atrioventricular septal defect for which the risk of reoperation for left atrioventricular valve regurgitation after complete repair is high and risk factors include leftward malposition of the atrial septum on the common atrioventricular valve.

Predictors of ECMO support in infants with tachycardia-induced cardiomyopathy.

The development of tachycardia-induced cardiomyopathy (TIC) is related to the rate and duration of supraventricular tachycardia (SVT). Infants may be more susceptible to TIC because early symptoms might be unrecognized. Extracorporeal membrane oxygenation (ECMO) may improve outcome in patients with SVT and TIC; however, clinical predictors of infants who require ECMO support have not been determined. The purpose of this study was to identify predictors of the need for ECMO in infants with SVT and TIC. Sixteen infants <6 months of age who experienced resolution of TIC following control of arrhythmia were identified. Three patients (19%) required ECMO support. Comparisons were made between patients who required ECMO and those who did not. The groups were similar with respect to age at presentation, type of SVT, rate of SVT, and degree of ventricular dysfunction. However, patients requiring ECMO had increased median M-mode-derived left ventricular end diastolic dimension (LVED) z-score when compared to the medically managed patents (+2.8 vs. 0.0, P = 0.009). No patient in the medically managed group had an LVED z-score >2.3. Infants presenting with SVT and TIC with LVED z-score >2 are at increased risk for requiring ECMO support and early use of ECMO should be considered.

Neonatal venoarterial extracorporeal membrane oxygenation cannulation technique.

Peripheral cannulation for initiation of neonatal venoarterial extracorporeal membrane oxygenation is an essential technical skill in the armamentarium of every congenital cardiac surgeon and is necessary for the care of newborns with congenital heart disease and other conditions presenting with cardiopulmonary failure. With certain exceptions, it is usually performed via a right neck cut-down to expose the right internal jugular vein and common carotid artery.   A strong understanding of the fundamental techniques, as well as strategies for avoiding common pitfalls, is critical to the success of cardiopulmonary rescue afforded by cannulation, especially considering the emergent conditions under which cannulation must usually be performed. We review here the operative approach and technique for neck cannulation for peripheral neonatal venoarterial extracorporeal membrane oxygenation.

Decision making for mechanical cardiac assist in pediatric cardiac surgery.

The practice of pediatric cardiac surgery has evolved to the point where the majority of patients operated on represent the most complex end of the spectrum of congenital heart disease. Given this, the potential role for mechanical cardiac assist will continue to expand. Although extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory assist, the increased use of centrifugal ventricular assist devices is changing the approach to the treatment of acute cardiac failure. A range of newly developed implantable and paracorporeal devices is beginning to make its way into the clinical practice of pediatric cardiac surgery. This article addresses the different types of support available for mechanical cardiac assist and the clinical considerations in selecting the appropriate device.

The Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) study: design and rationale.

BACKGROUND: Cardiopulmonary bypass induces marked and persistent depression of circulating thyroid hormones in infants and children, possibly contributing to postoperative morbidity. Clinical studies have evaluated parenteral triiodothyronine supplementation after cardiopulmonary bypass in children. However, these investigations had relatively small subject numbers as well as age and diagnosis heterogeneity, thereby limiting ability to determine clinical effect. A double-blind, randomized, placebo-controlled trial is needed to define clinical safety and efficacy of triiodothyronine supplementation in infants. METHODS AND RESULTS: The Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) study is a multicenter, randomized, clinical trial designed to determine safety and efficacy of triiodothyronine supplementation in children <2 years of age undergoing surgical procedures for congenital heart disease. Duration of mechanical ventilation after completion of cardiopulmonary bypass is the primary clinical outcome parameter with multiple secondary clinical and hemodynamic parameters. Nearly 200 patients will be randomly assigned to receive either triiodothyronine or placebo. Patient assignment will be performed using a stratified block randomization according to specific preoperative diagnosis. CONCLUSIONS: The TRICC study will provide important data regarding the efficacy and safety of triiodothyronine in this age-specific population undergoing surgery for congenital heart disease.

Thoracoscopic pericardial window creation and thoracic duct ligation in neonates.

OBJECTIVE: We describe 2 newborn infants with persistent pericardial effusion treated with thoracoscopic pericardial window and thoracic duct ligation. METHODS: Patient 1 was a premature female newborn who presented with severe cardiac anomalies, including dextrocardia. She was treated with pulmonary artery handing and pacemaker placement for complete cardiac block. Postoperatively, she developed pericarditis with persistent symptomatic pericardial effusion. She did not improve despite pericardial drain placement. She was treated with a thoracoscopic pericardial window. Patient 2 was a newborn male who presented with cardiac tamponade secondary to congenital chylopericardium. He did not respond to pericardial drain placement or medical management with fasting, total parenteral nutrition, and octreotide. He was treated with thoracoscopic pericardial window and thoracic duct ligation. RESULTS: Patient 1 improved rapidly. The pericardial effusion disappeared. The chest tube was removed 5 days following surgery. She died 6 weeks later of a cardiac arrhythmia secondary to pacemaker failure. The pericardial effusion had resolved. Patient 2 responded to the pericardial window and thoracic duct ligation. He was discharged 10 days following the procedure. CONCLUSIONS: Thoracoscopy provides an excellent approach to the pericardium. Pericardial windows and biopsy can be safely performed with this approach. The thoracic duct can be easily identified and ligated even in small babies. Recovery can be fast with minimal postoperative discomfort. Cosmetic results are excellent and length of hospitalization is minimized.

Modified Blalock-Taussig shunt versus ductal stenting for palliation of cardiac lesions with inadequate pulmonary blood flow.

OBJECTIVE: The modified Blalock-Taussig shunt is the most commonly used palliative procedure for infants with ductal-dependent pulmonary circulation. Recently, catheter-based stenting of the ductus arteriosus has been used by some centers to avoid surgical shunt placement. We evaluated the durability and safety of ductal stenting as an alternative to the modified Blalock-Taussig shunt. METHODS: A single-institution, retrospective review of patients undergoing modified Blalock-Taussig shunt versus ductal stenting was performed. Survival, procedural complications, and freedom from reintervention were the primary outcome variables. RESULTS: A total of 42 shunted and 13 stented patients with similar age and weight were identified. Survival to second-stage palliation, definitive repair, or 12 months was similar between the 2 groups (88% vs 85%; P = .742). The incidence of surgical or catheter-based reintervention to maintain adequate pulmonary blood flow was 26% in the shunted patients and 25% in the stented patients (P = 1.000). Three shunted patients (7%) required intervention to address contralateral pulmonary artery stenosis and 3 (7%) required surgical reintervention to address nonpulmonary blood flow-related complications. The need for ipsilateral or juxtaductal pulmonary artery intervention at, or subsequent to, second-stage palliation or definitive repair was similar between the 2 groups. CONCLUSIONS: Freedom from reintervention to maintain adequate pulmonary blood flow was similar between infants undergoing modified Blalock-Taussig shunt or ductal stenting as an initial palliative procedure. However, a greater percentage of shunted patients experienced procedure-related complications and distal branch pulmonary artery stenosis. Palliative ductal stenting appears to be a safe and effective alternative to modified Blalock-Taussig in selected infants.

One size does not fit all: the influence of age at surgery on outcomes following Norwood operation.

BACKGROUND: Given our large catchment area that often results in later presentation age, we sought to understand our institutional outcomes for the Norwood operation in the context of published data. Specifically, we studied whether operative and late death post-Norwood are dependent on age at operation. METHODS: Retrospective review of 105 consecutive infants undergoing Norwood (2004-2011) at our institution. Patients were divided into those undergoing Norwood ≤ 7 days of age (N = 43; 41%) and those undergoing Norwood > 7 days of age (N = 63; 59%). Operative mortality (≥30 days), interstage mortality (between Norwood and superior bidirectional Glenn), STS-mortality (operative death + in-hospital death), and late mortality, occurring any time following hospital discharge were compared among groups. Multivariable factors for mortality at each time-point were compared using logistic regression models. RESULTS: Underlying diagnosis was HLHS in 67 (64%) with the remainder (N = 38; 36%) being other single ventricle variants. Median age at surgery was 8 days (range 1-63 days) and mean weight at surgery was 3.2 ± 0.6 kg. Pulmonary blood flow was provided by a right ventricle-pulmonary artery conduit in 94% (N = 99). Overall operative survival was 92%, with 73% (N = 66) undergoing bidirectional Glenn. Median age was higher for operative survivors compared to non-survivors (12 days vs. 5 days; P = 0.036), with operative mortality higher for infants ≤7 days at Norwood compared to infants >7 days at Norwood (14% vs. 3%; P = 0.04). After censoring for in-hospital death, age ≤ 7 days was also associated with increased risk for late death (26% vs. 5%; P = 0.005). CONCLUSIONS: In contrast to other institutional series, infants at our center undergoing Norwood operation at an earlier age have worse outcomes. Adoption of published practice patterns could lead to different local outcomes because of intangible center-specific effects, underscoring the principle that results from one institution may not be generalizable to others. Targeted center-specific internal review, if possible, should precede externally recommended changes in practice.

Significance of positive mediastinal cultures in pediatric cardiovascular surgical procedure patients undergoing delayed sternal closure.

BACKGROUND: Many pediatric cardiac surgery centers obtain mediastinal cultures at the time of delayed sternal closure (DSC). There are no recommendations regarding how to treat patients with positive cultures. We explored the clinical significance of positive mediastinal cultures with regard to surgical site infections (SSI). METHODS: A retrospective study was performed on all patients who underwent DSC at our institution between December 2006 and December 2011. National Healthcare Safety Network criteria were used to prospectively identify SSIs. Univariate and multivariate logistic regression analyses were performed to evaluate potential risk factors for SSI and predictors for positive mediastinal cultures obtained at DSC. RESULTS: A total of 178 patients underwent DSC during the study period; 155 patients met the eligibility criteria for the study and were included in the analysis. Of the 155 included patients, 11 patients (7.1%) experienced SSI. Patients with a positive mediastinal culture obtained at DSC were more likely to experience SSI than were patients with a negative culture (p=0.003). In univariate analysis, a positive mediastinal culture was the only factor associated with SSI (odds ratio [OR], 7.4; 95% confidence interval [CI], 2.1 to 26.7). In multivariate analysis, age at operation≥2 weeks (adjusted OR [aOR], 4.9; 95% CI, 1.84 to 12.8), receipt of stress-dosed hydrocortisone while the chest was open (aOR, 2.9; 95% CI, 1.1 to 7.6), and gestational age≤37 weeks (aOR, 2.7; 95% CI, 1.01 to 7.27) were independent predictors for a positive mediastinal culture. CONCLUSIONS: Patients with positive mediastinal cultures obtained at DSC had a significantly higher rate of subsequent SSI, and a positive mediastinal culture was the only statistically significant predictor of SSI.

Tricuspid valve replacement with a melody stented bovine jugular vein conduit.

Atrioventricular valve replacement options are limited in infants and small children. The Melody stented bovine jugular vein conduit is being used with increasing frequency for percutaneous pulmonary valve replacement. The Melody valve can be serially dilated over time to accommodate the somatic growth of pediatric patients. We report the initial experience of using the Melody valve as a surgical tricuspid valve replacement in an infant.

Downsized Contegra graft as a right ventricle-to-pulmonary artery conduit in the setting of mediastinitis.

Polytetrafluoroethylene (PTFE) grafts are commonly used for construction of the right ventricle-to-pulmonary artery conduit in the modified Norwood procedure. Dehiscence of a PTFE conduit in the setting of purulent mediastinitis presents a challenging clinical problem because of limited availability of appropriately sized replacement vascular homografts. The Contegra bovine jugular vein graft is an alternative to placing another PTFE graft in an infected space when a homograft of appropriate size is not available. We describe the use of a downsized Contegra conduit to replace an infected PTFE right ventricle-to-pulmonary artery graft in a neonate with life-threatening purulent mediastinitis.

Benign mediastinal lymphadenopathy presenting as cor triatriatum.

This report describes a patient with a superior mediastinal mass and extensive intrathoracic lymphadenopathy referred for oncologic care. During her evaluation, an abnormal cardiovascular examination resulted in an echocardiographic evaluation and an unanticipated diagnosis of a highly obstructive left atrial cor triatriatum was uncovered. The patient underwent repair of cor triatriatum and lymph node biopsy shortly after the diagnosis was made. The biopsies revealed reactive lymph nodes with lymphatic dilation and no inflammatory or neoplastic features. To our knowledge, this case represents the first pediatric example of extensive mediastinal lymphadenopathy mimicking the appearance of a malignant process as a result of severe pulmonary venous hypertension.

Increased extracorporeal membrane oxygenation center case volume is associated with improved extracorporeal membrane oxygenation survival among pediatric patients.

OBJECTIVE: We sought to examine the relationship between extracorporeal membrane oxygenation center case volume and survival in pediatric patients requiring extracorporeal membrane oxygenation support. METHODS: Pediatric patients (≤ 20 years) undergoing extracorporeal membrane oxygenation cannulation were identified using the Healthcare Cost and Utilization Project Kids' Inpatient Database for 2000 to 2009. Annual hospital extracorporeal membrane oxygenation volume tertiles were <15 patients/year (low volume), 15 to 30 patients/year (medium volume), and >30 patients/year (high volume). Cases of extracorporeal membrane oxygenation were segregated by indication into cardiac and noncardiac groups. Cases of cardiac extracorporeal membrane oxygenation were mapped to Risk Adjustment for Congenital Heart Surgery categories to adjust for case complexity. Weighted multivariable logistic and linear regression models identified determinants of in-hospital mortality. RESULTS: Overall, 3867 cases of extracorporeal membrane oxygenation were identified, yielding a national estimate of 6333 ± 495 cases. Extracorporeal membrane oxygenation was used with nearly equivalent prevalence across volume tertiles for all Risk Adjustment for Congenital Heart Surgery categories, suggesting that patient selection for extracorporeal membrane oxygenation was fairly uniform. A higher annual extracorporeal membrane oxygenation volume tertile was associated with reduced in-hospital mortality (P = .01) within nearly all Risk Adjustment for Congenital Heart Surgery categories. After adjustment for Risk Adjustment for Congenital Heart Surgery category and other patient variables, lower extracorporeal membrane oxygenation volume remained an important determinant of in-hospital death (odds ratio, 1.75; 95% confidence interval, 1.03-2.94; P = .03). CONCLUSIONS: Higher extracorporeal membrane oxygenation case volume is associated with improved hospital survival in pediatric cardiac extracorporeal membrane oxygenation patients. The results of this study may support the paradigm of regionalized centers of excellence for managing pediatric cardiac extracorporeal membrane oxygenation patients.