Necrotizing Enterocolitis and Associated Mortality in Neonates With Congenital Heart Disease: A Multi-Institutional Study.

OBJECTIVE: There are scarce data about the prevalence and mortality of necrotizing enterocolitis in neonates with congenital heart disease. The purpose of this study is to provide a multi-institutional description and comparison of the overall prevalence and mortality of necrotizing enterocolitis in neonates with congenital heart disease. DESIGN: Retrospective multi-institutional study. SETTING: The Pediatric Health Information System database. PATIENTS: Neonates with congenital heart disease between 2004 and 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary study measure is the prevalence of necrotizing enterocolitis. Secondary measures include in-hospital mortality, hospital charges, ICU length of stay, hospital length of stay, and 30-day readmission. The prevalence of necrotizing enterocolitis was 3.7% (1,448/38,770) and varied significantly among different congenital heart disease diagnoses. The lowest prevalence of necrotizing enterocolitis was in transposition of the great arteries (n = 104, 2.1%). Compared with transposition of the great arteries, necrotizing enterocolitis occurred more frequently in neonates with hypoplastic left heart syndrome (odds ratio, 2.7; 95% CI, 2.1-3.3), truncus arteriosus (odds ratio, 2.6; 95% CI, 1.9-3.5), common ventricle (odds ratio, 2.1; 95% CI, 1.5-2.8), and aortic arch obstruction (odds ratio, 1.4; 95% CI, 1.1-1.7). Prematurity is a significant risk factor for necrotizing enterocolitis and for mortality in neonates with necrotizing enterocolitis, conferring varying risk by cardiac diagnosis. Unadjusted mortality associated with necrotizing enterocolitis was 24.4% (vs 11.8% in neonates without necrotizing enterocolitis; p < 0.001), and necrotizing enterocolitis increased the adjusted mortality in neonates with transposition of the great arteries (odds ratio, 2.5; 95% CI, 1.5-4.4), aortic arch obstruction (odds ratio, 1.8; 95% CI, 1.3-2.6), and tetralogy of Fallot (odds ratio, 1.6; 95% CI, 1.1-2.4). Necrotizing enterocolitis was associated with increased hospital charges (p < 0.0001), ICU length of stay (p = 0.001), and length of stay (p = 0.001). CONCLUSIONS: The prevalence of necrotizing enterocolitis among neonates with congenital heart disease is 3.7% and is associated with increased in-hospital mortality, length of stay, and hospital charges. The prevalence and associated mortality of necrotizing enterocolitis in congenital heart disease vary among different heart defects.

Significant mortality, morbidity and resource utilization associated with advanced heart failure in congenital heart disease in children and young adults.

BACKGROUND: Children with congenital heart disease (CHD) are at risk for advanced heart failure (AHF). We sought to define the mortality and resource utilization in CHD-related AHF in children and young adults. METHODS: All hospitalizations in the Pediatric Health Information System database involving patients ≤21 years old with a CHD diagnosis and heart failure requiring at least 7 days of continuous inotropic support between 2004 and 2015 were included. Hospitalizations including CHD surgery were excluded. RESULTS: Of 465,482 CHD hospitalizations, AHF was present in 2,712 (0.6%) [58% infant, 55% male, 30% single ventricle]. AHF therapies frequently used included extracorporeal membrane oxygenation (ECMO) (15%) and cardiac transplant (16%). Ventricular assist device (VAD) support was rare (3%), although VAD use significantly increased from 2004 to 2015 (P < .0010). Hospital mortality in CHD with AHF was 26%, with higher mortality associated with single ventricle heart disease (OR 1.64, 95% CI 1.23-2.19; P = .0009), infancy (OR 1.71, 95% CI 1.17-2.5; P = .0057), non-white race (OR 1.28, 95% CI 1.04-1.59; p=0.0234), and chronic complex comorbidities (OR 1.76, 95% CI 1.34-2.30; P < .0001). Over the 11-year study period, despite the significant increase in CHD-related AHF hospitalizations (P < .0001), hospital mortality improved (P = .0011). Median hospital costs were $252,000, a 6-fold increase above those without AHF, and was primarily driven by hospital length of stay (P < .0001). CONCLUSION: AHF in children with CHD in uncommon but increasing and is associated with significant morbidity, mortality and resource utilization. Approximately 1 in 5 children do not survive to hospital discharge. Many risk factors for mortality may not be modifiable, and further study is needed to identify modifiable risk factors and improve care for this complex population.

Characteristics and Outcomes of Pediatric Heart Failure-Related Emergency Department Visits in the United States: A Population-Based Study.

OBJECTIVES: To describe the frequency, characteristics, and outcomes of heart failure-related emergency department (ED) visits in pediatric patients. We aimed to test the hypothesis that these visits are associated with higher admission rates, mortality, and resource utilization. STUDY DESIGN: A retrospective analysis of the Nationwide Emergency Department Sample for 2010 of patients ≤18 years of age was performed to describe ED visits with and without heart failure. Cases were identified using International Classification of Disease, Ninth Revision, Clinical Modification codes and assessed for factors associated with admission, mortality, and resource utilization. RESULTS: Among 28.6 million pediatric visits to the ED, there were 5971 (0.02%) heart failure-related cases. Heart failure-related ED patients were significantly more likely to be admitted (59.8% vs 4.01%; OR 35.3, 95% CI 31.5-39.7). Among heart failure-related visits, admission was more common in patients with congenital heart disease (OR 5.0, 95% CI 3.3-7.4) and in those with comorbidities including respiratory failure (OR 78.3, 95% CI 10.4-591) and renal failure (OR 7.9, 95% CI 1.7-36.3). Heart failure-related cases admitted to the hospital had a higher likelihood of death than nonheart failure-related cases (5.9% vs 0.32%, P < .001). Factors associated with mortality included respiratory failure (OR 4.5, 95% CI 2.2-9.2) and renal failure (OR 7.8, 95% CI 2.9-20.7). Heart failure-related ED visits were more expensive than nonheart failure-related ED visits ($1460 [IQR $861-2038] vs $778 [IQR $442-1375] [P < .01].) CONCLUSIONS: Heart failure-related visits represent a minority of pediatric ED visits but are associated with increased hospital admission and resource utilization.

Elevated Troponin in the First 72 h of Hospitalization for Pediatric Viral Myocarditis is Associated with ECMO: An Analysis of the PHIS+ Database.

Serum troponin (Tn) is often elevated in viral myocarditis; however, its prognostic significance is unknown. We tested the hypothesis that abnormal serum Tn is associated with mortality in children hospitalized with myocarditis. We retrospectively studied data from six large children's hospitals participating in the Pediatric Health Information System Plus (PHIS+) database. Analysis was performed on patients hospitalized with viral myocarditis between 2007 and 2013, in whom at least one Tn was recorded within 72 h of admission. Abnormal baseline Tn was defined as any value outside the upper limit of normal within the first 72 h. Primary outcome was mortality. Secondary outcomes included mechanical support, defined as use of extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD), cardiac transplantation, intravenous immunoglobulin (IVIg), mechanical ventilation, and inotrope use. A total of 149 patients with myocarditis (61% male, 48% adolescents) across all PHIS+ centers had TnI (n = 113) or TnT (n = 36) recorded. At least one abnormal Tn was present in 81% of cases. Overall mortality was 7.3% and was not associated with abnormal baseline Tn. Abnormal baseline Tn was associated with ECMO (7.1 vs. 25.6%, p = 0.03) and IVIg (46.4 vs. 83.5%, p < 0.001). Abnormal baseline Tn was not associated with transplantation, mechanical ventilation or inotrope use. Abnormal Tn in the first 72 h of hospitalization for myocarditis was associated with the use of ECMO and IVIg, but was not associated with mortality. This finding may help risk stratify this population if it can be prospectively validated.

National Variation in the Use of Tracheostomy in Patients With Congenital Heart Disease.

OBJECTIVES: The postsurgical care of children with congenital heart disease may be complicated by the need for cardiorespiratory support, including tracheostomy. The variation of the use of tracheostomy across multiple pediatric cardiac surgical centers has not been defined. We describe multicenter variation in the use of tracheostomy in children undergoing congenital heart surgery. DESIGN: We retrospectively analyzed a multicenter cohort. SETTING: Pediatric Health Information Systems database retrospective cohort. PATIENTS: Children less than 18 years who underwent both tracheostomy and cardiac surgery (1/04-6/14). INTERVENTIONS: Univariate and multivariate statistics were performed, stratifying by high (≥ 75th percentile) and low (≤ 25th percentile) tracheostomy volume and adjusting for patient characteristics in multivariate models. MEASUREMENTS AND MAIN RESULTS: Out of 123,510 hospitalizations involving cardiac surgery, 1,292 tracheostomies (1.2%) were performed (46 hospitals). The rate of tracheostomy placement ranged from 0.3% to 2.5% with no difference in the rate of tracheostomy placement between high and low tracheostomy use centers (p = 0.8). The median time to tracheostomy was 63 days (interquartile range, 36-100), and there was no difference between high- and low-tracheostomy centers. High-tracheostomy centers had $420,000 lower hospital charges than low-volume centers (p = 0.03). Tracheostomy day greater than the median (63 d), Risk Adjustment for Congenital Heart Surgery-1 score 6, and extracorporeal membrane oxygenation were significantly associated with adjusted increased odds of mortality. Later hospital day of tracheostomy was associated with a $13,000/d increase in total hospital charges (p < 0.001). CONCLUSIONS: Variation in the usage of tracheostomy in infants and children undergoing congenital heart surgery exists across the country. High-tracheostomy centers had lower hospital charges. Late tracheostomy placement, higher congenital heart disease surgical risk, and extracorporeal membrane oxygenation use are independent predictors of in-hospital mortality in this population.

Variation in Antiarrhythmic Management of Infants Hospitalized with Supraventricular Tachycardia: A Multi-Institutional Analysis.

Supraventricular tachycardia (SVT) is the most frequent form of symptomatic tachyarrhythmia in infants. The purposes of this study were to describe practice patterns of the management of infants hospitalized with SVT and factors associated with 30-day hospital readmission. This was a multi-institutional, retrospective review of the pediatric health information system database of SVT hospitalizations from 2003 to 2013. High-volume centers (HVC) were defined as those at the upper quartile of admissions. Infants with an ICD-9 code of paroxysmal SVT were included. Antiarrhythmics investigated included amiodarone, atenolol, digoxin, esmolol, flecainide, procainamide, propafenone, propranolol, and sotalol. Frequency of antiarrhythmic use based on center volume was the primary end point. Rate of 30-day SVT readmission was the secondary end point. Analysis of factors associated with readmission was assessed by Chi-square analysis and expressed as odds ratio and 95 % confidence interval. A total of 851 patients (60 % male, 44 % neonates) were hospitalized at 43 hospitals. Propranolol, digoxin, and amiodarone were the most frequently utilized antiarrhythmics. HVCs represented 12 hospitals comprising 494 (58 %) patients. Although HVCs were more likely to utilize propranolol (OR 2.5, CI 1.5-4.1), there was no significant difference in the 30-day readmission rate between patients treated at HVCs versus non-HVCs (p = 0.9). The majority of infants with SVT are treated with a small number of antiarrhythmic medications during index hospitalization. Although hospital-to-hospital variation in antiarrhythmic choice exists, there appears to be no difference in readmission. The remaining practice variation may be related to intrinsic patient characteristics.

Characteristics and outcomes of heart failure-related intensive care unit admissions in children with cardiomyopathy.

OBJECTIVE: The purpose of this study was to describe patient characteristics and outcomes of heart failure (HF)-related intensive care unit (ICU) hospitalizations in children with cardiomyopathy (CM). METHODS AND RESULTS: A query of the Pediatric Health Information System database, a large administrative and billing database of 43 tertiary children's hospitals, was performed. A total of 17,309 HF-related ICU hospitalizations from 2005 to 2010 of 14,985 children ≤18 years old were analyzed. Of those, 2,058 (12%) hospitalizations for CM-HF in 1,599 (11%) children were identified. Classification into CM subtypes was not possible owing to database limitations. The number of yearly CM-HF hospitalizations significantly increased during the study period (P = .036). Overall mortality was 11%, and cardiac transplantation occurred in 20% of hospitalizations. Mechanical circulatory support (MCS) was used in 261 (13%) of hospitalizations. Renal failure, MCS, respiratory failure, sepsis, and vasoactive medications were associated with mortality on multivariable analysis. Significant comorbidities associated with these hospitalizations included arrhythmias in 42%, renal failure in 13%, cerebrovascular disease in 6%, and hepatic impairment in 5%. CONCLUSIONS: HF-related ICU hospitalizations in children with cardiomyopathy are increasing. These children are at high risk for poor outcomes with an in-hospital mortality of 11%.

Characterization of extracorporeal membrane oxygenation for pediatric cardiac arrest in the United States: analysis of the kids' inpatient database.

To characterize the overall use, cost, and outcomes of extracorporeal membrane oxygenation (ECMO) as an adjunct to cardiopulmonary resuscitation (CPR) among hospitalized infants and children in the United States, retrospective analysis of the 2000, 2003, and 2006 Kids' Inpatient Database (KID) was performed. All CPR episodes were identified; E-CPR was defined as ECMO used on the same day as CPR. Channeling bias was decreased by developing propensity scores representing the likelihood of requiring E-CPR. Univariable, multivariable, and propensity-matched analyses were performed to characterize the influence of E-CPR on survival. There were 8.6 million pediatric hospitalizations and 9,000 CPR events identified in the database. ECMO was used in 82 (0.9 %) of the CPR events. Median hospital charges for E-CPR survivors were $310,824 [interquartile range (IQR) 263,344-477,239] compared with $147,817 (IQR 62,943-317,553) for propensity-matched conventional CPR (C-CPR) survivors. Median LOS for E-CPR survivors (31 days) was considerably greater than that of propensity-matched C-CPR survivors (18 days). Unadjusted E-CPR mortality was higher relative to C-CPR (65.9 vs. 50.9 %; OR 1.9, 95 % confidence interval 1.2-2.9). Neither multivariable analysis nor propensity-matched analysis identified a significant difference in survival between groups. E-CPR is infrequently used for pediatric in-hospital cardiac arrest. Median LOS and charges are considerably greater for E-CPR survivors with C-CPR survivors. In this retrospective administrative database analysis, E-CPR did not significantly influence survival. Further study is needed to improve outcomes and to identify patients most likely to benefit from this resource-intensive therapy.

First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor.

SAR445088 is an anti-C1s humanized monoclonal antibody that inhibits activated C1s in the proximal portion of the classical complement system and has the potential to provide clinical benefit in the treatment of complement-mediated diseases. A phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of SAR445088 was conducted in 93 healthy participants to evaluate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Single (intravenous [i.v.] and subcutaneous [s.c.]) ascending doses (SAD) and multiple (s.c.) ascending doses (MAD) of SAR445088 were well-tolerated. The PK of SAR445088 was characterized by slow absorption after the s.c. dose and a long half-life (mean terminal half-life [t1/2 ] 8-15 weeks). Two PD assays were used to measure inhibition of the classical complement pathway (CP): Wieslab CP and complement mediated hemolytic capacity (CH50). The estimated half-maximal inhibitory concentration (IC50 ) and 90% inhibitory concentration (IC90 ) for the Wieslab CP assay were 96.4 and 458 µg/ml, respectively, and 16.6 and 57.0 µg/ml, respectively, for the CH50 assay. In summary, SAR445088 was well-tolerated and had favorable PK and PD profiles after SAD (i.v. or s.c.) and MAD (s.c.) in humans. These findings warrant further clinical investigations in patients with classical complement-mediated disorders.

Prevalence and outcomes of pediatric in-hospital cardiopulmonary resuscitation in the United States: an analysis of the Kids' Inpatient Database*.

OBJECTIVE: Population-based data on pediatric in-hospital cardiopulmonary resuscitation in the United States are scarce. Single-center studies and voluntary registries may skew the estimated prevalence and outcomes. This study aimed to determine the prevalence and outcomes of pediatric cardiopulmonary resuscitation on a national scale. DESIGN: A retrospective analysis of the Healthcare Cost and Utilization Project 2006 Kids' Inpatient Database was performed. Sample weighting was employed to produce national estimates. SETTING: Three thousand seven hundred thirty-nine hospitals in 38 states participating with the Kids' Inpatient Database. PATIENTS: All patients <20 yrs of age hospitalized in participating institutions in 2006. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary resuscitation was performed in 5,807 (95% confidence interval 5259-6355) children with prevalence of 0.77 per 1,000 admissions. Most patients (68%) were <1 yr old, and 44% were female. On multivariable analysis, cardiopulmonary resuscitation was associated with respiratory failure (odds ratio 41.5, 95% confidence interval 35.4-48.8), myocarditis (odds ratio 36.6, 95% confidence interval 21.9-61.0), acute renal failure (odds ratio 21.6, 95% confidence interval 17.5-26.7), heart failure (odds ratio 3.8, 95% confidence interval 3.0-4.8), and cardiomyopathy (odds ratio 3.8, 95% confidence interval 3.2-4.7). Overall mortality was 51.8% and greater among patients ≥1 yr (68%) vs. <1 yr (44%) (odds ratio 2.7, 95% confidence interval 2.3-3.2). Factors associated with mortality among patients receiving cardiopulmonary resuscitation on multivariable analysis included acute renal failure (odds ratio 1.5, 95% confidence interval 1.1-1.9), hepatic insufficiency (odds ratio 1.5, 95% confidence interval 1.01-2.4), sepsis (odds ratio 1.2, 95% confidence interval 1.01-1.4), and congenital heart disease (odds ratio 1.2, 95% confidence interval 1.01-1.5). CONCLUSIONS: Cardiopulmonary resuscitation is performed in approximately one in 1,300 pediatric hospitalizations. Approximately half of patients receiving cardiopulmonary resuscitation do not survive to discharge. Independent risk factors for mortality after receiving cardiopulmonary resuscitation included congenital heart disease, age ≥1 yr, acute renal failure, hepatic insufficiency, and sepsis.

Association between left ventricular mass index and cardiac function in pediatric dialysis patients.

BACKGROUND: Left ventricular mass index (LVMI) is a surrogate of left ventricular hypertrophy and a predictor of cardiac morbidity and mortality in adults with hypertension. LVMI has not been linked to cardiovascular endpoints in children. The aim of this study was to identify an association between elevated LVMI and echocardiographic markers of systolic and diastolic function. METHODS: The study was a retrospective review of chronic dialysis patients from June 1995 to December 2009 at a single tertiary care children's hospital. The upper limit cutoffs for LVMI were set at >38.6 g/m(2.7), >51 g/m(2.7), and by age and sex-based normative values. Sixty-three patients (mean age 14.1 years, 56% males) were enrolled in the study, with a total of 287 echocardiograms. RESULTS: Post-dialysis hypertension was associated with elevated LVMI in both the >51 g/m(2.7) [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.5-5.5] and normative (OR 3.4, 95% CI 1.5-7.7) models. Elevated LVMI, when defined by the >51 g/m(2.7) and normative models, was significantly associated with decreased shortening fraction (OR 4.1, 95% CI 1.7-9.8 and OR 5.4, 95% CI 1.3-22.9, respectively) and increased mitral E wave to lateral mitral tissue Doppler e' wave velocity ratio (E/e'; OR 3.5, 95% CI 1.1-11.2 and OR 4.5, 95% CI 1.0-21.6, respectively). CONCLUSIONS: Elevated LVMI is associated with decreased systolic and diastolic cardiac function, justifying its use as a surrogate of hypertensive cardiomyopathy in children undergoing chronic dialysis.

Intensive care management of neonates with d-transposition of the great arteries and common arterial trunk.

Although mortality rates for patients with d-transposition of the great arteries remain quite low, these patients have a unique circulation that requires careful management in the peri-operative period. Despite the improved mortality for patients with common arterial trunk, the course in the intensive care unit is remarkable for significant morbidity and utilisation of significant resources. Pre-operative patient management focuses on balancing competing circulations, pulmonary and systemic, which exist in parallel rather than in series, as in the normal circulation. Post-operative patient management in both lesions focuses on optimising systemic output, respiratory status, and mitigating the effects of cardiopulmonary bypass. In this article, we review pre- and post-operative intensive care management in neonates with d-transposition of the great arteries and common arterial trunk.

The outcome of pulmonary artery stents following surgical manipulation.

BACKGROUND: Pulmonary artery (PA) stents are utilized to treat branch pulmonary stenosis (BPS). Often patients with PA stents undergo subsequent cardiac surgery for other indications, and the stents can be manipulated during the procedure. OBJECTIVE: The purpose of this study was to evaluate the outcome of branch PA stenoses following surgical manipulation of previously implanted PA stents and to determine factors associated with future reintervention. METHODS: Catheterization data, operative reports, and clinical summaries were reviewed on patients with PA stents placed between September 1989 and December 2006 undergoing subsequent cardiac surgery. Surgical manipulation was recorded as removed, trimmed, or longitudinally transected, and patched. Those that were not manipulated were defined as untouched. RESULTS: 459 patients had branch PA stents placed. About 54 patients, with 70 stents in branch PA's. subsequently had further cardiac surgery. The median age of stent placement was 7.5 (0.5-32.4) years with a median age of surgery of 12.7 (5.1-39.6) years. Surgical manipulation was performed in 23 (33%) PA's and 47 (66%) stents were untouched. Stent removal occurred in 11 (16%), with transecting longitudinally and patching in 5 (7%), and trimming in 7 (10%). Comparing the surgical manipulation and the untouched groups, there was no difference in median age of stent placement [7.2 (0.5-30.2) versus 7.6 (1.8-32.4) years, p=0.40], wt [21.0 (5.3-86.5) versus 24.7 (9.0-96.0) kg, p=0.42], or residual catheterization gradient across the stent [3 (0-59) versus 4 (0-50) mmHg, p=0.81]. Catheter reintervention (stent n=6 or balloon dilation n=14) on the previously stented PAs was similar between the surgically manipulated (median 7.5 years) and untouched groups (median 11.5 years) (p=0.31). In multivariate analysis, the factors associated with future catheter reintervention were having the stent transected longitudinally and patched (p=0.003) and a lower weight (p=0.006) at the time of stent placement. CONCLUSIONS: Surgical stent manipulation is often performed in patients who have PA stents. Surgical manipulation does not alter the need for future reintervention and catheter re-intervention may be more likely when the stents are transected longitudinally and patched.

Resource utilization in children with paracorporeal continuous-flow ventricular assist devices.

BACKGROUND: Paracorporeal continuous-flow ventricular assist devices (PCF VAD) are increasingly used in pediatrics, yet PCF VAD resource utilization has not been reported to date. METHODS: Pediatric Interagency Registry for Mechanically Assisted Circulatory Support (PediMACS), a national registry of VADs in children, and Pediatric Health Information System (PHIS), an administrative database of children's hospitals, were merged to assess VAD implants from 19 centers between 2012 and 2016. Resource utilization, including hospital and intensive care unit length of stay (LOS), and costs are analyzed for PCF VAD, durable VAD (DVAD), and combined PCF-DVAD support. RESULTS: Of 177 children (20% PCF VAD, 14% PCF-DVAD, 66% DVAD), those with PCF VAD or PCF-DVAD are younger (median age 4 [IQR 0-10] years and 3 [IQR 0-9] years, respectively) and more often have congenital heart disease (44%; 28%, respectively) compared to DVAD (11 [IQR 3-17] years; 14% CHD); p < 0.01 for both. Median post-VAD LOS is prolonged ranging from 43 (IQR 15-82) days in PCF VAD to 72 (IQR 55-107) days in PCF-DVAD, with significant hospitalization costs (PCF VAD $450,000 [IQR $210,000-$780,000]; PCF-DVAD $770,000 [IQR $510,000-$1,000,000]). After adjusting for patient-level factors, greater post-VAD hospital costs are associated with LOS, ECMO pre-VAD, greater chronic complex conditions, and major adverse events (p < 0.05 for all). VAD strategy and underlying cardiac disease are not associated with LOS or overall costs, although PCF VAD is associated with higher daily-level costs driven by increased pharmacy, laboratory, imaging, and clinical services costs. CONCLUSION: Pediatric PCF VAD resource utilization is staggeringly high with costs primarily driven by pre-implantation patient illness, hospital LOS, and clinical care costs.

Pulmonary artery stents: long-term follow-up.

OBJECTIVES: Determine the long-term outcomes of branch pulmonary artery (PA) stents. BACKGROUND: PA stents in congenital heart disease effectively relieve stenoses in the short-term. Published long-term data are limited. METHODS: Patients enrolled in an FDA IDE protocol from 1989-92 were included. Clinical follow-up and catheterization data were evaluated. Patients were included if >5 year follow-up data was available or if mortality occurred following the initial procedure. RESULTS: There were five deaths: four due to progression of their underlying heart disease, and one from a complication during a follow-up catheterization. Clinical data for 43 surviving patients demonstrated 39 patients (91%) are in NYHA class I or II. Seven patients underwent surgical intervention during the follow-up period (five RV-PA conduit, two Fontan revisions), but none addressed PA stenosis. Final repeat catheterizations were performed in 36 patients (55 stents) 7.2 +/- 4.3 years post stent insertion with 1.2 +/- 0.9 further procedures with stent dilations. In this subgroup, the minimum vessel diameter increased from 4.7 +/- 1.8 to 13.4 +/- 2.4 mm (P < 0.001), and the pressure gradient improved from 41 +/- 25 to 9 +/- 11 mm Hg (P < 0.001). Higher initial gradient and smaller balloons were associated with a final stent diameter of <14 mm (P = 0.030 and 0.046). Jailed vessels occurred in 49% of stents with abnormal angiographic flow in 18/55. Six repeat catheterizations resulted in complications, including the one procedural death. CONCLUSION: Stents implants for PA stenoses provide effective improvement in vessel caliber in the long-term. Although repeat interventions are necessary, this procedure reduces RV pressure and provides an important alternative to surgery for residual PA obstruction.

Cardiac transplantation in children with Down syndrome, Turner syndrome, and other chromosomal anomalies: A multi-institutional outcomes analysis.

BACKGROUND: The purpose of this study was to describe the prevalence, characteristics, and outcomes in pediatric patients with chromosomal anomalies (CA) undergoing orthotopic heart transplantation (OHT). METHODS: A query of the database of the Pediatric Health Information System, a large administrative and billing database of 43 tertiary children's hospitals, was performed for the Years 2004 to 2016. Pediatric patients who received OHT were analyzed based on presence and type of CA. CA analyzed included: Down syndrome (DS); Turner syndrome (TS)/gonadal dysgenesis; conditions due to anomaly of unspecified chromosome; autosomal deletion; microdeletion; and autosomal anomaly. Healthcare-associated charge analysis during hospitalization for OHT and survival after OHT were assessed. RESULTS: A total of 3,080 hospitalizations were identified in which OHTs were performed. Of these OHTs, 64 (2.1%) were performed in patients with a concomitant diagnosis of CA. The presence of CA did not confer a higher risk of in-hospital mortality after OHT (odds ratio 1.2 [0.5 to 3.2], p = 0.651). Differences in in-hospital mortality between different types of CA, including DS and TS, did not reach statistical significance. Survival at 1-year post-OHT was similar in patients with CA compared to those without CA (p = 0.248). Length of stay after OHT was longer in patients with CA: 76 (interquartile range [IQR] 76 to 142 days vs 49 [IQR 21 to 98] days) (p < 0.001), respectively. Overall adjusted hospital charges were significantly higher in the CA group: $1.2 million (IQR $740,000 to $2.2 million) vs $792,000 (IQR $425,000 to $1.5 million] (p < 0.001), respectively. CONCLUSIONS: CA is present in ~2% of pediatric patients undergoing OHT. The presence of CA was not associated with increased mortality in pediatric patients undergoing OHT. Limitations of this study include the small number of patients available for analysis and a likely highly selective cohort of patients with CA.

Resource Utilization in Pediatric Patients Supported With Ventricular Assist Devices in the United States: A Multicenter Study From the Pediatric Interagency Registry for Mechanically Assisted Circulatory Support and the Pediatric Health Information System.

BACKGROUND: Few data exist on resource utilization with pediatric ventricular assist devices (VADs). We tested the hypothesis that device type and adverse events are associated with increased resource utilization in pediatric patients supported with VADs. METHODS AND RESULTS: The Pediatric Interagency Registry for Mechanically Assisted Circulatory Support, a national registry of VADs in patients <19 years old, and the Pediatric Health Information System, an administrative database, were merged. Univariate analysis was performed assessing the association of all factors with the total cost and length of stay first. Significant variables (P<0.05) were subjected to multivariable analysis. The study included 142 patients from 19 centers with VAD implants from October 2012 to June 2016. The median age was 9 years (interquartile range [IQR] 2-15), 84 (59%) supported with a continuous-flow VAD. Overall median hospital costs were $750 000 (IQR $539 000 to $1 100 000) with a median hospital length of stay of 81 days (IQR 54-128). On multivariable analysis, device type and postoperative complications were not associated with resource utilization. Factors associated with increased costs included patient age, lower-volume VAD center, being intubated, being on extracorporeal membrane oxygenation, number of complex chronic medical conditions, and length of stay. Among continuous-flow VAD patients, discharge to home before transplant versus remaining hospitalized was associated with lower hospital costs (median $600 000 [IQR $400 000 to $820 000] versus median $680 000 [IQR $500 000 to $970 000], P=0.03). CONCLUSION: VADs in pediatric patients are associated with high resource utilization. Increased resource utilization was associated with lower-volume VAD centers, disease severity at VAD implantation, and the presence of complex chronic medical conditions. Further study is needed to develop cost-effective strategies in this complex population.

Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm.

BACKGROUND: There is no nonparenteral medication for the rapid termination of paroxysmal supraventricular tachycardia. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of etripamil nasal spray, a short-acting calcium-channel blocker, for the rapid termination of paroxysmal supraventricular tachycardia (SVT). METHODS: This phase 2 study was performed during electrophysiological testing in patients with previously documented SVT who were induced into SVT prior to undergoing a catheter ablation. Patients in sustained SVT for 5 min received either placebo or 1 of 4 doses of active compound. The primary endpoint was the SVT conversion rate within 15 min of study drug administration. Secondary endpoints included time to conversion and adverse events. RESULTS: One hundred four patients were dosed. Conversion rates from SVT to sinus rhythm were between 65% and 95% in the etripamil nasal spray groups and 35% in the placebo group; the differences were statistically significant (Pearson chi-square test) in the 3 highest active compound dose groups versus placebo. In patients who converted, the median time to conversion with etripamil was <3 min. Adverse events were mostly related to the intranasal route of administration or local irritation. Reductions in blood pressure occurred predominantly in the highest etripamil dose. CONCLUSIONS: Etripamil nasal spray rapidly terminated induced SVT with a high conversion rate. The safety and efficacy results of this study provide guidance for etripamil dose selection for future studies involving self-administration of this new intranasal calcium-channel blocker in a real-world setting for the termination of SVT. (Efficacy and Safety of Intranasal MSP-2017 [Etripamil] for the Conversion of PSVT to Sinus Rhythm [NODE-1]; NCT02296190).

The validation of an LC-MS/MS assay for perhexiline and major hydroxy metabolites, and its application to therapeutic monitoring in patient plasma.

AIM: Perhexiline (PEX), being developed to treat hypertrophic cardiomyopathy, is toxic at levels above the therapeutic range. Plasma level monitoring is therefore essential. The absence of a UV-absorbing chromophore has in the past required quantitative analysis of PEX in plasma using lengthy derivatization methods, followed by HPLC and fluorescence detection. The routine and urgent analysis of a large number of patient plasma samples necessitates faster and reliable analytical methodology. RESULTS: An LC-MS/MS method, using two novel internal standards, has been validated for the quantitative measurement of PEX and its major hydroxy metabolites in human plasma. CONCLUSION: The assay has been applied to therapeutic drug monitoring (TDM), where PEX and the ratio of the drug to cis-hydroxy perhexiline, were measured at designated intervals.

Obesity and Diabetes Mellitus Adversely Affect Outcomes after Cardiac Surgery in Children's Hospitals.

OBJECTIVE: To assess how obesity or diabetes mellitus impacts outcomes in patients undergoing cardiac surgery in pediatric hospitals. DESIGN: A multi-institutional, matched case-control study of the Pediatric Health Information System database was performed. SETTING: Tertiary children's hospitals in the United States. PATIENTS: All cardiac surgical cases in patients with obesity or diabetes mellitus between 2004 and 2012 were included. Cases were matched to controls by age, sex, race, and Risk Adjustment for Congenital Heart Surgery score. OUTCOME MEASURES: Mortality, surgical complications, and hospital utilization. Differences in outcome measures were assessed by chi-square and Mann-Whitney tests. P value < .05 was significant. RESULTS: Six hundred twenty-nine cardiac surgical cases (median age 17 years [IQR 12-32]) with obesity or diabetes mellitus were matched to 629 controls. Cases demonstrated lower median household income than those in the control group ($38,031 [IQR $31,900-$48,844] vs. ($41,896 [IQR $32,854-$56,020], P < .001). Mortality was similar between cases and controls (22% vs. 1.9%, P =.692). Surgical complications occurred similarly between cases and controls (13.5% vs. 12.4%, P = .535). Cases had longer intensive care unit length of stay than controls (3 vs. 2 days, P = .001), resulting in longer overall hospital length of stay (5 vs. 4 days, P < .001). Cases also had a higher odds of undergoing mechanical ventilation for >96 hours (OR 2.0, 95% CI 1.1-3.7) and higher rate of total parenteral nutrition use (7.2% vs. 4.5%, P = .040). Median hospital charges were higher in cases (clinical: $6,696 vs. $5,872; laboratory: $14,168 vs. $12,251; pharmacy: $12,971 vs. $10,426; imaging: $6,259 vs. $5,660; P ≤ .030 for all). CONCLUSIONS: The presence of obesity or diabetes mellitus was associated with increased postoperative morbidity, hospital utilization, and cost in patients undergoing cardiac surgery in pediatric hospitals.