Objectives: Current central venous catheter utilization in patients within pediatric cardiac ICUs is not well elucidated. We aim to describe current use of central venous catheters in a multi-institutional cohort and to explore the prevalence and risk factors for central line–associated thrombosis and central line–associated bloodstream infections. Design: Observational analysis. Setting: Pediatric Cardiac Critical Care Consortium hospitals. Patients: Hospitalizations with at least one cardiac ICU admission from October 2013 to July 2016. Interventions: None. Measurements and Main Results: There were 17,846 hospitalizations and 69% included greater than or equal to one central venous catheter. Central venous catheter use was higher in younger patients (86% neonates). Surgical hospitalizations included at least one central venous catheter 88% of the time compared with 35% of medical hospitalizations. The most common location for central venous catheters was internal jugular (46%). Central venous catheters were in situ a median of 4 days (interquartile range, 2–10). There were 248 hospitalizations (2% overall, 1.8% medical, and 2.1% surgical) with at least one central line–associated thrombosis (271 total thromboses). Thrombosis was diagnosed at a median of 7 days (interquartile range, 4–14) after catheter insertion. There were 127 hospitalizations (1% overall, 1.4% medical, and 1% surgical) with at least one central line–associated bloodstream infection (136 total infections) with no association with catheter type or location. Central line–associated bloodstream infection was diagnosed at a median of 19 days (interquartile range, 8–36) after catheter insertion. Significant risk factors for central line–associated thrombosis and central line–associated bloodstream infection were younger age, greater surgical complexity, and total catheter days. Conclusions: Utilization of central venous catheters in pediatric cardiac ICUs differs according to indication for hospitalization. Although thrombosis and central line–associated bloodstream infection are infrequent complications of central venous catheter use in cardiac ICU patients, these events can have important short- and long-term consequences for patients. Total central venous catheter line days were the only modifiable risk factor identified. Future study must focus on understanding central venous catheter practices in high-risk patient subgroups that reduce the prevalence of thrombosis and central line–associated bloodstream infection.

Background The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant tetralogy of Fallot (TOF) and coarctation of the aorta (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied. Methods PHN CLS clinical data were linked to cost data from Children’s Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed-effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites. Results Data were successfully linked on 410 of 428 eligible patients (96%) from four active and four control sites. Mean adjusted cost per case for TOF repair was significantly reduced in the post-CPG period at active sites ($42,833 vs $56,304, p < 0.01) and unchanged at control sites ($47,007 vs $46,476, p = 0.91), with an overall cost reduction of 27% in active versus control sites (p = 0.03). Specific categories of cost reduced in the TOF cohort included clinical (−66%, p < 0.01), pharmacy (−46%, p = 0.04), lab (−44%, p < 0.01), and imaging (−32%, p < 0.01). There was no change in costs for CoA repair at active or control sites. Conclusions The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF but not CoA. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries.

The myosin heavy chain (MHC) isoforms, α-and β-MHC, are expressed in developmental-and chamber-specific patterns. Healthy human ventricle contains ∼2-10% α-MHC and these levels are reduced even further in the failing ventricle. While down-regulation of α-MHC in failing myocardium is considered compensatory, we previously demonstrated that persistent transgenic (TG) α-MHC expression in the cardiomyocytes is cardioprotective in rabbits with tachycardia-induced cardiomyopathy (TIC). We sought to determine if this benefit extends to other types of experimental heart failure and focused on two models relevant to human heart failure: myocardial infarction (MI) and left ventricular pressure overload. TG and nontransgenic rabbits underwent either coronary artery ligation at 8 months or aortic banding at 10 days of age. The effects of α-MHC expression were assessed at molecular, histological and organ levels. In the MI experiments, we unexpectedly found modest functional advantages to α-MHC expression. In contrast, despite subtle benefits in TG rabbits subjected to aortic banding, cardiac function was minimally affected. We conclude that the benefits of persistent α-MHC expression depend upon the mechanism of heart failure. Importantly, in none of the scenarios studied did we find any detrimental effects associated with persistent α-MHC expression. Thus manipulation of MHC composition may be beneficial in certain types of heart failure and does not appear to compromise heart function in others. Future considerations of myosin isoform manipulation as a therapeutic strategy should consider the underlying etiology of cardiac dysfunction.

The genetic, biochemical and molecular bases of human cardiac disease have been the focus of extensive research efforts for many years. Early animal models of cardiovascular disease used pharmacologic or surgical interventions, or took advantage of naturally occurring genetic abnormalities and the data obtained were largely correlative. The inability to directly alter an organism's genetic makeup and cellular protein content and accurately measure the results of that manipulation precluded rigorous examination of true cause-effect and structure-function relationships. Directed genetic manipulation in the mouse gave researchers the ability to modify and control the mammalian heart's protein content, resulting in the rational design of models that could provide critical links between the mutated or absent protein and disease. Two techniques that have proven particularly useful are transgenesis, which involves the random insertion of ectopic genetic material of interest into a "host" genome, and gene targeting, which utilizes homologous recombination at a pre-selected locus. Initially, transgenesis and gene targeting were used to examine systemic loss-of-function and gain-of-function, respectively, but further refinements in both techniques have allowed for investigations of organ-specific, cell type-specific, developmental stagesensitive and dose-dependent effects. Genetically engineered animal models of pediatric and adult cardiac disease have proven that, when used appropriately, these tools have the power to extend mere observation to the establishment of true causative proof. We illustrate the power of the general approach by showing how genetically engineered mouse models can define the precise signaling pathways that are affected by the gain-of-function mutation that underlies Noonan syndrome. Increasingly precise and modifiable animal models of human cardiac disease will allow researchers to determine not only pathogenesis, but also guide treatment and the development of novel therapies.

Objectives: Prolonged critical illness after congenital heart surgery disproportionately harms patients and the healthcare system, yet much remains unknown. We aimed to define prolonged critical illness, delineate between nonmodifiable and potentially preventable predictors of prolonged critical illness and prolonged critical illness mortality, and understand the interhospital variation in prolonged critical illness. Design: Observational analysis. Setting: Pediatric Cardiac Critical Care Consortium clinical registry. Patients: All patients, stratified into neonates (≤28 d) and nonneonates (29 d to 18 yr), admitted to the pediatric cardiac ICU after congenital heart surgery at Pediatric Cardiac Critical Care Consortium hospitals. Interventions: None. Measurements and Main Results: There were 2,419 neonates and 10,687 nonneonates from 22 hospitals. The prolonged critical illness cutoff (90th percentile length of stay) was greater than or equal to 35 and greater than or equal to 10 days for neonates and nonneonates, respectively. Cardiac ICU prolonged critical illness mortality was 24% in neonates and 8% in nonneonates (vs 5% and 0.4%, respectively, in nonprolonged critical illness patients). Multivariable logistic regression identified 10 neonatal and 19 nonneonatal prolonged critical illness predictors within strata and eight predictors of mortality. Only mechanical ventilation days and acute renal failure requiring renal replacement therapy predicted prolonged critical illness and prolonged critical illness mortality in both strata. Approximately 40% of the prolonged critical illness predictors were nonmodifiable (preoperative/patient and operative factors), whereas only one of eight prolonged critical illness mortality predictors was nonmodifiable. The remainders were potentially preventable (postoperative critical care delivery variables and complications). Case-mix–adjusted prolonged critical illness rates were compared across hospitals; six hospitals each had lower- and higher-than-expected prolonged critical illness frequency. Conclusions: Although many prolonged critical illness predictors are nonmodifiable, we identified several predictors to target for improvement. Furthermore, we observed that complications and prolonged critical care therapy drive prolonged critical illness mortality. Wide variation of prolonged critical illness frequency suggests that identifying practices at hospitals with lower-than-expected prolonged critical illness could lead to broader quality improvement initiatives.