James William Gaynor

Predictors of impaired neurodevelopmental outcomes at one year of age after infant cardiac surgery

OBJECTIVE For most newborns, congenital heart defects (CHD) appear to be isolated anomalies and the brain is presumed to have normal developmental potential. Most studies of neurodevelopmental outcomes have focused on operative management strategies. METHODS Infants with complex CHD and no identified syndromes other than 22q11 microdeletions enrolled in a study of apolipoprotein E (APOE) polymorphisms and developmental outcome were evaluated at one year of age; including genetic evaluation and the Bayley Scales of Infant Development-II [mental (MDI) and psychomotor developmental indices (PDI)]. RESULTS Five hundred and fifty infants enrolled and 359 (20 with 22q11) of 501 survivors (72%) returned. Mean MDI was 90+/-15 and PDI was 78+/-18. Genetic syndromes not identified at birth were confirmed in 28 (8.1%) and suspected in 51 (15.0%). By multivariable analysis, suspected/confirmed genetic syndromes and APOE varepsilon2 allele predicted lower MDI and PDI, all p<0.04. Lower birth weight (p<0.001) and preoperative intubation (p=0.012) predicted lower MDI. Higher hematocrit during the initial operation was associated with higher MDI (p=0.007). Longer postoperative length of stay was predictive of lower PDI (p=0.002). Additional operations with cardiopulmonary bypass were associated with lower MDI and PDI (both p<0.002), but use of deep hypothermic circulatory arrest was not. CONCLUSIONS Patient factors (birth weight and preoperative status) are significant determinants of neurodevelopmental outcomes as opposed to operative management strategies. In this cohort, genetic syndromes unsuspected at birth were surprisingly common and correlate with poor neurodevelopmental outcomes. Without multiple congenital anomalies, syndromes may be missed in infancy. Genetic evaluation should be considered in all infants with CHD.

Perinatal and early surgical outcome for the fetus with hypoplastic left heart syndrome: a 5-year single institutional experience.

To review our experience with the prenatal diagnosis of hypoplastic left heart syndrome (HLHS). Our goal was to establish the benchmark for perinatal and early surgical outcome in the current era, from a center with an aggressive surgical approach and a cohort with a high level of intention‐to‐treat.

Mechanical Environment, Donor Age, and Presence of Endothelium Interact to Modulate Porcine Artery Viability Ex Vivo

AbstractThough ex vivo culture of arteries is a widely used model of native arteries and is closely aligned with efforts to generate tissue-engineered arteries, the effects of culture conditions on artery viability are poorly characterized. To investigate factors regulating long-term viability of cultured arteries, carotid arteries from neonatal and adolescent pigs were perfused for up to 27 days with steady laminar flow ranging from ∼2% to ∼200% of physiological flow rates. Arteries from neonatal animals (2 weeks old, ∼5 kg) were susceptible to spontaneous progressive endothelial denudation followed by deterioration of the vessel wall that spread from luminal to abluminal regions. Subphysiological levels of flow and pressure abrogated this deterioration. Arteries harvested from adolescent (6 months old, ∼100 kg) animals maintained viability and retained structure for at least 9 days as assessed by normal histology, presence of intact endothelium, normal mitochondrial activity, and low levels of cell death and proliferation, unless the vessels were subjected to superphysiological levels of flow or the endothelium was intentionally denuded. Adolescent arteries perfused at subphysiological, but not physiological, flow rates maintained viability and normal structure for at least 27 days. These data indicate that under the appropriate conditions, arteries may be cultured long term but careful attention to the viability is merited.

Thromboxane A2-receptor blockade improves cerebral protection for deep hypothermic circulatory arrest.

OBJECTIVE Following the use of deep hypothermic circulatory arrest in cardiac surgery, cerebral blood flow and cerebral oxygen metabolism are impaired. These may result from abnormal cerebral vasospasm. Powerful vasoconstrictors including endothelins and thromboxane A2 could mediate these processes. We investigated possible involvement of these two factors by assessing the effects of (a) phosphoramidon-an inhibitor of endothelin converting enzyme, and (b) vapiprost (GR32191B)-a specific thromboxane A2-receptor antagonist, on the recovery of cerebral blood flow and cerebral oxygen metabolism following deep hypothermic circulatory arrest. METHODS A total of 18 1-week-old piglets were randomised into three groups (n = 6 per group). At induction, the control group received saline; group PHOS received phosphoramidon 30 mg kg-1 intravenously. Group VAP received vapiprost 2 mg kg-1 at induction and at 30 min intervals thereafter. All groups underwent cardiopulmonary bypass cooling to 18 degrees C, exposed to 60 min of deep hypothermic circulatory arrest, rewarmed and reperfused for 1 h. Cerebral blood flow was measured with radio-labeled microspheres: cerebral oxygen metabolism was calculated at baseline before deep hypothermic circulatory arrest and at 1 h of reperfusion and rewarming. RESULTS In the control group, cerebral blood flow decreased to 40.2 +/- 2.0% of baseline after deep hypothermic circulatory arrest and cerebral oxygen metabolism decreased to 50.0 +/- 5.5% (P < 0.0005). The responses in group PHOS were similar. In group VAP, cerebral blood flow and cerebral oxygen metabolism were 64.3 +/- 10.6 and 80.1 +/- 9.8% of baseline, respectively, after deep hypothermic circulatory arrest. Thus, treatment with vapiprost significantly improved recovery of cerebral blood flow (P = 0.046) and cerebral oxygen metabolism (P = 0.020) following deep hypothermic circulatory arrest. No such improvement was seen after treatment with phosphoramidon. CONCLUSIONS Thromboxane A2 mediates impairments in cerebral perfusion and metabolism following deep hypothermic circulatory arrest. These changes were attenuated by blockade of thromboxane A2-receptors using vapiprost. Endothelins are not shown to be involved. Better knowledge of injury mechanisms will enable development of more effective cerebral protection strategies and allow safer application of deep hypothermic circulatory arrest.

Contribution of Congenital Heart Disease to Neuropsychiatric Outcome in School-Age Children with 22q11.2 Deletion Syndrome

Children with 22q11.2 deletion syndrome (22q11DS) present with congenital heart disease (CHD) and high prevalence of psychiatric disorders and neurocognitive deficits. Although CHD has been implicated in neurodevelopment, its role in the neuropsychiatric outcome in 22q11DS is poorly understood. We investigated whether CHD contributes to the high prevalence of psychiatric disorders and neurocognitive impairments in 22q11DS. Fifty‐four children ages 8–14 years with 22q11DS and 16 age‐matched non‐deleted children with CHD participated. They were assessed using semi‐structured interviews and a Computerized Neurocognitive Battery. CHD status was assessed using available medical records. Prevalence of psychiatric disorders and cognitive profiles were compared among the groups. There were no significant differences between the prevalence of psychiatric disorders in the 22q11DS with and without CHD. In 22q11DS with CHD, the prevalence rates were 41% anxiety disorders, 37% ADHD and 71% psychosis spectrum. In 22q11DS without CHD, the rates were 33% anxiety disorders, 41% ADHD and 64% psychosis spectrum. In comparison, the non‐deleted CHD group had lower rates of psychopathology (25% anxiety disorders, 6% ADHD, and 13% psychosis spectrum). Similarly, the 22q11DS groups, regardless of CHD status, had significantly greater neurocognitive deficits across multiple domains, compared to the CHD‐only group. We conclude that CHD in this sample of children with 22q11.2DS does not have a major impact on the prevalence of psychiatric disorders and is not associated with increased neurocognitive deficits. These findings suggest that the 22q11.2 deletion status itself may confer significant neuropsychiatric vulnerability in this population.

The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000 to 2010: Morbidity, Mortality, and Hospital Charges.

Objective: The use of ventricular assist devices has increased dramatically in adult heart failure patients. However, the overall use, outcome, comorbidities, and resource utilization of ventricular assist devices in pediatric patients have not been well described. We sought to demonstrate that the use of ventricular assist devices in pediatric patients has increased over time and that mortality has decreased. Design: A retrospective study of the Pediatric Health Information System database was performed for patients 20 years old or younger undergoing ventricular assist device placement from 2000 to 2010. Interventions: None. Measurements and Main Results: Four hundred seventy-five pediatric patients were implanted with ventricular assist devices during the study period: 69 in 2000–2003 (era 1), 135 in 2004–2006 (era 2), and 271 in 2007–2010 (era 3). Median age at ventricular assist device implantation was 6.0 years (interquartile range, 0.5–13.8), and the proportion of children who were 1–12 years old increased from 29% in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003). Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic inflammatory response syndrome (34%). Two hundred forty-seven patients (52%) underwent heart transplantation and 327 (69%) survived to hospital discharge. Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004). Median hospital length of stay increased (37 d [interquartile range, 12–64 d] in era 1 vs 69 d [interquartile range, 35–130] in era 3; p < 0.001) and median adjusted hospital charges increased (

Hyperglycaemia after Stage I palliation does not adversely affect neurodevelopmental outcome at 1 year of age in patients with single-ventricle physiology.

630,630 [interquartile range,

Outcomes Following Single and Recurrent In-Hospital Cardiac Arrests in Children With Heart Disease: A Report From American Heart Association's Get With the Guidelines Registry-Resuscitation.

227,052–

Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation.

853,318] in era 1 vs

Biventricular Repair in Interrupted Aortic Arch Type C With Aortic Atresia

1,577,983 [interquartile range,