Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways

<p>Abstract</p> <p>Background</p> <p>Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways.</p> <p>Methods</p> <p>To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot.</p> <p>Results</p> <p>OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21.</p> <p>Conclusion</p> <p>The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways.</p

Native atrial septal restriction after Fontan palliation successfully treated with transcatheter Diabolo stent

A 6-year-old male child born with hypoplastic left heart syndrome (HLHS) was palliated with an extracardiac nonfenestrated Fontan procedure (18-mm Gore-Tex tube graft). He developed low-pressure (mean Fontan pressure 10 mmHg) protein-losing enteropathy 6 months after Fontan palliation. After initially responding to medical therapy and transcatheter pulmonary artery stent implantation, he developed medically refractory protein-losing enteropathy. At this time, his transthoracic echocardiogram showed new restriction across his native atrial septum with an 8 mmHg mean gradient. Cardiac catheterization now showed high-pressure (mean Fontan pressure 18-20 mmHg) protein-losing enteropathy and a new 6 mmHg mean gradient across the atrial septum. To avoid cardiopulmonary bypass, he underwent successful transcatheter relief of atrial septal restriction and creation of a fenestration with rapid clinical and biochemical improvement of his protein-losing enteropathy

Comparison of growth and feeding method in infants with and without genetic abnormalities after neonatal cardiac surgery

AbstractIntroduction:Congenital heart disease (CHD) is multifactorial in origin, resulting from an interaction between environmental and genetic factors. Multifactorial growth delay is common in infants with CHD. The impact of a genetic abnormality and CHD on the growth of an infant is lacking in the literature. The aim of this study is to compare the growth and method of feeding following neonatal cardiac surgery in infants with normal versus abnormal genetic testing.Methods:A retrospective chart review of neonates who underwent a Risk Adjustment in Congenital Heart Surgery IV–VI procedure between 1 January, 2006 and 22 September, 2016 was performed at our institution. Weight, length, head circumference measurements, and feeding method were collected at birth, time of neonatal surgery, and monthly up to 6 months of age.Results:A total of 53 infants met inclusion criteria, of which 22 had abnormal genetic testing. Approximately 90% of infants were discharged following neonatal cardiac surgery with supplemental tube feeds. At each monthly follow-up visit, more infants were exclusively fed orally: 80% of infants with normal genetics at 5 months post-operative follow-up versus 60% of infants with abnormal genetic testing, although statistically insignificant. Growth was not different among the two groups.Conclusions:Infants with critical CHD with or without genetic abnormalities are at risk for growth delays and many need supplemental tube feeds post-operatively and throughout follow-up. Infants with genetic abnormalities are slower to achieve oral feeds and more likely to require tube feedings. It is important to have a systematic protocol for managing these high-risk infants.</jats:sec

Acquired ventricular septal defect due to infective endocarditis

Acquired intracardiac left-to-right shunts are rare occurrences. Chest trauma and myocardial infection are well-known causes of acquired ventricular septal defect (VSD). There have been several case reports describing left ventricle to right atrium shunt after infective endocarditis (IE). We present here a patient found to have an acquired VSD secondary to IE of the aortic and tricuspid valves in the setting of a known bicuspid aortic valve. This is the first case reported of acquired VSD in a pediatric patient in the setting of IE along with literature review of acquired left-to-right shunts

Abstract 14975: Increased Morbidity and Mortality in Patients With Hypoplastic Left Heart Syndrome and Genetic Abnormalities

Introduction: Hypoplastic left heart syndrome (HLHS) is a genetically heterogenous, severe form of congenital heart disease. Hypothesis: Patients with reported genetic abnormalities will have worse outcomes than those without reported genetic abnormalities. Methods: This was a retrospective review of patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase I registry. Registry enrollment occurred at discharge following stage 1 palliation. Patients were placed into one of three groups: major syndromes (Turner, Down, CHARGE, DiGeorge, Jacobsen, VATER, heterotaxy), other genetic abnormality, or no reported genetic abnormality. Demographic and clinical variables were compared using Pearson Chi-square, one-way ANOVA, or Kruskal-Wallis test. Tukey post-hoc test was applied to adjust p-values for pairwise group comparisons. Outcomes of length of stay, death, and combined outcomes of death, not a candidate for stage 2 palliation and transplant were compared among the groups. Results: Of the 2182 patients, major syndromes were reported in 110 (5%), other genetic abnormalities in 126 (5.8%) and no abnormalities in 1946 (89.2%). Those with major syndromes weighed less at birth and the time of stage I palliation, were more likely to be female and have a primary cardiac diagnosis of unbalanced AVC. Those with major syndromes or other genetic abnormalities were more likely to have moderate to severe AV valve regurgitation, moderate to severe ventricular dysfunction, arrhythmia requiring therapy, and major anomalies of other organ systems compared to those with no abnormalities. Patients with no reported genetic abnormalities reached full oral feeds sooner after the Norwood (19 vs 24 days), were more likely to be discharged on all oral feeds (75% vs 59% and 62%) and were discharged earlier (35 vs 45 and 43 days). For the outcome of death, there was no significant difference among the groups. The combined outcome of death, not a candidate for stage 2 palliation, and heart transplant was more likely in those with a major syndrome after adjusting for covariates. Conclusions: Patients with HLHS and major syndromes or other genetic abnormalities experience greater morbidity and mortality during the interstage period. </jats:p

Neuropathology of Congenital Heart Disease in an Inpatient Autopsy Cohort 2000–2017

Background As a result of medical and surgical advancements in the management of congenital heart disease ( CHD ), survival rates have improved substantially, which has allowed the focus of CHD management to shift toward neurodevelopmental outcomes. Previous studies of the neuropathology occurring in CHD focused on cases preceding 1995 and reported high rates of white matter injury and intracranial hemorrhage, but do not reflect improvements in management of CHD in the past 2 decades. The purpose of this study is therefore to characterize the neuropathological lesions identified in subjects dying from CHD in a more‐recent cohort from 2 institutions. Methods and Results We searched the autopsy archives at 2 major children's hospitals for patients with cyanotic congenital cardiac malformations who underwent autopsy. We identified 50 cases ranging in age from 20 gestational weeks to 46 years. Acquired neuropathological lesions were identified in 60% (30 of 50) of subjects upon postmortem examination. The most common lesions were intracranial hemorrhage, most commonly subarachnoid (12 of 50; 24%) or germinal matrix (10 of 50; 20%), hippocampal injuries (10 of 50; 20%), and diffuse white matter gliosis (8 of 50; 16%). Periventricular leukomalacia was rare (3 of 50). Twenty‐six subjects underwent repair or palliation of their lesions. Of the 50 subjects, 60% (30 of 50) had isolated CHD , whereas 24% (12 of 50) were diagnosed with chromosomal abnormalities (trisomy 13, 18, chromosomal deletions, and duplications) and 16% (8/50) had multiple congenital anomalies. Conclusions In the modern era of pediatric cardiology and cardiac surgery, intracranial hemorrhage and microscopic gray matter hypoxic‐ischemic lesions are the dominant neuropathological lesions identified in patients coming to autopsy. Rates of more severe focal lesions, particularly periventricular leukomalacia, have decreased compared with historical controls. </jats:sec

Abstract 14970: Normative Echocardiographic Data for Premature Infants Between 23 to 26- and 6/7-weeks Gestational Age

Background: Echocardiography is utilized to assess cardiac structure and function. In infants, children, and adolescents, a normative data set can be utilized to evaluate cardiac size relative to patient body size and provides the clinician with a quantified z-score based on body surface area. A complete normative data set for premature infants is not yet available. The aim of this study was to develop a normative data set for commonly measured cardiac structures in a cohort of premature infants. Methods and Results: Single center retrospective echocardiographic study in a cohort of premature infants without congenital heart disease. A total of 184 infants admitted at the University of Iowa’s Neonatal Intensive Care Unit between 2009-2019 were included in the study. All infants were between 23 to 26- and 6/7-weeks gestational age. We considered patients with a patent ductus arteriosus and/or a patent foramen ovale as having normal intra-cardiac anatomy given their prematurity. Some infants had numerous echocardiograms during this time interval which resulted in 439 utilized echocardiogram. Each echocardiogram used was interpreted individually regardless if the patient had multiple between the gestational ages of 23 and 26- and 6/7-weeks. Commonly examined cardiac structures were assessed via 2-dimensional and M-mode echocardiography. The mean and standard deviations were obtained for each cardiac structure and grouped by week of gestational age ( Table 1 ). Conclusions: We present normative data for commonly measured cardiac structures based on gestational age in a premature patient population. This information is valuable for clinicians to assess for appropriate cardiac structural development and may be utilized to guide clinical management and need for possible intervention as the child continues to develop and grow. </jats:p

Bovine arch anatomy influences recoarctation rates in the era of the extended end-to-end anastomosis.

OBJECTIVES: Arch branching has never been shown to influence recoarctation after extended end-to-end anastomosis via thoracotomy, yet in each study bovine arch identification is grossly underreported. This study aims to (1) assess chart review reliability in bovine arch identification; (2) determine recoarctation risk with a bovine arch; and (3) explore an anatomic explanation for recurrent arch obstruction based on arch anatomy. PATIENTS: A total of 49 consecutive patients underwent thoracotomy with extended end-to-end aortic coarctation repair at a single institution (2007-2012). METHODS: Echocardiograms from these patients were reviewed for arch anatomy and compared with the echocardiographic reports. Recurrent arch obstruction was defined as an echocardiographic gradient across the repair of 20 mm Hg or greater. For cases with angiographic images (n = 17), a scaled clamping distance between the left subclavian artery and the maximal proximal clamp location on orthogonal projections was then calculated across arch anatomies. RESULTS: Chart review identified 6.1% (3/49) of patients with a bovine arch compared with 28.6% (14/49) on targeted image review. A total of 28.6% (4/14) of patients with a bovine arch had a follow-up gradient of 20 mm Hg or greater. Only 5.7% (2/35) of patients with normal arch branching had a follow-up gradient of 20 mm Hg or greater. The mean clamping index was significantly diminished in patients with bovine arch anatomy. CONCLUSIONS: Arch anatomy often goes undocumented on preoperative imaging, yet children undergoing extended end-to-end repair with bovine arch anatomy are at a significantly increased risk of recoarctation. This may be due to a reduced clampable distance to facilitate repair. These results should be considered in the preoperative assessment, parental counseling, and surgical approach for children with discrete aortic coarctation