Congenitally Corrected Transposition of the Great Arteries: Fetal Diagnosis, Associations, and Postnatal Outcome: A Fetal Heart Society Research Collaborative Study.

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

Pilot Study of Blood Pressure in Girls With Turner Syndrome: An Awareness Gap, Clinical Associations, and New Hypotheses.

Cardiovascular disease is the major factor that reduces lifespan in Turner syndrome. High blood pressure (BP) is common in Turner syndrome and is the most easily treatable cardiovascular risk factor. We studied the prevalence of elevated screening systemic BP, awareness of the problem, and its clinical associations in a large group of girls attending the annual meeting of the Turner Syndrome Society of the United States. Among 168 girls aged 2 to 17 years, 42% had elevated screening BP (systolic and diastolic), yet only 8% reported a previous diagnosis of hypertension. History of aortic coarctation repair (17%) was positively associated with elevated systolic BP (52% versus 32%; P<0.05). Elevated systolic BP was positively associated with obesity (56% versus 31%; P<0.05). Because the prevalence of obesity in the studied population was similar to Center for Disease Control published data for obesity in all girls and the prevalence of increased BP is approximately twice that of the general population, the Turner syndrome phenotype/genotype probably includes an intrinsic risk for hypertension. Obesity and repaired aortic coarctation increase this risk further. There seems to be a BP awareness gap in girls with Turner syndrome. Because girls living with Turner syndrome are a sensitized population for hypertension, further study may provide clues to genetic factors leading to a better understanding of essential hypertension in the general population.

Aortic dimensions in Turner syndrome.

In Turner syndrome, linear growth is less than the general population. Consequently, to assess stature in Turner syndrome, condition-specific comparators have been employed. Similar reference curves for cardiac structures in Turner syndrome are currently unavailable. Accurate assessment of the aorta is particularly critical in Turner syndrome because aortic dissection and rupture occur more frequently than in the general population. Furthermore, comparisons to references calculated from the taller general population with the shorter Turner syndrome population can lead to over-estimation of aortic size causing stigmatization, medicalization, and potentially over-treatment. We used echocardiography to measure aortic diameters at eight levels of the thoracic aorta in 481 healthy girls and women with Turner syndrome who ranged in age from two to seventy years. Univariate and multivariate linear regression analyses were performed to assess the influence of karyotype, age, body mass index, bicuspid aortic valve, blood pressure, history of renal disease, thyroid disease, or growth hormone therapy. Because only bicuspid aortic valve was found to independently affect aortic size, subjects with bicuspid aortic valve were excluded from the analysis. Regression equations for aortic diameters were calculated and Z-scores corresponding to 1, 2, and 3 standard deviations from the mean were plotted against body surface area. The information presented here will allow clinicians and other caregivers to calculate aortic Z-scores using a Turner-based reference population. © 2015 Wiley Periodicals, Inc.

The importance of small for gestational age in the risk assessment of infants with critical congenital heart disease.

BACKGROUND: Infants with critical congenital heart disease who require cardiothoracic surgical intervention may have significant post-operative mortality and morbidity. Infants who are small for gestational age <10th percentile with foetal growth restriction may have end-organ dysfunction that may predispose them to increased morbidity or mortality. METHODS: A single-institution retrospective review was performed in 230 infants with congenital heart disease who had cardiothoracic surgical intervention <60 days of age. Pre-, peri-, and post-operative morbidity and mortality markers were collected along with demographics and anthropometric measurements. RESULTS: There were 230 infants, 57 (23.3%) small for gestational age and 173 (70.6%) appropriate for gestational age. No significant difference was noted in pre-operative markers - gestational age, age at surgery, corrected gestational age, Society for Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality score; or post-operative factors - length of stay, ventilation days, arrhythmias, need for extracorporeal membrane oxygenation, vocal cord dysfunction, hearing loss; or end-organ dysfunction - gastro-intestinal, renal, central nervous system, or genetic. Small for gestational age infants were more likely to have failed vision tests (p = 0.006). Small for gestational age infants were more likely to have increased 30-day (p = 0.005) and discharge mortality (p = 0.035). Small for gestational age infants with normal birth weight (>2500 g) were also at increased risk of 30-day mortality compared with appropriate for gestational age infants (p = 0.045). CONCLUSIONS: Small for gestational age infants with congenital heart disease who undergo cardiothoracic surgery <60 days of age have increased risk of mortality and failed vision screening. Assessment of foetal growth restriction as part of routine pre-operative screening may be beneficial.

Costello syndrome and related disorders.

PURPOSE OF REVIEW: Costello syndrome is a rare congenital disorder affecting multiple organ systems, encompassing severe failure to thrive, cardiac anomalies including hypertrophic cardiomyopathy and atrial tachycardia, tumor predisposition, and cognitive impairment. Costello syndrome shares findings with cardio-facio-cutaneous syndrome and the diagnosis can be challenging. The discovery of gene mutations underlying these and other closely related disorders allows for molecular confirmation of a clinical diagnosis. RECENT FINDINGS: The identification of germline HRAS mutations in Costello syndrome, and mutations in BRAF, MEK1 and MEK2 in cardio-facio-cutaneous syndrome, uncovered the biologic mechanism for the shared phenotypic findings based on the close interaction of the gene products within the Ras-mitogen-activated protein kinase pathway. Changes in other genes encoding mitogen-activated protein kinase pathway proteins are responsible for Noonan syndrome and the KRAS mutation phenotype. SUMMARY: Costello syndrome is caused by heterozygous de-novo point mutations in HRAS, resulting in increased activation of the mitogen-activated protein kinase pathway. Despite their overlapping presentation, Costello syndrome and its related disorders are distinct, and the phenotypes become more distinctive with age. Molecular testing is available and a clinical diagnosis should be reconsidered if it is inconsistent with the molecular result.

Gene expression profile of bioreactor-cultured cardiac cells: activation of morphogenetic pathways for tissue engineering.

Cells grown in three-dimensional (3D) culture take on in vivo phenotypes and organize into tissue-like structures. Understanding the pathways and mechanisms contributing to this in vitro tissuegenesis is a critical goal of tissue engineering. To identify pathways relevant to cardiac tissue engineering, we compared mRNA expression profiles from bioreactor-cultured 3D aggregates of primary neonatal rat heart cells (NRHCs), which form layered structures similar to cardiac tissue, and standard plate-cultured NRHCs, which do not. In a series of two experiments, NRHCs were grown on solid microcarrier surfaces within clinostatically rotated polytetrafluoroethylene (PTFE) vessels and compared to parallel cultures grown on standard tissue culture plates without rotation. After 1, 4, and 6 days, gene expression profiles were analyzed using Affymetrix Rat Genome U34A (RG-U34A) arrays. The results were validated using real-time PCR, and the data set was filtered to generate a list of 93 probe sets that were substantially the same in replicate samples but substantially different between the bioreactor and plate groups. Cluster analysis indicated that the bioreactor and plate samples had similar expression patterns on day 1 but that these patterns diverged thereafter. Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis revealed a number of statistically significant gene groupings, including groups associated with muscle development and morphogenesis. Further analysis of the annotated gene list indicated that 13 of the 93 filtered genes were associated with endothelial cells, blood vessels, or angiogenesis. These results suggest that 3D aggregate culture of NRHCs in bioreactors is associated with the differential expression of morphogenic and angiogenic pathways similar to those seen during cardiac development.

Aristotle score predicts outcome in patients requiring extracorporeal circulatory support following repair of congenital heart disease.

Extracorporeal membrane oxygenation (ECMO) has become the standard technique of mechanical support for the failing circulation following repair of congenital heart lesions. The objective of this study was to identify predictors of survival in patients requiring postcardiotomy ECMO. The Aristotle score, a method developed to evaluate quality of care based on complexity, was investigated as a potential predictor of outcome. Between 2003 and 2005, 37 patients required ECMO following corrective surgery for congenital heart disease. Records were reviewed retrospectively with emphasis on factors affecting survival to discharge. The comprehensive Aristotle complexity score was calculated for each patient. Overall, 28 patients (76%) survived to decannulation and 17 patients (46%) survived to discharge. There were 24 (65%) neonates and 10 patients (27%) with single ventricle physiology, with a hospital survival of 42% (10 of 24) and 50% (5 of 10), respectively. Univariate factors associated with survival included Aristotle score, duration of support, reexploration, multiple organ failure, and number of complications. Age, weight, and single-ventricle physiology were not significant. In a logistic regression model, an Aristotle score < 14 was identified as a predictor of survival (OR 0.12, CI 0.02-0.87). The Aristotle score is predictive of outcome in patients requiring postcardiotomy ECMO and may serve as a uniform criterion when comparing and evaluating quality of care and performance in this complex patient population.

Low-dose oral sildenafil for patients with pulmonary hypertension: a cost-effective solution in countries with limited resources.

INTRODUCTION: Pulmonary arterial hypertension, both primary and secondary, continues to pose a therapeutic problem. In this study, we evaluate the efficacy and safety of a low-dose of oral sildenafil in 10 patients with pulmonary arterial hypertension. METHODS: We administered a single daily dose of 0.5 milligrams per kilogram of sildenafil for 3 months to 10 patients with pulmonary arterial hypertension. Their average age was 26.8 years. Diagnoses were primary pulmonary arterial hypertension in 3 patients, and secondary pulmonary arterial hypertension due to congenital cardiac disease in the remaining 7 patients. Outcome measures included the clinical state, the mean pulmonary arterial pressure, and the indexed pulmonary vascular resistance; the latter two assessed at the beginning and at the end of the treatment period by cardiac catheterization. We also analysed the cost of the treatment. RESULTS: Oral treatment was well tolerated, and resulted in an improvement of the functional capacity in 9 of the 10 patients. Pulmonary arterial pressure decreased from 70 to 60 millimetres of mercury (p equal to 0.05), and indexed pulmonary vascular resistance decreased from 21.8 to 15.8 Wood units per square metre (p equal to 0.006). The mean cost per patient for 3 months on oral treatment with sildenafil was 120.99 American dollars. CONCLUSIONS: A low dose of 0.5 milligrams per kilogram per day of oral sildenafil, instead of 1 to 4 milligrams per kilogram per day, provided early clinical and haemodynamic improvements, and proved less expensive. Additional experience is now required to define more reliably the true long-term benefits of this therapy.

Complicaciones tempranas de la cirugía tiroidea en el HEODRA-León enero 1997- diciembre 2002 / Early complications of the Thyroid surgery in the HEODRA- Leon january 1997- december 2002

El presente estudio de tipo descriptivo, se realizó en el servicio de cirugía general del HEODRA de enero de 1997 a diciembre del 2002. En este período se realizaron 142 cirugías sobre las glándulas tiroides. Se presentaron 9 complicaciones para un 6.3 porciento, las más frecuentes fueron: 4 hipocalcemia, 2 Hematomas, 2 lesiones del nervio laríngeo recurrente. El principal diagnóstico de ingreso a cirugía por enfermedad tiroidea fue el nódulo tiroideo con 27.4 porciento y el principal tipo de cirugía fue la Lobectomía con 30.2 porciento, la mortalidad en el estudio fue de 0...