bims-hylehe Biomed news
on Hypoplastic left heart syndrome
Issue of 2018‒09‒09
eleven papers selected by
Richard James
University of Pennsylvania


  1. Ann Thorac Surg. 2018 Aug 29. pii: S0003-4975(18)31163-9. [Epub ahead of print]
    Soquet J, Mufti HN, Jones B, Konstantinov IE, Brink J, Brizard CP, d'Udekem Y.
      BACKGROUND: Chylothorax is a rare but severe complication after pediatric cardiac surgery and is related to significant morbidity and mortality. It is suspected to be more frequent after single ventricle staged palliation procedures, but focused studies on chylothorax in patients with univentricular heart physiology are scarce.METHODS: From January 2008 to December 2016, a total of 289 patients underwent 376 cavopulmonary connection (CC) procedures over 9 years (superior cavopulmonary connection, SCPC = 199; Fontan completion = 177). Patients were classified according to whether they had a chylothorax (Group 1) or not (Group 2). Chylothorax was confirmed on a pleural fluid test.
    RESULTS: The rate of chylothorax following a CC procedure was 19.7% (74/376): 15.6% after SCPC and 24.3% after Fontan completion. Mean follow-up was 4.3 years +/- 0.1. Systemic right ventricle was more frequent in Group 1 than Group 2 (64.9% vs 46% respectively, p = 0.003). Chylothorax was associated with a higher rate of early reoperation (p = 0.001) and late failure of the CC (p < 0.001). Late mortality was also more frequent in Group 1 than in Group 2 (17.6% vs 4.3%, p < 0.001). By multivariate analysis, having a systemic right ventricle was the only identified predictor for the development of chylothorax (OR 2.49, 95% CI 1.4 - 4.7, p = 0.004).
    CONCLUSIONS: The incidence of chylothorax in patients undergoing the univentricular pathway is higher than previously suggested. Having a systemic right ventricle is a significant risk factor for developing a chylothorax after a cavopulmonary connection.
    Keywords:  CHD; CHD univentricular heart; Fontan; Glenn; Norwood operation; chyle; hypoplastic left heart syndrome
    DOI:  https://doi.org/10.1016/j.athoracsur.2018.06.077
  2. Am J Crit Care. 2018 Sep;27(5): 410-416
    Tran NN, Kumar SR, Hodge FS, Macey PM.
      BACKGROUND: Congenital heart disease (CHD) is a leading birth defect in the United States, affecting about 40 000 neonates each year. Despite efforts to prevent developmental delays, many children with CHD have neurological deficits that last into adulthood, influencing employability, self-care, and quality of life.OBJECTIVE: To determine if neonates with CHD have impaired cerebral autoregulation and poorer neurodevelopmental outcomes compared with healthy controls.
    METHODS: A total of 44 full-term neonates, 28 with CHD and 16 without, were enrolled in the study. Inclusion criteria included confirmed diagnosis of CHD, stable hemodynamic status, and being no more than 12 days old. Exclusion criteria included intraventricular hemorrhage and intubation. Cerebral autoregulation was determined by measuring regional cerebral oxygenation during a postural change. The Einstein Neonatal Neurobehavioral Assessment Scale was used to measure overall neurodevelopmental outcomes (motor, visual, and auditory functions).
    RESULTS: Of the 28 neonates with CHD, 8 had single-ventricle physiology. A χ2 analysis indicated no significant difference in impaired cerebral autoregulation between neonates with CHD and controls (P = .38). Neonates with CHD had lower regional cerebral oxygenation than did neonates without CHD (P < .001). Regression analyses with adjustments for cerebral autoregulation indicated that neonates with CHD had poorer total neurodevelopmental outcomes scores (β = 9.3; P = .02) and motor scores (β = 7.6; P = .04).
    CONCLUSION: Preoperative neonates with CHD have poorer developmental outcomes and more hypoxemia than do controls.
    DOI:  https://doi.org/10.4037/ajcc2018672
  3. Int J Cardiol. 2018 Aug 29. pii: S0167-5273(18)31268-3. [Epub ahead of print]
    Tretter JT, Oechslin EN, Veldtman GR.
      
    Keywords:  Adult congenital heart disease; Congenital heart disease; Echocardiography
    DOI:  https://doi.org/10.1016/j.ijcard.2018.04.008
  4. Prenat Diagn. 2018 Sep 01.
    Chakraborty A, Gorla SR, Swaminathan S.
      OBJECTIVES: The objective of this study was to analyze the benefits associated with prenatal diagnosis of complex congenital heart disease (CHD) on preoperative morbidity, 30-day and 1-year mortality in this population.METHOD: This was a retrospective review of patients with complex CHD born at our tertiary care center over a 10-year period. Date analysis using student T-test and chi square test.
    RESULTS: The overall rate of prenatal detection of complex CHD was 68.1%. A steady increase in the number of complex CHD diagnosed prenatally was noted during the study period. The prenatal diagnosis of complex CHD was associated with significant reduction in the incidence of the following preoperative parameters: antibiotic use, mechanical ventilation, inotropic support, hepatic and renal dysfunction, and acidosis. These beneficial effects were more significant in ductal dependent cardiac anomalies. However there were no neonatal and infant survival benefits in association with prenatal diagnosis.
    CONCLUSION: Prenatal diagnosis of complex CHD leads to improved preoperative morbidity, especially in patients with ductal dependent cardiac anomalies. No survival benefits were noted with prenatal diagnosis of complex CHD.
    DOI:  https://doi.org/10.1002/pd.5351
  5. Int J Cardiol. 2018 Aug 22. pii: S0167-5273(18)33953-6. [Epub ahead of print]
    Baggen VJM, Venema E, Živná R, van den Bosch AE, Eindhoven JA, Witsenburg M, Cuypers JAAE, Boersma E, Lingsma H, Popelová JR, Roos-Hesselink JW.
      AIMS: To develop and validate a clinically useful risk prediction tool for patients with adult congenital heart disease (ACHD).METHODS AND RESULTS: A risk model was developed in a prospective cohort of 602 patients with moderate/complex ACHD who routinely visited the outpatient clinic of a tertiary care centre in the Netherlands (2011-2013). This model was externally validated in a retrospective cohort of 402 ACHD patients (Czech Republic, 2004-2013). The primary endpoint was the 4-year risk of death, heart failure, or arrhythmia, which occurred in 135 of 602 patients (22%). Model development was performed using multivariable logistic regression. Model performance was assessed with C-statistics and calibration plots. Of the 14 variables that were selected by an expert panel, the final prediction model included age (OR 1.02, 95%CI 1.00-1.03, p = 0.031), congenital diagnosis (OR 1.52, 95%CI 1.03-2.23, p = 0.034), NYHA class (OR 1.74, 95%CI 1.07-2.84, p = 0.026), cardiac medication (OR 2.27, 95%CI 1.56-3.31, p < 0.001), re-intervention (OR 1.41, 95%CI 0.99-2.01, p = 0.060), BMI (OR 1.03, 95%CI 0.99-1.07, p = 0.123), and NT-proBNP (OR 1.63, 95%CI 1.45-1.84, p < 0.001). Calibration-in-the-large was suboptimal, reflected by a lower observed event rate in the validation cohort (17%) than predicted (36%), likely explained by heterogeneity and different treatment strategies. The externally validated C-statistic was 0.78 (95%CI 0.72-0.83), indicating good discriminative ability.
    CONCLUSION: The proposed ACHD risk score combines six readily available clinical characteristics and NT-proBNP. This tool is easy to use and can aid in distinguishing high- and low-risk patients, which could further streamline counselling, location of care, and treatment in ACHD.
    Keywords:  Adverse events; Congenital heart disease; Prediction model; Prognosis; Risk
    DOI:  https://doi.org/10.1016/j.ijcard.2018.08.059
  6. Trends Cardiovasc Med. 2018 Aug 22. pii: S1050-1738(18)30170-1. [Epub ahead of print]
    Nebigil CG, Désaubry L.
      Congenital heart disease is the most common birth defect, affecting 1.35 million newborns every year. Heart failure is a primary cause of late morbidity and mortality after myocardial infarction. Heart development is involved in several rounds of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Errors in these processes contribute to congenital heart disease, and exert deleterious effects on the heart and circulation after myocardial infarction. The identification of factors that are involved in heart development and disease, and the development of new approaches for the treatment of these disorders are of great interest. G protein coupled receptors (GPCRs) comprise 40% of clinically used drug targets, and their signaling are vital components of the heart during development, cardiac repair and in cardiac disease pathogenesis. This review focuses on the importance of EMT program in the heart, and outlines the newly identified GPCRs as potential therapeutic targets of reprogramming EMT to support cardiac cell fate during heart development and after myocardial infarction. More specifically we discuss prokineticin, serotonin, sphingosine-1-phosphate and apelin receptors in heart development and diseases. Further understanding of the regulation of EMT/MET by GPCRs during development and in the adult hearts can provide the following clinical exploitation of these pathways.
    Keywords:  Apelin, Serotonin; Cardiac progenitor cells, Cardiac stem cells; Congenital heart disease; Epithelial to Mesenchymal Transformation (EMT); GPCR; Heart development; Heart failure; Prokineticin; Sphingosine-1-phosphate
    DOI:  https://doi.org/10.1016/j.tcm.2018.08.007
  7. Ann Thorac Surg. 2018 Aug 30. pii: S0003-4975(18)31172-X. [Epub ahead of print]
    Kiener A, Kelleman M, McCracken C, Kochilas L, St Louis JD, Oster ME.
      BACKGROUND: The arterial switch operation (ASO) became the procedure of choice for dextro-transposition of the great arteries (d-TGA) almost 30 years ago, but the long-term results of this operation are unknown. We aimed to compare the long-term transplant-free survival of patients with d-TGA who underwent ASO vs. atrial switch in the Pediatric Cardiac Care Consortium (PCCC).METHODS: We performed a retrospective cohort study of d-TGA patients undergoing ASO or atrial switch in the US between 1982 and 1991. Long-term transplant-free survival was obtained by linking PCCC data with the National Death Index and the Organ Procurement and Transplant Network. Kaplan-Meier survival plots were constructed and multivariable regression was used to compare long-term transplant-free survival.
    RESULTS: Of 554 d-TGA patients who underwent ASO (n=259) or atrial switch (n=295) the 20-year overall transplant-free survival was 82.1% for those undergoing ASO and 76.3% for those who had atrial switch procedure. Adjusted overall transplant-free survival beyond 10 years post-operation was superior for ASO compared to atrial switch (HR=0.07, 95% CI 0.01-0.52, p-value=0.009). During this time period the ASO had higher in-hospital mortality than the atrial switch (21.6% vs 12.9%, p=0.007). After excluding those with in-hospital mortality, the transplant-free survival 20 years post-repair was 97.7% for the ASO vs. 86.3% for the atrial switch.
    CONCLUSIONS: Despite initial higher in-hospital mortality for ASO during the study period, there is a significant long-term transplant-free survival advantage for ASO as compared to atrial switch for d-TGA surgery. Ongoing monitoring is required to assess late risk of cardiovascular disease.
    DOI:  https://doi.org/10.1016/j.athoracsur.2018.06.084
  8. Semin Fetal Neonatal Med. 2018 Aug 17. pii: S1744-165X(18)30093-3. [Epub ahead of print]
    Neu J, Pammi M.
      Necrotizing enterocolitis (NEC) is a disease of preterm infants and associated with significant mortality and morbidity. Although the pathogenesis of NEC is not clear, microbial dysbiosis, with a bloom of the phylum Proteobacteria, has been reported. Antibiotics and the use of H2 blockers, which affect the gut microbiome, are associated with increased incidence of NEC. In association with dysbiosis, inflammatory processes are upregulated with increased Toll-like receptor signaling, leading to translocation of nuclear factor kappa-β, a transcription factor that induces transcription of various pro-inflammatory cytokines and chemokines. Microbial metabolites, short chain fatty acids including acetate and butyrate, may modulate immunity, inflammation, intestinal integrity and regulate transcription by epigenetic mechanisms. Evaluation of microbiome and metabolome may provide biomarkers for early diagnosis of NEC and microbial therapeutic approaches to correct microbial dysbiosis.
    Keywords:  Intestinal; Microbiome; Necrotizing enterocolitis; Preterm
    DOI:  https://doi.org/10.1016/j.siny.2018.08.001
  9. J Pediatr. 2018 Aug 29. pii: S0022-3476(18)30942-9. [Epub ahead of print]
    Cuello-Garcia CA, Mai SHC, Simpson R, Al-Harbi S, Choong K.
      OBJECTIVE: To characterize how early mobilization is defined in the published literature and describe the evidence on safety and efficacy on early mobilization in critically ill children.STUDY DESIGN: Systematic search of randomized and nonrandomized studies assessing early mobilization-based physical therapy in critically ill children under 18 years of age in MEDLINE, Embase, CINAHL, CENTRAL, the National Institutes of Health, Evidence in Pediatric Intensive Care Collaborative, Physiotherapy Evidence Database, and the Mobilization-Network. We extracted data to identify the types of mobility-based interventions and definitions for early, as well as barriers, feasibility, adverse events, and efficacy outcomes (mortality, morbidities, and length of stay).
    RESULTS: Of 1199 titles found, we included 11 studies (2 pilot trials and 9 observational studies) and 1 clinical practice guideline in the analyses. Neurodevelopmentally appropriate increasing mobility levels have been described for critically ill children, and "early" mobilization was defined as either a range (within 48-72 hours) from admission to the pediatric intensive care unit or when clinical safety criteria are met. Current evidence suggests that early mobilization is safe and feasible and institutional practice guidelines significantly increase the frequency of rehabilitation consults, improve the proportion of patients who receive early mobilization, and reduce the time to mobilization. However, there were inconsistencies in populations and interventions across studies, and imprecision and risk of bias in included studies that precluded us from pooling data to evaluate the efficacy outcomes of early mobilization.
    CONCLUSIONS: The definition of early mobilization varies, but seems to be feasible and safe in critically ill children. The efficacy for early mobilization in this population is yet undetermined because of the low certainty of the evidence available.
    Keywords:  critical illness; early mobilization; mobility physiotherapy; pediatrics; recovery
    DOI:  https://doi.org/10.1016/j.jpeds.2018.07.037
  10. J Pediatr. 2018 Aug 29. pii: S0022-3476(18)30915-6. [Epub ahead of print]
    Dailey-Schwartz AL, Tadros HJ, Azamian MS, Lalani SR, Morris SA, Allen HD, Kim JJ, Landstrom AP.
      OBJECTIVE: To determine the prevalence, spectrum, and prognostic significance of copy number variants of undetermined significance (cnVUS) seen on chromosomal microarray (CMA) in neonates with hypoplastic left heart syndrome (HLHS).STUDY DESIGN: Neonates with HLHS who presented to Texas Children's Hospital between June 2008 and December 2016 were identified. CMA results were abstracted and compared against copy number variations (CNVs) in ostensibly healthy individuals gathered from the literature. Findings were classified as normal, consistent with a known genetic disorder, or cnVUS. Survival was then compared using Kaplan-Meier analysis. Secondary outcomes included tracheostomy, feeding tube at discharge, cardiac arrest, and extracorporeal membrane oxygenation (ECMO).
    RESULTS: Our study cohort comprised 105 neonates with HLHS, including 70 (66.7%) with normal CMA results, 9 (8.6%) with findings consistent with a known genetic disorder, and 26 (24.7%) with a cnVUS. Six of the 26 (23.0%) neonates with a cnVUS had a variant that localized to a specific region of the genome seen in the healthy control population. One-year survival was 84.0% in patients with a cnVUS, 68.3% in those with normal CMA results, and 33.3% in those with a known genetic disorder (P = .003). There were no significant differences in secondary outcomes among the groups, although notably ECMO was used in 15.7% of patients with normal CMA and was not used in those with cnVUS and abnormal results (P = .038).
    CONCLUSIONS: Among children with HLHS, cnVUSs detected on CMA are common. The cnVUSs do not localize to specific regions of the genome, and are not associated with worse outcomes compared with normal CMA results.
    Keywords:  copy number variation; genetic test; mutation variant of undetermined significance
    DOI:  https://doi.org/10.1016/j.jpeds.2018.07.022