RESUMO
Neonates who require surgery for congenital heart disease (CHD) frequently have difficulty with oral feeds post-operatively and may require a feeding tube at hospital discharge. The purpose of this study was to determine the effect of oral or nasal intubation route on feeding method at hospital discharge. This was a non-blinded randomized control trial of 62 neonates who underwent surgery for CHD between 2018 and 2021. Infants in the nasal (25 patients) and oral (37 patients) groups were similar in terms of pre-operative risk factors for feeding difficulties including completed weeks of gestational age at birth (39 vs 38 weeks), birthweight (3530 vs 3100 g), pre-operative PO intake (92% vs 81%), and rate of pre-operative intubation (22% vs 28%). Surgical risk factors were also similar including Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category (3.9 vs 4.1), shunt placement (32% vs 41%), cardiopulmonary bypass time (181 vs 177 min), and cross-clamp time (111 vs 105 min). 96% of nasally intubated patients took full oral feeds by discharge as compared with 78% of orally intubated infants (p = 0.05). Nasally intubated infants reach full oral feeds an average of 3 days earlier than their orally intubated peers. In this cohort of patients, nasally intubated infants reach oral feeds more quickly and are less likely to require supplemental tube feeding in comparison to orally intubated peers. Intubation route is a potential modifiable risk factor for oral aversion and appears safe in neonates. The study was approved by the University of Virginia Institutional Review Board for Health Sciences Research and was retrospectively registered on clinicaltrials.gov (NCT05378685) on May 18, 2022.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Cirurgia Torácica , Recém-Nascido , Lactente , Humanos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/etiologia , Intubação Gastrointestinal/efeitos adversos , Nutrição Enteral/métodosRESUMO
OBJECTIVE: A standardised multi-site approach to manage paediatric post-operative chylothorax does not exist and leads to unnecessary practice variation. The Chylothorax Work Group utilised the Pediatric Critical Care Consortium infrastructure to address this gap. METHODS: Over 60 multi-disciplinary providers representing 22 centres convened virtually as a quality initiative to develop an algorithm to manage paediatric post-operative chylothorax. Agreement was objectively quantified for each recommendation in the algorithm by utilising an anonymous survey. "Consensus" was defined as ≥ 80% of responses as "agree" or "strongly agree" to a recommendation. In order to determine if the algorithm recommendations would be correctly interpreted in the clinical environment, we developed ex vivo simulations and surveyed patients who developed the algorithm and patients who did not. RESULTS: The algorithm is intended for all children (<18 years of age) within 30 days of cardiac surgery. It contains rationale for 11 central chylothorax management recommendations; diagnostic criteria and evaluation, trial of fat-modified diet, stratification by volume of daily output, timing of first-line medical therapy for "low" and "high" volume patients, and timing and duration of fat-modified diet. All recommendations achieved "consensus" (agreement >80%) by the workgroup (range 81-100%). Ex vivo simulations demonstrated good understanding by developers (range 94-100%) and non-developers (73%-100%). CONCLUSIONS: The quality improvement effort represents the first multi-site algorithm for the management of paediatric post-operative chylothorax. The algorithm includes transparent and objective measures of agreement and understanding. Agreement to the algorithm recommendations was >80%, and overall understanding was 94%.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Quilotórax , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Quilotórax/diagnóstico , Quilotórax/etiologia , Quilotórax/terapia , Humanos , Período Pós-OperatórioRESUMO
Neonatal aortic thrombosis is a rare occurrence but can be life-threatening. Most aortic thrombosis in neonates is related to umbilical artery catheters. A case of a neonate with a spontaneous aortic thrombosis is described here along with a comprehensive review of the literature for cases of neonatal aortic thrombosis not related to any intravascular device or procedure. The aetiologies of these spontaneous thromboses and the relevance of hypercoagulable disorders are discussed. The cases were analysed for odds of death by treatment method adjusted for era. The reference treatment method was thrombolysis and anticoagulation. No other treatment modality had significantly lower odds than the reference. Surgery alone had higher odds for death than the reference, but this may be confounded by severity of case. The management recommendations for clinicians encountering neonates with spontaneous neonatal aortic thrombosis are discussed.
Assuntos
Aorta Torácica/patologia , Doenças da Aorta/diagnóstico , Fibrinolíticos/uso terapêutico , Trombose/diagnóstico , Doenças da Aorta/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Terapia Trombolítica , Trombose/tratamento farmacológicoRESUMO
Cardiac hypertrophy is a common response of cardiac myocytes to stress and a predictor of heart failure. While in vitro cell culture studies have identified numerous molecular mechanisms driving hypertrophy, it is unclear to what extent these mechanisms can be integrated into a consistent framework predictive of in vivo phenotypes. To address this question, we investigate the degree to which an in vitro-based, manually curated computational model of the hypertrophy signaling network is able to predict in vivo hypertrophy of 52 cardiac-specific transgenic mice. After minor revisions motivated by in vivo literature, the model concordantly predicts the qualitative responses of 78% of output species and 69% of signaling intermediates within the network model. Analysis of four double-transgenic mouse models reveals that the computational model robustly predicts hypertrophic responses in mice subjected to multiple, simultaneous perturbations. Thus the model provides a framework with which to mechanistically integrate data from multiple laboratories and experimental systems to predict molecular regulation of cardiac hypertrophy.
Assuntos
Cardiomegalia/genética , Insuficiência Cardíaca/genética , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Cardiomegalia/fisiopatologia , Biologia Computacional , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Humanos , Camundongos , Camundongos Transgênicos , Miocárdio/patologia , Miócitos Cardíacos/patologia , Transdução de Sinais/genéticaRESUMO
Hemoglobin levels (Hgb) of infants with a single ventricle (SV) are traditionally maintained high to maximize oxygen-carrying capacity during stage 1 palliation (S1P), stage 2 palliation (S2P), and between stages (IS). A single-center observational cohort study was performed to determine if red blood cell transfusion during the convalescent phase of the S1P (late S1P transfusion) to achieve higher Hgb is associated with benefits during the IS including improved growth and decreased acute medical events. 137 infants <1 year with SV with SIP undergoing care from January 2008 to June 2015 were retrospectively evaluated. 78 (57%) infants received a late S1P transfusion. Median Hgb at S1P discharge was 15.9 g/dL (IQR 14.7-17.1) and median Hgb S2P at admission was 15.3 g/dL (IQR 14-16.3). Median daily weight gain was 22 g/day during IS (IQR 17-26) and median daily length gain was 0.09 cm (IQR 0.06-0.11). Hgb at SIP discharge was not associated with IS growth or fewer IS acute events. However, late S1P transfusions were associated with illness severity at S1P and more complicated S1P care. Our data suggest that SV infants after S1P, who are steadily recovering, do not benefit from late transfusion to raise their hemoglobin level at discharge.
Assuntos
Transfusão de Eritrócitos/métodos , Cardiopatias Congênitas/sangue , Hemoglobinas/análise , Desenvolvimento Infantil , Estudos de Coortes , Transfusão de Eritrócitos/efeitos adversos , Técnica de Fontan/efeitos adversos , Técnica de Fontan/métodos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/terapia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Humanos , Lactente , Recém-Nascido , Cuidados Paliativos/métodos , Alta do Paciente , Estudos Retrospectivos , Aumento de PesoRESUMO
TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood. We tested the requirements for Tbx3 in these processes. We generated a unique series of Tbx3 hypomorphic and conditional mouse mutants with varying levels and locations of Tbx3 activity within the heart, and developed techniques for evaluating in vivo embryonic conduction system function. Disruption of Tbx3 function in different regions of the developing heart causes discrete phenotypes and lethal arrhythmias: sinus pauses and bradycardia indicate sinoatrial node dysfunction, whereas preexcitation and atrioventricular block reveal abnormalities in the atrioventricular junction. Surviving Tbx3 mutants are at increased risk for sudden death. Arrhythmias induced by knockdown of Tbx3 in adults reveal its requirement for conduction system homeostasis. Arrhythmias in Tbx3-deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers. These findings indicate that Tbx3 is required for the conduction system to establish and maintain its correct molecular identity and functional properties. In conclusion, Tbx3 is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner. TBX3 and its regulatory targets merit investigation as candidates for human arrhythmias.
Assuntos
Arritmias Cardíacas/fisiopatologia , Dosagem de Genes , Sistema de Condução Cardíaco/fisiopatologia , Homeostase/genética , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/genética , Alelos , Animais , Animais Recém-Nascidos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/patologia , Bloqueio Atrioventricular/complicações , Bloqueio Atrioventricular/diagnóstico por imagem , Bloqueio Atrioventricular/patologia , Bloqueio Atrioventricular/fisiopatologia , Nó Atrioventricular/patologia , Nó Atrioventricular/fisiopatologia , Conexina 43/metabolismo , Eletrocardiografia , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/patologia , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Sistema de Condução Cardíaco/anormalidades , Sistema de Condução Cardíaco/diagnóstico por imagem , Sistema de Condução Cardíaco/patologia , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Camundongos , Mutação/genética , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recombinação Genética/genética , Análise de Sobrevida , Proteínas com Domínio T/metabolismo , UltrassonografiaRESUMO
OBJECTIVE: To measure neurodevelopment at 3 years of age in children with single right-ventricle anomalies and to assess its relationship to Norwood shunt type, neurodevelopment at 14 months of age, and patient and medical factors. STUDY DESIGN: All subjects in the Single Ventricle Reconstruction Trial who were alive without cardiac transplant were eligible for inclusion. The Ages and Stages Questionnaire (ASQ, n = 203) and other measures of behavior and quality of life were completed at age 3 years. Medical history, including measures of growth, feeding, and complications, was assessed through annual review of the records and phone interviews. The Bayley Scales of Infant Development, Second Edition (BSID-II) scores from age 14 months were also evaluated as predictors. RESULTS: Scores on each ASQ domain were significantly lower than normal (P < .001). ASQ domain scores at 3 years of age varied nonlinearly with 14-month BSID-II. More complications, abnormal growth, and evidence of feeding, vision, or hearing problems were independently associated with lower ASQ scores, although models explained <30% of variation. Type of shunt was not associated with any ASQ domain score or with behavior or quality-of-life measures. CONCLUSION: Children with single right-ventricle anomalies have impaired neurodevelopment at 3 years of age. Lower ASQ scores are associated with medical morbidity, and lower BSID-II scores but not with shunt type. Because only a modest percentage of variation in 3-year neurodevelopmental outcome could be predicted from early measures, however, all children with single right-ventricle anomalies should be followed longitudinally to improve recognition of delays.
Assuntos
Deficiências do Desenvolvimento/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Sistema Nervoso/crescimento & desenvolvimento , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
The important roles that T-box genes play in the morphogenesis of the heart and its conduction system has long been established, and a number of disorders are linked to mutations in these T-box genes. Holt-Oram syndrome (HOS), the classic heart and hand syndrome, is clinically typified by radial ray upper limb abnormalities and cardiac malformations, and is caused by mutations involving TBX5. Another member of the T-box gene family, TBX3, is found in close proximity to TBX5 on chromosome 12q24. Mutations in TBX3 cause ulnar-mammary syndrome (UMS), which is distinguished by upper limb malformations affecting the ulnar ray, apocrine, and mammary gland hypoplasia, and genital defects. While disorders involving isolated mutations of TBX5 and TBX3 have been well described, contiguous deletions of these T-box genes remain exceptional. We report on a patient with features of both HOS and UMS consisting of bilateral symmetric limb malformations, congenital cardiac defects, and rapidly progressive cardiac conduction disease.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Fenótipo , Deleção de Sequência , Proteínas com Domínio T/genética , Doenças Mamárias , Pré-Escolar , Hibridização Genômica Comparativa , Eletrocardiografia , Estudos de Associação Genética , Cardiopatias Congênitas , Comunicação Interatrial , Humanos , Lactente , Deformidades Congênitas das Extremidades Inferiores , Masculino , Ulna/anormalidades , Deformidades Congênitas das Extremidades SuperioresRESUMO
OBJECTIVES: To safely optimize blood testing and costs for pediatric cardiac surgical patients without adversely impacting patient outcomes. DESIGN: This is a quality improvement cohort project with pre- and postintervention groups. SETTING: University-affiliated pediatric cardiac ICU in a tertiary care children's hospital. PATIENTS: All patients were surgical patients for whom Risk Adjustment for Congenital Heart Surgery categories allowed for stratification by complexity. The preintervention group was treated in 2010 and the postintervention group in 2011. INTERVENTIONS: Laboratory ordering processes were analyzed, and practice changed to limit standing blood test orders and requires individualized ordering. MEASUREMENTS AND MAIN RESULTS: Three hundred nineteen patients were studied in 2010 and 345 in 2011. Groups were similar in median age, weight, length of stay (ICU length of stay), and Risk Adjustment for Congenital Heart Surgery category. There was a reduction in the total blood tests per patient (24 vs 38; p < 0.0001) and length of stay adjusted tests per patient-day (10.4 vs 14.4; p = 0.0001) in the postintervention group. The largest test reductions were blood gases and single electrolytes. Adverse outcomes, such as extubation failure (6.4% vs 5.6%), central catheter-associated bloodstream infection (2.2 vs 1.5), and hospital mortality (0.6% vs 0.6%), were not significantly different between the groups. Cost analysis demonstrated an overall laboratory cost savings of 32%. In addition, the volume of packed RBC transfusions was also significantly decreased in the postintervention group among the most complex patients (Risk Adjustment for Congenital Heart Surgery, 6). CONCLUSIONS: Blood testing rates were safely decreased in postoperative pediatric cardiac patients by changing laboratory ordering practices. In addition, packed RBC transfusion was decreased among the most complex patients.
Assuntos
Análise Química do Sangue/estatística & dados numéricos , Cardiopatias Congênitas/cirurgia , Unidades de Terapia Intensiva Pediátrica/normas , Cuidados Pós-Operatórios/normas , Melhoria de Qualidade , Procedimentos Desnecessários , Extubação , Análise Química do Sangue/economia , Testes de Coagulação Sanguínea/economia , Testes de Coagulação Sanguínea/estatística & dados numéricos , Procedimentos Cirúrgicos Cardíacos , Eletrólitos/sangue , Transfusão de Eritrócitos/estatística & dados numéricos , Hemoglobinometria/economia , Hemoglobinometria/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Intubação Intratraqueal , Longevidade , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Medição de Risco , TempoRESUMO
BACKGROUND: Dietary modification is the mainstay of treatment for postoperative chylothorax in children. However, optimal fat-modified diet (FMD) duration to prevent recurrence is unknown. Our aim was to determine the association between FMD duration and chylothorax recurrence. METHODS: Retrospective cohort study conducted across 6 pediatric cardiac intensive care units within the United States. Patients aged <18 years who developed chylothorax within 30 days after cardiac surgery between January 2020 and April 2022 were included. Patients with a Fontan palliation, who died, or were lost to follow-up or within 30 days of resuming a regular diet were excluded. FMD duration was defined as the first day of a FMD when chest tube output was <10 mL/kg/d without increasing until the resumption of a regular diet. Patients were classified into 3 groups (<3 weeks, 3-5 weeks, >5 weeks) based on FMD duration. RESULTS: A total of 105 patients were included: <3 weeks (n = 61) 3-5 weeks (n = 18), and >5 weeks (n = 26). Demographic, surgical, and hospitalization characteristics were not different across groups. In the >5 weeks group, chest tube duration was longer compared with the <3 weeks and 3-5 weeks groups (median, 17.5 days [interquartile range, 9-31] vs 10 and 10.5 days; P = .04). There was no recurrence of chylothorax within 30 days once chylothorax was resolving regardless of FMD duration. CONCLUSIONS: FMD duration was not associated with recurrence of chylothorax, suggesting that FMD duration can safely be shortened to at least <3 weeks from time of resolving chylothorax.
RESUMO
BACKGROUND: Electroencephalographic seizures (ESs) after neonatal cardiac surgery are often subclinical and have been associated with poor outcomes. An accurate ES prediction model could allow targeted continuous electroencephalographic monitoring (CEEG) for high-risk neonates. METHODS: ES prediction models were developed and validated in a multicenter prospective cohort where all postoperative neonates who underwent cardiopulmonary bypass (CPB) also underwent CEEG. RESULTS: ESs occurred in 7.4% of neonates (78 of 1053). Model predictors included gestational age, head circumference, single-ventricle defect, deep hypothermic circulatory arrest duration, cardiac arrest, nitric oxide, extracorporeal membrane oxygenation, and delayed sternal closure. The model performed well in the derivation cohort (c-statistic, 0.77; Hosmer-Lemeshow, P = .56), with a net benefit (NB) over monitoring all and none over a threshold probability of 2% in decision curve analysis (DCA). The model had good calibration in the validation cohort (Hosmer-Lemeshow, P = .60); however, discrimination was poor (c-statistic, 0.61), and in DCA there was no NB of the prediction model between the threshold probabilities of 8% and 18%. By using a cut point that emphasized negative predictive value in the derivation cohort, 32% (236 of 737) of neonates would not undergo CEEG, including 3.5% (2 of 58) of neonates with ESs (negative predictive value, 99%; sensitivity, 97%). CONCLUSIONS: In this large prospective cohort, a prediction model of ESs in neonates after CPB had good performance in the derivation cohort, with an NB in DCA. However, performance in the validation cohort was weak, with poor discrimination, poor calibration, and no NB in DCA. These findings support CEEG of all neonates after CPB.
Assuntos
Ponte Cardiopulmonar/efeitos adversos , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Convulsões/diagnóstico , Convulsões/etiologia , Estudos de Coortes , Eletroencefalografia , Feminino , Humanos , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Curva ROC , Fatores de RiscoRESUMO
Children in the intensive care unit (ICU) are at high risk of developing delirium, given their underlying disease processes, the adverse effects of treatments and medications, and the stressful, abnormal environment. If prevention and nonpharmacologic measures to treat delirium are unsuccessful, atypical antipsychotics are considered, although they are not approved by Food and Drug Administration for the treatment of pediatric delirium and could have significant adverse side effects. This case report presents three pediatric patients with hyperactive ICU delirium that risked life-threating complications who were successfully treated with short courses of atypical antipsychotic medications.
RESUMO
Branch pulmonary stenosis may develop after repair of congenital heart disease. Echocardiography, used for the serial evaluation of these patients, yields Doppler gradients that are used in decisions regarding the need for intervention for branch pulmonary stenosis. The purpose of this study was to assess the value of Doppler echocardiography in quantifying the degree of branch pulmonary stenosis in patients who were postoperative. Patients after repair of transposition of the great arteries (n = 14), truncus arteriosus (n = 12), or tetralogy of Fallot (n = 14) who underwent echocardiography within 3 months of a postoperative catheterization were identified. Doppler peak instantaneous gradients were compared with catheter peak-to-peak gradients. Despite significant correlation between Doppler and catheterization peak gradients, Doppler gradients tended to overestimate the catheterization gradients, and the agreement between the 2 measurements was poor. These findings suggest that Doppler gradients should be interpreted cautiously in this setting.
Assuntos
Cateterismo Cardíaco , Ecocardiografia Doppler , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Estenose da Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/cirurgia , Adolescente , Velocidade do Fluxo Sanguíneo/fisiologia , Criança , Proteção da Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Bem-Estar do Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Artéria Pulmonar/fisiopatologia , Estenose da Valva Pulmonar/etiologia , Resultado do Tratamento , Utah , Cirurgia VídeoassistidaRESUMO
The transcription factor TBX3 plays critical roles in development and TBX3 mutations in humans cause Ulnar-mammary syndrome. Efforts to understand how altered TBX3 dosage and function disrupt the development of numerous structures have been hampered by embryonic lethality of mice bearing presumed null alleles. We generated a novel conditional null allele of Tbx3: after Cre-mediated recombination, no mRNA or protein is detectable. In contrast, a putative null allele in which exons 1-3 are deleted produces a truncated protein that is abnormally located in the cytoplasm. Heterozygotes and homozygotes for this allele have different phenotypes than their counterparts bearing a true null allele. Our observations with these alleles in mice, and the different types of TBX3 mutations observed in human ulnar-mammary syndrome, suggest that not all mutations observed in humans generate functionally null alleles. The possibility that mechanisms in addition to TBX3 haploinsufficiency may cause UMS or other malformations merits investigation in the human UMS population.
Assuntos
Anormalidades Múltiplas/genética , Doenças Mamárias/genética , Mutação , Proteínas com Domínio T/genética , Ulna/metabolismo , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/metabolismo , Animais , Doenças Mamárias/embriologia , Doenças Mamárias/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Coração/embriologia , Membro Posterior/anormalidades , Membro Posterior/embriologia , Membro Posterior/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas com Domínio T/metabolismo , Ulna/anormalidades , Ulna/embriologiaRESUMO
OBJECTIVES: We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial. METHODS: Potential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality. RESULTS: Analysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations. CONCLUSIONS: Innate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization.
Assuntos
Procedimento de Blalock-Taussig/efeitos adversos , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/cirurgia , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimentos de Norwood/efeitos adversos , Procedimento de Blalock-Taussig/mortalidade , Intervalo Livre de Doença , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Mortalidade Hospitalar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Mortalidade Infantil , Recém-Nascido , Estimativa de Kaplan-Meier , Tempo de Internação , Análise Multivariada , América do Norte , Procedimentos de Norwood/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Função VentricularRESUMO
OBJECTIVES: The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths. METHODS: There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the timing, location, and other factors for each event. RESULTS: The most common cause of death was cardiovascular (42%), followed by unknown cause (24%) and multisystem organ failure (7%). The median age at death for subjects dying during the 12 months was 1.6 months (interquartile range, 0.6 to 3.7 months), with the highest number of deaths occurring during hospitalization related to the Norwood procedure. The most common location of death was at a Single Ventricle Reconstruction trial hospital (74%), followed by home (13%). There were 29 sudden, unexpected deaths (18%), although in retrospect, 12 were preceded by a prodrome. CONCLUSIONS: In infants with a single right ventricle undergoing staged repair, the majority of deaths within 12 months of the procedure are due to cardiovascular causes, occur in a hospital, and within the first few months of life. Increased understanding of the circumstances surrounding the deaths of these single ventricle patients may reduce the high mortality rate.
Assuntos
Procedimento de Blalock-Taussig/mortalidade , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/cirurgia , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimentos de Norwood/mortalidade , Procedimento de Blalock-Taussig/efeitos adversos , Causas de Morte , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Mortalidade Hospitalar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Mortalidade Infantil , Recém-Nascido , Estimativa de Kaplan-Meier , América do Norte , Procedimentos de Norwood/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Função VentricularRESUMO
We targeted the reverse tetracycline controlled transactivator (rtTA) to the Foxa2 locus (Foxa2(ITA)) to generate a system for regulating Cre-recombinase activity within Foxa2 expression domains, including the endoderm, notochord, and floor plate of early mouse embryos. The use of an internal ribosomal entry site to obtain rtTA expression preserves Foxa2 function of the targeted allele. Cre activity with this system reflects the level of endogenous Foxa2 activity and is also tightly controlled by doxycycline. The location of Cre activity within the broader Foxa2 expression domain can be restricted by altering the timing of doxycycline administration. Isolated floor plate expression can be obtained in this manner. This system will provide a useful tool for manipulating gene expression in endoderm, notochord, and floor plate, all of which are tissues with important structural and patterning functions during embryogenesis.
Assuntos
Sistema Nervoso Central/metabolismo , Endoderma/metabolismo , Fator 3-beta Nuclear de Hepatócito/genética , Integrases/genética , Notocorda/metabolismo , Transgenes , Animais , Sistema Nervoso Central/embriologia , Doxiciclina/farmacologia , Desenvolvimento Embrionário/genética , Dosagem de Genes , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Marcação de Genes , Fator 3-beta Nuclear de Hepatócito/metabolismo , Integrases/metabolismo , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Elementos Reguladores de TranscriçãoRESUMO
Fibroblast growth factor 8 (Fgf8) is a secreted signaling protein expressed in numerous temporospatial domains that are potentially relevant to cardiovascular development. However, the pathogenesis of complex cardiac and outflow tract defects observed in Fgf8-deficient mice, and the specific source(s) of Fgf8 required for outflow tract formation and subsequent remodeling are unknown. A detailed examination of the timing and location of Fgf8 production revealed previously unappreciated expression in a subset of primary heart field cells; Fgf8 is also expressed throughout the anterior heart field (AHF) mesoderm and in pharyngeal endoderm at the crescent and early somite stages. We used conditional mutagenesis to examine the requirements for Fgf8 function in these different expression domains during heart and outflow tract morphogenesis. Formation of the primary heart tube and the addition of right ventricular and outflow tract myocardium depend on autocrine Fgf8 signaling in cardiac crescent mesoderm. Loss of Fgf8 in this domain resulted in decreased expression of the Fgf8 target gene Erm, and aberrant production of Isl1 and its target Mef2c in the anterior heart field, thus linking Fgf8 signaling with transcription factor networks that regulate survival and proliferation of the anterior heart field. We further found that mesodermal- and endodermal-derived Fgf8 perform specific functions during outflow tract remodeling: mesodermal Fgf8 is required for correct alignment of the outflow tract and ventricles, whereas activity of Fgf8 emanating from pharyngeal endoderm regulates outflow tract septation. These findings provide a novel insight into how the formation and remodeling of primary and anterior heart field-derived structures rely on Fgf8 signals from discrete temporospatial domains.