RESUMO
Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.
Assuntos
Cardiopatias Congênitas , Progesterona , Humanos , Progesterona/uso terapêutico , Feminino , Cardiopatias Congênitas/tratamento farmacológico , Cardiopatias Congênitas/complicações , Masculino , Gravidez , Método Duplo-Cego , Lactente , Adulto , Recém-Nascido , Desenvolvimento Infantil/efeitos dos fármacos , Progestinas/uso terapêutico , Transtornos do NeurodesenvolvimentoRESUMO
OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.
Assuntos
Mortalidade Hospitalar , Síndrome do Coração Esquerdo Hipoplásico , Procedimentos de Norwood , Humanos , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Recém-Nascido , Procedimentos de Norwood/mortalidade , Procedimentos de Norwood/métodos , Procedimentos de Norwood/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Feminino , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: Neonatal interventional strategies for pulmonary atresia with intact ventricular septum are based on tricuspid valve hypoplasia and right ventricle-dependent coronary circulation. We sought to evaluate long-term outcomes comparing biventricular (BiV) versus single-ventricle (SV) strategies. METHODS: Retrospective review was performed of 119 patients diagnosed with pulmonary atresia with intact ventricular septum from 1995 to 2018. Descriptive statistics summarized patient characteristics and a multivariable Cox survival model was used to compare treatment strategies. RESULTS: Of 119 patients, 62 (52.1%) were male and 13 (10.9%) had a chromosomal abnormality. BiV was pursued in 53.8% (64 out of 119) and SV in 46.2% (55 out of 119) with median tricuspid valve z scores of -1.59 (interquartile range, -3.03 to 0.21) and -5.12 (interquartile range, -5.60 to -4.06), respectively. The median follow-up was 6 years (interquartile range, 2-15 years). Overall survival at 1, 3, and 10 years was 82.4% (98 out of 119), 80.6% (96 out of 119) and 79.8% (95 out of 119), respectively. End states include 36 (30.3%) BiV, 33 (27.7%) SV, 22 (18.5%) alive without definitive end state, 21 (17.6%) death before end state, 4 (3.4%) 1-and-a-half ventricle, and 3 (2.5%) transplants. No SV were converted to BiV, whereas 4 out of 64 (6.3%) BiV were converted to SV. After adjusting for gender, chromosomal abnormalities, gestational age, and birth weight, SV patients had a significantly higher hazard of mortality (hazard ratio, 9.0; 95% CI, 2.65-30.69; P < .001). Mortality was higher in those with right ventricle-dependent coronary circulation (41.9% [13 out of 31]) compared with those without right ventricle-dependent coronary circulation (7.3% [6 out of 82]) (P < .001). CONCLUSIONS: Pulmonary atresia with intact ventricular septum remains a challenging lesion for those patients on the SV pathway, particularly with right ventricle-dependent coronary circulation.
Assuntos
Cardiopatias Congênitas , Atresia Pulmonar , Septo Interventricular , Feminino , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Recém-Nascido , Masculino , Atresia Pulmonar/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: We investigated the incidence and predictors of failure to undergo the Fontan in children with hypoplastic left heart syndrome who survived superior cavopulmonary connection. METHODS: The cohort consists of all patients with hypoplastic left heart syndrome who survived to hospital discharge after superior cavopulmonary connection between 1988 and 2017. The primary outcome was attrition, which was defined as death, nonsuitability for the Fontan, or cardiac transplantation before the Fontan. Subjects were excluded if they were awaiting the Fontan, were lost to follow-up, or underwent biventricular repair. The study period was divided into 4 eras based on changes in operative or medical management. Attrition was estimated with 95% confidence intervals, and predictors were identified using adjusted, logistic regression models. RESULTS: Of the 856 hospital survivors after superior cavopulmonary connection, 52 died, 7 were deemed unsuitable for Fontan, and 12 underwent or were awaiting heart transplant. Overall attrition was 8.3% (71/856). Attrition rate did not change significantly across eras. A best-fitting multiple logistic regression model was used, adjusting for superior cavopulmonary connection year and other influential covariates: right ventricle to pulmonary artery shunt at Norwood (P < .01), total support time at superior cavopulmonary connection (P < .01), atrioventricular valve reconstruction at superior cavopulmonary connection (P = .02), performance of other procedures at superior cavopulmonary connection (P = .01), and length of stay after superior cavopulmonary connection (P < .01). CONCLUSIONS: In this study spanning more than 3 decades, 8.3% of children with hypoplastic left heart syndrome failed to undergo the Fontan after superior cavopulmonary connection. This attrition rate has not decreased over 30 years. Use of a right ventricle to pulmonary artery shunt at the Norwood procedure was associated with increased attrition.
Assuntos
Técnica de Fontan , Derivação Cardíaca Direita , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Fatores Etários , Feminino , Técnica de Fontan/efeitos adversos , Técnica de Fontan/mortalidade , Derivação Cardíaca Direita/efeitos adversos , Derivação Cardíaca Direita/mortalidade , Transplante de Coração , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico por imagem , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Lactente , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Background The superior cavo-pulmonary connection was introduced at our institution in 1988 for infants undergoing surgery for hypoplastic left heart syndrome. Patients with hypoplastic left heart syndrome remain at high risk for mortality in the time period between the Norwood procedure and the superior cavo-pulmonary connection. The primary objectives of this study were to compare interstage mortality across 4 eras and analyze factors that may impact interstage mortality. Methods and Results Patients with hypoplastic left heart syndrome who underwent the Norwood procedure, were discharged from the hospital, and were eligible for superior cavo-pulmonary connection between January 1, 1988, and December 31, 2017, were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated with 95% CIs. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality. There were 1111 patients who met the inclusion criteria. Overall, interstage mortality was 120/1111 (10.8%). Interstage mortality was significantly lower in era 4 relative to era 1 (4.6% versus 13.4%; P=0.02) during the time that age at the superior cavo-pulmonary connection was the lowest (135 days; P<0.01) and the interstage monitoring program was introduced. In addition, use of the right ventricle to pulmonary artery shunt was associated with decreased interstage mortality (P=0.02) and was more routinely practiced in era 4. Conclusions During this 30-year experience, the risk of interstage mortality decreased significantly in the most recent era. Factors that coincide with this finding include younger age at superior cavo-pulmonary connection, introduction of an interstage monitoring program, and increased use of the right ventricle to pulmonary artery shunt.
Assuntos
Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimentos de Norwood/mortalidade , Fatores Etários , Peso ao Nascer , Criança , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Lactente , Tempo de Internação , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: The objective of this study was to estimate hospital mortality and length of stay (LOS) for children with hypoplastic left heart syndrome undergoing superior cavopulmonary connection (SCPC). METHODS: All hypoplastic left heart syndrome interstage survivors who underwent SCPC between 1 January 1988 and 31 December 2017 were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated using standard binomial proportions. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality and LOS. RESULTS: The most common procedures for the cohort (n = 958) were Hemi-Fontan (57.3%) or Bidrectional Glenn shunt (35.7%). The mortality was 4.1% overall and decreased in all 3 later eras compared to era 1. Factors associated with mortality in a multiple covariate model included longer total support time, earlier gestational age, longer LOS at the Norwood Procedure and need for additional procedures. Overall, the median LOS was 7.0 days with a decrease from eras 1 to 2 and plateaued in eras 3 and 4. Predictors of longer LOS included genetic anomaly, longer Norwood LOS, additional procedures, lower weight at surgery and longer total support time. The type of SCPC was not associated with mortality or LOS. CONCLUSIONS: In this large cohort of patients with hypoplastic left heart syndrome undergoing SCPC, hospital mortality has decreased significantly. LOS initially declined but plateaued in recent eras. The risk factors for mortality and longer LOS are related to patient and procedural complexity, especially the need for additional procedures at the time of SCPC.
Assuntos
Técnica de Fontan , Síndrome do Coração Esquerdo Hipoplásico , Procedimentos de Norwood , Criança , Humanos , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Lactente , Tempo de Internação , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD. METHODS: Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n = 4) and control animals (112 days; n = 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n = 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days. RESULTS: Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance. CONCLUSIONS: Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.
Assuntos
Encéfalo/patologia , Oxigenação por Membrana Extracorpórea/métodos , Hipóxia Fetal/terapia , Cardiopatias Congênitas/complicações , Oxigênio/sangue , Prenhez , Animais , Encéfalo/embriologia , Modelos Animais de Doenças , Feminino , Hipóxia Fetal/sangue , Hipóxia Fetal/etiologia , Idade Gestacional , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/diagnóstico , Imageamento por Ressonância Magnética , Gravidez , Ovinos , Ultrassonografia Pré-NatalRESUMO
OBJECTIVES: Interventricular septal hematoma (IVSH) is a rare complication, which may result from ventricular septal defect (VSD) repair. IVSH can result in conduction and/or hemodynamic abnormalities related to impaired ventricular filling or outflow tract obstruction. We report the novel use of extracorporeal membrane oxygenation (ECMO) for management. METHODS: Echocardiography reports (January 1980 to December 2016) were searched for the term "hematoma" in our institutional database and reviewed to determine appropriate cases. Charts and imaging (reports) data were abstracted. All intraoperative and select postoperative echocardiograms were reread by a pediatric cardiologist. RESULTS: N = 12 patients with IVSH. Mean age and weight at surgery were 59 ± 41 days and 3.4 (2.9-5.1) kg, respectively, while the most frequent diagnosis was tetralogy of Fallot. Although all patients had intraoperative transesophageal echocardiography (TEE), only 55% (6 of 11, missing [m] = 1) of IVSH were discovered intraoperatively. Of the 5 patients not discovered intraoperatively (m = 1), IVSH was postoperatively detected secondary to arrhythmia/decompensation by echocardiogram 10.1 ± 7.9 hours postoperatively. Five patients (42%) were managed with ECMO (1 unable to separate from bypass). Overall mortality was 33%. For patients in whom ECMO was used, 2 of 5 (40%) survived. Mean time to IVSH resolution in all survivors was 20 ± 185 days. CONCLUSIONS: IVSH from VSD repair can result in clinical decompensation and mortality. This may relate to the high proportion missed intraoperatively. ECMO should be considered an important modality, which can allow for IVSH resolution. However, considerations must be made to allow for appropriate anticoagulation to avoid hematoma expansion and repeat imaging during ECMO to continually assess the interventricular septum.
Assuntos
Oxigenação por Membrana Extracorpórea , Comunicação Interventricular/cirurgia , Hematoma/terapia , Complicações Pós-Operatórias/terapia , Ecocardiografia Transesofagiana , Oxigenação por Membrana Extracorpórea/mortalidade , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Hematoma/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Septo Interventricular/cirurgiaRESUMO
OBJECTIVE: Fontan surgical planning is an image-based, collaborative effort, which is hypothesized to result in improved patient outcomes. A common motivation for Fontan surgical planning is the progression (or concern for progression) of pulmonary arteriovenous malformations. The purpose of this study was to evaluate the accuracy of surgical planning predictions, specifically hepatic flow distribution (HFD), a known factor in pulmonary arteriovenous malformation progression, and identify methodological improvements needed to increase prediction accuracy. METHODS: Twelve single-ventricle patients who were enrolled in a surgical planning protocol for Fontan surgery with pre- and postoperative cardiac imaging were included in this study. Computational fluid dynamics were used to compare HFD in the surgical planning prediction and actual postoperative conditions. RESULTS: Overall, HFD prediction error was 17 ± 13%. This error was similar between surgery types (15 ± 18% and 18 ± 10% for revisions vs Fontan completions respectively; P = .73), but was significantly lower (6 ± 7%; P = .05) for hepatic to azygous shunts. Y-grafts and extracardiac conduits showed a strong correlation between prediction error and discrepancies in graft insertion points (r = 0.99; P < .001). Improving postoperative anatomy prediction significantly reduced overall HFD prediction error to 9 ± 6% (P = .03). CONCLUSIONS: Although Fontan surgical planning can offer accurate HFD predictions for specific graft types, methodological improvements are needed to increase overall accuracy. Specifically, improving postoperative anatomy prediction was shown to be an important target for future work. Future efforts and refinements to the surgical planning process will benefit from an improved understanding of the current state and will rely heavily on increased follow-up data.
Assuntos
Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Técnica de Fontan , Cardiopatias Congênitas/cirurgia , Circulação Hepática , Imageamento por Ressonância Magnética , Modelagem Computacional Específica para o Paciente , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Técnica de Fontan/efeitos adversos , Georgia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Humanos , Hidrodinâmica , Lactente , Masculino , Modelos Cardiovasculares , Seleção de Pacientes , Philadelphia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Hypoplastic left heart syndrome is one of the most common and challenging lesions requiring surgical intervention in the neonatal period. The Norwood procedure for hypoplastic left heart syndrome was first reported in 1983. The objective of this study was to describe early outcomes after the Norwood procedure at a single institution over 30 years. METHODS: This retrospective cohort study included all patients with hypoplastic left heart syndrome (and variants) who underwent the Norwood procedure between January 1984 and May 2014 at a single institution. The study period was divided into 6 eras: era 1, 1984 to 1988; era 2, 1989 to 1993; era 3, 1994 to 1998; era 4, 1999 to 2003; era 5, 2004 to 2008; and era 6, 2009 to 2014. The primary outcome was in-hospital mortality after the Norwood procedure. Binomial point estimates complete with 95% confidence intervals (CL0.95) were computed for the entire cohort and by era. RESULTS: During the study period, 1663 infants underwent the Norwood procedure. Overall in-hospital mortality was 25.9% (CL0.95, 23.8-28.0). Mortality by chronologic era was 40.4% (CL0.95, 34.9-45.9), 33.6% (CL0.95, 29.2-37.9), 28.7% (CL0.95, 22.8-34.6), 14.9% (CL0.95, 10.4-19.3), 11.2% (CL0.95, 7.4-15.0), and 15.7% (CL0.95, 10.3-21.1). Survival was improved in eras 4 to 6 compared with eras 1 to 3 (P all < .03). Anomalous pulmonary drainage, moderate to severe atrioventricular valve regurgitation, lower birth weight, earlier era, younger gestational age, genetic anomaly, preterm birth, race other than white or African-American, and lower weight at the Norwood procedure were associated with increased mortality. Mortality was greatest in patients with 3 or more risk factors. In the best-fitting multiple covariate model, anomalous pulmonary venous drainage, gestational age in weeks, genetic anomaly, and race other than white and African American were statistically significant contributors, after adjusting for era. CONCLUSIONS: Survival after the Norwood procedure has plateaued despite improvements in diagnosis, perioperative care, and surgical techniques. Nonmodifiable patient characteristics are important determinants of the risk of mortality.
Assuntos
Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimentos de Norwood , Feminino , Mortalidade Hospitalar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Recém-Nascido , Masculino , Procedimentos de Norwood/mortalidade , Procedimentos de Norwood/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Background Healthcare resource utilization is substantial for single-ventricle cardiac defects ( SVCD ), with effort commencing at time of fetal diagnosis through staged surgical palliation. We sought to characterize and identify variables that influence resource utilization for SVCD from fetal diagnosis through death, completed staged palliation, or cardiac transplant. Methods and Results Patients with a prenatal diagnosis of SVCD at our institution from 2004 to 2011 were screened. Patients delivered with intent to treat who received cardiac care exclusively at our institution were included. Primary end points included the total days hospitalized and the numbers of echocardiograms and cardiac catheterizations. Subanalysis was performed on survivors of completed staged palliation on the basis of Norwood operation, dominant ventricular morphology, and additional risk factors. Of 202 patients born with intent to treat, 136 patients survived to 6 months after completed staged palliation. The median number of days hospitalized per patient-year was 25.1 days, and the median numbers of echocardiograms and catheterizations per patient-year were 7.2 and 0.7, respectively. Mortality is associated with increased resource utilization. Survivors had a cumulative length of stay of 57 days and underwent a median of 21 echocardiograms and 2 catheterizations through staged palliation. Right-ventricle-dominant lesions requiring Norwood operation are associated with increased resource utilization among survivors of staged palliation. Conclusions For fetuses with SVCD , those with dominant right-ventricular morphology requiring Norwood operation demand increased resource utilization regardless of mortality. Our findings provide insight into care for SVCD , facilitate precise prenatal counseling, and provide information about the resources utilized to successfully manage SVCD .
Assuntos
Cateterismo Cardíaco/tendências , Ecocardiografia/tendências , Técnica de Fontan/tendências , Recursos em Saúde/tendências , Cardiopatias Congênitas/terapia , Transplante de Coração/tendências , Ventrículos do Coração/cirurgia , Cuidados Paliativos/tendências , Ultrassonografia Pré-Natal/tendências , Técnica de Fontan/efeitos adversos , Técnica de Fontan/mortalidade , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Ventrículos do Coração/anormalidades , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Lactente , Recém-Nascido , Tempo de Internação/tendências , Philadelphia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Industrial chemicals are increasingly recognized as potential developmental neurotoxicants. Di(2-ethylhexyl) phthalate (DEHP), used to impart flexibility and temperature tolerance to polyvinylchloride, and bisphenol A (BPA), used to manufacture polycarbonate, are commonly present in medical devices. The magnitude of exposure in neonates during hospitalization for cardiac operations is unknown. METHODS: We quantified urinary concentrations of DEHP metabolites and BPA preoperatively and postoperatively in neonates undergoing cardiac operations and their mothers. Urinary concentrations of these biomarkers reflect recent exposures (half-lives are approximately 6 to 24 hours). Biomarker concentrations in mothers' and infants' preoperative and postoperative samples were compared. RESULTS: Operations were performed in 18 infants (mean age, 5 ± 4 [SD] days). The maternal sample was obtained on postpartum day 4 ± 4. The preoperative urine sample was obtained on day-of-life 4 ± 2 and the postoperative sample on day-of-life 6 ± 4. Mean maternal concentrations for DEHP metabolites and BPA were at the 50th percentile for females in the United States general population. Infant preoperative concentrations of 1 DEHP metabolite and BPA were significantly higher than maternal concentrations. Postoperative concentrations for all DEHP metabolites were significantly greater than preoperative concentrations. CONCLUSIONS: There is considerable perioperative exposure to DEHP and BPA for neonates undergoing cardiac operations. Infant concentrations for both BPA and DEHP metabolites were significantly higher than maternal concentrations, consistent with the infant's exposure to medical devices. Further study is needed to determine the potential role of these suspect neurotoxicants in the etiology of neurodevelopmental disability after cardiac operations.
Assuntos
Compostos Benzidrílicos/efeitos adversos , Dietilexilftalato/efeitos adversos , Exposição Ambiental/efeitos adversos , Equipamentos e Provisões/efeitos adversos , Cardiopatias Congênitas/cirurgia , Neurotoxinas/efeitos adversos , Fenóis/efeitos adversos , Compostos Benzidrílicos/urina , Biomarcadores/urina , Dietilexilftalato/urina , Feminino , Seguimentos , Cardiopatias Congênitas/urina , Humanos , Recém-Nascido , Masculino , Neurotoxinas/urina , Fenóis/urina , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Veno-arterial extracorporeal membrane oxygenation is frequently used in patients with cardiac disease. We evaluated short-term outcomes and identified factors associated with hospital mortality in cardiac patients supported with veno-arterial extracorporeal membrane oxygenation. METHODS: A retrospective review of patients supported with veno-arterial extracorporeal membrane oxygenation at a university-affiliated children's hospital was performed. RESULTS: A total of 253 patients with cardiac disease managed with extracorporeal membrane oxygenation were identified; survival to discharge was 48%, which significantly improved from 39% in an earlier era (1995-2001) (p=0.01). Patients were categorised into surgical versus non-surgical groups on the basis of whether they had undergone cardiac surgery before or not, respectively. The most common indication for extracorporeal membrane oxygenation was extracorporeal cardiopulmonary resuscitation: 96 (51%) in the surgical group and 45 (68%) in the non-surgical group. In a multiple covariate analysis, single-ventricle physiology (p=0.01), duration of extracorporeal membrane oxygenation (p<0.01), and length of hospital stay (p=0.03) were associated with hospital mortality. Weekend or night shift cannulation was associated with mortality in non-surgical patients (p=0.05). CONCLUSION: We report improvement in survival compared with an earlier era in cardiac patients supported with extracorporeal membrane oxygenation. Single-ventricle physiology continues to negatively impact survival, along with evidence of organ dysfunction during extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, and length of stay.
Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Oxigenação por Membrana Extracorpórea , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Mortalidade Hospitalar , Feminino , Ventrículos do Coração/cirurgia , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Logísticos , Masculino , Philadelphia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Hypoxic-ischemic white matter brain injury commonly occurs in neonates with critical congenital heart disease. Recent work has shown that longer time to surgery is associated with increased risk for this injury. In this study we investigated changes in perinatal cerebral hemodynamics during the transition from fetal to neonatal circulation to ascertain mechanisms that might underlie this risk. METHODS: Neonates with either transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS) were recruited for preoperative noninvasive optical monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using diffuse optical spectroscopy and diffuse correlation spectroscopy, 2 noninvasive optical techniques. Measurements were acquired daily from day of consent until the morning of surgery. Temporal trends in these measured parameters during the preoperative period were assessed with a mixed effects model. RESULTS: Forty-eight neonates with TGA or HLHS were studied. Cerebral oxygen saturation was significantly and negatively correlated with time, and oxygen extraction fraction was significantly and positively correlated with time. Cerebral blood flow did not significantly change with time during the preoperative period. CONCLUSIONS: In neonates with TGA or HLHS, increasing cerebral oxygen extraction combined with an abnormal cerebral blood flow response during the time between birth and heart surgery leads to a progressive decrease in cerebral tissue oxygenation The results support and help explain the physiological basis for recent studies that show longer time to surgery increases the risk of acquiring white matter injury.
Assuntos
Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Transposição dos Grandes Vasos/fisiopatologia , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Circulação Cerebrovascular , Estado Terminal , Feminino , Humanos , Síndrome do Coração Esquerdo Hipoplásico/complicações , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Recém-Nascido , Leucoencefalopatias/etiologia , Leucoencefalopatias/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Fatores de Risco , Espectroscopia de Luz Próxima ao Infravermelho , Fatores de Tempo , Transposição dos Grandes Vasos/complicações , Transposição dos Grandes Vasos/diagnóstico , Transposição dos Grandes Vasos/cirurgiaRESUMO
BACKGROUND: Remote ischemic preconditioning (RIPC) is a mechanism to protect tissues from injury during ischemia and reperfusion. We investigated the neuroprotective effects of RIPC in neonates undergoing cardiac surgery. METHODS: The outcome was white matter injury (WMI), assessed by the change in volume of WMI from preoperative to postoperative brain magnetic resonance imaging (MRI). Patients were randomized to RIPC or SHAM. RIPC was induced prior to cardiopulmonary bypass by four 5-minute cycles of blood pressure cuff inflation to produce ischemia of the lower extremity. For patients randomized to SHAM, the cuff was positioned, but not inflated. RESULTS: The study included 67 patients, with 33 randomized to RIPC and 34 randomized to SHAM. Preoperative and postoperative MRIs were available in 50 patients, including 26 of the 33 RIPC patients and 24 of the 34 SHAM patients. There were no differences in baseline and operative characteristics for either the overall study group or the group with evaluable MRIs. WMI was identified in 28% of the patients preoperatively and in 62% postoperatively. There was no difference in the prevalence of WMI by treatment group (p > 0.5). RIPC patients had an average change in WMI of 600 mL3, and SHAM subjects had an average WMI change of 107 mL3. There was no significant difference in the mean value of WMI change between patients who received RIPC and those who received SHAM treatments (p = 0.178). CONCLUSIONS: In this randomized, blinded clinical trial, there was no evidence that use of RIPC provides neuroprotection in neonates undergoing repair of congenital heart defects with cardiopulmonary bypass.
Assuntos
Isquemia Encefálica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Precondicionamento Isquêmico/métodos , Substância Branca/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Feminino , Seguimentos , Idade Gestacional , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/mortalidade , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroproteção , Medição de Risco , Método Simples-Cego , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Substância Branca/patologiaRESUMO
OBJECTIVES: The MBL2 gene is the major genetic determinant of mannose-binding lectin (MBL)-an acute phase reactant. Low MBL levels have been associated with adverse outcomes in preterm infants. The MBL2Gly54Asp missense variant causes autosomal dominant MBL deficiency. We tested the hypothesis that MBL2Gly54Asp is associated with worse neurodevelopmental outcomes after cardiac surgery in neonates. METHODS: This is an analysis of a previously described cohort of patients with nonsyndromic congenital heart disease who underwent cardiac surgery with cardiopulmonary bypass before age 6 months (n = 295). Four-year neurodevelopment was assessed in 3 domains: Full-Scale Intellectual Quotient, the Visual Motor Integration development test, and the Child Behavior Checklist to assess behavior problems. The Child Behavior Checklist measured total behavior problems, pervasive developmental problems, and internalizing/externalizing problems. A multivariable linear regression model, adjusting for confounders, was fit. RESULTS: MBL2Gly54Asp was associated with a significantly increased covariate-adjusted pervasive developmental problem score (ß = 3.98; P = .0025). Sensitivity analyses of the interaction between age at first surgery and MBL genotype suggested effect modification for the patients with MBL2Gly54Asp (Pinteraction = .039), with the poorest neurodevelopment outcomes occurring in children who had surgery earlier in life. CONCLUSIONS: We report the novel finding that carriers of MBL2Gly54Asp causing autosomal dominant MBL deficiency have increased childhood pervasive developmental problems after cardiac surgery, independent of other covariates. Sensitivity analyses suggest that this effect may be larger in children who underwent surgery at earlier ages. These data support the role of nonsyndromic genetic variation in determining postsurgical neurodevelopment-related outcomes in children with congenital heart disease.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transtornos Globais do Desenvolvimento Infantil/etiologia , Desenvolvimento Infantil , Cardiopatias Congênitas/cirurgia , Lectina de Ligação a Manose/deficiência , Erros Inatos do Metabolismo/genética , Mutação de Sentido Incorreto , Sistema Nervoso/crescimento & desenvolvimento , Fatores Etários , Lista de Checagem , Comportamento Infantil , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/psicologia , Pré-Escolar , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Masculino , Lectina de Ligação a Manose/genética , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/fisiopatologia , Destreza Motora , Exame Neurológico , Fenótipo , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Pregnancies with congenital heart disease in the foetus have an increased prevalence of pre-eclampsia, small for gestational age and preterm birth, which are evidence of an impaired maternal-foetal environment (MFE). METHODS: The impact of an impaired MFE, defined as pre-eclampsia, small for gestational age or preterm birth, on outcomes after cardiac surgery was evaluated in neonates (n = 135) enrolled in a study evaluating exposure to environmental toxicants and neuro-developmental outcomes. RESULTS: The most common diagnoses were transposition of the great arteries (n = 47) and hypoplastic left heart syndrome (n = 43). Impaired MFE was present in 28 of 135 (21%) subjects, with small for gestational age present in 17 (61%) patients. The presence of an impaired MFE was similar for all diagnoses, except transposition of the great arteries (P < 0.006). Postoperative length of stay was shorter for subjects without an impaired MFE (14 vs 38 days, P < 0.001). Hospital mortality was not significantly different with or without impaired MFE (11.7% vs 2.8%, P = 0.104). However, for the entire cohort, survival at 36 months was greater for those without an impaired MFE (96% vs 68%, P = 0.001). For patients with hypoplastic left heart syndrome, survival was also greater for those without an impaired MFE (90% vs 43%, P = 0.007). CONCLUSIONS: An impaired MFE is common in pregnancies in which the foetus has congenital heart disease. After cardiac surgery in neonates, the presence of an impaired MFE was associated with lower survival at 36 months of age for the entire cohort and for the subgroup with hypoplastic left heart syndrome.
Assuntos
Doenças Fetais , Fetoscopia , Cardiopatias Congênitas , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/mortalidade , Doenças Fetais/cirurgia , Fetoscopia/efeitos adversos , Fetoscopia/mortalidade , Fetoscopia/estatística & dados numéricos , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Gravidez , Resultado do TratamentoRESUMO
OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis. RESULTS: DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming. CONCLUSIONS: DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.
Assuntos
Córtex Cerebral/metabolismo , Parada Circulatória Induzida por Hipotermia Profunda , Mitocôndrias/fisiologia , Animais , Animais Recém-Nascidos , Ponte Cardiopulmonar , Respiração Celular/fisiologia , Metabolismo Energético/fisiologia , Feminino , Hemodinâmica/fisiologia , Microdiálise/métodos , Espécies Reativas de Oxigênio/metabolismo , Sus scrofaRESUMO
BACKGROUND: Calls for public reporting of outcomes in congenital heart surgery have led to several different reporting schemes, including a star rating system and benchmark procedure-specific mortality data tables. Important unanswered questions remain about the optimal format and content of public reporting of congenital heart surgery outcomes. METHODS: In conjunction with three parent advocacy groups, we developed a questionnaire to gauge parents' attitudes regarding the format and content of an "optimal" public reporting scheme. Parents were solicited for participation through email lists of members of parent advocacy groups and from a cohort of parents whose children had undergone an STS benchmark procedure of the Society of Thoracic Surgeons at the Children's Hospital of Philadelphia after January 1, 2007. RESULTS: The 1,297 responses received provided complete data for analysis. Nearly all the participants were mothers of children with congenital heart disease, and most were white. About half of the children were diagnosed prenatally, and 63% underwent initial repair of the defect in the neonatal period. Parents identified survival statistics, surgeon-specific experience, and complication rates as most important. Presented with three display formats for mortality rates, most parents (89%) identified a numeric procedure-based approach as the best format, and more than half identified the hospital star rating system as the worst format. CONCLUSIONS: Parents of children with congenital heart disease identify survival statistics, surgeon-specific experience, and complication rates as the most important outcome measures to report publicly. Additionally, parents preferred mortality data to be presented in a procedure-specific format using a numeric procedure-based approach, as opposed to the star rating system.