RESUMEN
BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes. RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001). CONCLUSIONS: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).
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Procedimientos Quirúrgicos Cardíacos , Metilprednisolona , Humanos , Metilprednisolona/efectos adversos , Estudios Prospectivos , InsulinaRESUMEN
BACKGROUND: Obesity increases the risk of post-operative arrhythmias in adults undergoing cardiac surgery, but little is known regarding the impact of obesity on post-operative arrhythmias after CHD surgery. METHODS: Patients undergoing CHD surgery from 2007 to 2019 were prospectively enrolled in the parent study. Telemetry was assessed daily, with documentation of all arrhythmias. Patients aged 2-20 years were categorised by body mass index percentile for age and sex (underweight <5, normal 5-85, overweight 85-95, and obese >95). Patients aged >20 years were categorised using absolute body mass index. We investigated the impact of body mass index category on arrhythmias using univariate and multivariate analysis. RESULTS: There were 1250 operative cases: 12% underweight, 65% normal weight, 12% overweight, and 11% obese. Post-operative arrhythmias were observed in 38%. Body mass index was significantly higher in those with arrhythmias (18.8 versus 17.8, p = 0.003). There was a linear relationship between body mass index category and incidence of arrhythmias: underweight 33%, normal 38%, overweight 42%, and obese 45% (p = 0.017 for trend). In multivariate analysis, body mass index category was independently associated with post-operative arrhythmias (p = 0.021), with odds ratio 1.64 in obese patients as compared to normal-weight patients (p = 0.036). In addition, aortic cross-clamp time (OR 1.007, p = 0.002) and maximal vasoactive-inotropic score in the first 48 hours (OR 1.03, p = 0.04) were associated with post-operative arrhythmias. CONCLUSION: Body mass index is independently associated with incidence of post-operative arrhythmias in children after CHD surgery.
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Cardiopatías Congénitas , Delgadez , Niño , Humanos , Adulto Joven , Delgadez/complicaciones , Delgadez/cirugía , Sobrepeso/complicaciones , Factores de Riesgo , Obesidad/complicaciones , Obesidad/epidemiología , Índice de Masa Corporal , Arritmias Cardíacas/etiología , Arritmias Cardíacas/complicaciones , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess the prevalence of psychiatric disorders and associated therapies in children during their heart transplantation admission. STUDY DESIGN: All pediatric heart transplant recipients (1999-2016) were included from a linked administrative and clinical registry database. Psychiatric disorders and associated therapies were identified using International Classification of Diseases or billing codes during the transplant admission. Data were analyzed using standard descriptive statistics. Multivariable logistic regression assessed factors independently associated with psychiatric disorders or therapies. RESULTS: A total of 3073 pediatric heart transplant recipients were included. Psychiatric disorders were present in 434 (14.1%) patients during the heart transplant admission, with adjustment disorders being the most common. Antidepressant therapy was prescribed to 212 patients (6.9%) and selective serotonin reuptake inhibitors were most commonly used. Psychiatric diagnoses (8.4% vs 18.1%; P < .001) and the use of antidepressants (4.5% vs 8.9%; P < .001) increased over time (era 1, 1999-2009 vs era 2, 2010-2016). Psychiatric disorders were present in 39.8% of patients ≥8 years of age requiring ventricular assist device support at heart transplantation. The need for ventricular assist device support was independently associated with psychiatric diagnoses (aOR, 1.57; 95% CI, 1.18-2.1; P = .002) and antidepressant therapy (aOR, 2.11; 95% CI. 1.43-3.12; P < .001). CONCLUSIONS: Psychiatric disorders are common in pediatric heart transplant recipients, especially among those bridged with ventricular assist device support. Psychiatric diagnoses and the use of antidepressants has increased over time, likely representing improved recognition of psychiatric comorbidities in this vulnerable population. Access to psychiatric services represents an important component of the multidisciplinary team caring for pediatric heart transplant recipients.
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Trastornos de Adaptación/complicaciones , Ansiedad/complicaciones , Trastorno Depresivo/complicaciones , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Corazón Auxiliar , Trastornos de Adaptación/epidemiología , Adolescente , Antidepresivos/uso terapéutico , Ansiedad/epidemiología , Niño , Preescolar , Estudios Transversales , Bases de Datos Factuales , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/epidemiología , Femenino , Insuficiencia Cardíaca/psicología , Humanos , Lactante , Recién Nacido , Masculino , Análisis Multivariante , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto JovenRESUMEN
We present a case report of severed epicardial atrial lead salvage using an IS-1 lead extender. A 37-year-old male with single ventricle physiology, Fontan palliation, sinus node dysfunction, recurrent atrial tachycardias, and atrial fibrillation resulting in failing Fontan physiology presented with failure of the atrial pacing lead. The patient was initially paced with an epicardial system that had to be removed due to pocket infection, and the epicardial leads were cut and abandoned. Given his significant sinus node dysfunction he required atrial pacing to allow for rhythm control. The failing Fontan physiology of the patient precluded him from undergoing surgery for epicardial lead placement or a complex intravascular lead placement procedure (although anatomically feasible). We considered the option of salvaging the existing epicardial atrial leads to provide atrial pacing, allowing for rhythm control and improvement of his failing Fontan physiology as a bridge to a more permanent pacing solution. This case report is important because it demonstrates how a lead extender can be used to salvage a severed pacemaker lead. This may be useful for patients in whom implantation of new leads is not promptly feasible due to patient anatomy and/or clinical status.
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Procedimiento de Fontan , Marcapaso Artificial , Adulto , Estimulación Cardíaca Artificial , Procedimiento de Fontan/efectos adversos , Humanos , Masculino , Pericardio/cirugía , Síndrome del Seno Enfermo/terapiaRESUMEN
Primary graft dysfunction following HTx is associated with significant morbidity and mortality. This study aimed to assess the incidence of, risk factors for, and outcomes of children requiring ECMO within 24 hours of HTx. This study utilized a linked PHIS/SRTR database of pediatric HTx recipients (2002-2016). Post-HTx ECMO was identified using inpatient billing data. Logistic regression assessed risk factors for post-HTx ECMO. Kaplan-Meier analyses assessed in-hospital mortality and post-discharge survival. A total of 2820 patients were included with 224 (7.9%) requiring ECMO. Independent risk factors for post-HTx ECMO include age <1 year (aOR: 2.2, 95% CI: 1.3-3.7, P = 0.006) or 1-5 years (aOR: 2.1, 95% CI: 1.3-3.4, P = 0.002), and ECMO support at HTx (aOR: 27.4, 95% CI: 15.2-49.6, P < 0.001). Survival to discharge decreased with increasing duration of post-HTx ECMO support; 89% for 1-3 days, 79.1% for 4-6 days, 63.2% for 7-9 days, and 18.8% for ≥10 days. There was no difference in long-term survival for patients requiring post-HTx ECMO who survived to hospital discharge (P = 0.434). There are identifiable risk factors associated with the need for ECMO in the post-HTx period. Length of time on ECMO post-HTx is strongly associated with the risk of in-hospital mortality. Patients who require ECMO early post-HTx and survive to discharge have comparable outcomes to patients who did not require ECMO.
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Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/métodos , Adolescente , Niño , Preescolar , Femenino , Rechazo de Injerto/etiología , Supervivencia de Injerto , Trasplante de Corazón/mortalidad , Corazón Auxiliar , Humanos , Incidencia , Lactante , Estimación de Kaplan-Meier , Masculino , Disfunción Primaria del Injerto/etiología , Análisis de Regresión , Factores de Riesgo , Resultado del TratamientoRESUMEN
There are limited published data addressing the costs associated with pediatric heart transplantation and no studies evaluating the variation in costs across centers. We aimed to describe center variation in pediatric heart transplant costs and assess the association of transplant hospitalization costs with patient outcomes. Using a linkage between the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases, hospital costs were assessed for patients (< 18 years of age) undergoing heart transplantation (2007-2016). Severity-adjusted patient costs were calculated using generalized linear mixed-effects models with a random hospital intercept. Center variation in hospital cost was described after adjusting for the predicted risk of in-hospital mortality. Post-transplant survival was compared between low- and high-cost centers using Cox proportional hazard models. A total of 2156 patients were included from 24 centers. There was 3.7-fold variation in transplant hospitalization costs across centers, ranging from $329,477 to $1,226,507. Patients transplanted at high-cost centers have a higher predicted risk of in-hospital mortality (8.1% vs. 6.1%, p < 0.001). Both early (p = 0.008) and long-term (p = 0.003) post-transplant survival were better in patients transplanted at low-cost centers. Transplant at low-cost centers was associated with improved post-transplant survival, independent of patient-specific risk (adjusted hazard ratio 0.72; 95%CI 0.57-0.92, p = 0.008). There is wide variation in cost for pediatric heart transplant inpatient care among U.S. centers with low-cost centers demonstrating the best patient survival. Differences in patient populations likely contribute to these findings, but cannot account for all the variation seen. This suggests that variability in the delivery of care across centers may influence post-transplant survival.
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Trasplante de Corazón/economía , Costos de Hospital/estadística & datos numéricos , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Femenino , Trasplante de Corazón/mortalidad , Mortalidad Hospitalaria , Humanos , Lactante , Masculino , Modelos de Riesgos Proporcionales , Sistema de Registros , Tasa de Supervivencia , Estados UnidosRESUMEN
BACKGROUND: Pediatric mechanical circulatory support (MCS) has evolved considerably over the past decade. Though marked improvements in waitlist survival have been realized, costs have not been reassessed. This project aimed to assess contemporary MCS costs in children bridged to heart transplant (HT). METHODS: All pediatric HT recipients (2002-2016) were identified from a unique, linked PHIS/SRTR dataset. Costs were calculated from hospital charges, inflated to 2016 Dollars and adjusted for patient-specific characteristics using generalized linear mixed-effects models. Costs and length of stay (LOS) were compared across support strategies at the time of HT (no MCS, VAD, or ECMO) with select subgroup analyses. RESULTS: A total of 2873 pediatric HT recipients were included; no MCS: 2268 (78.9%), VAD: 470 (16.4%), and ECMO: 135 (4.7%). Both VAD and ECMO were associated with greater total hospitalization costs compared to no MCS ($755,345 and $808,771 vs. $457,086; Pâ¯<â¯.001). Total costs and LOS were similar between VAD and ECMO groups; however, costs and LOS were greatest for VAD-supported patients in the pre-HT period and greatest for ECMO-supported patients post-HT. Post-HT costs and LOS were similar between patients who did not require MCS and those supported with a VAD ($324,887 and 18 days vs. $329,198 and 18 days respectively, pâ¯=â¯NS). Outpatients with VAD support at HT demonstrated significantly lower total costs compared to those who were inpatient with continuous flow devices ($552,222 vs. $663,071, Pâ¯=â¯.003). CONCLUSIONS: MCS as a bridge to HT in children is associated with greater total costs. While costs are similar between VAD and ECMO groups, the majority of costs associated with VAD support is incurred pre-HT while ECMO costs are incurred primarily post-HT. Discharging patients on VAD support awaiting HT may represent a strategy to reduce costs in this population.
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Oxigenación por Membrana Extracorpórea/métodos , Costos de la Atención en Salud , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Corazón Auxiliar/economía , Listas de Espera/mortalidad , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Oxigenación por Membrana Extracorpórea/economía , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Lactante , Masculino , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
There is controversy regarding the management of projectile embolization, a rare complication of penetrating trauma. We present the case of a 5-year-old, 20 kg male with retrograde venous projectile embolization following traumatic injury with a pellet gun. The projectile was successfully removed utilizing a novel, percutaneous approach.
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Embolia/cirugía , Cuerpos Extraños/cirugía , Lesiones Cardíacas/cirugía , Heridas por Arma de Fuego/complicaciones , Preescolar , Embolia/etiología , Cuerpos Extraños/complicaciones , Lesiones Cardíacas/complicaciones , Lesiones Cardíacas/etiología , Humanos , Masculino , Heridas por Arma de Fuego/cirugíaRESUMEN
BACKGROUND: Many pediatric heart transplant recipients live a significant distance from their transplant center. This results in families either traveling long distances or relying on outside physicians to assume aspects of their care. Distance has been implicated to play a role in congenital heart disease outcomes, but its impact on heart transplantation has not been reported. The aim of this study was to assess the impact of distance on pediatric heart transplant outcomes. METHODS: The Scientific Registry of Transplant Recipients database was queried for all pediatric heart transplant recipients from large US children's hospitals (1987-2014). Patients were stratified into 4 groups (<20, 20-50, 50-100, and >100 miles) based on distance. Survival curves were generated and compared using the log-rank test. Cox proportional hazards regression was performed to adjust for differences between groups. RESULTS: A total of 4768 patients were included in the analysis, of which 1435 (30.1%) were <20 miles, 940 (19.7%) were 20 to 50 miles, 806 (16.9%) were 50 to 100 miles, and 1587 (33.3%) were >100 miles from their transplant center. There was no difference in posttransplant survival based on distance after adjusting for patient age, gender, ethnicity, blood type, diagnosis, listing status, and the need for pretransplant ventricular assist device, extracorporeal membrane oxygenation, or ventilator support. CONCLUSION: There is no significant difference in graft survival after pediatric heart transplantation based on patient distance from their transplant center. Our data suggest the current strategy of transitioning some aspects of transplant care to local physicians or management from a distance does not increase posttransplant mortality risk.
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Geografía/estadística & datos numéricos , Cardiopatías Congénitas/cirugía , Trasplante de Corazón/rehabilitación , Trasplante de Corazón/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Sobrevivientes/estadística & datos numéricos , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Large clinical, research, and administrative databases are increasingly utilized to facilitate pediatric heart transplant (HTx) research. Linking databases has proven to be a robust strategy across multiple disciplines to expand the possible analyses that can be performed while leveraging the strengths of each dataset. We describe a unique linkage of the Scientific Registry of Transplant Recipients (SRTR) database and the Pediatric Health Information System (PHIS) administrative database to provide a platform to assess resource utilization in pediatric HTx. METHODS: All pediatric patients (1999-2016) who underwent HTx at a hospital enrolled in the PHIS database were identified. A linkage was performed between the SRTR and PHIS databases in a stepwise approach using indirect identifiers. To determine the feasibility of using these linked data to assess resource utilization, total and post-HTx hospital costs were assessed. RESULTS: A total of 3188 unique transplants were identified as being present in both databases and amenable to linkage. Linkage of SRTR and PHIS data was successful in 3057 (95.9%) patients, of whom 2896 (90.8%) had complete cost data. Median total and post-HTx hospital costs were $518,906 (IQR $324,199-$889,738), and $334,490 (IQR $235,506-$498,803) respectively with significant differences based on patient demographics and clinical characteristics at HTx. CONCLUSIONS: Linkage of the SRTR and PHIS databases is feasible and provides an invaluable tool to assess resource utilization. Our analysis provides contemporary cost data for pediatric HTx from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric HTx population.
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Investigación Biomédica , Cardiología , Sistemas de Información en Salud/estadística & datos numéricos , Cardiopatías Congénitas/cirugía , Trasplante de Corazón/estadística & datos numéricos , Sistema de Registros , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Femenino , Hospitales Pediátricos , Humanos , Lactante , Masculino , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
The use of status exceptions (SE) was recently publicized as a strategy to reduce waitlist times for children awaiting heart transplant (HTx). The aim of this study was to assess SE use across UNOS regions and compare survival in patients listed using a SE to those listed by standard criteria. The OPTN database was queried for all pediatric patients listed for HTx (2000-2014). SE use was compared across UNOS regions. Survival curves were generated and compared using the log-rank test. 1A SE use is uncommon, being utilized in 108 of 4587 pediatric 1A listings (2.4%). There is significant variability in SE use across UNOS regions (0.7%-16.4% of 1A listings, P < .001). Waitlist survival is significantly higher in candidates listed using a 1A SE compared to those listed by standard criteria (P = .001) and is similar to 1B listings. Regional variation in 1A SE use has the potential to introduce bias into a system designed to be equitable. Waitlist survival in patients listed using a SE is similar to those listed status 1B, suggesting these patients may not require 1A status. Careful review of pediatric heart allocation policies is needed to optimize patient outcomes and ensure a fair and unbiased allocation system.
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Equidad en Salud , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Obtención de Tejidos y Órganos/métodos , Niño , Preescolar , Bases de Datos Factuales , Femenino , Geografía , Insuficiencia Cardíaca/mortalidad , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Asignación de Recursos , Tiempo de Tratamiento , Resultado del Tratamiento , Estados Unidos , Listas de EsperaRESUMEN
There are limited published data on pediatric organ donation rates. The aim of this study was to describe the trends in pediatric organ donation over time and to assess the regional variation in pediatric deceased organ donation. OPTN data were utilized to assess the trends in pediatric organ donation over time. The number of deceased pediatric organ donors was indexed using regional mortality data obtained from the National Center for Health Statistics and compared across UNOS regions and two different eras. The number of pediatric deceased organ donors has declined in the recent era, largely driven by fewer adolescent donors. For all age groups, there is significant regional variation in organ donation rates, with identifiable high- and low-performing regions. Expansion of the donor pool may be possible by optimizing organ donation in regions demonstrating lower recruitment of pediatric donors. Using the region with the highest donation rate for each age group as the gold standard, we estimate a potential 24% increase in the number of donors if all regions performed comparably, equating to 215 new pediatric donors annually.
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Trasplante de Órganos , Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/tendencias , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Muerte , Humanos , Lactante , Recién Nacido , Pediatría/métodos , Estados UnidosRESUMEN
Bleeding and thrombosis are well-known potential complications of VAD support. We present a pediatric patient who developed massive bilateral pulmonary emboli while on BiVAD support that was successfully treated with intravenous tPA and bridged to heart transplant.
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Fibrinolíticos/uso terapéutico , Insuficiencia Cardíaca/terapia , Corazón Auxiliar/efectos adversos , Embolia Pulmonar/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Trasplante de Corazón , Humanos , Lactante , Masculino , Embolia Pulmonar/etiologíaRESUMEN
PURPOSE: The bidirectional Glenn (BDG) procedure involves the anastomosis of the superior vena cava (SVC) to the pulmonary artery, increasing central venous pressure (CVP). We hypothesize that this increase in CVP triggers an acute neurologic insult, leading to ventriculomegaly. METHODS: In this retrospective analysis in a tertiary care children's hospital, we identified 167 patients who underwent the BDG procedure between August 2006 and July 2013. Within this initial cohort, 24 patients had head imaging (CT, MRI, or ultrasound) performed both before and after the BDG. RESULTS: From head imaging available from these 24 patients, we measured the frontal-occipital horn ratio (FOR), a well-validated measure of lateral ventricle size. Using central venous catheter data, we assessed postoperative CVP at 12, 24, and 48 h. Paired t tests and linear regression were used to evaluate our cohort. Median age at surgery was 4.9 months. Paired analysis revealed that median FOR significantly increased between preoperative (median 0.38, IQR 0.37-0.41) and postoperative (median 0.42, IQR 0.40-0.45) head images (p = 0.005). Increasing change in FOR was associated with increased 12-h (R(2) = 0.369, p = 0.003) but not 24- or 48-h postoperative CVP. CONCLUSIONS: To our knowledge, our study is the first to demonstrate ventriculomegaly developing after the BDG. Physiologically, increasing CVP after the BDG was associated with greater change in lateral ventricle size. This supports the contention that increasing CVP produced during the BDG may damage the developing brain. This study has informed a prospective evaluation of a link between the BDG procedure and neurologic outcomes.
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Procedimiento de Fontan/métodos , Hidrocefalia/cirugía , Resultado del Tratamiento , Femenino , Hospitales Pediátricos , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: Hemolysis, occurring during cardiopulmonary bypass, is associated with lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass. DESIGN: Single-center prospective randomized double-blinded study. SETTING: University-affiliated pediatric hospital. PATIENTS: Thirty children undergoing elective surgical correction of a congenital heart defect. INTERVENTIONS: Patients were randomized to acetaminophen (OFIRMEV [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass. MEASUREMENT AND MAIN RESULTS: Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes), and acute kidney injury were measured throughout the perioperative period. Cardiopulmonary bypass was associated with a significant increase in free hemoglobin (from a prebypass level of 9.8 ± 6.2 mg/dL to a peak of 201.5 ± 42.6 mg/dL postbypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans compared with placebo (p = 0.02 for effect of study drug). There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation. Acetaminophen did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney injury. CONCLUSION: Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary bypass.
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Acetaminofén/farmacología , Analgésicos no Narcóticos/farmacología , Puente Cardiopulmonar/efectos adversos , Furanos/sangre , Hemólisis/efectos de los fármacos , Isoprostanos/sangre , Peroxidación de Lípido/efectos de los fármacos , Lesión Renal Aguda/etiología , Proteínas de Fase Aguda/orina , Biomarcadores/sangre , Biomarcadores/orina , Niño , Preescolar , Creatinina/sangre , Método Doble Ciego , Femenino , Furanos/orina , Haptoglobinas/metabolismo , Cardiopatías Congénitas/cirugía , Hemoglobinas/metabolismo , Humanos , Lactante , Isoprostanos/orina , Lipocalina 2 , Lipocalinas/orina , Masculino , Proyectos Piloto , Proteínas Proto-Oncogénicas/orinaRESUMEN
BACKGROUND: Arterial switch operation (ASO) has supplanted physiologic repairs for transposition of the great arteries and related anomalies. As survival rates have increased, so has the potential need for cardiac reoperations to address ASO-related complications arising later in life. METHODS: The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2021) was reviewed to assess prevalence and types of cardiac reoperations for patients aged ≥10 years with prior ASO for transposition of the great arteries or double-outlet right ventricle/transposition of the great arteries type. A hierarchical stratification designating 13 procedure categories was established a priori by investigators. Each eligible surgical hospitalization was assigned to the single highest applicable hierarchical category. Outcomes were compared across procedure categories, excluding hospitalizations limited to pacemaker-only and mechanical circulatory support-only procedures. Variation during the study period in relative proportions of left heart vs non-left heart procedure category encounters was assessed. RESULTS: There were 698 cardiac surgical hospitalizations for patients aged 10 to 35 years at 100 centers. The most common left heart procedure categories were aortic valve procedures (n = 146), aortic root procedures (n = 117), and coronary artery procedures (n = 40). Of 619 hospitalizations eligible for outcomes analysis, major complications occurred in 11% (67/619). Discharge mortality was 2.3% (14/619). Year-by-year analysis of surgical hospitalizations reveals substantial growth in numbers for the aggregate of all procedure categories. Growth in relative proportions of left heart vs non-left heart procedures was significant (P = .0029; Cochran-Armitage trend test). CONCLUSIONS: This large multicenter study of post-ASO reoperations beyond early childhood documents year-over-year growth in total reoperations. Left-sided heart procedures recently had the highest rate of rise. These observations have implications for counseling, surveillance, and management.
RESUMEN
The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal's sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.
RESUMEN
BACKGROUND: Against the background of earlier studies, recent patterns in surgical management of tetralogy of Fallot (TOF) were assessed. METHODS: A retrospective review of The Society of Thoracic Surgeons (STS) Congenital Database (2010-2020) was performed on patients aged <18 years with TOF or pulmonary stenosis and primary procedure TOF surgical repair or palliation. Procedural frequencies were examined by epoch. Demographics, clinical variables, and outcomes were compared between the initial palliation and primary repair groups. Among those operated on at 0 to 60 days of age, variation in palliation rates across hospitals was assessed. RESULTS: The 12,157 operations included 11,307 repairs (93.0%) and 850 palliations (7.0%); 68.5% of all palliations were modified Blalock-Taussig-Thomas shunts. Of 1105 operations on neonates, 45.4% (502) were palliations. Among neonates, palliations declined from 49.0% (331 of 675) in epoch 1 (2010-2015) to 39.8% (171 of 430) in epoch 2 (2016-2020; P = .0026). Overall, the most prevalent repair technique (5196 of 11,307; 46.0%) was ventriculotomy with transanular patch, which was also used in 520 of 894 (58.2%) of repairs after previous cardiac operations. Patients undergoing initial palliation demonstrated more preoperative STS risk factors (50.1% vs 24.3% respectively; P < .0001) and more major morbidity and mortality than patients undergoing primary repair (21.2% vs 7.46%; P < .0001). In the 0- to 60-day age group, risk factor-adjusted palliation rates across centers varied considerably, with 32 of 99 centers performing significantly more or significantly fewer palliations than predicted on the basis of their case mix. CONCLUSIONS: Surgical palliation rates have decreased across all age groups despite increasing prevalence of risk factors. Ventriculotomy with transanular patch remains the most prevalent repair type. The considerable center-level variation in rates of palliation was not completely explained by case mix.
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Procedimientos Quirúrgicos Cardíacos , Cirujanos , Tetralogía de Fallot , Recién Nacido , Humanos , Lactante , Tetralogía de Fallot/cirugía , Cuidados Paliativos/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Arteria Pulmonar/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Failure to thrive (FTT), defined as weight or height less than the lowest 2.5 percentile for age, is prevalent in up to 66% of children with congenital heart disease (CHD). Risk stratification methods to identify those who would benefit from early intervention are currently lacking. We aimed to identify a novel growth biomarker to aid clinical decision-making in children with CHD. METHODS: This is a cross-sectional study of patients 2 months to 10 years of age with any CHD undergoing cardiac surgery. Preoperative weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ) were calculated and assessed for association with preoperative plasma biomarkers: growth differentiation factor 15 (GDF-15), fibroblast growth factor 21, leptin, prealbumin, and C-reactive protein (CRP). RESULTS: Of the 238 patients included, approximately 70% of patients had WAZ/HAZ < 0 and 34% had FTT. There was a moderate correlation between GDF-15 and WAZ/HAZ. When stratified by age, the correlation of GDF-15 to WAZ and HAZ was strongest in children under 2 years of age and persisted in the setting of inflammation (CRP > 0.5â mg/dL). Diagnoses commonly associated with congestive heart failure had high proportions of FTT and median GDF-15 levels. Prealbumin was not correlated with WAZ or HAZ. CONCLUSIONS: GDF-15 represents an important growth biomarker in children with CHD, especially those under 2 years of age who have diagnoses commonly associated with CHF. Our data do not support prealbumin as a long-term growth biomarker.
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Factor 15 de Diferenciación de Crecimiento , Cardiopatías Congénitas , Niño , Humanos , Lactante , Leptina , Estudios Transversales , Proteína C-Reactiva , Cardiopatías Congénitas/cirugía , BiomarcadoresRESUMEN
BACKGROUND: Patients after heart transplantation are at increased risk for malignancy secondary to immunosuppression and oncogenic viral infections. Most common among children is posttransplant lymphoproliferative disorder (PTLD), occurring in 5% to 10% of patients. We used a national database to examine the incidence and risk factors for posttransplant malignancy. METHODS: The United Network for Organ Sharing database was queried for pediatric (<18 years) heart transplant recipients from October 1987 through November 2019. Freedom from malignancy after transplant was assessed with Kaplan-Meier analysis. Cox regression was performed to generate hazard ratios (HRs) and 95% CIs for risk of malignancy development. RESULTS: Of 8581 pediatric heart transplant recipients, malignancy developed in 8.1% over median follow-up time of 6.3 years, with PTLD compromising 86.4% of the diagnosed cancers. The incidence of PTLD development was 1.3% at 1 year and 4.5% at 5 years. Older age at the time of transplant was protective against the development of malignancy (HR, 0.98; 95% CI, 0.96-0.99; P < .001), whereas a history of previous malignancy (HR, 1.9; 95% CI, 1.2-3.0; P = .007) and Ebstein-Barr virus (EBV) recipient-donor mismatch (HR, 1.7; 95% CI, 1.3-2.2; P < .001) increased the risk. Induction therapy, used in 78.9% of the cohort, did not increase malignancy risk (P = .355) nor did use of maintenance tacrolimus (P = .912). CONCLUSIONS: PTLD occurred after 7% of pediatric heart transplants, with risk increased by younger age and EBV mismatch, highlighting the importance of PTLD monitoring in EBV-seronegative recipients. Induction therapy, used in most of the pediatric heart transplants, does not seem to increase posttransplant malignancy nor does tacrolimus, the most commonly used calcineurin inhibitor.