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BACKGROUND: Children hospitalized with acute decompensated heart failure (ADHF) frequently require intravenous vasoactive (IVV) support drugs and are at risk for adverse cardiovascular (ACV) outcomes. We wished to assess whether serial changes in B-type natriuretic peptide (BNP) levels are associated with successful weaning off IVV support and/or prespecified ACV outcomes in children hospitalized with ADHF. METHODS AND RESULTS: Children hospitalized with ADHF from 2005 to 2021 at our institution were assessed for serial changes in BNP, weaning off of IVV support, and ACV outcomes. Changes in BNP level were evaluated using linear mixed-effects modeling. Bonferroni correction was used to adjust for multiple hypothesis testing. In 131 hospitalizations of children with ADHF, the median age was 4.8 years, with 74% receiving IVV support. ACV outcomes occurred in 62 children. IVV support was associated with lower admission left ventricular ejection fraction (26.7% versus 32%, P=0.002), more severe left ventricular dilation (left ventricular internal diastolic dimension Z score 5.9 versus 3.1, P=0.021) moderate or more mitral regurgitation (41.3% versus 20.6%, P=0.038), and qualitative right ventricular systolic dysfunction (in 45.4% versus 11.8%, P<0.001). Decline in BNP levels was more rapid in patients who were successfully weaned from IVV support (-0.20 versus -0.03 2log pg/mL per day, P<0.001) and in the non-ACV group (-0.17 versus -0.03 2log pg/mL per day, P<0.001). Right ventricular systolic dysfunction was an independent risk factor for ACV (odds ratio, 2.49; P=0.045). CONCLUSIONS: The declining rate of serial BNP levels was associated with weaning from IVV support and no ACV outcomes in children hospitalized with ADHF. Right ventricular systolic dysfunction was associated with ACV outcomes.
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Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade.
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Insuficiencia Cardíaca , Humanos , Niño , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Lagunas en las EvidenciasRESUMEN
BACKGROUND: Sacubitril/valsartan has been approved for the management of heart failure (HF) with reduced ejection fraction in adults. PANORAMA-HF trial (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) investigated its effects on clinical outcomes in pediatric patients with HF. METHODS: PANORAMA-HF is a multicenter, Phase II/III study using an adaptive, seamless, 2-part design. The study aimed to evaluate the pharmacokinetics and pharmacodynamics of single doses of sacubitril/valsartan (Part 1), and the efficacy and safety of sacubitril/valsartan versus enalapril administered twice daily for 52 weeks (Part 2) in pediatric patients with HF due to left ventricular systolic dysfunction with biventricular heart physiology. An innovative trial design using a novel global rank assessment of severity was employed. For analysis, eligible patients were stratified into 3 age groups (Group 1, 6 to <18 years; Group 2a, 2 to <6 years; and Group 3a, 1 month to <2 years) and functional classification (New York Heart Association/Ross class I/II and III/IV). RESULTS: We report the key demographic, baseline, and clinical characteristics of 375 pediatric patients randomized to receive the study medication. The mean age for patients in Groups 1, 2a, and 3a was 12.2, 3.2, and 1.3 years, respectively. About 70% of patients had a prior HF hospitalization, 85% had New York Heart Association/Ross class I/II HF, and ≈8% were angiotensin-converting enzyme inhibitor/angiotensin receptor blocker naïve. CONCLUSIONS: Compared to other pediatric HF studies, PANORAMA-HF recruited a relatively homogeneous pediatric HF population across 3 age groups, enabling a more robust evaluation of pharmacokinetics/pharmacodynamics and efficacy/safety of sacubitril/valsartan. Most patients had mildly symptomatic HF at baseline. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02678312.
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Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Niño , Adolescente , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/inducido químicamente , Estudios Prospectivos , Tetrazoles/efectos adversos , Volumen Sistólico/fisiología , Resultado del Tratamiento , Valsartán/uso terapéutico , Valsartán/efectos adversos , Aminobutiratos/efectos adversos , Compuestos de Bifenilo/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Combinación de MedicamentosRESUMEN
Medical therapy for pediatric heart failure is based on a detailed mechanistic understanding of the underlying causes, which are diverse and unlike those encountered in most adult patients. Diuresis and improved perfusion are the immediate goals of care in the child with acute decompensated heart failure. Conversion to maintenance oral therapy for heart failure is based on the results of landmark studies in adults, as well as recent pediatric clinical trials and heart failure guidelines. There will continue to be an important role for newer drugs, some of which are in active trials in adults, and some of which are already approved for use in children. The need to plan for clinical trials in children during drug development for heart failure is emphasized.
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Insuficiencia Cardíaca , Adulto , Niño , Insuficiencia Cardíaca/tratamiento farmacológico , HumanosRESUMEN
Pediatric heart failure (HF) is an important clinical condition with high morbidity, mortality, and costs. Due to the heterogeneity in clinical presentation and etiologies, the development of therapeutic strategies is more challenging in children than adults. Most guidelines recommending drug therapy for pediatric HF are extrapolated from studies in adults. Unfortunately, even using all available treatment, progression to cardiac transplantation is common. The development of prospective clinical trials in the pediatric population has significant obstacles, including small sample sizes, slow recruitment rates, challenging endpoints, and high costs. However, progress is being made as evidenced by the recent introduction of ivabradine and of sacubitril/valsartan. In the last 5 years, new drugs have also been developed for HF with reduced ejection fraction (HFrEF) in adults. The use of well-designed prospective clinical trials will be fundamental in the evaluation of safety and efficacy of these new drugs on the pediatric population. The aim of this article is to review the clinical presentation and management of acute and chronic pediatric heart failure, focusing on systolic dysfunction in patients with biventricular circulation and a systemic left ventricle. We discuss the drugs recently approved for children and those emerging, or in use for adults with HFrEF.
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Background In adults with heart failure, elevated heart rate is associated with lower survival. We determined whether an elevated heart rate was associated with an increased risk of death or heart transplant in children with dilated cardiomyopathy. Methods and Results The study is an analysis of the Pediatric Cardiomyopathy Registry and includes baseline data, annual follow-up, and censoring events (transplant or death) in 557 children (51% male, median age 1.8 years) with dilated cardiomyopathy diagnosed between 1994 and 2011. An elevated heart rate was defined as 2 or more SDs above the mean heart rate of children, adjusted for age. The primary outcomes were heart transplant and death. Heart rate was elevated in 192 children (34%), who were older (median age, 2.3 versus 0.9 years; P<0.001), more likely to have heart failure symptoms (83% versus 67%; P<0.001), had worse ventricular function (median fractional shortening z score, -9.7 versus -9.1; P=0.02), and were more often receiving anticongestive therapies (96% versus 86%; P<0.001) than were children with a normal heart rate. Controlling for age, ventricular function, and cardiac medications, an elevated heart rate was independently associated with death (adjusted hazard ratio [HR] 2.6; P<0.001) and with death or transplant (adjusted HR 1.5; P=0.01). Conclusions In children with dilated cardiomyopathy, elevated heart rate was associated with an increased risk of death and cardiac transplant. Further study is warranted into the association of elevated heart rate and disease severity in children with dilated cardiomyopathy and as a potential target of therapy.
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Cardiomiopatía Dilatada/mortalidad , Frecuencia Cardíaca , Cardiomiopatía Dilatada/fisiopatología , Niño , Preescolar , Femenino , Trasplante de Corazón/estadística & datos numéricos , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de RiesgoRESUMEN
The frequency, indications, and outcomes for readmission following pediatric heart transplantation are poorly characterized. A better understanding of this phenomenon will help guide strategies to address the causes of readmission. Data from the Clinical Trials in Organ Transplantation for Children (CTOTC-04) multi-institutional collaborative study were utilized to determine incidence of, and risk factors for, hospital readmission within 30 days and 1 year from initial hospital discharge. Among 240 transplants at 8 centers, 227 subjects were discharged and had follow-up. 129 subjects (56.8%) were readmitted within one year; 71 had two or more readmissions. The 30-day and 1-year freedom from readmission were 70.5% (CI: 64.1%, 76.0%) and 42.2% (CI: 35.7%, 48.7%), respectively. The most common indications for readmissions were infection followed by rejection and fever without confirmed infection, accounting for 25.0%, 10.6%, and 6.2% of readmissions, respectively. Factors independently associated with increased risk of first readmission within 1 year (Cox proportional hazard model) were as follows: transplant in infancy (P = .05), longer transplant hospitalization (P = .04), lower UNOS urgency status (2/IB vs 1A) at transplant (P = .04), and Hispanic ethnicity (P = .05). Hospital readmission occurs frequently in the first year following discharge after heart transplantation with highest risk in the first 30 days. Infection is more common than rejection as cause for readmission, with death during readmission being rare. A number of patient factors are associated with higher risk of readmission. A fuller understanding of these risk factors may help tailor strategies to reduce unnecessary hospital readmission.
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Trasplante de Corazón , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Estimación de Kaplan-Meier , Masculino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: This review highlights recent advances in the diagnosis and management of children with heart failure. We emphasize the clinical approach to patient care in the areas of acute decompensated heart failure, chronic heart failure, and failure of the patient with single ventricle physiology. RECENT FINDINGS: Important guidelines regarding the recognition and management of heart failure in children have been proposed and adopted, providing guidance for early recognition and ongoing management. Early diuresis, and avoidance of excessive inotropic agent use, in favor of milrinone as an inotropic-vasodilator agent, are emphasized. Close monitoring of airway pressures to improve ventricular filling, and extubation to positive pressure or high-flow nasal cannula therapy are also important. Chronic heart failure therapy requires combination treatment with diuretics, and the three major classes of drugs. Management of the failing Fontan requires attention to the hepatic, pulmonary and lymphatic circulations. SUMMARY: Improved outcomes in children with heart failure are possible. Inherent in this success is the engagement of an interdisciplinary team-based approach to care, with early recognition and escalation of care for specific patients who are not improving as predicted.
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Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Niño , HumanosRESUMEN
BACKGROUND: Immunosuppression strategies have changed over time in pediatric heart transplantation. Thus, comorbidity profiles may have evolved. Clinical Trials in Organ Transplantation in Children-04 is a multicenter, prospective, cohort study assessing the impact of pre-transplant sensitization on outcomes after pediatric heart transplantation. This sub-study reports 1-year outcomes among recipients without pre-transplant donor-specific antibodies (DSAs). METHODS: We recruited consecutive candidates (<21 years) at 8 centers. Sensitization status was determined by a core laboratory. Immunosuppression was standardized as follows: Thymoglobulin induction with tacrolimus and/or mycophenolate mofetil maintenance. Steroids were not used beyond 1 week. Rejection surveillance was by serial biopsy. RESULTS: There were 240 transplants. Subjects for this sub-study (nâ¯=â¯186) were non-sensitized (nâ¯=â¯108) or had no DSAs (nâ¯=â¯78). Median age was 6 years, 48.4% were male, and 38.2% had congenital heart disease. Patient survival was 94.5% (95% confidence interval, 90.1-97.0%). Freedom from any type of rejection was 67.5%. Risk factors for rejection were older age at transplant and presence of non-DSAs pre-transplant. Freedom from infection requiring hospitalization/intravenous anti-microbials was 75.4%. Freedom from rehospitalization was 40.3%. New-onset diabetes mellitus and post-transplant lymphoproliferative disorder (PTLD) occurred in 1.6% and 1.1% of subjects, respectively. There was no decline in renal function over the first year. Corticosteroids were used in 14.5% at 1 year. CONCLUSIONS: Pediatric heart transplantation recipients without DSAs at transplant and managed with a steroid avoidance regimen have excellent short-term survival and a low risk of first-year diabetes mellitus and PTLD. Rehospitalization remains common. These contemporary observations allow for improved caregiver and/or patient counseling and provide the necessary outcomes data to help design future randomized controlled trials.
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Suero Antilinfocítico/uso terapéutico , Trasplante de Corazón , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Tacrolimus/uso terapéutico , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Glucocorticoides , Humanos , Lactante , Masculino , Medición de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Unlike the adult heart failure (HF) patient population, there is scarce information on the overall burden of HF in the pediatric population across geographies and within different age groups. AREAS COVERED: A systematic review aims to describe and quantify the economic, humanistic, and societal burden of pediatric (age <18 years) HF on patients and caregivers. Eighteen published studies over a period of 10 years (1 January 2006-20 May 2016) were identified through Embase, Medline, Cochrane Library and selected congresses. Studies from the US reported higher HF-related hospitalization-rates in infants aged <1 year (49.3%-63.9%) versus children aged 1-12 years (18.7%-30.9%) in HF diagnosed patients. Across the studies, the average length of hospital stay was 15 days, increasing to 26 days for infants. Average annual hospital charges were higher for infants (US$176,000) versus children aged 1-10 years (US$132,000) in the US. In Germany, diagnosis-related group (DRG)-based hospital-allowances per HF-case increased from 3,498 in 1995 to 4,250 in 2009. EXPERT OPINION: To our knowledge, this is the first systematic review, which provides valuable insights into the burden of HF in children and adolescents, and strengthens current knowledge of pediatric HF. However, there is a need for larger population-based studies with wider geographical coverage.
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Costo de Enfermedad , Insuficiencia Cardíaca/epidemiología , Hospitalización/estadística & datos numéricos , Adolescente , Factores de Edad , Cuidadores/estadística & datos numéricos , Niño , Preescolar , Insuficiencia Cardíaca/economía , Costos de Hospital/estadística & datos numéricos , Hospitalización/economía , Humanos , Lactante , Recién Nacido , Tiempo de Internación/estadística & datos numéricosRESUMEN
BACKGROUND: Children with congenital heart disease (CHD) are at risk for advanced heart failure (AHF). We sought to define the mortality and resource utilization in CHD-related AHF in children and young adults. METHODS: All hospitalizations in the Pediatric Health Information System database involving patients ≤21 years old with a CHD diagnosis and heart failure requiring at least 7 days of continuous inotropic support between 2004 and 2015 were included. Hospitalizations including CHD surgery were excluded. RESULTS: Of 465,482 CHD hospitalizations, AHF was present in 2,712 (0.6%) [58% infant, 55% male, 30% single ventricle]. AHF therapies frequently used included extracorporeal membrane oxygenation (ECMO) (15%) and cardiac transplant (16%). Ventricular assist device (VAD) support was rare (3%), although VAD use significantly increased from 2004 to 2015 (P < .0010). Hospital mortality in CHD with AHF was 26%, with higher mortality associated with single ventricle heart disease (OR 1.64, 95% CI 1.23-2.19; P = .0009), infancy (OR 1.71, 95% CI 1.17-2.5; P = .0057), non-white race (OR 1.28, 95% CI 1.04-1.59; p=0.0234), and chronic complex comorbidities (OR 1.76, 95% CI 1.34-2.30; P < .0001). Over the 11-year study period, despite the significant increase in CHD-related AHF hospitalizations (P < .0001), hospital mortality improved (P = .0011). Median hospital costs were $252,000, a 6-fold increase above those without AHF, and was primarily driven by hospital length of stay (P < .0001). CONCLUSION: AHF in children with CHD in uncommon but increasing and is associated with significant morbidity, mortality and resource utilization. Approximately 1 in 5 children do not survive to hospital discharge. Many risk factors for mortality may not be modifiable, and further study is needed to identify modifiable risk factors and improve care for this complex population.
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Recursos en Salud/estadística & datos numéricos , Cardiopatías Congénitas/complicaciones , Insuficiencia Cardíaca/epidemiología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/epidemiología , Insuficiencia Cardíaca/etiología , Mortalidad Hospitalaria/tendencias , Humanos , Lactante , Masculino , Morbilidad/tendencias , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Risk assessment in heart transplantation is critical for candidate selection, but current models inadequately assess individual risk of postoperative mortality. We sought to identify risk factors and develop a scoring system to predict mortality after heart transplantation in children. METHODS: The records of patients undergoing heart transplantation at our institution from 2010 through 2016 were reviewed. Clinical characteristics were recorded and compared between survivors and nonsurvivors. We used Cox proportional hazard modeling of factors associated with postoperative mortality to develop a risk factor score. RESULTS: There were 74 patients who underwent heart transplantation at a mean age of 8.8 ± 6.6 years. Congenital heart disease was the most common indication, comprising 48.6% of the cohort. Overall mortality was 18.9%, with 10 of 14 dying within 30 days of the operation or during the initial postoperative admission (early mortality). Preoperative factors associated with overall mortality were single-ventricle congenital heart disease (hazard ratio [HR], 3.2; p = 0.042), biventricular assist device (HR, 4.8; p = 0.043), history of four or more sternotomies (HR, 3.9; p = 0.023), panel reactive antibody exceeding 10% (HR, 4.4; p = 0.013), any previous operation at another institution (HR, 3.2; p = 0.038), and pulmonary vein disease (HR, 4.7; p = 0.045). Each risk factor was assigned a point value, based on similar magnitude of the HRs. A score of 4 or higher predicted mortality with 57% sensitivity and 90% specificity. CONCLUSIONS: In this single-center pediatric cohort, postheart transplantation mortality could be predicted using patient-specific risk factors. The cumulative effect of these risk factors predicted mortality with high specificity.
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Causas de Muerte , Rechazo de Injerto/mortalidad , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/cirugía , Trasplante de Corazón/mortalidad , Trasplante de Corazón/métodos , Centros Médicos Académicos , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Cardiopatías Congénitas/diagnóstico , Humanos , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Philadelphia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Periodo Preoperatorio , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores SexualesRESUMEN
Serum troponin (Tn) is often elevated in viral myocarditis; however, its prognostic significance is unknown. We tested the hypothesis that abnormal serum Tn is associated with mortality in children hospitalized with myocarditis. We retrospectively studied data from six large children's hospitals participating in the Pediatric Health Information System Plus (PHIS+) database. Analysis was performed on patients hospitalized with viral myocarditis between 2007 and 2013, in whom at least one Tn was recorded within 72 h of admission. Abnormal baseline Tn was defined as any value outside the upper limit of normal within the first 72 h. Primary outcome was mortality. Secondary outcomes included mechanical support, defined as use of extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD), cardiac transplantation, intravenous immunoglobulin (IVIg), mechanical ventilation, and inotrope use. A total of 149 patients with myocarditis (61% male, 48% adolescents) across all PHIS+ centers had TnI (n = 113) or TnT (n = 36) recorded. At least one abnormal Tn was present in 81% of cases. Overall mortality was 7.3% and was not associated with abnormal baseline Tn. Abnormal baseline Tn was associated with ECMO (7.1 vs. 25.6%, p = 0.03) and IVIg (46.4 vs. 83.5%, p < 0.001). Abnormal baseline Tn was not associated with transplantation, mechanical ventilation or inotrope use. Abnormal Tn in the first 72 h of hospitalization for myocarditis was associated with the use of ECMO and IVIg, but was not associated with mortality. This finding may help risk stratify this population if it can be prospectively validated.
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Oxigenación por Membrana Extracorpórea , Miocarditis/sangre , Troponina/sangre , Adolescente , Biomarcadores/sangre , Niño , Bases de Datos Factuales , Femenino , Trasplante de Corazón , Corazón Auxiliar , Hospitalización , Humanos , Inmunoglobulinas Intravenosas , Lactante , Masculino , Miocarditis/mortalidad , Miocarditis/terapia , Pronóstico , Respiración Artificial , Estudios RetrospectivosRESUMEN
Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days-12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30-132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15-100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.
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Cardiomiopatía Hipertrófica/tratamiento farmacológico , Disopiramida/administración & dosificación , Ventrículos Cardíacos/diagnóstico por imagen , Función Ventricular Izquierda/fisiología , Adolescente , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Ecocardiografía Doppler , Electrocardiografía , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Retrospectivos , Bloqueadores del Canal de Sodio Activado por Voltaje/administración & dosificación , Adulto JovenAsunto(s)
Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Ensayos Clínicos como Asunto/métodos , Desarrollo de Medicamentos/métodos , Determinación de Punto Final , Selección de Paciente , Adolescente , Factores de Edad , Antihipertensivos/uso terapéutico , Fármacos Cardiovasculares/efectos adversos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Niño , Preescolar , Consenso , Humanos , Hipolipemiantes/uso terapéutico , Lactante , Recién Nacido , Evaluación de Necesidades , Participación de los Interesados , Resultado del TratamientoRESUMEN
Anti-HLA donor-specific antibodies are associated with worse outcomes after organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase posttransplantation morbidity and mortality. We address this clinical challenge in a prospective, multicenter, observational cohort study of children listed for heart transplantation (Clinical Trials in Organ Transplantation in Children-04 [CTOTC-04]). Outcomes were compared among sensitized recipients who underwent transplantation with positive crossmatch, nonsensitized recipients, and sensitized recipients without positive crossmatch. Positive crossmatch recipients received antibody removal and augmented immunosuppression, while other recipients received standard immunosuppression with corticosteroid avoidance. This first CTOTC-04 report summarizes study rationale and design and relates pretransplantation sensitization status using solid-phase technology. Risk factors for sensitization were explored. Of 317 screened patients, 290 were enrolled and 240 underwent transplantation. Core laboratory evaluation demonstrated that more than half of patients were anti-HLA sensitized. Greater than 80% of sensitized patients had class I (with or without class II) HLA antibodies, and one-third of sensitized patients had at least 1 HLA antibody with median fluorescence intensity of ≥8000. Logistic regression models demonstrated male sex, weight, congenital heart disease history, prior allograft, and ventricular assist device are independent risk factors for sensitization.
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Antígenos HLA/inmunología , Trasplante de Corazón/métodos , Isoanticuerpos/inmunología , Proyectos de Investigación , Donantes de Tejidos , Tolerancia al Trasplante/inmunología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión , Lactante , Recién Nacido , Isoanticuerpos/sangre , Masculino , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Trasplante HomólogoRESUMEN
While the epidemiology of adult heart failure has been extensively researched, this systematic review addresses the less well characterized incidence and prevalence of pediatric HF. The search strategy used Cochrane methodology and identified 83 unique studies for inclusion. Studies were categorized according to whether the HF diagnosis was reported as primary (n = 10); associated with other cardiovascular diseases (CVDs) (n = 49); or associated with non-CVDs (n = 24). A narrative synthesis of the evidence is presented. For primary HF, the incidence ranged from 0.87/100,000 (UK and Ireland) to 7.4/100,000 (Taiwan). A prevalence of 83.3/100,000 was reported in one large population-based study from Spain. HF etiology varied across regions with lower respiratory tract infections and severe anemia predominating in lower income countries, and cardiomyopathies and congenital heart disease major causes in higher income countries. Key findings for the other categories included a prevalence of HF associated with cardiomyopathies ranging from 36.1% (Japan) to 79% (US); associated with congenital heart disease from 8% (Norway) to 82.2% (Nigeria); associated with rheumatic heart diseases from 1.5% (Turkey) to 74% (Zimbabwe); associated with renal disorders from 3.8% (India) to 24.1% (Nigeria); and associated with HIV from 1% (US) to 29.3% (Brazil). To our knowledge, this is the first systematic review of the topic and strengthens current knowledge of pediatric HF epidemiology. Although a large body of research was identified, heterogeneity in study design and diagnostic criteria limited the ability to compare regional data. Standardized definitions of pediatric HF are required to facilitate cross-regional comparisons of epidemiological data.
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Insuficiencia Cardíaca/epidemiología , Adolescente , Niño , Preescolar , Insuficiencia Cardíaca/etiología , Humanos , Incidencia , Lactante , Prevalencia , Factores de RiesgoRESUMEN
OBJECTIVES: To describe the frequency, characteristics, and outcomes of heart failure-related emergency department (ED) visits in pediatric patients. We aimed to test the hypothesis that these visits are associated with higher admission rates, mortality, and resource utilization. STUDY DESIGN: A retrospective analysis of the Nationwide Emergency Department Sample for 2010 of patients ≤18 years of age was performed to describe ED visits with and without heart failure. Cases were identified using International Classification of Disease, Ninth Revision, Clinical Modification codes and assessed for factors associated with admission, mortality, and resource utilization. RESULTS: Among 28.6 million pediatric visits to the ED, there were 5971 (0.02%) heart failure-related cases. Heart failure-related ED patients were significantly more likely to be admitted (59.8% vs 4.01%; OR 35.3, 95% CI 31.5-39.7). Among heart failure-related visits, admission was more common in patients with congenital heart disease (OR 5.0, 95% CI 3.3-7.4) and in those with comorbidities including respiratory failure (OR 78.3, 95% CI 10.4-591) and renal failure (OR 7.9, 95% CI 1.7-36.3). Heart failure-related cases admitted to the hospital had a higher likelihood of death than nonheart failure-related cases (5.9% vs 0.32%, P < .001). Factors associated with mortality included respiratory failure (OR 4.5, 95% CI 2.2-9.2) and renal failure (OR 7.8, 95% CI 2.9-20.7). Heart failure-related ED visits were more expensive than nonheart failure-related ED visits ($1460 [IQR $861-2038] vs $778 [IQR $442-1375] [P < .01].) CONCLUSIONS: Heart failure-related visits represent a minority of pediatric ED visits but are associated with increased hospital admission and resource utilization.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Insuficiencia Cardíaca/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Servicio de Urgencia en Hospital/economía , Femenino , Insuficiencia Cardíaca/economía , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. STUDY DESIGN: This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. CONCLUSION: The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function.
Asunto(s)
Aminobutiratos/administración & dosificación , Enalapril/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Isquemia Miocárdica/complicaciones , Tetrazoles/administración & dosificación , Valsartán/administración & dosificación , Disfunción Ventricular Izquierda/complicaciones , Función Ventricular Izquierda/fisiología , Adolescente , Aminobutiratos/farmacocinética , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacocinética , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Compuestos de Bifenilo , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Quimioterapia Combinada , Enalapril/farmacocinética , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Humanos , Lactante , Recién Nacido , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Estudios Prospectivos , Sístole , Tetrazoles/farmacocinética , Factores de Tiempo , Resultado del Tratamiento , Valsartán/farmacocinética , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Complement-dependent cytotoxicity cross-match (CDCXM) is used for evaluation of preformed HLA-specific antibodies in patients undergoing heart transplantation. Flow cytometry cross-match (FCXM) is a more sensitive assay and used with increasing frequency. To determine the clinical relevance of a positive FCXM in the context of negative CDCXM in heart transplantation, the United Network for Organ Sharing (UNOS) database was analyzed. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess graft survival for three different patient cohorts defined by cross-match results: T-cell and B-cell CDCXM+ ("CDCXM+" cohort), CDCXM- but T-cell and/or B-cell FCXM+ ("FCXM+" cohort), and T-cell/B-cell CDCXM- and FCXM- ("XM-" cohort). During the study period, 2558 patients met inclusion criteria (10.7% CDCXM+, 18.8% FCXM+, 65.5% XM-). CDCXM+ patients had significantly decreased graft survival compared to FCXM+ and XM- cohorts (P = .003 and <.001, respectively). CDCXM- and FCXM+ patients did not have decreased graft survival compared to XM- patients (P = .09). In multivariate analysis, only CDCXM+ was associated with decreased graft survival (HR 1.22, 95% CI 1.01-1.49). In conclusion, positive FCXM in the context of negative CDCXM does not confer increased risk of graft failure. Further study is needed to understand implications of CDCXM and FCXM testing in heart transplant recipients.