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The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de-identified clinical information and multi-omics data from research participants for broad data sharing and secondary analyses. Through the DS-Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan.
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Enfermedad de Alzheimer , Investigación Biomédica , Síndrome de Down , Estados Unidos/epidemiología , Humanos , Longevidad , National Institutes of Health (U.S.)RESUMEN
Congenital heart disease (CHD) is the most common birth defect in the United States. Neonates with CHD are often cared for by neonatologists in addition to cardiologists. However, there is a paucity of rigorous evidence and limited clinical trials regarding the management of neonates with CHD. In this review, we will describe some of the challenges of research in this field. The Pediatric Heart Network serves as an example of how a research network can effectively overcome barriers to conduct and execute well-designed multicenter studies.
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Cardiopatías Congénitas , Recién Nacido , Humanos , Niño , Estados Unidos , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/terapia , Neonatólogos , Estudios Multicéntricos como AsuntoRESUMEN
The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.
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Consumo de Oxígeno , Sulfonamidas , Humanos , Niño , Sulfonamidas/uso terapéutico , Ejercicio Físico , Pirimidinas/uso terapéutico , Prueba de Esfuerzo , Tolerancia al EjercicioRESUMEN
The National Heart, Lung, and Blood Institute convened a workshop in August 2021 to identify opportunities in pediatric and congenital cardiovascular research that would improve outcomes for individuals with congenital heart disease across the lifespan. A subsidiary goal was to provide feedback on and visions for the Pediatric Heart Network. This paper summarizes several key research opportunities identified in the areas of: data quality, access, and sharing; aligning cardiovascular research with patient priorities (eg, neurodevelopmental and psychological impacts); integrating research within clinical care and supporting implementation into practice; leveraging creative study designs; and proactively enriching diversity of investigators, participants, and perspectives throughout the research process.
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Enfermedades Cardiovasculares , Humanos , Niño , Enfermedades Cardiovasculares/terapia , Corazón , Longevidad , Exactitud de los Datos , Proyectos de InvestigaciónRESUMEN
BACKGROUND: The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. METHODS: This multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies. CONCLUSION: The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.
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COVID-19/complicaciones , Corazón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Síndrome de Respuesta Inflamatoria Sistémica , Adulto , Niño , Humanos , National Heart, Lung, and Blood Institute (U.S.) , SARS-CoV-2 , Volumen Sistólico , Estados Unidos , Función Ventricular Izquierda , Adulto JovenRESUMEN
Women are under-represented as leaders of cardiovascular randomized controlled trials, representing 1 in 10 lead authors of cardiovascular trials published in high-impact journals. Although the proportion of cardiovascular specialists who are women has increased in recent years, the proportion of cardiovascular clinical trialists who are women has not. This gap, underpinned by systemic sexism, has not been adequately addressed. The benefits of diverse randomized controlled trial leadership extend to patients and professionals. In this position statement, we present strategies adopted by some organizations to end gender inequality in research leadership. We offer an actionable roadmap for early-career researchers, scientists, academic institutions, professional societies, trial sponsors, and journals to follow, with the goal of harnessing the strength of women and under-represented groups as research leaders and facilitating a just culture in the cardiovascular clinical trial enterprise.
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Cardiología , Ensayos Clínicos como Asunto/organización & administración , Liderazgo , Publicaciones Periódicas como Asunto , Médicos Mujeres/organización & administración , Sexismo/etnología , Femenino , Humanos , Masculino , Estados UnidosRESUMEN
BACKGROUND: Little is known about geographical variation in infant mortality due to congenital heart disease (CHD) and the social determinants of health that might mediate such variation. We aimed to examine US county-level estimates of infant mortality due to CHD to understand geographical patterns and factors that might influence variation in mortality. METHODS: This US population-based cohort study used linked livebirth-infant death cohort files from the US National Center for Health Statistics from Jan 1, 2006, to Dec 31, 2015. All deaths attributable to congenital heart disease in infants in a given year were included. We used hierarchical Bayesian models to estimate rates of infant mortality due to congenital heart disease for all US counties. We mapped model-based estimates to explore geographical patterns. Covariates included infant sex, gestational age, maternal race and ethnicity, percentage of the county population below the poverty level, and proximity of the county to a US News & World Report 2015 top-50 ranked paediatric cardiac centre. FINDINGS: From 2006 to 2015, 40 847 089 livebirths occurred, of which there were 13 988 infant deaths attributed to congenital heart disease, with an unadjusted infant mortality rate due to CHD of 0·34 per 1000 livebirths (95% CI 0·34-0·35). Kentucky and Mississippi had the greatest proportions of counties with a predicted rate of infant mortality due to CHD above the 95th percentile. All counties in Connecticut, Massachusetts, and Rhode Island had a predicted rate below the fifth percentile. In the model, lower mortality risk correlated with closer proximity to a top-50 ranked paediatric cardiac centre (odds ratio [OR] 0·890, 95% credible interval [CrI] 0·840-0·942), whereas higher mortality risk correlated with higher levels of poverty (OR 1·181, 95% CrI 1·125-1·239). INTERPRETATION: Substantial geographical variation exists in infant mortality due to CHD in the USA, highlighting the potential importance of bolstering care delivery for infants from economically deprived communities and areas remote from top-performing paediatric cardiac centres. FUNDING: None.
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Cardiopatías Congénitas/mortalidad , Estudios de Cohortes , Demografía , Femenino , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Masculino , Vigilancia de la Población , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
The National Heart, Lung, and Blood Institute (NHLBI) has played an important role in funding the clinical science that supports many contemporary cardiology practice guidelines and in shaping the conduct of cardiovascular clinical trials. This Perspective outlines contemporary funding options as well as select important NHLBI policies, philosophy, and priorities.
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Enfermedades Cardiovasculares/terapia , Ensayos Clínicos como Asunto , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Estados UnidosRESUMEN
BACKGROUND: The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies. METHODS: Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations. Memoranda, Core Lab reports, and adjudication logs were reviewed. A centre-level questionnaire provided information regarding local processes for data collection. Descriptive statistics were used, and chi-square tests determined differences in imaging quality. RESULTS: For the 19 participating centres, challenges with enrolment included variations in Institutional Review Board definitions of "retrospective" eligibility, overestimation of non-White participants, centre categorisation of Hispanic participants that differed from National Institutes of Health definitions, and exclusion of potential participants due to missing demographic data. Institutional Review Board amendments resolved many of these challenges. There was an unanticipated burden imposed on centres due to high numbers of echocardiograms that were reviewed but failed to meet submission criteria. Additionally, image transfer software malfunctions delayed Core Lab image review and feedback. Between the early and late study periods, the proportion of unacceptable echocardiograms submitted to the Core Lab decreased (14 versus 7%, p < 0.01). Most protocol violations were from eligibility violations and inadvertent protected health information disclosure (overall 2.5%). Adjudication committee reviews led to protocol changes. CONCLUSIONS: Numerous challenges encountered during the Normal Echocardiogram Database Study prolonged study enrolment. The retrospective design and flaws in image transfer software were key impediments to study completion and should be considered when designing future studies collecting echocardiographic images as a primary outcome.
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Ecocardiografía/estadística & datos numéricos , Cardiopatías Congénitas/diagnóstico , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Valores de Referencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. METHODS: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. RESULTS: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus -9±193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level. CONCLUSIONS: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02741115.
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Cardiopatías/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adolescente , Niño , Método Doble Ciego , Esquema de Medicación , Ejercicio Físico , Femenino , Procedimiento de Fontan , Cardiopatías/congénito , Cardiopatías/cirugía , Frecuencia Cardíaca , Humanos , Masculino , Péptido Natriurético Encefálico/sangre , Consumo de Oxígeno , Inhibidores de Fosfodiesterasa 5/efectos adversos , Efecto Placebo , Pirimidinas/efectos adversos , Sulfonamidas/efectos adversos , Trombosis/diagnóstico , Trombosis/etiología , Resultado del TratamientoRESUMEN
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
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Ensayos Clínicos como Asunto/organización & administración , Eficiencia Organizacional/normas , Cardiopatías/terapia , Niño , Bases de Datos Factuales , Humanos , Estados UnidosRESUMEN
BACKGROUND: The reliability of left ventricular (LV) systolic functional indices calculated from blinded echocardiographic measurements of LV size has not been tested in a large cohort of healthy children. The objective of this study was to estimate interobserver variability in standard measurements of LV size and systolic function in children with normal cardiac anatomy and qualitatively normal function. METHODS: The Pediatric Heart Network Normal Echocardiogram Database collected normal echocardiograms from healthy children ≤18 years old distributed equally by age, gender, and race. A core lab used two-dimensional echocardiograms to measure LV dimensions from which a separate data coordinating center calculated LV volumes and systolic functional indices. To evaluate interobserver variability, two independent expert pediatric echocardiographic observers remeasured LV dimensions on a subset of studies, while blinded to calculated volumes and functional indices. RESULTS: Of 3,215 subjects with measurable images, 552 (17%) had a calculated LV shortening fraction (SF) < 25% and/or LV ejection fraction (EF) < 50%; the subjects were significantly younger and smaller than those with normal values. When the core lab and independent observer measurements were compared, individual LV size parameter intraclass correlation coefficients were high (0.81-0.99), indicating high reproducibility. The intraclass correlation coefficients were lower for SF (0.24) and EF (0.56). Comparing reviewers, 40/56 (71%) of those with an abnormal SF and 36/104 (35%) of those with a normal SF based on core lab measurements were calculated as abnormal from at least one independent observer. In contrast, an abnormal EF was less commonly calculated from the independent observers' repeat measures; only 9/47 (19%) of those with an abnormal EF and 8/113 (7%) of those with a normal EF based on core lab measurements were calculated as abnormal by at least one independent observer. CONCLUSIONS: Although blinded measurements of LV size show good reproducibility in healthy children, subsequently calculated LV functional indices reveal significant variability despite qualitatively normal systolic function. This suggests that, in clinical practice, abnormal SF/EF values may result in repeat measures of LV size to match the subjective assessment of function. Abnormal LV functional indices were more prevalent in younger, smaller children.
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Ecocardiografía , Función Ventricular Izquierda , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Valores de Referencia , Reproducibilidad de los Resultados , Sístole , WisconsinRESUMEN
As we commemorate the 70th Anniversary of the National Heart, Lung, and Blood Institute (NHLBI) and celebrate important milestones that have been achieved by the Division of Cardiovascular Sciences (DCVS), it is imperative that DCVS and the Extramural Research community at-large continue to address critical public health challenges that persist within the area of Cardiovascular Diseases (CVD). The NHLBI's Strategic Vision, developed with extensive input from the extramural research community and published in 2016, included overarching goals and strategic objectives that serve to provide a general blueprint for sustaining the legacy of the Institute by leveraging opportunities in emerging scientific areas (e.g., regenerative medicine, omics technology, data science, precision medicine, and mobile health), finding new ways to address enduring challenges (e.g., social determinants of health, health inequities, prevention, and health promotion), and training the next generation of heart, lung, blood, and sleep researchers. DCVS has developed a strategic vision implementation plan to provide a cardiovascular framing for the pursuit of the Institute's overarching goals and strategic objectives garnered from the input of the broader NHLBI community. This plan highlights six scientific focus areas that demonstrate a cross-cutting and multifaceted approach to addressing cardiovascular sciences, including 1) addressing social determinants of cardiovascular health (CVH) and health inequities, 2) enhancing resilience, 3) promoting CVH and preventing CVD Across the lifespan, 4) eliminating hypertension-related CVD, 5) reducing the burden of heart failure, and 6) preventing vascular dementia. These priorities will guide our efforts in Institute-driven activities in the coming years but will not exclude development of other novel ideas or the support of investigator-initiated grant awards. The DCVS Strategic Vision implementation plan is a living document that will evolve with iterative dialogue with the NHLBI community and adapt as the dynamic scientific landscape changes to seize emerging opportunities.
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Cardiología/normas , Enfermedades Cardiovasculares/terapia , National Heart, Lung, and Blood Institute (U.S.) , Guías de Práctica Clínica como Asunto , Cardiología/economía , Cardiología/tendencias , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Humanos , Estados UnidosRESUMEN
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network - Cardiac Networks United - that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups - heart centre executives, research leaders, learning health system experts, and parent advocates - offer their perspectives on the need for this new collaborative effort.
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Recolección de Datos/métodos , Cardiopatías Congénitas , Relaciones Interinstitucionales , Relaciones Interprofesionales , Cardiología , Humanos , Servicios de Información , Padres , Pediatría , Desarrollo de Programa , Mejoramiento de la Calidad , Sistema de RegistrosRESUMEN
Background/Aims Identifying predictors of recruitment success in clinical trials, particularly prior to study launch, could contribute to higher study completion rates and improved scientific return on investment. This article evaluates the performance of clinical trials funded by the National Heart, Lung, and Blood Institute that began recruitment before and after implementation of National Heart, Lung, and Blood Institute's 2009 Accrual Policy and identifies study-related factors that predict recruitment success. Methods A retrospective analysis of National Heart, Lung, and Blood Institute's cardiovascular clinical trials with initial funding from 1996 to 2012 was performed to assess recruitment success. Success was defined as ≥100% enrollment of the proposed sample size within the duration initially proposed by investigators. Trials were assigned to categories (pre-policy vs post-policy) based on whether the first patient was enrolled before or after the 2009 Accrual Policy implementation. Potential determinants of successful recruitment were evaluated using multivariable logistic regression. Results Of 167 trials analyzed, 26.3% met the definition of success. Twenty-four trials (14.4%) were terminated early and 15 (62.5%) for insufficient recruitment. Trials failed due to <100% enrollment (22.8%), longer duration (19.8%), or both (31.1%). Trials testing behavioral interventions, those conducted within a National Heart, Lung, and Blood Institute-funded network, and those with normal controls were predictive of success. The proportion of successful clinical trials increased from 23% in the pre-policy era to 30% post-policy, although the difference was not statistically significant ( p = 0.29). Conclusion Enrollment success rates for National Heart, Lung, and Blood Institute's clinical trials are concerning. The 2009 National Heart, Lung, and Blood Institute Accrual Policy did not significantly improve trial success. Clinical trials testing behavioral interventions, those conducted within networks, and those with normal controls were predictive of recruitment success. Components of networks may provide model practices to help other trials attain success, including close attention to oversight activities such as recruitment plans, real-time enrollment monitoring, corrective action plans to address shortfalls, and close sponsor-investigator collaborations.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Selección de Paciente , Terminación Anticipada de los Ensayos Clínicos/estadística & datos numéricos , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Estudios Retrospectivos , Tamaño de la Muestra , Estados UnidosRESUMEN
The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double-blind, placebo-controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co, Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation.
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Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Procedimiento de Fontan , Cardiopatías Congénitas/terapia , Cuidados Posoperatorios/métodos , Pirimidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Sulfonamidas/uso terapéutico , Humanos , Estudios Longitudinales , Inhibidores de Fosfodiesterasa 5/uso terapéuticoRESUMEN
The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate-corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (-0.298 ± 0.139 vs 0.141 ± 0.139/year, p = 0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618 mm Hg) predicted a smaller annual decrease in ARz (p ≤0.001). Upper-quartile aortic-root EM (>914 mm Hg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p = 0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.
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Enfermedades de la Aorta/tratamiento farmacológico , Atenolol/administración & dosificación , Losartán/administración & dosificación , Síndrome de Marfan/diagnóstico por imagen , Síndrome de Marfan/tratamiento farmacológico , Rigidez Vascular/efectos de los fármacos , Adolescente , Aorta/diagnóstico por imagen , Aorta/efectos de los fármacos , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/etiología , Técnicas de Imagen Cardíaca/métodos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Estimación de Kaplan-Meier , Modelos Lineales , Síndrome de Marfan/complicaciones , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoAsunto(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
Uhl's anomaly, first reported in 1952, is an extremely rare congenital cardiac defect characterized by partial or complete loss of the right ventricular myocardium and unknown etiology. Fewer than 100 cases have been described. The response to medical management is poor and there is no known ideal surgical approach or timing for treatment. We report the case of a previously active adolescent male presenting with cardiac arrest, who underwent successful bidirectional cavopulmonary anastomosis ("Glenn" anastomosis) with right atrial reduction and right ventricular free wall plication.