Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Association Between Serial B-Type Natriuretic Peptide Levels, Vasoactive Drug Weaning, and Adverse Cardiovascular Outcomes in Pediatric Heart Failure.

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.

Research Gaps in Pediatric Heart Failure: Defining the Gaps and Then Closing Them Over the Next Decade.

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.

Baseline Characteristics of Pediatric Patients With Heart Failure Due to Systemic Left Ventricular Systolic Dysfunction in the PANORAMA-HF Trial.

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.

Drug Treatment of Heart Failure in Children: Gaps and Opportunities.

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.

Recent and Upcoming Drug Therapies for Pediatric Heart Failure.

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.

Elevated Heart Rate and Survival in Children With Dilated Cardiomyopathy: A Multicenter Study From the Pediatric Cardiomyopathy Registry.

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.

Hospital readmission following pediatric heart transplantation.

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.

Update on pediatric heart failure.

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 outcomes for low-risk pediatric heart transplant recipients and steroid avoidance: A multicenter cohort study (Clinical Trials in Organ Transplantation in Children - CTOTC-04).

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.

Systematic literature review on the economic, humanistic, and societal burden of heart failure in children and adolescents.

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.

Significant mortality, morbidity and resource utilization associated with advanced heart failure in congenital heart disease in children and young adults.

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.

Cumulative Effect of Preoperative Risk Factors on Mortality After Pediatric Heart Transplantation.

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.

Elevated Troponin in the First 72 h of Hospitalization for Pediatric Viral Myocarditis is Associated with ECMO: An Analysis of the PHIS+ Database.

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.

Disopyramide use in infants and children with hypertrophic cardiomyopathy.

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.

Study rationale, design, and pretransplantation alloantibody status: A first report of Clinical Trials in Organ Transplantation in Children-04 (CTOTC-04) in pediatric heart transplantation.

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.

Systematic Literature Review on the Incidence and Prevalence of Heart Failure in Children and Adolescents.

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).

Characteristics and Outcomes of Pediatric Heart Failure-Related Emergency Department Visits in the United States: A Population-Based Study.

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.

Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study).

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).

Value of a flow cytometry cross-match in the setting of a negative complement-dependent cytotoxicity cross-match in heart transplant recipients.

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.

Emergency department utilization in pediatric heart transplant recipients.

We used the NEDS database (2010) to evaluate ED utilization in PED HT recipients compared to other patient populations with focus on characteristics of ED visits, risk factors for admission, and charges. We analyzed 433 ED visits by PED HT recipients (median age 8 [range: 0-18] years). The most common primary diagnosis category was infectious (n=163, 37.

Left Ventricular Rotational Mechanics in Children After Heart Transplantation.

Background: Left ventricular (LV) dysfunction after orthotopic heart transplantation (OHT) is multifactorial and can be an indicator of graft rejection or coronary artery vasculopathy. Analysis of rotational mechanics may help in the early diagnosis of ventricular dysfunction. Studies describing the left ventricular rotational strain in children after OHT are lacking.