A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Academy of Pediatrics, American Heart Association, American Society of Echocardiography, Heart Rhythm ...Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Pediatric Echocardiography Rating Panel Robert M. Campbell, MD, FACC, FAHA, FAAP, FHRS, Chairlow * Pamela S. Douglas, MD, MACC, FAHA, FASE, Moderatorlow * Louis I. Bezold, MD, FACC, FAAP, FASEdagger William B. Blanchard, MD, FACC, FAHA, FAAPlow * Jeffrey R. Boris, MD, FACClow * Bryan Cannon, MDdouble dagger Gregory J. Ensing, MD, FACC, FASE§ Craig E. Fleishman, MD, FACC, FASE|| Mark A. Fogel, MD, FACC, FAHA, FAAP¶ B. Kelly Han, MD, FACC# Shabnam Jain, MD, MPH, FAAPlow * Mark B. Lewin, MD|| Richard Lockwood, MDlow *low * G. Paul Matherne, MD, MBA, FACC, FAHAdaggerdagger David Nykanen, MD, FACCdouble daggerdouble dagger Catherine L. Webb, MD, FACC, FAHA, FASEdaggerdagger Robert Wiskind, MD, FAAPlow *American College of Cardiology representative.American Academy of Pediatrics representative.Heart Rhythm Society representative.American Society of Echocardiography representative.Society of Pediatric Echocardiography representative.Society for Cardiovascular Magnetic Resonance representative.Society of Cardiovascular Computed Tomography representative.Health Plan representative.American Heart Association representative.Society for Cardiovascular Angiography and Interventions representative.
Dravet syndrome is a rare, treatment-resistant developmental epileptic encephalopathy characterised by multiple types of frequent, disabling seizures. Fenfluramine has been reported to have ...antiseizure activity in observational studies of photosensitive epilepsy and Dravet syndrome. The aim of the present study was to assess the efficacy and safety of fenfluramine in patients with Dravet syndrome.
In this randomised, double-blind, placebo-controlled clinical trial, we enrolled children and young adults with Dravet syndrome. After a 6-week observation period to establish baseline monthly convulsive seizure frequency (MCSF; convulsive seizures were defined as hemiclonic, tonic, clonic, tonic-atonic, generalised tonic-clonic, and focal with clearly observable motor signs), patients were randomly assigned through an interactive web response system in a 1:1:1 ratio to placebo, fenfluramine 0·2 mg/kg per day, or fenfluramine 0·7 mg/kg per day, added to existing antiepileptic agents for 14 weeks. The primary outcome was the change in mean monthly frequency of convulsive seizures during the treatment period compared with baseline in the 0·7 mg/kg per day group versus placebo; 0·2 mg/kg per day versus placebo was assessed as a key secondary outcome. Analysis was by modified intention to treat. Safety analyses included all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov with two identical protocols NCT02682927 and NCT02826863.
Between Jan 15, 2016, and Aug 14, 2017, we assessed 173 patients, of whom 119 patients (mean age 9·0 years, 64 54% male) were randomly assigned to receive either fenfluramine 0·2 mg/kg per day (39), fenfluramine 0·7 mg/kg per day (40) or placebo (40). During treatment, the median reduction in seizure frequency was 74·9% in the fenfluramine 0·7 mg/kg group (from median 20·7 seizures per 28 days to 4·7 seizures per 28 days), 42·3% in the fenfluramine 0·2 mg/kg group (from median 17·5 seizures per 28 days to 12·6 per 28 days), and 19·2% in the placebo group (from median 27·3 per 28 days to 22·0 per 28 days). The study met its primary efficacy endpoint, with fenfluramine 0·7 mg/kg per day showing a 62·3% greater reduction in mean MCSF compared with placebo (95% CI 47·7–72·8, p<0·0001); fenfluramine 0·2 mg/kg per day showed a 32·4% reduction in mean MCSF compared with placebo (95% CI 6·2–52·3, p=0·0209). The most common adverse events (occurring in at least 10% of patients and more frequently in the fenfluramine groups) were decreased appetite, diarrhoea, fatigue, lethargy, somnolence, and decreased weight. Echocardiographic examinations revealed valve function within the normal physiological range in all patients during the trial and no signs of pulmonary arterial hypertension.
In Dravet syndrome, fenfluramine provided significantly greater reduction in convulsive seizure frequency compared with placebo and was generally well tolerated, with no observed valvular heart disease or pulmonary arterial hypertension. Fenfluramine could be an important new treatment option for patients with Dravet syndrome.
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...we would like to emphasize that these recommendations followed strict methodology consistent with other ESPNIC guidelines and are evidence-based, not expert-consensus guidelines 10. ...we agree ...with McNamara et al. that these guidelines are not for use by any neonatologist. ...POCUS is not an alternative to NPE or specialist echocardiography 7, which involves comprehensive training in hemodynamic evaluation and protocol-based assessments. Singh Y, Tissot C, Fraga MV, Yousef N, Cortes RG, Lopez J, Sanchez-de-Toledo J, Brierley J, Colunga JM, Raffaj D, Da Cruz E, Durand P, Kenderessy P, Lang HJ, Nishisaki A, Kneyber MC, Tissieres P, Conlon TW, De Luca D. International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).
Objectives We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle ...anomalies enrolled in the Single Ventricle Reconstruction trial. Methods Potential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality. Results Analysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations. Conclusions Innate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization.
Cardiovascular magnetic resonance (CMR) is widely used for diagnostic imaging in the pediatric population. In addition to structural congenital heart disease (CHD), for which published guidelines are ...available, CMR is also performed for non-structural pediatric heart disease, for which guidelines are not available. This article provides guidelines for the performance and reporting of CMR in the pediatric population for non-structural ("non-congenital") heart disease, including cardiomyopathies, myocarditis, Kawasaki disease and systemic vasculitides, cardiac tumors, pericardial disease, pulmonary hypertension, heart transplant, and aortopathies. Given important differences in disease pathophysiology and clinical manifestations as well as unique technical challenges related to body size, heart rate, and sedation needs, these guidelines focus on optimization of the CMR examination in infants and children compared to adults. Disease states are discussed, including the goals of CMR examination, disease-specific protocols, and limitations and pitfalls, as well as newer techniques that remain under development.
Objective
Fenfluramine, which was previously approved as a weight loss drug, was withdrawn in 1997 when reports of cardiac valvulopathy emerged. The present study was conducted in part to ...characterize the cardiovascular safety profile of low‐dose fenfluramine when used in a pediatric population to reduce seizure frequency in patients with Dravet syndrome.
Methods
Patients 2‐ to 18‐years‐old with Dravet syndrome who had completed any of three randomized, placebo‐controlled clinical trials of fenfluramine were offered enrollment in this open‐label extension (OLE) study. All patients were treated with fenfluramine starting at a dose of 0.2 mg/kg/day (oral solution dosed twice per day), which was titrated to maximal effect with a dose limit of 0.7 mg/kg/day (maximum 26 mg/day) or 0.4 mg/kg/day (maximum 17 mg/day) in patients receiving concomitant stiripentol. Standardized echocardiographic examinations were conducted at Week 4 or 6 and then every 3 months during the OLE study to monitor cardiac valve function and structure and pulmonary artery pressure. The primary end point for the echocardiography analysis was the number of patients who developed valvular heart disease or pulmonary artery hypertension (PAH) during treatment.
Results
A total of 232 patients were enrolled in the study. The average age of patients was 9.1 ± 4.7 years, and 55.2% were male. The median duration of treatment with fenfluramine was 256 days (range = 58‐634 days), and the mean dose of fenfluramine was 0.41 mg/kg/day. No cases of valvular heart disease or PAH were observed.
Significance
Longitudinal echocardiography over a median 8.4 months of treatment with fenfluramine suggests a low risk of developing cardiac valvulopathy and PAH when used to treat pediatric patients with Dravet syndrome.
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