Browsing by Author "Bijelic, Maja (56807060700)"

Background: Angiotensin-converting enzyme inhibitors, such as enalapril, are foundational in treating pediatric heart failure. However, they are often administered off-label to young children using extemporaneous formulations. This study, conducted as part of the EU-funded Labeling of Enalapril from Neonates up to Adolescents (LENA) project, aimed to evaluate the acceptability and palatability of an age-appropriate enalapril orodispersible minitablet (ODMT). These factors are critical for ensuring adherence, efficacy, and safety in pediatric patients. Methods: An 8-week trial was conducted in children with heart failure caused by dilated cardiomyopathy or congenital heart disease. Enalapril ODMTs (0.25 mg or 1.0 mg) were dose-titrated and administered to 38 children aged 0–6 months and 22 children aged 6 months to 6 years. This study aimed to assess its acceptability and palatability, key factors contributing to adherence, and therefore, efficacy and safety. Results: Across all 169 assessments in 38 children aged 0–6 months and 22 aged 6 months to 6 years, complete or partial swallowability was observed, and the acceptability rate was 100%. There were no cases of choking, inhalation/coughing, or spitting out. A favorable or neutral rating was observed in 96% of palatability assessments based on observations of facial expressions. Acceptability and palatability were higher in subjects aged 6 months–6 years than 0–6 months, with no significant influence from repeated administration. Conclusions: Enalapril ODMTs are widely accepted and well-tolerated among young children, including neonates, with heart failure. These findings suggest that ODMTs are a suitable and effective method for administering pediatric medicinal products. © 2025 by the authors.

Background: It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients. Methods: We conducted a cross-sectional study of children and adolescents with SMA types 2 and 3 between July 2018 and July 2019. All patients underwent a comprehensive cardiac evaluation, including history-taking, physical examination, electrocardiography, echocardiography, measurement of cardiac biomarkers (cardiac troponin T [cTnT] and N-terminal pro–brain natriuretic peptide [NT-proBNP]), and 24-hour Holter monitoring. Results: In total, 42 patients were enrolled (27 and 15 with SMA type 2 and 3, respectively). No patient had structural heart disease, except for one with mitral valve prolapse. None had signs of ventricular dysfunction on echocardiography. Both cTnT and NT-proBNP levels were normal in all patients. Electrocardiography showed sinus tachycardia in seven patients (16.7%), and prolonged P-R interval in one (2.4%). Holter monitoring detected benign ventricular arrhythmias in two patients (4.8%), and rare supraventricular premature beats in one. The mean 24-hour heart rate was elevated in six patients (14.3%), whereas both the minimum 24-hour heart rate and the maximum R-R interval were increased in 23 (54.8%). Discussion: The prevalence of cardiac disease in pediatric patients with SMA types 2 and 3 is low; however, these patients may have increased resting heart rates. A complete cardiac history and physical examination are a useful screen. Additional cardiac investigations may be performed as needed. © 2020 Wiley Periodicals LLC

Background: It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients. Methods: We conducted a cross-sectional study of children and adolescents with SMA types 2 and 3 between July 2018 and July 2019. All patients underwent a comprehensive cardiac evaluation, including history-taking, physical examination, electrocardiography, echocardiography, measurement of cardiac biomarkers (cardiac troponin T [cTnT] and N-terminal pro–brain natriuretic peptide [NT-proBNP]), and 24-hour Holter monitoring. Results: In total, 42 patients were enrolled (27 and 15 with SMA type 2 and 3, respectively). No patient had structural heart disease, except for one with mitral valve prolapse. None had signs of ventricular dysfunction on echocardiography. Both cTnT and NT-proBNP levels were normal in all patients. Electrocardiography showed sinus tachycardia in seven patients (16.7%), and prolonged P-R interval in one (2.4%). Holter monitoring detected benign ventricular arrhythmias in two patients (4.8%), and rare supraventricular premature beats in one. The mean 24-hour heart rate was elevated in six patients (14.3%), whereas both the minimum 24-hour heart rate and the maximum R-R interval were increased in 23 (54.8%). Discussion: The prevalence of cardiac disease in pediatric patients with SMA types 2 and 3 is low; however, these patients may have increased resting heart rates. A complete cardiac history and physical examination are a useful screen. Additional cardiac investigations may be performed as needed. © 2020 Wiley Periodicals LLC

Background: The angiotensin-converting enzyme inhibitor (ACEI) enalapril is often administered to infants and young children with heart failure (HF) in various dosing regimens and formulations not adapted for their age. Methods: This prospective, two-center, open-label 8-week study evaluated an age-appropriate formulation of orodispersible minitablets (ODMTs) of enalapril (0.25 mg and 1 mg) in children aged 0 to 6 years with HF due to congenital heart disease. An age/weight-based dosing schedule was followed. Measures of echocardiographic parameters, blood pressure, heart rate, modified Ross score, and biochemistry were obtained over the 8-week period. The following two groups were assessed: ACEI-naïve and ACEI-pretreated patients. Results: In total, 53 children (age range of 0.05 to 4.8 years) were enrolled and 29 were ACEI-naïve. The average enalapril dose was 0.098 mg/kg (0.06–0.17 mg/kg) in the naïve group and 0.15 mg/kg (0.07–0.3 mg/kg) in pretreated patients. After 8 weeks, the modified Ross score and left ventricular diastolic dimension (LVD) z-score showed a significant decrease in both groups (p < 0.005). During 8 weeks follow-up, there were no difference in the z-scores for the systolic blood pressure (p = 0.071) or heart rate (p = 0.146). Conclusions: Pediatric patients treated with ODMTs of enalapril for 8 weeks had favorable improvements in LVD and HF symptoms. © 2024 by the authors.

Background: Balloon valvuloplasty is the primary treatment for congenital aortic valve stenosis in our centre. We sought to determine independent predictors of reintervention (surgical repair or repeated balloon dilation) after primary valvuloplasty. Methods: We retrospectively studied patients with congenital aortic valve stenosis who underwent balloon valvuloplasty during 2004-2018. The following risk factors were analysed: aortic valve insufficiency after balloon valvuloplasty >+1/4, post-procedural gradient across the aortic valve ≥35 mmHg, pre-interventional gradient across the valve, annulus size, use of rapid pacing, and balloon/annulus ratio. Primary outcome was aortic valve reintervention. Results: In total, 99 patients (median age 4 years, range 1 day to 26 years) underwent balloon valvuloplasty for congenital aortic valve stenosis. After a mean follow-up of 4.0 years, 30% had reintervention. Adjusted risks for reintervention were significantly increased in patients with post-procedural aortic insufficiency grade >+1/4 and/or residual gradient ≥35 mmHg (HR 2.55, 95% CI 1.13-5.75, p = 0.024). Pre-interventional gradient, annulus size, rapid pacing, and balloon/annulus ratio were not associated with outcome. Conclusion: Post-procedural aortic valve insufficiency grade >+1/4 and/or residual gradient ≥35 mmHg in patients undergoing balloon valvuloplasty for congenital aortic valve stenosis confers an increased risk for reintervention in mid-term follow-up. © The Author(s), 2023. Published by Cambridge University Press.