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.

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.

Background/Objectives: Hypertrophic cardiomyopathy (HCM) in childhood is associated with a risk of adverse cardiovascular events despite preserved left ventricular (LV) ejection fraction (EF). The aim of this study was to evaluate echocardiographic parameters of longitudinal LV systolic function and determine their relationship with cardiac magnetic resonance (CMR) findings and major adverse cardiovascular events (MACE) in children and adolescents with HCM. Methods: This single-centre prospective observational study enrolled 31 children and adolescents with HCM and preserved LV EF. Echocardiographic assessment included mitral annular plane systolic excursion (MAPSE), tissue Doppler mitral annulus systolic velocity (s′), mitral annular displacement index (MADI), and LV global longitudinal strain (GLS). Investigated CMR parameters encompassed LV mass, maximal wall thickness, and late gadolinium enhancement (LGE). Associations between echocardiographic and CMR findings were analyzed, and the discriminative value of longitudinal function parameters for MACE was assessed. Results: Impaired longitudinal systolic function was frequently detected in our cohort. Lower MAPSE and s′ z-scores were present in 61.3% of patients, reduced MADI in 96.8%, and reduced LV GLS in all subjects. Patients with MACE showed significantly lower MADI (p < 0.001) and worse LV GLS (p = 0.003). An exploratory LV GLS cut-off value of −12.1% showed discrimination for MACE in this cohort, with 75% sensitivity and 95.7% specificity. Echocardiographic parameters significantly correlated with CMR markers of hypertrophy and fibrosis, particularly LV GLS, which demonstrated the strongest associations with LV mass and the presence and extent of LGE. Conclusions: Echocardiographic parameters of longitudinal LV systolic function could contribute to closer clinical surveillance in children and adolescents with HCM. LV GLS may identify subtle myocardial dysfunction and provide exploratory prognostic information; however, its role in risk stratification requires prospective validation in larger pediatric HCM cohorts.

Background/Objectives: We assessed the prevalence of impaired coronary flow veloc-ity reserve (CFVR) and aimed to identify echocardiographic and clinical predictors of coronary microvascular dysfunction in adolescents after neonatal arterial switch op-eration (ASO). Methods: This single-center, cross-sectional study included patients that underwent neonatal ASO for simple D-transposition of the great arteries (D-TGA) during 1998-2013. All patients were evaluated by echocardiography with global left ventricu-lar strain measurement (GLS) and cardiac catheterization, including coronary angi-ography. Coronary flow velocity reserve was assessed by transthoracic Doppler echo-cardiography in the left anterior descending artery (LAD) using adenosine induced hyperemia. Patients were stratified into two groups according to CFVR: group with impaired CFVR (< 2.5) and group with normal CFVR (≥2.5). Spearman correlation was used to assess relationship between CFVR and echocardiographic variables. Binary lo-gistic regression was used to determine independent predictors of impaired CFVR. Results: Out of 48 patients included (median age 16 years, age range 13 to 23 years, 71% male), impaired CFVR was found in 21 patients (44%). These patients had de-creased longitudinal tricuspid annular plane systolic excursion (TAPSE), greater Z-scores for left ventricular end-systolic dimensions and higher mean pulmonary ar-tery pressures (mPAP). CFVR showed modest but significant positive correlations with tricuspid annular plane systolic excursion (TAPSE). Left pulmonary artery branch ste-nosis, reduced TAPSE and mPAP≥ 20 mmHg, were significantly associated with im-paired CFVR, while decreased TAPSE remained independent predictor in multivaria-ble analysis (odds ratio 5.6, 95% confidence interval 1.24-25.26, p=0.025). Conclusions: Impaired CFVR is highly prevalent in adolescents after neonatal ASO. Importantly, impaired CFVR is associated with right ventricular dysfunction.

Background/Objectives: We assessed the prevalence of impaired coronary flow velocity reserve (CFVR) and aimed to identify echocardiographic and clinical predictors of coronary microvascular dysfunction in adolescents after neonatal arterial switch operation (ASO). Methods: This single-center, cross-sectional study included patients that underwent neonatal ASO for simple D-transposition of the great arteries (D-TGA) during 1998–2013. All patients were evaluated by echocardiography with global left ventricular strain measurement (GLS) and cardiac catheterization, including coronary angiography. Coronary flow velocity reserve was assessed by transthoracic Doppler echocardiography in the left anterior descending artery (LAD) using adenosine induced hyperemia. Patients were stratified into two groups according to CFVR: group with impaired CFVR (<2.5) and group with normal CFVR (≥2.5). Spearman correlation was used to assess the relationship between CFVR and echocardiographic variables. Binary logistic regression was used to determine independent predictors of impaired CFVR. Results: Out of 48 patients included (median age 16 years, age range 13 to 23 years, 71% male), impaired CFVR was found in 21 patients (44%). These patients had decreased longitudinal tricuspid annular plane systolic excursion (TAPSE), greater Z scores for left ventricular end-systolic dimensions and higher mean pulmonary artery pressures (mPAP). CFVR showed modest but significant positive correlations with tricuspid annular plane systolic excursion (TAPSE). Left pulmonary artery branch stenosis, reduced TAPSE and mPAP ≥ 20 mmHg, were significantly associated with impaired CFVR, while decreased TAPSE remained independent predictor in multivariable analysis (odds ratio 5.6, 95% confidence interval 1.24–25.26, p = 0.025). Conclusions: Impaired CFVR appears to be frequently observed in adolescents after uncomplicated neonatal ASO for simple D-TGA. Importantly, impaired CFVR is associated with right ventricular dysfunction.