Wearable cardioverter-defibrillator as bridging to ICD in pediatric hypertrophic cardiomyopathy with myocardial bridging - a case report.

BACKGROUND: There is only limited experience with wearable cardioverter-defibrillators (WCD) in pediatric patients. We report on the successful application of a WCD in an adolescent patient with hypertrophic cardiomyopathy and myocardial bridging. CASE PRESENTATION: A 15-year-old girl presented with a history of recurrent syncope, dyspnea, and vertigo with exercise. Diagnostic work-up revealed non-obstructive hypertrophic cardiomyopathy and signs of myocardial ischemia with exercise. Given this high-risk constellation, the patient was scheduled for prophylactic implantation of an implantable cardioverter-defibrillator (ICD). One month after initial presentation and days prior to the planned ICD implantation, the patient collapsed during an episode of sustained ventricular tachycardia (VT) while running. VT was terminated by WCD shock delivery. Following this event, computerized tomography scan revealed myocardial bridging of the left anterior descending coronary artery causing a 90% stenosis in systole. After coronary surgery, life threatening arrhythmias have not recurred, but due to progressive heart failure, the patient underwent successful heart transplantation after 2 years. CONCLUSIONS: The reported case highlights the importance and applicability of WCDs and the potentially malign nature of myocardial bridging in pediatric high-risk patients.

First clinical experience with the Kora pacemaker system in congenital complete heart block in newborn infants.

BACKGROUND: To report first clinical experience on three cases of congenital complete heart block and the use of a pacemaker system with a maximum lower rate interval of 95 beats per minute. METHODS: We retrospectively analyzed three patients treated with a pacemaker system with a maximum lower rate interval of 95 beats per minute suffering from congenital complete heart block. We report a follow up period of 2.9 years, focusing on the patients' growth, development, and adverse events, as well as pacemaker function. RESULTS: In all three patients pacemaker function was impeccable, including minute ventilation sensor rate adaption. All patients showed limited growths as expected, adequate development, good feeding tolerability and circadiane heart rate adaption. One patient experienced skin traction and revision. All patients showed high aortic velocity time integral values after birth. CONCLUSION: The use of a pacemaker system with a maximum lower rate interval of 95 beats per minute in infants suffering from congenital complete heart block and showing high aortic VTI values seems to be feasible and to result in limited growths but adequate development.

The right ventricular outflow tract in pediatric pulmonary hypertension-Data from the European Pediatric Pulmonary Vascular Disease Network.

OBJECTIVE: The right ventricular outflow tract (RVOT) is pivotal for adequate RV function and known to be adversely affected by elevated pulmonary arterial pressure (PAP) in adults with pulmonary hypertension (PH). Aim of this study was to determine the effects of increased RV pressure afterload in children with PH on RVOT size, function, and flow parameters. METHODS: We conducted a transthoracic echocardiographic study in 51 children with PH (median age: 5.3 years; range 1.5 months to 18 years) and determined the following RVOT variables: RVOT diameter, RVOT velocity time integral (VTI), ratio of tricuspid regurgitation velocity (TRV)/RVOT VTI, and RVOT systolic excursion (SE). RESULTS: In our pediatric PH cohort, the age-specific RVOT diameter z-score was higher compared to normal values. Deviation from normal RVOT diameter values increased with age, disease severity, and New York Heart Association functional class. Significant correlations were found between RVOT diameter and the RV end-diastolic area and right atrial area. The age-specific RVOT VTIz-score values were significantly lower in children with PH vs healthy controls. The TRV/RVOT VTI ratio increased with rising systolic RV pressure, while the RVOT SE was similar between PH children and control subjects. CONCLUSIONS: In pediatric PH cohort, the RVOT VTI is decreased, and the TRV/RVOT VTI ratio and the RVOT diameter increased compared to healthy subjects. Assessment of RVOT variables, together with established RV parameters, allows for a comprehensive assessment of global right heart size and performance in children with PH.

Right Ventricular Outflow Tract (RVOT) Changes in Children with an Atrial Septal Defect: Focus on RVOT Velocity Time Integral, RVOT Diameter, and RVOT Systolic Excursion.

OBJECTIVE: Aim of the study was to determine the influence of right heart volume overload in children with atrial septal defect (ASD) on right ventricular outflow tract (RVOT) variables. METHODS: A prospective study was conducted in 115 children (age range: 2 days-18.1 years) with a moderate to large ASD. We determined effects of age, body length (BL), body weight (BW), and body surface area (BSA) on the variables RVOT diameter, RVOT velocity time integral (VTI), and RVOT systolic excursion (SE), and tested the predictive value of published normal values for age, BW, BL, and BSA in our ASD patients. RESULTS: In our pediatric ASD patients, the age-specific RVOT diameter (z-score: +2.2, 95% CI: 2.0-2.4, P < 0.001) was significantly increased compared to normal values with 54% of our ASD patients having a z-score >2.0. The age-specific RVOT VTI z-score (z-score: +3.6, 95% CI: 3.2-3.9, P < 0.001) was significantly increased compared to normal values with 81% of our ASD patients having a z-score >2.0. The age-specific RVOT SE z-score was not increased but slightly lower compared to normal values (z-score: -0.5, 95% CI: -0.7 to -0.3, P < 0.001) with 3% of our ASD patients having a z-score >2.0 while 12% of the patients had a z-score <-2. CONCLUSION: In our study population, we show the RVOT VTI and diameter to be relevant predictors in identifying an enlarged RVOT size and flow in children with moderate to large ASD.

Echocardiographic Reference Values for Right Atrial Size in Children with and without Atrial Septal Defects or Pulmonary Hypertension.

Right atrial (RA) size may become a very useful, easily obtainable, echocardiographic variable in patients with congenital heart disease (CHD) with right-heart dysfunction; however, according studies in children are lacking. We investigated growth-related changes of RA dimensions in healthy children. Moreover, we determined the predictive value of RA variables in both children with secundum atrial septal defect (ASD) and children with pulmonary hypertension (PH) secondary to CHD (PH-CHD). This is a prospective study in 516 healthy children, in 80 children with a secundum ASD (>7 mm superior-inferior dimension), and in 42 children with PH-CHD. We determined three RA variables, i.e., end-systolic major-axis length, end-systolic minor-axis length, and end-systolic area, stratified by age, body weight, length, and surface area. RA end-systolic length and area z scores were increased in children with ASD and PH-CHD when compared to those variables in the healthy control population. Using the Youden Index to determine the best cutoff scores in sex- and age-specific RA dimensions, we observed a sensitivity and specificity up to 94 and 91 %, respectively, in ASD children and 98 and 94 %, respectively, in PH-CHD children. We provide normal values (z scores -2 to +2) for RA size and area in a representative, large pediatric cohort. Enlarged RA variables with scores >+2 were predictive of secundum ASD and PH-CHD. Two-dimensional determination of RA size can identify enlarged RAs in the setting of high volume load (ASD) or pressure load (PH-CHD).

Right Ventricular Outflow Tract Velocity Time Integral Determination in 570 Healthy Children and in 52 Pediatric Atrial Septal Defect Patients.

Determination of the right ventricular outflow tract velocity time integral (RVOT VTI) is an important part of the noninvasive investigation of pulmonary blood flow in adults; however, age-related pediatric reference data are lacking. We examined growth-related changes of RVOT VTI values in children and the predictive value of RVOT VTI values in identifying enhanced pulmonary blood flow in children with secundum type atrial septal defect (ASD). A prospective study was conducted in a group of 570 healthy children and 52 children with a moderate-sized to large ASD. We determined the effects of age, body length (BL), body weight (BW), and body surface area (BSA) on RVOT VTI values. The predictive value of normal values stratified for age, BW, BL, and BSA was tested in our 52 ASD children. RVOT VTI values ranged from mean 9.7 ± 1.2 cm in neonates to 23.3 ± 2.7 cm in children with 18 years of age and showed a positive correlation with age, BL, BSA, and BW. In our population, RVOT VTI z-scores showed a high specificity for detecting ASD patients (>97 %) with sensitivity up to 71 %. We provide normal ranges and calculated z-scores of pediatric RVOT VTI values. Normal RVOT VTI z-scores might be additional predictors in identifying increased pulmonary blood flow in patients with ASD.

A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5.

BACKGROUND: Rearrangements involving chromosome 5p often result in two syndromes, Cri-du-chat (CdC) and Trisomy 5p, caused by a deletion and duplication, respectively. The 5p15.2 has been defined as a critical region for CdC syndrome; however, genotype-phenotype studies allowed isolation of particular characteristics such as speech delay, cat-like cry and mental retardation, caused by distinct deletions of 5p. A varied clinical outcome was also observed in patients with Trisomy 5p. Duplications of 5p10-5p13.1 manifest themselves in a more severe phenotype, while trisomy of regions distal to 5p13 mainly causes mild and indistinct features. Combinations of a terminal deletion and inverted duplication of 5p are infrequent in literature. Consequences of these chromosomal rearrangements differ, depending on size of deletion and duplication in particular cases, although authors mainly describe the deletion as the cause of the observed clinical picture. CASE PRESENTATION: Here we present a 5-month-old Slovenian girl, with de novo terminal deletion and inverted duplication of chromosome 5p. Our patient presents features of both CdC and Trisomy 5. The most prominent features observed in our patient are a cat-like cry and severe malformations of the right ear. CONCLUSION: The cat-like cry, characteristic of CdC syndrome, is noted in our patient despite the fact that the deletion is not fully consistent with previously defined cat-like cry critical region in this syndrome. Features like dolichocephaly, macrocephaly and ear malformations, associated with duplication of the critical region of Trisomy 5p, are also present, although this region has not been rearranged in our case. Therefore, the true meaning of the described chromosomal rearrangements is discussed.

Mild Acquired von Willebrand Syndrome and Cholestasis in Pediatric and Adult Patients with Fontan Circulation.

Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.

Normal Echocardiographic Reference Values of the Right Ventricular to Left Ventricular Endsystolic Diameter Ratio and the Left Ventricular Endsystolic Eccentricity Index in Healthy Children and in Children With Pulmonary Hypertension.

Background: An accurate assessment of the right and left ventricle and their interaction is important in pediatric pulmonary hypertension (PH). Our objective was to provide normal reference values for the right ventricular to left ventricular endsystolic (RV/LVes) ratio and the LV endsystolic eccentricity index (LVes EI) in healthy children and in children with PH. Methods: We conducted an echocardiographic study in 769 healthy children (median age: 3.36 years; range: 1 day-18 years) and validated abnormal values in 44 children with PH (median age: 2.1 years; range: 0.1 months-17.7 years). We determined the effects of gender, age, body length, body weight, and body surface area (BSA) on RV/LVes ratio and LVes EI values. The RV/LVes ratio and LVes EI were measured from the parasternal short axis view between papillary muscle from the endocardial to endocardial surfaces. Results: Both, the RV/LVes ratio and the LVes EI were highly age-dependent: (i) neonates RV/LVes ratio [median 0.83 (range 0.53-1.37)], LVes EI [1.21 (0.92-1.45)]; (ii) 12-24 months old: RV/LVes ratio: [0.55 (0.35-0.80)], LVes EI: [1.0 (0.88-1.13)]; iii) 18th year of life RV/LVes ratio: [0.53 (0.32-0.74)], LVes EI: [1.0 (0.97-1.07)]. Healthy neonates had high LVes EI and RV/LVes ratios, both gradually decreased within the first year of life and until BSA values of about 0.5 m2, body weight to about 15 kg and body length to about 75 cm, but were almost constant thereafter. Children (>1 year) and adolescents with PH had significantly higher RV/LVes ratio (no PH: median 0.55, IQR 0.49-0.60; PH: 1.02, 0.87-1.26; p < 0.001) and higher LVes EI values (no PH: 1.00, 0.98-1.00; PH: 1.53, 1.26-1.71; p < 0.001) compared to those without PH. To predict the presence of PH in children > 1 year, we found the following best cutoff values: RV/LVes ratio ≥ 0.67 (sensitivity: 1.00, specificity: 0.95) and LVes EI ≥ 1.06 (sensitivity: 1.00, specificity: 0.97). Conclusion: We provide normal echocardiographic reference values of the RV/LVes ratio and LVes EI in healthy children, as well as statistically determined cutoffs for the increased values in children with PH.

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series.

Background: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. Methods: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). Results: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. Conclusion: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.

Successful Postnatal Cardiopulmonary Resuscitation Due to Defibrillation.

An asphyxiated term neonate required postnatal resuscitation. After six minutes of cardio-pulmonary resuscitation (CPR) and two doses of epinephrine, spontaneous circulation returned, but was shortly followed by ventricular fibrillation. CPR and administration of magnesium, calcium gluconate, and sodium bicarbonate did not improve the neonate's condition. A counter shock of five Joule was delivered and the cardiac rhythm immediately converted to sinus rhythm. The neonate was transferred to the neonatal intensive care unit and received post-resuscitation care. Due to prolonged QTc and subsequently suspected long-QT syndrome propranolol treatment was initiated. The neonate was discharged home on day 14 without neurological sequelae.

Safety and efficacy of the endothelin receptor antagonist macitentan in pediatric pulmonary hypertension.

BACKGROUND: Macitentan, a dual endothelin receptor antagonist (ERA), was approved in 2014 for the treatment of adults with idiopathic pulmonary arterial hypertension (PAH). Once-per-day dosing and low potential hepatic toxicity make macitentan an appealing therapeutic option for children with PAH, but reports on its use in pediatric patients are still lacking. METHODS: Prospective observational study of 18 children [10 male; median age: 8.5, minimum (min.): 0.6, maximum (max.): 16.8 years] with pulmonary hypertension (PH). Four of these 18 patients were treatment-naïve and started on a de novo macitentan therapy. The remaining 14/18 children were already on a PH-targeted pharmacotherapy (sildenafil or bosentan as monotherapy or in combination). Nine children who were on bosentan were switched to macitentan. We analyzed the 6-minute walking distance (6MWD), NYHA functional class (FC)/modified ROSS score, invasive hemodynamics, echocardiographic variables and the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: The median follow up was 6 months (min.: 0.5, max.: 30). Macitentan treatment was associated with improvement of invasive hemodynamics, e.g., the ratio of mean pulmonary arterial pressure/mean systemic arterial pressure decreased from a median of 62% (min.: 30%, max.: 87%) to 49% (min.: 30%, max.: 69%), P<0.05; pulmonary vascular resistance index (PVRi) decreased from a median of 7.6 (min.: 3.3, max.: 11.5) to 4.8 Wood units × m2 body surface area (min.: 2.5, max.: 10), P<0.05. The tricuspid annular plane systolic excursion (TAPSE) increased from a median of 1.4 (min.: 0.8, max.: 2.8) to 1.9 (min.: 0.8, max.: 2.7) cm, (P<0.05). NT-proBNP values decreased from a median of 272 (min.: 27, max.: 2,010) to 229 (min.: 23, max.: 814) pg/mL under macitentan therapy (P<0.05). The 6MWD and NYHA FC/modified ROSS score did not change significantly. CONCLUSIONS: This is the first prospective study of macitentan pharmacotherapy in infants and children with PH <12 years of age. Except in one patient, macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT-proBNP values.

Normal Pediatric Values of the Subcostal Tricuspid Annular Plane Systolic Excursion (S-TAPSE) and Its Value in Pediatric Pulmonary Hypertension.

BACKGROUND: The clinical value of determination of right ventricular (RV) function in adults using echocardiographic determination of the subcostal tricuspid annular plane systolic excursion (S-TAPSE) has previously been reported. We aim to provide representative, normal reference values for S-TAPSE in the pediatric age group. Moreover, validation of abnormal S-TAPSE values in children with impaired RV function, such as pulmonary hypertension (PH), is intended. METHODS: We propose a prospective echocardiographic study in 658 healthy children and in 27 children with PH (age: 1 day to 18 years; BSA 0.2-2.0 m2). We correlated the effects of body surface area (BSA) on S-TAPSE values of our healthy subjects and children with PH. S-TAPSE values were compared with apically derived TAPSE values. RESULTS: S-TAPSE values ranged from a mean of 0.65 ± 0.16 cm in healthy neonates to 1.79 ± 0.33 cm in 18-year-old healthy adolescents. S-TAPSE values increased with increasing age (P = 0.841, P < 0.001), body weight (P = 0.852, P < 0.001), body length (P = 0.846, P < 0.001), and BSA (P = 0.851, P < 0.001) in a nonlinear way in our healthy patients group. No difference in healthy male and female patients could be observed. In our 27 patients with PH (age range: 0.6 to 15.7 years) the median BSA specific S-TAPSE z-score ranged from -3.24 to 1.10, depending on restraint of RV function. CONCLUSION: The provided S-TAPSE normal reference values and z-scores may assist to identify children with impaired RV function. Abnormal S-TAPSE values will help to identify impaired RV function in pediatric patients with PH.

Right ventricular base/apex ratio in the assessment of pediatric pulmonary arterial hypertension: Results from the European Pediatric Pulmonary Vascular Disease Network.

BACKGROUND: Echocardiographic determination of RV end-systolic base/apex (RVES b/a) ratio was proposed to be of clinical value for assessment of pulmonary arterial hypertension (PAH) in adults. HYPOTHESIS: We hypothesized that the RVES b/a ratio will be affected in children with PAH and aimed to correlate RVES b/a ratio with conventionally used echocardiographic and hemodynamic variables, and with New York Heart Association (NYHA) functional class. METHODS: First we determined normal pediatric values for RVES b/a ratio in 157 healthy children (68 males; age range, 0.5-17.7 years). We then conducted an echocardiographic study in 51 children with PAH (29 males; age range, 0.3-17.8 years). RESULTS: RVES b/a ratio was lower compared with age- and sex-matched healthy controls (P < 0.001). In children with PAH, RVES b/a ratio decreased with worsening NYHA class. RVES b/a ratio inversely correlated with RV/LV end-systolic diameter ratio (ρ = -0.450, P = 0.001) but did not correlate with RV systolic function parameters (eg, tricuspid annular plane systolic excursion) and correlated with cardiac catheterization-determined pulmonary vascular resistance index (ρ = -0.571, P < 0.001). ROC analysis unraveled excellent performance of RVES b/a ratio to detect PAH in children (AUC: 0.95, 95% CI: 0.89-1.00, P < 0.001). CONCLUSIONS: The RVES b/a ratio decreased in children with PAH compared with age- and sex-matched healthy subjects. The RVES b/a ratio inversely correlated with both echocardiographic and hemodynamic indicators of increased RV pressure afterload and with NYHA class, suggesting that RVES b/a ratio reflects disease severity in PAH children.

Normal Reference Values and z Scores of the Pulmonary Artery Acceleration Time in Children and Its Importance for the Assessment of Pulmonary Hypertension.

BACKGROUND: Pulsed-wave Doppler determination of the pulmonary artery acceleration time (PAAT) as a surrogate for pulmonary artery pressure was found to be of clinical value for assessment of pulmonary hypertension (PH) with studies to date exclusively performed in adults. This study aims to provide representative, normal reference values for PAAT in children of all ages. Moreover, we validated abnormal PAAT values in 54 children with PH. METHODS AND RESULTS: We conducted a prospective echocardiographic study in 756 healthy children (aged 1 day to 18 years) and in 54 children with PH. Possible associations of age, body length, body weight, body surface area, and heart rate on PAAT were investigated. The PAAT correlated positively with age (r=0.848), body length (r=0.871), body surface area (r=0.856), and body weight (r=0.825) and negatively with heart rate (r=-0.906). PAAT increased with age (neonates: median: 81 ms, range: 53-104; 18th year of life: median: 151 ms, range: 107-187). Receiver operating characteristic analysis for detecting PH patients using age-specific z scores showed an excellent performance of PAAT (P<0.001; area under the curve, 0.98; 95% confidence interval, 0.97-0.99) with a best cutoff score according to Youden index of -1.565 (sensitivity: 92%, specificity: 96%). PAAT values of PH patients negatively correlated (ρ=-0.497) with pulmonary vascular resistance. CONCLUSIONS: The PAAT normal reference values and z scores we provide here will be useful to identify children with a shortened PAAT. Abnormal PAAT values with scores <-2 were predictive of PH.

Reference values and calculation of z-scores of echocardiographic measurements of the normal pediatric right ventricle.

Determination of right ventricular (RV) size and function has gained more interest in recent years in adults and children, especially in patients with congenital heart disease. Data on normal RV size parameters in children are scant. The aim of this study was to investigate growth-related changes in RV internal dimensions in a healthy pediatric cohort and the predictive value of RV parameters in identifying enlarged right ventricles in children with secundum-type atrial septal defects (ASD). A prospective study was conducted in a group of 576 healthy children (aged 1 day to 18 years) and 37 children (aged 1.4 to 17.7 years) with moderate-sized to large ASDs. The effects of age, body length, body weight, and body surface area were determined on the following RV parameters: end-diastolic basal diameter, end-diastolic midcavity diameter, end-diastolic length, end-systolic length, end-diastolic area, and end-systolic area. The predictive value of normal values stratified for age, body weight, body length, and body surface area was tested in children with ASDs. RV end-diastolic basal diameter, end-diastolic midcavity diameter, end-diastolic length, end-systolic length, end-diastolic area, and end-systolic area showed positive correlations with age, body length, body surface area, and body weight. In this population, RV z scores showed high specificity for detecting patients with ASDs, with sensitivity up to 89%, especially in children <8 years of age. In conclusion, the normal ranges of pediatric RV internal dimensions are provided. The z scores of these RV parameters were also calculated. Normal RV z scores might be important predictors in identifying enlarged right ventricles in patients with ASDs.