Holiday heart syndrome: an upcoming tachyarrhythmia in today's youth?

Atrial fibrillation is one of the most common arrhythmias in the adult population, in children, however, only a few case reports of isolated atrial fibrillation exist.1 Aside from post-operative AF due to atrial scar formation or suture lines and atrial enlargement in CHD (e.g., mitral stenosis), alcohol consumption represents a rare cause of AF in adolescents. We report on the latter.

Right ventricular end-systolic remodeling index in the assessment of pediatric pulmonary arterial hypertension. The European Pediatric Pulmonary Vascular Disease Network (EPPVDN).

BACKGROUND: Echocardiographic determination of the right ventricular end-systolic remodeling index (RVES RI) has clinical value for the assessment of pulmonary hypertension (PH) in adults. We aim to determine RVES RI values in pediatric PH and to correlate RVES RI data with echocardiographic variables and NYHA functional class (FC). METHODS: Prospective echocardiography study in 49 children with PH. The 49 matched control subjects were chosen from 123 healthy children used to construct pediatric normal reference values. The associations with invasive hemodynamic variables were also investigated in a validation cohort of 12 PH children and matched controls. RESULTS: RVES RI was increased in children with PH vs. healthy controls (1.45 ± 0.16 vs. 1.16 ± 0.06; p < 0.01; confirmed in the validation cohort). RVES RI was associated with invasive hemodynamic variables, i.e. the mean pulmonary artery pressure. RVES RI values increased with worsening NYHA-FC. The highest RVES RI values were observed in PH children with NYHA FC 3 (1.60 ± 0.12). CONCLUSIONS: RVES RI is a useful indicator of RV remodeling and dilation in the setting of increased RV pressure load, especially when the degree of regurgitation of the tricuspid and pulmonary valves is insufficient to numerically estimate RV systolic pressure and mPAP, due to incomplete Doppler envelopes.

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.

Antiarrhythmic Drug Dosing in Children-Review of the Literature.

Antiarrhythmic drugs represent a mainstay of pediatric arrhythmia treatment. However, official guidelines and consensus documents on this topic remain scarce. There are rather uniform recommendations for some medications (including adenosine, amiodarone, and esmolol), while there are only very broad dosage recommendations for others (such as sotalol or digoxin). To prevent potential uncertainties and even mistakes with regard to dosing, we summarized the published dosage recommendations for antiarrhythmic drugs in children. Because of the wide variations in availability, regulatory approval, and experience, we encourage centers to develop their own specific protocols for pediatric antiarrhythmic drug therapy.

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.

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.

Ventricular-ventricular interaction variables correlate with surrogate variables of clinical outcome in children with pulmonary hypertension.

Determination of biventricular dimensions, function, and ventricular-ventricular interactions (VVI) is an essential part of the echocardiographic examination in adults with pulmonary hypertension (PH); however, data from according pediatric studies are sparse. We hypothesized that left and right heart dimensions/function and VVI variables indicate disease severity and progression in children with PH. Left heart, right heart, and VVI variables (e.g. end-systolic LV eccentricity index [LVEI], right ventricular [RV]/left ventricular [LV] dimension ratio) were echocardiographically determined in 57 children with PH, and correlated with New York Heart Association (NYHA) functional class (FC), N-terminal-pro brain natriuretic peptide (NT-proBNP), and invasive hemodynamic variables (e.g. pulmonary vascular resistance index [PVRi]). Clinically sicker patients (higher NYHA FC) had lower LV ejection fraction (LVEF) and higher LVEI - a surrogate of LV compression. In PH children, the ratio of systolic pulmonary arterial pressure divided by systolic systemic arterial pressure (sPAP/sSAP) and the PVRi correlated well with the LVEI ( P < 0.001). Patients with more severe PH (sPAP/sSAP ratio, PVRi) had increased RV/LV and right-to-left atrial dimension ratios ( P < 0.01). When stratified using NYHA-FC, sicker PH children had greater RV and right atrial dimensions with lower exercise capacity, while the tricuspid annular plane systolic excursion as surrogate for longitudinal systolic RV function decreased. Consistent with previous studies, serum NT-proBNP correlated with both, sPAP/sSAP ratio ( P < 0.001) and NYHA FC ( P < 0.01). Taken together, the VVI variables LVEI and RV/LV dimension ratio are associated with lower FC, worse hemodynamics, and higher NT-proBNP levels, thus highlighting the importance of ventricular interdependence in pediatric PH.

Cardiac and Pulmonary Cystic Echinococcosis With Massive Obstruction of the Pulmonary Vessel System in a 16-Year-Old Girl.

We describe herein the management of a 16-year-old girl with cystic echinococcosis of the right ventricle and massive obstruction of the pulmonary vessel system by parasitic metastatic dissemination. After resection of the cardiac cyst, pulmonary thromboendarterectomy was performed to remove parts of the obstructive parasitic material. The treatment reduced the elevated pulmonary arterial pressure, improving the patient's overall condition.

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.

Effect of rivaroxaban, in contrast to heparin, is similar in neonatal and adult plasma.

Neonates have lower levels of clotting factors as well as inhibitors. Effects of heparin in neonatal plasma differ from those in adult plasma, and dosage recommendations cannot be extrapolated from adult trials. Riveroxaban is an oral direct factor Xa inhibitor that can achieve an anticoagulant effect without dependence on anti-thrombin. We performed comparative thrombin generation measurements in neonatal cord and adult plasma with different concentrations of unfractionated heparin and rivaroxaban to evaluate the potential of rivaroxaban in neonatal anticoagulation. The impact of heparin or rivaroxaban on the neonatal and adult hemostatic system was determined measuring calibrated automated thrombin generation and activated partial thromboplastin time in platelet-poor plasma pools of 15 adult samples or 15 neonatal cord samples and addition of seven increasing concentrations of heparin or rivaroxaban, respectively, to the pooled samples. Lag time, time to peak and peak height of thrombin generation in neonatal cord samples were significantly less affected by different heparin concentrations than in adult samples, whereas the impact on reduction of endogenous thrombin potential was higher in neonatal cord samples. The impact of rivaroxaban on thrombin generation parameters showed better comparability between neonatal cord and adult samples. Both anticoagulants showed the same differences in activated partial thromboplastin time between adult and neonatal plasma at each concentration. Rivaroxaban shows a very similar pattern in neonatal cord and adult plasma in suppressing thrombin generation and prolonging activated partial thromboplastin time values, suggesting that dose finding may be easier with rivaroxaban in neonates.

Thrombin generation in pediatric patients with Crohn's disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolic complications. The pathogenesis of IBD is not really clear and a high thrombin activity might contribute to the pathogenesis. We measured thrombin generation by means of calibrated automated thrombography (CAT), a new tool better reflecting overall hemostasis, in children with Crohn's disease (CD) during active and inactive disease and compared it to conventional markers of activity. We wanted to see whether children with CD have a higher potential for thrombin generation and if there is a correlation between hypercoagulability and disease activity. METHODS: Plasma samples were collected from 22 patients with CD and from 61 healthy children. Thrombin generation was measured by means of CAT. The disease activity was estimated using the Pediatric Crohn's Disease Activity Index (PCDAI). In addition, F1+2, TAT, tissue factor pathway inhibitor (TFPI), fibrinogen, prothrombin (FII), antithrombin (AT), erythrocyte sedimentation rate (ESR), platelet count, α2-globulin, and orosomucoide were measured. RESULTS: In all patients we found a significantly higher endogenous thrombin potential (ETP) and higher peak values during active disease. In accordance with this we also found significantly higher mean ETP values during active disease compared with the control group. We observed a significantly positive correlation between PCDAI and thrombin generation parameters. CONCLUSIONS: Our study clearly shows that the active state of CD in children is associated with the potential for high thrombin generation, but this seems to be caused mainly by the inflammatory process and not by a preexisting propensity for high thrombin generation.