Comprehensive Evaluation of Pediatric Patients with Ebstein Anomaly Requires Both Echocardiography and Cardiac Magnetic Resonance Imaging.

With the trend towards childhood surgery in patients with Ebstein anomaly (EA), thorough imaging is crucial for patient selection. This study aimed to assess biventricular function by echocardiography and cardiac magnetic resonance (CMR) and compare EA severity classifications. Twenty-three patients (8-17 years) underwent echocardiography and CMR. Echocardiographic parameters included tricuspid annular plane systolic excursions (TAPSE), fractional area change of the functional right ventricle (fRV-FAC), fRV free wall peak systolic myocardial velocity (fRVs'), and tricuspid regurgitation (TR). End-diastolic and end-systolic volume (EDV resp. ESV), fRV- and LV ejection fraction (EF) and TR were obtained by CMR. EA severity classifications included displacement index, Celermajer index and the total-right/left-volume index. Median fRV-FAC was 38% (IQR 33-42). TAPSE and fRVs' were reduced in 39% and 75% of the patients, respectively. Echocardiographic TR was visually graded as mild, moderate, or severe in nine, six and eight patients, respectively. By CMR, median fRVEF was 49% (IQR 36-58) and TR was graded as mild, moderate, or severe in nine, twelve and two patients, respectively. In 70% of cases, fRV-EDV was higher than LV-EDV. LVEF was decreased in 17 cases (74%). There was excellent correlation between echocardiography-derived fRV-FAC and CMR-derived fRVEF (rho = 0.812, p < 0.001). While echocardiography is a versatile tool in the complex geometry of the Ebstein heart, it has limitations. CMR offers a total overview and has the advantage of reliable volume assessment of both ventricles. Comprehensive evaluation of pediatric patients with EA may therefore require a synergistic implementation of echocardiography and CMR.

Dealing with Ebstein's anomaly.

Ebstein's anomaly is a complex congenital disorder of the tricuspid valve. Presentation in neonatal life and (early) childhood is common. Disease severity and clinical features vary widely and require a patient-tailored treatment. In this review, we describe the natural history of children and adolescents with Ebstein's anomaly, including symptoms and signs presenting at diagnosis. Current classification strategies of Ebstein's anomaly are discussed. We report on diagnostic methods for establishing the severity of disease that might enhance decision on the timing of surgical intervention. Furthermore, we describe different surgical options for severely ill neonates and multiple surgical interventions after infancy. Only with ample knowledge and understanding of the above, this complex and diverse group of patients can be correctly treated in order to improve not only duration, but also quality of life.

Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics.

BACKGROUND: Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (∆CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). METHODS: Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. RESULTS: In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ∆CFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant. CONCLUSIONS: Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.

Development of a digital Childhood Health Assessment Questionnaire for systematic monitoring of disease activity in daily practice.

OBJECTIVE: To develop a reliable and user-friendly digital Childhood HAQ (CHAQ) to facilitate systematic monitoring of disease activity at the outpatient clinic in juvenile idiopathic arthritis (JIA) patients. METHODS: The digital CHAQ was tested with patients who visited the outpatient paediatric rheumatology clinic of the Erasmus MC Sophia Children's Hospital. These patients completed in a randomized order the paper form and digital CHAQ while being observed. Validity was tested by comparing outcomes with the paper form CHAQ. User-friendliness was evaluated through a short questionnaire. RESULTS: A digital CHAQ was developed and revised several times according to our observations. Outcome is automatically calculated and can be printed. Fifty-one patients completed both the digital and paper form CHAQ. Correlation coefficient between both outcomes of the CHAQ Disability Index was 0.974. No statistically significantly differences in median outcome were found in visual analogue scale (VAS) pain (25.6 vs 25.9 mm) and VAS well-being (20.1 vs 19.5 mm). Although the mean time (5.06 min) to complete the digital CHAQ was significantly longer than the mean time (3.75 min) to complete the paper form, the majority of patients (75%) preferred the digital version. User-friendliness received maximum positive score. CONCLUSION: We developed a reliable and user-friendly digital CHAQ, which can be easily and systematically completed during routine clinic visits. Such digitalization of questionnaires can be applied in any field to make systematic monitoring of disease activity in daily practice possible.

[Diagnostic image. A girl with a distended and painful abdomen]. / Een meisje met een progressief bolle en pijnlijke buik.

A 17-month-old girl was admitted with dyspnoea and a distended and painful abdomen, due to infiltration of leukemic white blood cells in the thymus and organomegaly based on T-cell acute lymphatic leukemia.

Emerging clinical applications of strain imaging and three-dimensional echocardiography for the assessment of ventricular function in adult congenital heart disease.

Management of congenital heart disease (CHD) in adults (ACHD) remains an ongoing challenge due to the presence of residual hemodynamic lesions and development of ventricular dysfunction in a large number of patients. Echocardiographic imaging plays a central role in clinical decision-making and selection of patients who will benefit most from catheter interventions or cardiac surgery.. Recent advances in both strain imaging and three-dimensional (3D)-echocardiography have significantly contributed to a greater understanding of the complex pathophysiological mechanisms involved in CHD. The aim of this paper is to provide an overview of emerging clinical applications of speckle-tracking imaging and 3D-echocardiography in ACHD with focus on functional assessment, ventriculo-ventricular interdependency, mechanisms of electromechanical delay, and twist abnormalities in adults with tetralogy of Fallot (TOF), a systemic RV after atrial switch repair or in double discordance ventricles, and in those with a Fontan circulation.

Paediatric Ebstein's anomaly: how clinical presentation predicts mortality.

BACKGROUND: Forecasting the prognosis of a child when diagnosed with Ebstein's anomaly is difficult. We, therefore, studied which factors at the time of diagnosis are associated with death during childhood. METHODS: All consecutive patients (0-18 years) diagnosed with Ebstein's anomaly in the Netherlands between 1980 and 2014 were included. Survival curves were obtained using the Kaplan-Meier method. By using the Cox proportional hazard model, we analysed the factors (at diagnosis) that were associated with death. RESULTS: We included 176 patients. Thirty-one patients (18%) died before the age of 18 years. The 1-year survival was 84% and remained stable at 82% from 35 months after diagnosis and onwards. Modified Ross Heart Failure Class 4 at the time of diagnosis was the most important risk factor for death during childhood (HR 12.5, 95% CI 4.4 to 35.9). Furthermore, diagnosis in the neonatal period (HR 4.2, 95% CI 1.5 to 12.0), severe tricuspid valve regurgitation (HR 2.4, 95% CI 1.2 to 5.0), severe right ventricular outflow tract obstruction (HR 3.7, 95% CI 1.8 to 7.7) and a patent ductus arteriosus (HR 2.8, 95% CI 1.3 to 6.0) at the time of diagnosis were univariately associated with death. Multivariable analysis showed that presentation with Heart Failure Class 4 and a ventricular septal defect is the strongest predictor of death in childhood and adolescence. CONCLUSION: Patients with Ebstein's anomaly presenting with Heart Failure Class 4 and a ventricular septal defect have a high risk of death during childhood.

First-in-child use of the oral selective prostacyclin IP receptor agonist selexipag in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. Selexipag is a selective prostacyclin receptor agonist with vasodilatory, anti-proliferative, anti-inflammatory, and pro-angiogenic properties. However, no clinical data on its therapeutic use in children with PAH are currently available. Here, we report the case of a 12-year-old girl who presented in World Health Organization (WHO) functional class III and right ventricular (RV) failure with recurrent syncope, dizziness, and progressive fatigue for two years. Cardiac catheterization revealed severe precapillary PAH: mean right atrial pressure (RAP) = 10-13 mmHg, right ventricular end-diastolic pressure (RVEDP) = 13 mmHg, left ventricular end-diastolic pressure (LVEDP) = 7 mmHg, mean pulmonary arterial pressure (PAP) = 81 mmHg, and mean aorta ascendens pressure = 89 mmHg. The pulmonary vascular resistance index (PVRi) was 25.2 WU × m2. An oral combination therapy was started with a phosphodiesterase type 5 inhibitor (sildenafil 3 × 20 mg) and an endothelin-1 receptor antagonist (bosentan 2 × 62.5 mg). No significant clinical/hemodynamic improvement was seen after nine months of dual therapy, so that the patient was transferred to our institution. We agreed upon the off-label add-on use of oral selexipag. Within ten days, we up-titrated selexipag to a final (max. adult) dose of 1600 mcg twice daily. After six months, the patient had: (1) decrease in PVR index, pulmonary artery acceleration time, RAP, RVEDP, right atrial/RV size; (2) re-gain of vasoreactivity; and (3) improvement of cardiac index, 6-minute walking distance, functional class, body weight, and CAMPHOR score. Our encouraging results suggest the consideration of off-label use of oral selexipag in children with severe PAH, preferably in a protocol-driven prospective study.

Surgical outcome in pediatric patients with Ebstein's anomaly: A multicenter, long-term study.

OBJECTIVE: Surgical outcomes of pediatric patients with Ebstein's anomaly are often described as part of all-age-inclusive series. Our objective is to focus on patients treated surgically in childhood (0-18 y). We study the intended treatment (biventricular or 1.5 ventricle repair or univentricular palliation), freedom from unplanned reoperation and survival of this specific age group, in a nationwide study. DESIGN: Records of all Ebstein's anomaly patients born between 1980 and 2013 were reviewed. Demographic variables, intraoperative procedures and postoperative outcomes were analyzed. RESULTS: Sixty-three patients underwent 109 operations. Median follow-up after diagnosis was 121 months (range 0-216 months). Twenty-nine (46%) patients required surgery in the first year of life, including 21 who required neonatal surgery. The intended treatment was biventricular (n = 37, 59%) and 1.5 ventricle (n = 5, 8%) repair or univentricular (n = 21, 33%) palliation. The one-, five-, and 10-year freedom from unplanned reoperation was 89%, 79%, and 75% respectively. There were nine (14%) in hospital deaths (within 30 d after surgery). Causes of death were low cardiac output syndrome, cardiac failure, hypoxemia, pulmonary hypertension or an unknown cause. There were no late deaths. CONCLUSIONS: Surgery in childhood represents the worse spectrum of disease, biventricular repair is often not applied. Patients often face revision surgery. Mortality is limited to the immediate postsurgical period.

Regional ventricular performance and exercise training in children and young adults after repair of tetralogy of Fallot: randomized controlled pilot study.

BACKGROUND: Public-health guidelines recommend patients with congenital heart disease to exercise. Studies have shown that patients with congenital heart disease can improve physical exercise capacity. The effect of training on regional ventricular performance has hardly been studied. We performed a pilot study to assess whether an exercise training program would result in adverse changes of regional ventricular performance in patients with corrected tetralogy of Fallot. METHODS AND RESULTS: Multicenter prospective randomized controlled pilot study in patients with tetralogy of Fallot aged 10 to 25 years. A 12-week standardized aerobic dynamic exercise training program (3 one-hour sessions per week) was used. Pre- and post-training cardiopulmonary exercise tests, MRI, and echocardiography, including tissue-Doppler imaging, were performed. Patients were randomized to the exercise group (n=28) or control group (n=20). One patient in the exercise group dropped out. Change in tissue-Doppler imaging parameters was similar in the exercise group and control group (change in right ventricle free wall peak velocity E' exercise group, 0.8±2.6 cm/s; control group, 0.9±4.1; peak velocity A' exercise group, 0.4±2.4 m/s; control group 4.6±18.1 cm/s). CONCLUSIONS: This randomized controlled pilot study provides preliminary data suggesting that regional ventricular performance is well maintained during 3-month aerobic dynamic exercise training in children and young adults with repaired tetralogy of Fallot. This information might help patients adhere to current public-health guidelines. CLINICAL TRIAL REGISTRATION: URL: http//:www.trialregister.nl. Unique identifier: NTR2731.