Diagnosing ARVC in Pediatric Patients Applying the Revised Task Force Criteria: Importance of Imaging, 12-Lead ECG, and Genetics.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially lethal disease that is well described in adults. In pediatric patients, however, identification of patients at risk of adverse events of ARVC remains a challenge. We aimed to determine which criteria of the revised Task Force Criteria (rTFC), alone or combined, have an impact on diagnosis of ARVC when compared to disease-specific genetic mutations in pediatric patients ≤ 18 years. Between September 2010 and December 2013, 48 consecutive young patients ≤ 18 years of age (mean 14, range of 12.9-15.1 years) underwent contrast-enhanced magnetic resonance imaging (CMR), genetic testing, and comprehensive clinical work-up for ARVC criteria to test for clinically suspected ARVC. As specified by the rTFC, patients were grouped into four categories: "definite," "borderline," "possible," and "none" ARVC. Of the 48 patients, 12 were found to have gene mutations of either the desmoplakin (9/12) or plakophilin (3/12) locus. According to rTFC 12/48 patients were considered as "definite" ARVC (25%), while 10/12 (83.3%) had an ARVC-specific gene mutation. Of the remaining 36 patients, 6 (12.5%) were grouped as "borderline" ARVC, 7 (14.6%) as "possible" ARVC (including the remaining two genetic mutations), and 22 (45.8%) as "none" ARVC, respectively. Statistical analysis of ARVC criteria in patients diagnosed with "definite" ARVC revealed high prevalence of positive findings by imaging (CMR and echocardiography) and positive genetics. The positive predictive value to detect "definite" ARVC by genotyping was 83.3%, while the negative predictive value was 94%. Logistic regression analyses for different criteria combinations revealed that imaging modalities (echo and CMR combined) and abnormalities of 12-lead ECG were significant markers (p < 0.01). Positive results of endomyocardial biopsies or arrhythmia on ECG or Holter as defined by the rTFC were not significant in this analysis. The rTFC for ARVC should be used with caution in children and adolescents suspected for ARVC. 12-Lead ECG and imaging modalities (CMR and echo) were of major value, positive results should prompt genetic testing.

BNP and haematological parameters are markers of severity of Ebstein's anomaly: correlation with CMR and cardiopulmonary exercise testing.

AIMS: Ebstein's anomaly (EA) involves a displaced and dysplastic tricuspid valve resulting in an atrialized portion of the right ventricle and an enlargement of the functional right ventricle and right atrium. Biomarkers targeting heart failure such as brain natriuretic peptide (BNP) or haematological parameters [haemoglobin (Hb) and haematocrit (Hct)] are upregulated in states of pulmonary hypoperfusion. We hypothesized that decreased pulmonary perfusion dependent on the stage of right heart failure is a possible mechanism in EA, and that it can be correlated with cardiac magnetic resonance (CMR) parameters. The aim of this study was to investigate the relationship between BNP and haematological parameters with functional parameters from CMR and exercise testing in patients with EA. METHODS AND RESULTS: Twenty-five patients with non-corrected EA were studied prospectively (mean age 26 ± 14 years). BNP level was increased (74 ± 127 ng/L), and in 16% markedly above the heart failure cut-off level of 100 ng/L. Hb and Hct were increased above normal levels in 20 and 24% of patients, respectively. BNP and Hct/Hb correlated with CMR [total right/left (R/L)-Volume-Index, right atrium-end-diastolic volume index (EDVi), functional right ventricle (fRV)-EDVi, fRV-ejection fraction (EF), tricuspid regurgitation, pulmonary artery flow, and left ventricular EF] and exercise testing [workload/kg, oxygen uptake (VO2), ventilatory response to carbon dioxide production (VE/VCO2), oxygen (O2) pulse, and heart rate reserve]. The higher BNP and haematological parameters, the higher was the disease severity and the more limited was the physical exercise capacity. CONCLUSION: In this EA cohort, BNP levels and haematological parameters correlated well with functional data from CMR and exercise testing. The total R/L-Volume-Index and BNP, and to some extent hematological parameters, may be useful as prognostic markers in patients with EA.

The total right/left-volume index: a new and simplified cardiac magnetic resonance measure to evaluate the severity of Ebstein anomaly of the tricuspid valve: a comparison with heart failure markers from various modalities.

BACKGROUND: The classification of clinical severity of Ebstein anomaly still remains a challenge. The aim of this study was to focus on the interaction of the pathologically altered right heart with the anatomically-supposedly-normal left heart and to derive from cardiac magnetic resonance (CMR) a simple imaging measure for the clinical severity of Ebstein anomaly. METHODS AND RESULTS: Twenty-five patients at a mean age of 26±14 years with unrepaired Ebstein anomaly were examined in a prospective study. Disease severity was classified using CMR volumes and functional measurements in comparison with heart failure markers from clinical data, ECG, laboratory and cardiopulmonary exercise testing, and echocardiography. All examinations were completed within 24 hours. A total right/left-volume index was defined from end-diastolic volume measurements in CMR: total right/left-volume index=(RA+aRV+fRV)/(LA+LV). Mean total right/left-volume index was 2.6±1.7 (normal values: 1.1±0.1). This new total right/left-volume index correlated with almost all clinically used biomarkers of heart failure: brain natriuretic peptide (r=0.691; P=0.0003), QRS (r=0.432; P=0.039), peak oxygen consumption/kg (r=-0.479; P=0.024), ventilatory response to carbon dioxide production at anaerobic threshold (r=0.426; P=0.048), the severity of tricuspid regurgitation (r=0.692; P=0.009), tricuspid valve offset (r=0.583; P=0.004), and tricuspid annular plane systolic excursion (r=0.554; P=0.006). Previously described severity indices ([RA+aRV]/[fRV+LA+LV]) and fRV/LV end-diastolic volume corresponded only to some parameters. CONCLUSIONS: In patients with Ebstein anomaly, the easily acquired index of right-sided to left-sided heart volumes from CMR correlated well with established heart failure markers. Our data suggest that the total right/left-volume index should be used as a new and simplified CMR measure, allowing more accurate assessment of disease severity than previously described scoring systems.

Combination therapy of infantile hemangiomas with pulsed dye laser and Nd:YAG laser is effective and safe.

BACKGROUND: Infantile hemangiomas (IH) can cause severe complications such as obstruction, ulceration or heart failure. Therefore, in certain difficult-to-treat areas, or when there is no sign of involution, early and effective therapy is required. In rare instances, systemic treatments, like the beta-blocker propranolol and oral corticosteroids, can cause serious side effects. Effective and well-tolerated local treatment options are thus desirable as additive or alternative methods. PATIENTS AND METHODS: In this retrospective interdisciplinary study, 38 children with 77 IH were treated with pulsed dye laser (PDL) (595 nm) and Nd:YAG laser (1,064 nm). The treatment success and side effects were evaluated according to objective and subjective parameters, including hemangioma thickness measured by ultrasound and the parents' evaluation of treatment. RESULTS: All 77 treated IH responded to the therapy, of which 52.8 % healed after the end of treatment and 47.2 % had only minimum residual components. The success of treatment was assessed by the parents in 92.6 % as very good or good. Transient blistering occurred as the main side effect in 45.9 %. CONCLUSIONS: Combination therapy with PDL and Nd:YAG laser represents an effective local method for IH with minimal side effects.

Hyperkalemia complicating propranolol treatment of an infantile hemangioma.

Propranolol treatment was recently reported to be successful for the management of severe infantile hemangioma. Known adverse effects of propranolol treatment include transient bradycardia, hypotension, hypoglycemia, and bronchospasm (in patients with underlying spastic respiratory illnesses), which led to a general recommendation to gradually increase propranolol dosage and closely monitor patients' hemodynamics at the onset of therapy. To date, no serious or unexpected adverse effects that required specific intervention have been reported. In this report, we describe the case of a 17-week-old female preterm infant who presented with a large, ulcerated, cutaneous-subcutaneous hemangioma of the right lateral thoracic wall, which we treated successfully with propranolol. A few days into therapy, a potentially life-threatening adverse effect, severe hyperkalemia, was observed and required treatment with loop diuretics, fluids, and nebulized salbutamol to normalize her serum potassium levels. This therapy could be gradually tapered and finally discontinued only after several weeks of propranolol treatment. Our case report indicates that, at least during the initial phase of the propranolol treatment of infantile hemangioma, close monitoring of serum electrolytes, besides the monitoring of hemodynamics and blood glucose, is necessary.

Successful treatment of a large hemangioma with propranolol.

Hemangiomas are the most common vascular tumors in children. They occur in 8-12% of all infants and in 22% of premature infants (female: male = 3: 1). Hemangiomas are usually sporadic; their etiology is unknown. A premature female infant, born at 28 weeks of gestation, presented with a large hemangioma of the right thoracic wall. Within the first few weeks, the hemangioma showed rapid horizontal and vertical growth as well as ulceration, which led us to initiate systemic therapy. The effectiveness of propranolol (non-selective ss-blocker) in the management of severe cases of hemangioma has been shown in a recent series of cases. We began oral propranolol treatment, in close interdisciplinary cooperation. After a few days of therapy, the tumor had stopped expanding. After 18 weeks, there has been marked regression but the therapy is still being continued. We propose that propranolol may be an effective and relatively well tolerable alternative in the management of selected cases of severe hemangiomas in infancy, providing interdisciplinary cooperation between dermatologists and pediatricians is available.