Does obesity affect the non-invasive measurement of cardiac output performed by electrical cardiometry in children and adolescents?

Electrical cardiometry (EC) is a non-invasive and inexpensive method for hemodynamic assessment and monitoring. However, its feasibility for widespread clinical use, especially for the obese population, has yet to be determined. In this study, we evaluated the agreement and reliability of EC compared to transthoracic Doppler echocardiography (TTE) in normal, overweight, and obese children and adolescents. We measured stroke volume (SV) and cardiac output (CO) of 131 participants using EC and TTE simultaneously. We further divided these participants according to BMI percentiles for subanalyses: <85% normal weight (n = 41), between 85 and 95% overweight (n = 7), and >95% obese (n = 83). Due to small sample size of the overweight group, we combined overweight and obese groups (OW+OB) with no significant change in results (SV and CO) before and after combining groups. There were strong correlations between EC and TTE measurements of SV (r = 0.869 and r = 0.846; p < 0.0001) and CO (r = 0.831 and r = 0.815; p < 0.0001) in normal and OW+OB groups, respectively. Bias and percentage error for CO measurements were 0.240 and 29.7%, and 0.042 and 29.5% in the normal and OW+OB groups, respectively. Indexed values for SV were lower in the OW+OB group than in the normal weight group when measured by EC (p < 0.0001) but no differences were seen when measured by TTE (p = 0.096). In all weight groups, there were strong correlations and good agreement between EC and TTE. However, EC may underestimate hemodynamic measurements in obese participants due to fat tissue.

Small coronary artery fistulae in childhood: a 6-year experience of 31 cases in a tertiary paediatric cardiac centre.

BACKGROUND: This study describes the incidence and course of children with small coronary artery fistulae over a period of 6 years who presented at a paediatric tertiary-care centre. Materials and methods Age at diagnosis, mode of presentation, location (origin and drainage), and association with a cardiac defect were documented and analysed. All patients obtained an electrocardiogram, and older patients were further evaluated with an exercise treadmill test. RESULTS: A total of 31 patients were diagnosed with coronary artery fistula via transthoracic echocardiogram and comprised 0.43% of our entire patient group. Mean age was 6.14 years (standard deviation 5.4); 16 patients (52%) had associated cardiac defects. In the remaining 15 patients, the coronary artery fistula was discovered incidentally during diagnostic work-up for heart murmur or chest pain. Among all, 26 patients (84%) had left-sided and five patients (16%) had right-sided coronary artery fistulae. All right coronary artery fistula patients had associated cardiac defects; this was true for 42% of the patients with left coronary artery fistulae. None of the patients required any intervention due to the fistula, and spontaneous closure occurred in 12 patients (39%). CONCLUSION: Small coronary artery fistulae in children are frequently an incidental finding, and many will close spontaneously. Our data are supportive of a conservative, observant approach in asymptomatic patients with small coronary artery fistula in the paediatric population.

The Health Initiative Program for Kids (HIP Kids): effects of a 1-year multidisciplinary lifestyle intervention on adiposity and quality of life in obese children and adolescents--a longitudinal pilot intervention study.

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents. METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted of fifteen 90-minute educational sessions led by a dietitian, exercise specialist, and social worker. Anthropometric measures, body composition, and QoL (Pediatric Quality of Life Inventory 4.0), were assessed at baseline, 3 months, and 12 months. Laboratory values were measured at baseline and 12 months. The primary outcome measures were change in BMI and BMI z-score, secondary outcome measures included change in QoL and body composition. A paired sample t-test was used to assess within-group differences and 95% confidence intervals were reported for the mean differences. RESULTS: 42 obese children and adolescents (21 girls) completed the 1-year intervention (mean age 12.8 ± 3.14 years). Mean baseline BMI was 31.96 ± 5.94 kg/m(2) and BMI z-score was +2.19 ± 0.34. Baseline QoL (self-assessments and parental assessments) was impaired: mean baseline scores were 74.5 ± 16.5 and 63.7 ± 19.4 for physical functioning and 69.0 ± 14.9 and 64.0 ± 18.3 for emotional functioning, respectively. At 12 months, BMI z-score had decreased (-0.07 ± 0.11, 95% CI: -0.11 to -0.04). BMI (0.80 ± 1.57 kg/m(2), 95% CI 0.31 to 1.29) and fat-free mass (4.02 ± 6.27 kg, 95% CI 1.90 to 6.14) increased, but % body fat and waist circumference did not. Both the parent-reported physical (11.3 ± 19.2, 95% CI 4.7 to 17.9) and emotional (7.7 ± 15.7, 95% CI 2.3 to 13.0) functioning QoL scores and the children's self-reported physical (5.3 ± 17.1, 95% CI 0.5 to 11.1) and emotional (7.9 ± 14.3, 95% CI 3.2 to 12.7) functioning scores significantly improved. CONCLUSIONS: Following a 1-year intervention, the participants' BMI z-scores and QoL improved, while other adiposity-related measures of body composition remained unchanged. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000015622 .

Anterosuperior diverticula of the right ventricle: morphological spectrum and long-term outcome of a distinct cardiac anomaly.

Right-ventricular diverticula (RVD), although rare, have particular characteristics. Our study describes the morphology of anterosuperior diverticula of the right ventricle (RV) and patient outcome for this anomaly. Retrospective analysis was performed on all patients with anterosuperior RVD diagnosed in two tertiary referral centres. From January 1982 to December 2012, five patients were diagnosed with anterosuperior RVD (median 4 months). Four patients had perimembranous ventricular septal defects (VSDs) with no clinical symptoms related to RVD. Communication of the RVD with the RV was located either close to the VSD (two patients) or in the anterior free wall of the RV opposite the VSD (two patients). In the remaining patient, the diverticulum was connected with the left ventricle (LV) by a tunnel-like structure originating from the left-ventricular outflow tract; the RVD communicated with the RV by way of a restrictive opening. Four patients underwent surgical repair including patch closure of the VSD (one patient) and patch closure of the VSD through an incision of the RVD followed by plication of the diverticulum or closure of its communication with the RV (three patients). All patients remained asymptomatic during a median follow-up of 14.8 years. Anterosuperior RVD is a specific congenital cardiovascular anomaly frequently associated with additional congenital heart disease. There are significant variations in how the RVD communicates with the RV with each requiring a different surgical repair strategy. According to the experience in our small cohort, the long-term prognosis of patients with anterosuperior RVD appears excellent after surgical correction of associated congenital heart disease.

Are the children and adolescents with congenital heart disease living in Southwestern Ontario really overweight and obese?

OBJECTIVE: To assess the prevalence of overweight and obesity in children with congenital heart disease and compare them with age-matched healthy children in Southwestern Ontario, Canada. METHODS: We compared the Center of Disease Control weight and body mass index z-scores of 1080 children, aged 2 to 18 years, who presented to our paediatric cardiology outpatient clinic from 2008 to 2010 for congenital heart disease with 1083 healthy controls. RESULTS: In all, 18.2% of the children with congenital heart disease and 20.8% of healthy children were identified to be either overweight or obese. Overall, the weight category distribution had been similar between the congenital heart disease and healthy control groups, as well as between the congenital heart disease subgroups. There was no difference in normal weight and overweight/obese categories between children with congenital heart disease and healthy children. The underweight category, however, showed a significantly higher prevalence in congenital heart disease compared with healthy children (6.8 and 4.5%, respectively, p = 0.03). CONCLUSION: The prevalence of overweight/obesity did not differ in children with congenital heart disease compared with age-matched healthy children; however, it is still high (18.2%). Obesity may represent an additional risk factor for the long-term cardiovascular health of congenital heart disease patients aside from the underlying heart defect.

Non-invasive measurement of cardiac output in obese children and adolescents: comparison of electrical cardiometry and transthoracic Doppler echocardiography.

The objective of this study was to evaluate the reliability and accuracy of electrical cardiometry (EC) for the noninvasive determination of cardiac output (CO) in obese children and adolescents. We compared these results with those obtained by transthoracic echocardiography. Sixty-four participants underwent simultaneous measurement of CO. Cardiac output was measured by EC using the ICON(®) device. Simultaneously CO was determined by using transthoracic Doppler echocardiography from parasternal long-axis and apical view. The median age was 12.52 years (range 7.9-17.6 years) and 36 (56 %) were female. A strongly significant correlation was found between the COEC and COEcho measurements (p < 0.0001, r = 0.91). Significant correlations were also found between CO and age (r = 0.37, p = 0.002), weight (r = 0.57, p < 0.0001), height (0.60, p < 0.0001) and BMI (r = 0.42, p = 0.001). The mean difference between the two methods (COEC - COEcho) was 0.015 l min(-1). According to the Bland and Altman method, the upper and lower limits of agreement, defined as mean difference ±2 SD, were +1.21 and -0.91 l min(-1), respectively. Compared to the transthoracic Doppler echocardiography, Electrical Cardiometry provides accurate and reliable CO measurements in obese children and adolescents.

Cardiac footprints of a neonatal vein of Galen malformation.

Vein of Galen arterio-venous malformation is a rare congenital anomaly, which presents in the neonatal period. High output heart failure in the absence of an underlying structural heart defect points towards the condition and is an important contributing factor for morbidity and mortality. We describe a case of a term newborn who presented with respiratory distress and cardiomegaly. The characteristic echocardiographic findings of high output cardiac failure were found and eventually led to the diagnosis of an underlying vein of Galen arterio-venous malformation. The relevant literature is discussed.

Bleeding diathesis in Noonan syndrome: is acquired von Willebrand syndrome the clue?

INTRODUCTION: Noonan syndrome (NS) is characterized by dysmorphic facies, short stature and congenital heart defects. Various haemostatic disorders have been described in NS patients, but not all were related to bleeding, which itself is present in up to 65%. Several subgroups of NS - especially those with PTPN11 mutation - are associated with pulmonary stenosis. As it is known that some heart defects are prone to a shear stress related destruction of the von Willebrand factor as an important haemostatic component, we aimed to find out, whether the pulmonary stenosis could be responsible for such a mechanism in NS patients. PATIENTS, METHODS AND RESULTS: We investigated the haemostatic system in 15 children with genetically proven NS (14 with PTPN11, one with SOS1 mutation). Platelet count, basic coagulation parameters, fibrinogen and antithrombin were normal in all patients, none had a relevant reduction of coagulation factor activities. Five patients had pulmonary valve stenosis with systolic gradients>60 mmHg. In three of them a deficiency of the high molecular weight multimers and a pathologic collagen-binding capacity were detected, suggesting acquired von Willebrand syndrome. Nine of our patients indicated a relevant bleeding diathesis and complained of easy bruising, three reported spontaneous gum bleeding. IN CONCLUSION: the destruction of the von Willebrand factor could explain the bleeding in some of the NS patients with pulmonary valve stenosis. Our finding is of clinical relevance since most of these patients require either interventional cardiac catheterization or open heart surgery which may be complicated by the haemorrhagic tendency.

N-terminal pro-brain natriuretic peptide level as a screening tool for cardiac involvement in paediatric diseases of extracardiac origin.

BACKGROUND: Serum concentrations of N-terminal natriuretic pro-brain natriuretic peptide (NT-proBNP) correlate well with the severity of cardiac disease in children and adults. There are also paediatric illnesses of extracardiac origin that may cause deterioration of the cardiac function in some patients (pts). A high NP level can signify a concomitant cardiac involvement in respiratory distress, or secondary to a systemic disease. OBJECTIVE: To assess the potential of NT-proBNP as a screening tool for cardiac involvement in paediatric diseases of extracardiac origin. METHODS: A literature search was performed in PubMed for the relevant studies with the subject brain natriuretic peptide (BNP) and NT-proBNP from 1995 to 2010 with stress on characteristics of the natriuretic peptides, paediatric reference values and systemic paediatric diseases with potential influence on the myocardial performance. The main focus has been NT-proBNP being the most stable NP and correlating well with BNP. RESULTS: Most studies agree that a high NT-proBNP level indicates cardiac dysfunction in different systemic diseases such as thalassemia and cystic fibrosis or in pts after chemotherapy. In special clinical scenarios as sepsis or respiratory distress, NT-proBNP helps to narrow down the differential diagnosis or can be used for risk stratification. CONCLUSION: NT-proBNP can serve as a screening tool in various primarily non-cardiac paediatric diseases. Together with the clinical picture, a high level suggests further assessment by a paediatric cardiologist.

Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (ToF), the most frequent cyanotic congenital heart disease, is associated with a wide range of intra- and extracardiac phenotypes. In order to get further insight into genotype-phenotype correlation, a large cohort of 230 unselected patients with ToF was comprehensively investigated. METHODS AND RESULTS: 230 patients with ToF were studied by karyotyping, comprehensive 22q11.2 deletion testing and sequencing of TBX1, NKX2.5 and JAG1, as well as molecular karyotyping in selected patients. Pathogenic genetic aberrations were found in 42 patients (18%), with 22q11.2 deletion as the most common diagnosis (7.4%), followed by trisomy 21 (5.2%) and other chromosomal aberrations or submicroscopic copy number changes (3%). Mutations in JAG1 were detected in three patients with Alagille syndrome (1.3%), while NKX2.5 mutations were seen in two patients with non-syndromic ToF (0.9%). One patient showed a recurrent polyalanine stretch elongation within TBX1 which represents a true mutation resulting in loss of transcriptional activity due to cytoplasmatic protein aggregation. CONCLUSION: This study shows that 22q11.2 deletion represents the most common known cause of ToF, and that the associated cardiac phenotype is distinct for obstruction of the proximal pulmonary artery, hypoplastic central pulmonary arteries and subclavian artery anomalies. Atrioventricular septal defect associated with ToF is very suggestive of trisomy 21 and almost excludes 22q11.2 deletion. We report a further patient with a recurrent polyalanine stretch elongation within TBX1 and for the first time link TBX1 cytoplasmatic protein aggregation to congenital heart defects.

Thrombosis of an extracardiac Fontan tunnel: combined treatment of thrombolysis and stenting.

Obstruction of the so-called Fontan tunnel represents a life-threatening complication and requires immediate intervention. We describe the successful use of prolonged thrombolysis with rt-PA, allowing stent placement in an extracardiac tunnel in a 7-year-old boy.

Aminoterminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels for Monitoring Interventions in Paediatric Cardiac Patients with Stenotic Lesions.

Background. Serum concentration of NT-proBNP correlates well with the severity of cardiac disease in adults. Few studies have been performed on the applicability of NT-proBNP for monitoring children with congenital heart disease. Objective. To assess the potential of NT-proBNP for monitoring the success of interventions in children with stenotic cardiac lesions. Methods. NT-proBNP was measured in 42 children aged 1 day to 17 years (y) before and 6 to 12 weeks after surgical or interventional correction of obstructive lesions of the heart. Comparison is made with the clinical status and echocardiographic data of the child. Results. NT-proBNP levels (median 280, range 10-263,000 pg/mL) were above the reference value in all but 6 patients (pts) prior to the intervention. Higher levels were found in more compromised patients. The 35 children with clinical improvement after the procedure showed a decline of their NT-proBNP level in all but 4 patients, whose levels remained unchanged. Five patients with unchanged gradients despite a therapeutic intervention also demonstrated unchanged NT-proBNP levels after the intervention. Thus, the success rate of the procedure correlated well to clinical and echocardiographic findings. Conclusion. NT-proBNP can be used to assess the efficiency of an intervention.

Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays.

BACKGROUND: Using array techniques, it was recently shown that about 10% of patients with mental retardation of unknown origin harbour cryptic chromosomal aneusomies. However, data analysis is currently not standardised and little is known about its sensitivity and specificity. METHODS: We have developed an electronic data analysis tool for gene-mapping SNP arrays, a software tool that we call Copy Number Variation Finder (CNVF). Using CNVF, we analysed 104 unselected patients with mental retardation of unknown origin with a genechip mapping 100K SNP array and established an optimised set of analysis parameters. RESULTS: We detected deletions as small as 20 kb when covered by at least three single-nucleotide polymorphisms (SNPs) and duplications as small as 150 kb when covered by at least six SNPs, with only one false-positive signal in six patients. In 9.1% of patients, we detected apparently disease-causing or de novo aberrations ranging in size from 0.4 to 14 Mb. Morphological anomalies in patients with de novo aberrations were equal to that of unselected patients when measured with de Vries score. CONCLUSION: Our standardised CNVF data analysis tool is easy to use and has high sensitivity and specificity. As some genomic regions are covered more densely than others, the genome-wide resolution of the 100K array is about 400-500 kb for deletions and 900-1000 kb for duplications. The detection rate of about 10% of de novo aberrations is independent of selection of patients for particular features. The incidental finding in two patients of heterozygosity for the 250 kb recurrent deletion at the NPH1 locus, associated with autosomal recessive juvenile nephronophthisis, which was inherited from a healthy parent, highlights the fact that inherited aberrations might be disease-related even though not causal for mental retardation.

Prophylaxis of thromboembolic complications after the Fontan operation (total cavopulmonary anastomosis).

OBJECTIVES: Thrombotic events have been reported as a major cause of morbidity after the Fontan procedure. There is no consensus concerning the postoperative mode and duration of anticoagulation prophylaxis. In a retrospective study, we evaluated the results of a prophylactic regimen on the basis of the surgical technique, potentially predisposing risk factors, and specific sequelae. METHODS: We evaluated 142 surviving patients after total cavopulmonary anastomosis (mean follow-up was 91.1 +/- 43.9 months). Prophylactic antithrombotic treatment was initiated in 86 patients with partial prosthetic venous pathway with acetylsalicylic acid; 45 patients with complete autologous tissue venous pathway or partial prosthetic venous pathway received no anticoagulation, and 11 patients received warfarin sodium (Coumadin). During long-term follow-up, 22 patients (12 after acetylsalicylic acid medication) crossed over to warfarin. RESULTS: Thrombotic events occurred in 10 patients (7%), with systemic venous thrombus formation in 8 (5.6%), stroke in 2 (1.4%), and a peak incidence during the first postoperative year. Eight of 10 patients were receiving heparin therapy mainly for prolonged postoperative immobilization. During follow-up, none of the 74 patients receiving acetylsalicylic acid and 1 of 40 patients without medication presented with thrombus formation. Under warfarin medication, 1 of 28 patients had an asymptomatic thrombus. Expected freedom from a thromboembolic event was 92% at 5 years and 79% at 10 years. There was no association with coagulation factor abnormalities. Protein-losing enteropathy was present in 4 of 10 patients. CONCLUSION: A prophylactic anticoagulation strategy that considers the surgical technique and potential predisposing circumstances proved effective in the prevention of late thrombotic complications after total cavopulmonary anastomosis. There is no need for routine anticoagulation during long-term follow-up after Fontan-type surgery in pediatric patients.

Laterality of the aortic arch and anomalies of the subclavian artery-reliable indicators for 22q11.2 deletion syndromes?

UNLABELLED: A variety of cardiac defects, encompassing truncus arteriosus, tetralogy of Fallot, pulmonary atresia with ventricular septal defect and interrupted aortic arch, are generally summarised as conotruncal malformations. Patients with these cardiac defects were frequently found to have a common microdeletion on chromosome 22, the so-called monosomy 22q11.2. The aim of our study was to determine whether the laterality of the aortic arch or the presence of subclavian artery anomalies (SAA) represent markers for monosomy 22q11.2 in these patients. 170 patients with these cardiac anomalies were recruited at presentation in the paediatric cardiology units of two tertiary referral centres from 1994 until 2003. Of the 170 children and young adults, 33 had interrupted aortic arch, 35 tetralogy of Fallot, 31 truncus arteriosus communis and 71 pulmonary atresia with ventricular septal defect. All were screened for monosomy 22q11.2 and the results were correlated with the laterality of the aortic arch and the presence of SAA contralateral to the aortic arch (aberrant origin from the descending aorta, isolation, distal ductal origin from the pulmonary artery and cervical origin of the right subclavian artery). Monosomy 22q11.2 was present in 59/170 patients (35%). A left aortic arch (LAA) was found in 118 (69%), a right aortic arch (RAA) in 52 (31%) patients. Almost 50% of the patients with RAA (46%), but only 30% of the patients with LAA had monosomy 22q11.2 ( P=0.054). A total of 47 patients (28%) had an anomaly of the subclavian artery, 81% of whom had monosomy 22q11.2. This deletion was found in decreasing percentage in patients with LAA+SAA (85%) >RAA+SAA (75%) >RAA without SAA (28%) >LAA without SAA (13%). CONCLUSION: In patients with conotruncal malformations, anomalies of the subclavian arteries are the most important anatomical marker for the presence of monosomy 22q11.2, independent of the laterality of the aortic arch. Therefore, we recommend cytogenetic testing for this microdeletion in all patients with subclavian artery anomalies and conotruncal malformations.

Genotype-phenotype correlations in Noonan syndrome.

OBJECTIVE: To study genotype-phenotype correlations in a cohort of clinically well-characterized pediatric patients with Noonan syndrome (NS). Study design Fifty-seven unrelated patients with the clinical diagnosis of NS ascertained according to standardized inclusion criteria were prospectively enrolled. Mutational analysis was performed by direct sequencing of the entire coding sequence of the PTPN11 gene. RESULTS: Sixteen known and 3 novel PTPN11 mutations could be detected in 60% of index patients, in all familial and in 52% of the sporadic cases. Presence of pulmonic stenosis, short stature, easy bruising, and thorax deformities was significantly associated with a PTPN11 mutation, whereas cardiomyopathy was more common in patients without a mutation. On average, PTPN11 mutation-negative probands fulfilled fewer clinical criteria of NS, but more than half-among them all with cardiomyopathy-had the full clinical picture of NS indistinguishable from typical cases with PTPN11 mutation. CONCLUSIONS: The phenotype of NS due to PTPN11 mutations is clinically unambiguous in the majority of patients and represents a highly penetrant trait. Individuals with the clinical diagnosis of NS but without a PTPN11 mutation presumably represent a heterogeneous group in which patients with cardiomyopathy appear to constitute an interesting subgroup for future research.