Low agreement between cardiologists diagnosing left ventricular hypertrophy in children with end-stage renal disease.

BACKGROUND: Monitoring of the appearance of left ventricular hypertrophy (LVH) by echocardiography is currently recommended for in the management of children with End-stage renal disease (ESRD). In order to investigate the validity of this method in ESRD children, we assessed the intra- and inter-observer reproducibility of the diagnosis LVH. METHODS: Echocardiographic measurements in 92 children (0-18 years) with ESRD, made by original analysists, were reassessed offline, twice, by 3 independent observers. Smallest detectable changes (SDC) were calculated for continuous measurements of diastolic interventricular septum (IVSd), Left ventricle posterior wall thickness (LVPWd), Left ventricle end-diastolic diameter (LVEDd), and Left ventricle mass index (LVMI). Cohen's kappa was calculated to assess the reproducibility of LVH defined in two different ways. LVH(WT) was defined as Z-value of IVSd and/or LVPWd>2 and LVH(MI) was defined as LVMI> 103 g/m² for boys and >84 g/m² for girls. RESULTS: The intra-observer SDCs ranged from 1.6 to 1.7 mm, 2.0 to 2.6 mm and 17.7 to 30.5 g/m² for IVSd, LVPWd and LVMI, respectively. The inter-observer SDCs were 2.6 mm, 2.9 mm and 24.6 g/m² for IVSd, LVPWd and LVMI, respectively. Depending on the observer, the prevalence of LVH(WT) and LVH(MI) ranged from 2 to 30% and from 8 to 25%, respectively. Kappas ranged from 0.4 to 1.0 and from 0.1 to 0.5, for intra-and inter- observer reproducibility, respectively. CONCLUSIONS: Changes in diastolic wall thickness of less than 1.6 mm or LVMI less than 17.7 g/m² cannot be distinguished from measurement error in individual children, even when measured by the same observer. This limits the use of echocardiography to detect changes in wall thickness in children with ESRD in routine practice.

A multicentric study of disease-related stress, and perceived vulnerability, in parents of children with congenital cardiac disease.

Parents of children with congenitally malformed hearts can suffer from stress as a result of the medical condition of their child. In this cross-sectional study, we aimed to describe levels of parental stress, and perceived vulnerability, in parents of children who underwent major cardiac surgery, by using both generic and disease-related measures for assessment. We included parents of children who underwent open-heart surgery over the period 2002 through 2007 in the Center for congenital Anomalies Heart Amsterdam/Leiden, abbreviated to provide the acronym CAHAL. In total, we assessed 114 mothers and 82 fathers of 131 children, using the Pediatric Inventory for Parents, short form, General Health Questionnaire, Parental Stress Index-Short Form, State-Trait Anxiety Index and the Child Vulnerability Scale. Compared to the reference groups of the instruments used, parents of children with congenitally malformed hearts did not report higher generic nor disease-related stress scores, and parenting levels of stress were also comparable to reference groups. State anxiety levels, however, were higher in mothers of children with congenitally malformed hearts. Both fathers and mothers reported significantly higher rates of perceived vulnerability than did parents of healthy children. Risk factors for increased anxiety and perceived vulnerability were found in the number of surgical procedures, the time past since the last procedure, and ethnicity. Severity of the lesion did not influence parental levels of stress, but parents of children with hypoplastic left heart syndrome did report higher levels of stress than other parents. Psychosocial screening of parents of children with congenitally malformed hearts is important in order to provide appropriate counselling to those parents most in need.

Validation and reproducibility of aortic pulse wave velocity as assessed with velocity-encoded MRI.

PURPOSE: To validate magnetic resonance imaging (MRI) assessment of aortic pulse wave velocity (PWV(MRI)) with PWV determined from invasive intra-aortic pressure measurements (PWV(INV)) and to test the reproducibility of the measurement by MRI. MATERIALS AND METHODS: PWV(MRI) was compared with PWV(INV) in 18 nonconsecutive patients scheduled for catheterization for suspected coronary artery disease. Reproducibility of PWV(MRI) was tested in 10 healthy volunteers who underwent repeated measurement of PWV(MRI) at a single occasion. Velocity-encoded MRI was performed on all participants to assess PWV(MRI) in the total aorta (Ao(total)), the proximal aorta (Ao(prox)), and the distal aorta (Ao(dist)). RESULTS: The results are expressed as mean +/- SD, Pearson correlation coefficient (PCC), and intraclass correlation (ICC). Good agreement between PWV(MRI) and PWV(INV) was found for Ao(total) (6.5 +/- 1.1 m/s vs. 6.1 +/- 0.8 m/s; PCC = 0.53), Ao(prox) (6.5 +/- 1.3 m/s vs. 6.2 +/- 1.1 m/s; PCC = 0.69), and for Ao(dist) (6.9 +/- 1.1 m/s vs. 6.1 +/- 1.0 m/s; PCC = 0.71). Reproducibility of PWV(MRI) was high for Ao(total) (4.3 +/- 0.5 m/s vs. 4.6 +/- 0.7 m/s; ICC = 0.90, P < 0.01), Ao(prox) (4.3 +/- 0.9 m/s vs. 4.7 +/- 1.0 m/s; ICC = 0.87, P < 0.01), and Ao(dist) (4.3 +/- 0.6 m/s vs. 4.4 +/- 0.8 m/s; ICC = 0.92, P < 0.01). CONCLUSION: MRI assessment of aortic pulse wave velocity shows good agreement with invasive pressure measurements and can be determined with high reproducibility.

The effect of bosentan in patients with a failing Fontan circulation.

OBJECTIVES: To investigate the effect of bosentan in patients with a failing Fontan circulation. DESIGN: A multicentric open label, non-controlled study. SETTING: 5 tertiary care centres for congenital cardiology. PATIENTS: We included 10 patients with a failing Fontan circulation. Their median age at inclusion was 12.12 years, with a range from 4.41 to 33,41 years. The median interval between the Fontan operation and inclusion was 7.84 years, with a range from 1.96 to 12,18 years. Participants received half the usual dose of bosentan for 4 weeks, and then the full dose for a further 12 weeks. MAIN MEASURES OF OUTCOMES: We assessed saturations of oxygen at rest and during exercise, using a 6 minutes walk test, at baseline, and during and after 16 weeks of treatment. At each visit, we assessed blood chemistry and hepatic function, and asked the patients to complete a questionnaire concerning quality of life. All medical events and possible side effects were recorded. RESULTS: Of the cohort, 1 patient withdrew. The changes in saturations of oxygen, exercise performance, and scores for the questionnaire did not reach statistical significance for the whole group. We noted, nonetheless, that saturations of oxygen and/or exercise capacity improved in 5 of the patients. This was further confirmed when those patients deteriorated again when the drug was discontinued. CONCLUSIONS: Our study failed to show significant improvement after 3 months of treatment with bosentan in a small group of patients with failing Fontan circulations. Some individuals, nonetheless, did improve. When planning larger trials, it would be better to identify those patients who might potentially benefit from the treatment prior to commencing the trial.

Johanson-Blizzard syndrome caused by identical UBR1 mutations in two unrelated girls, one with a cardiomyopathy.

We report on two apparently unrelated girls with Johanson-Blizzard syndrome (JBS), in both children caused by a homozygous IVS26+5G>A mutation in the UBR1 gene. In both cases the parents are consanguineous and more sibs are affected. The somewhat mild phenotype (with no or slight mental retardation) in these two JBS families might be explained by residual UBR1 activity. One case has a dilated cardiomyopathy, a symptom only rarely reported in JBS, but of important clinical significance.

Aortic elasticity and left ventricular function after arterial switch operation: MR imaging--initial experience.

PURPOSE: To prospectively assess aortic dimensions, aortic elasticity, aortic valve competence, and left ventricular (LV) systolic function in patients after the arterial switch operation (ASO) by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Informed consent was obtained from all participants for this local ethics committee-approved study. Fifteen patients (11 male patients, four female patients; mean age, 16 years +/- 4 [standard deviation]; imaging performed 16.1 years after surgery +/- 3.7) and 15 age- and sex-matched control subjects (11 male subjects, four female subjects; mean age, 16 years +/- 4) were evaluated. Velocity-encoded MR imaging was used to assess aortic pulse wave velocity (PWV), and a balanced turbo-field-echo sequence was used to assess aortic root distensibility. Standard velocity-encoded and multisection-multiphase imaging sequences were used to assess aortic valve function, systolic LV function, and LV mass. The two-tailed Mann-Whitney U test and Spearman rank correlation coefficient were used for statistical analysis. RESULTS: Patients treated with the ASO showed aortic root dilatation at three predefined levels (mean difference, 5.7-9.4 mm; P < or = .007) and reduced aortic elasticity (PWV of aortic arch, 5.1 m/sec +/- 1.2 vs 3.9 m/sec +/- 0.7, P = .004; aortic root distensibility, [2.2 x 10(-3)] x mm Hg(-1) +/- 1.8 vs [4.9 x 10(-3)] x mm Hg(-1) +/- 2.9, P < .01) compared with control subjects. Minor degrees of aortic regurgitation (AR) were present (AR fraction, 5% +/- 3 in patients vs 1% +/- 1 in control subjects; P < .001). Patients had impaired systolic LV function (LV ejection fraction [LVEF], 51% +/- 6 vs 58% +/- 5 in control subjects; P = .003), in addition to enlarged LV dimensions (end-diastolic volume [EDV], 112 mL/m(2) +/- 13 vs 95 mL/m(2) +/- 16, P = .007; end-systolic volume [ESV], 54 mL/m(2) +/- 11 vs 39 mL/m(2) +/- 7, P < .001). Degree of AR predicted decreased LVEF (r = 0.41, P = .026) and was correlated with increased LV dimensions (LV EDV: r = 0.48, P = .008; LV ESV: r = 0.67, P < .001). CONCLUSION: Aortic root dilatation and reduced elasticity of the proximal aorta are frequently observed in patients who have undergone the ASO, in addition to minor degrees of AR, reduced LV systolic function, and increased LV dimensions.

Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects.

BACKGROUND: With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism. AIM OF THE STUDY: To investigate associations between the maternal dietary intake of fats, riboflavin and nicotinamide, and CHD risk in the offspring. METHODS: A case-control family study was conducted in 276 mothers of a child with a CHD comprising of 190 outflow tract defects (OTD) and 86 non-outflow tract defects (non-OTD) and 324 control mothers of a non-malformed child. Mothers filled out general and food frequency questionnaires at 16 months after the index-pregnancy, as a proxy of the habitual food intake in the preconception period. Nutrient intakes (medians) were compared between cases and controls by Mann-Whitney U test. Odds ratios (OR) for the association between CHDs and nutrient intakes were estimated in a logistic regression model. RESULTS: Case mothers, in particular mothers of a child with OTD, had higher dietary intakes of saturated fat, 30.9 vs. 29.8 g/d; P < 0.05. Dietary intakes of riboflavin and nicotinamide were lower in mothers of a child with an OTD than in controls (1.32 vs. 1.41 mg/d; P < 0.05 and 14.6 vs. 15.1 mg/d; P < 0.05, respectively). Energy, unsaturated fat, cholesterol and folate intakes were comparable between the groups. Low dietary intakes of both riboflavin (<1.20 mg/d) and nicotinamide (<13.5 mg/d) increased more than two-fold the risk of a child with an OTD, especially in mothers who did not use vitamin supplements in the periconceptional period (OR 2.4, 95%CI 1.4-4.0). Increasing intakes of nicotinamide (OR 0.8, 95%CI 0.7-1.001, per unit standard deviation increase) decreased CHD risk independent of dietary folate intake. CONCLUSIONS: A maternal diet high in saturated fats and low in riboflavin and nicotinamide seems to contribute to CHD risk, in particular OTDs.

Maternal global methylation status and risk of congenital heart diseases.

OBJECTIVE: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring. METHODS: As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use. RESULTS: Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls. CONCLUSION: Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome.

Determinants of right ventricular outflow tract conduit longevity: a multinational analysis.

OBJECTIVE: The need for conduit replacement in the growing child remains a major problem after right ventricular outflow tract reconstruction. We compared two diverse surgical centers with considerable practice variation in Europe and the United States to identify modifiable risk factors that can increase conduit longevity. DESIGN: Retrospective analysis of 194 patients (56 Europe, 138 United States) who underwent primary right ventricular to pulmonary artery conduit placement between January 1987 and March 2003. PATIENTS: Diagnoses included tetralogy of Fallot with pulmonary atresia, truncus arteriosus, transposition of the great arteries with ventricular septal defect and pulmonary stenosis, and double-outlet right ventricle. RESULTS: Median age was 7.3 months (range 2 days-29.9 years). Types of conduits included aortic homografts (n = 111), pulmonary homografts (n = 48), Contegra conduits (Medtronic, Inc, Minneapolis, MN) (n = 23), and synthetic conduits (n = 12). Freedom from conduit failure at 5 years was 50% (58% Europe, 48% United States, P = NS). On multivariate analysis, smaller conduit diameter (hazard ratio [HR] 1.15, P < .001) and conduits other than pulmonary homografts (synthetic conduits [HR 3.17, P = .01], Contegra conduits [HR 2.80, P = .02], aortic homografts [HR 1.56, P = .05]) predicted shorter time to conduit failure. In addition, time to failure was longer for patients undergoing transcatheter intervention. Different surgical techniques in conduit preparation and insertion did not influence conduit longevity. CONCLUSIONS: Analysis of the two diverse surgical centers showed that to increase conduit longevity, one should choose the largest possible conduit, use a pulmonary homograft, and consider children whose conduits develop obstruction as candidates for transcatheter intervention.

MR imaging of right ventricular function after the Ross procedure for aortic valve replacement: initial experience.

PURPOSE: To prospectively assess right ventricular (RV) function after the Ross procedure by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: The local ethics committee approved the study and informed consent was obtained from all participants prior to enrollment in the study. Seventeen patients (15 male, two female; mean age +/- standard deviation, 19 years +/- 3.9; imaging performed 8.3 years after surgery +/- 3.2) and 17 matched controls (15 male, two female; mean age +/- standard deviation, 20 years +/- 3.9) were studied by using MR imaging. Standard velocity-encoded and multisection multiphase imaging sequences were used to assess homograft valve function, systolic and diastolic RV function, and RV mass. The two-tailed Mann-Whitney U test and the Spearman rank correlation coefficient were used for statistical analysis. RESULTS: Minor degrees of homograft stenosis (peak flow velocity between 1.5 and 3.0 m/sec across the homograft valve) were found in 12 of 17 patients but not in controls (P < .001). A larger RV mass was present in Ross patients than in controls (17.0 g/m(2) +/- 4.8 vs 10.9 g/m(2) +/- 5.6, P = .004). In addition, impaired diastolic RV function was found, as shown by a decreased mean tricuspid valve early filling phase-atrial contraction phase (E/A) peak flow velocity ratio (1.56 +/- 0.75 vs 2.05 +/- 0.58, P = .03). Peak flow velocity across the homograft valve correlated with RV mass (r = 0.38, P = .03) and tricuspid valve E/A peak flow velocity ratio (r = 0.39, P = .02). RV systolic function was normal in Ross patients (mean RV ejection fraction, 52% +/- 8 vs 51% +/- 5; P = .74). CONCLUSION: RV hypertrophy and RV diastolic dysfunction are frequently observed in patients after the Ross procedure, even in the absence of overt homograft stenosis. RV systolic function is still preserved.

Transcatheter closure of perimembranous ventricular septal defects in infants and children using the Amplatzer perimembranous ventricular septal defect occluder.

There are very few published reports of the transcatheter closure of perimembranous ventricular septal defects (PMVSDs) using the Amplatzer PMVSD occluder with encouraging initial results. This report presents initial and 1-year results from 54 patients with PMVSDs who underwent transcatheter closure at 5 different institutions with the Amplatzer PMVSD occluder. Sixty-five patients with PMVSDs were enrolled at 5 European centers. Eleven of the 65 patients did not fulfill the patient selection criteria at the initial echocardiographic evaluation or at cardiac catheterization. As a result, a total of 54 patients underwent attempted transcatheter closure using the Amplatzer PMVSD occluder. The median age of the patients was 5.1+/-3.6 years (range 0.3 to 13), and the median weight 18.5+/-10.3 kg (range 5 to 45). Devices were permanently implanted in 49 of 54 patients. Complete occlusion of the communication at 1-year follow-up was observed in 46 of 49 patients (94%). Main early procedural complications included (1) device embolization (2 patients), (2) severe bradycardia with hemodynamic compromise (2 patients), and (3) Mobitz II (2:1) heart block (1 patient). Late procedural complications included complete heart block (1 patient). No other complications were observed during follow-up. In conclusion, the Amplatzer PMVSD occluder is promising device that can be used for transcatheter closure in selected patients with PMVSDs. Further studies and long-term follow-up are required before this technique enters routine clinical practice.

Reduced aortic elasticity and dilatation are associated with aortic regurgitation and left ventricular hypertrophy in nonstenotic bicuspid aortic valve patients.

OBJECTIVES: This study sought to assess elasticity and dimensions of the aorta and their impact on aortic valve competence and left ventricular (LV) function in patients with a nonstenotic bicuspid aortic valve (BAV). BACKGROUND: Intrinsic pathology of the aortic wall is a possible explanation for reduced aortic elasticity and aortic dilatation in patients with BAVs, even in the absence of a stenotic aortic valve. The relationship between aortic wall elasticity, aortic dimensions, aortic valve competence, and LV function in patients with BAVs has not previously been studied with magnetic resonance imaging. METHODS: Magnetic resonance imaging was performed in 20 patients with nonstenotic BAVs (mean +/- SD, age 27 +/- 11 years) and 20 matched control patients. RESULTS: The BAV patients showed reduced aortic elasticity as indicated by increased pulse wave velocity in the aortic arch and descending aorta (5.6 +/- 1.3 m/s vs. 4.5 +/- 1.1 m/s, p = 0.01; and 5.2 +/- 1.8 m/s vs. 4.3 +/- 0.9 m/s, p = 0.03, respectively), and reduced aortic root distensibility (3.1 +/- 1.2 x 10(-3) mm Hg(-1) vs. 5.6 +/- 3.2 x 10(-3) mm Hg(-1), p < 0.01). In addition, BAV patients showed aortic root dilatation as compared with control patients (mean difference 3.6 to 4.2 mm, p < or = 0.04 at all 4 predefined levels). Minor degrees of aortic regurgitation (AR) were present in 11 patients (AR fraction 6 +/- 8% vs. 1 +/- 1%, p < 0.01). The LV ejection fraction was normal (55 +/- 8% vs. 56 +/- 6%, p = 0.61), whereas LV mass was significantly increased in patients (54 +/- 12 g/m2 vs. 46 +/- 12 g/m2, p = 0.04). Dilatation at the level of the aortic annulus (r = 0.45, p = 0.044) and reduced aortic root distensibility (r = 0.37, p = 0.041) correlated with AR fraction. Increased pulse wave velocity in the aortic arch correlated with increased LV mass (r = 0.42, p = 0.041). CONCLUSIONS: Reduced aortic elasticity and aortic root dilatation were frequently present in patients with nonstenotic BAVs. In addition, reduced aortic wall elasticity was associated with severity of AR and LV hypertrophy.

Aortic root dysfunctioning and its effect on left ventricular function in Ross procedure patients assessed with magnetic resonance imaging.

BACKGROUND: This study evaluated the diameters and distensibility of the aortic root as well as the degree of aortic regurgitation (AR) and its effect on left ventricular (LV) function in patients 8.2 +/- 3.1 years after they underwent the Ross procedure, with a comparison of these parameters between patients and matched healthy subjects. METHODS: Eighteen Ross procedure patients (16 male patients, age [mean +/- SD] 19.2 +/- 3.8 years) and 18 matched healthy subjects (16 male patients, age [mean +/- SD] 19.7 +/- 4.2 years) underwent magnetic resonance imaging. Measurements for diameters (at 4 levels) and the distensibility of the aortic root were performed using a steady-state free precession sequence. Aortic flow was assessed with a velocity-encoded phase-contrast sequence. Left ventricular systolic function was assessed with a gradient-echo sequence in the short-axis plane. Comparison of parameters was performed using the Mann-Whitney U test. Correlations between diameters, distensibility, AR fraction, and LV systolic function were expressed with Spearman rank correlation coefficients. Linear regression analysis was used to identify predictors of LV systolic dysfunction. RESULTS: Aortic root diameters were increased in Ross procedure patients as compared with healthy subjects (mean difference 6.3-11.6 mm, P < or = .02 at all 4 levels). Distensibility of the aortic root was lower in patients (1.9 +/- 1.1 vs 7.8 +/- 3.3 mm Hg(-1), P < .01). An AR fraction > 5% was present in 14 of the 18 patients (mean AR fraction 8% +/- 5% vs 1% +/- 1%, P < .01). Left ventricular ejection fraction was lower in patients (50% +/- 6% vs 57% +/- 6%, P < .01). Dilatation, decreased distensibility, and AR fraction were correlated with impaired LV systolic function (P < .05 for all). The AR fraction predicted impaired LV systolic function (P < .01). CONCLUSIONS: Magnetic resonance imaging shows dilatation and decreased distensibility of the aortic root, AR, and consequent impaired LV systolic function in patients after the Ross procedure.

Persistent ductus arteriosus in the Brown-Norway inbred rat strain.

Persistent ductus arteriosus (PDA) is a common cardiovascular anomaly in children caused by the pathologic persistence of the left sixth pharyngeal arch artery. The inbred Brown-Norway (BN) rat presents with increased vascular fragility due to an aortic elastin deficit resulting from decreased elastin synthesis. The strikingly high prevalence of PDA in BN rats in a pilot study led us to investigate this vascular anomaly in 12 adolescent BN rats. In all BN rats, a PDA was observed macroscopically, whereas a ligamentum arteriosum was found in adult controls. The macroscopic appearance of the PDA was tubular (n = 2), stenotic (n = 8), or diverticular (n = 2). The PDA had the structure of a muscular artery with intimal thickening. In the normal closing ductus of the neonatal controls, the media consisted of layers of smooth muscle cells (SMCs) intermingled with layers of elastin. The intima was thin and poor in elastin. By contrast, the media of PDA in BN rats elastin lamellae were absent and the intima contained many elastic fibers. The abnormal distribution of elastin in the PDA of BN rats suggests that impaired elastin metabolism is related to the persistence of the ductus and implicates a genetically determined factor that may link the PDA with aortic fragility.

Widened coronary arteries in a feverish child.

A 3-year-old girl with fever of unknown origin after a visit to Surinam was seen at our hospital. Signs and symptoms were indicative of either Kawasaki syndrome or an acute viral or (atypical) bacterial illness. No cardiac abnormalities were noted at echocardiography. She was treated with intravenous immunoglobulin and clarithromycin and made a quick recovery. Serologically, the diagnosis of murine typhus was made; a flea-borne rickettsiosis caused by Rickettsia typhi. A follow-up echocardiography 1 week later showed a dilated left coronary artery, which was normal again 4 weeks later. We suggest that this phenomenon was a manifestation of rickettsial vasculitis.

Stenting of the vertical vein in obstructed total anomalous pulmonary venous return as rescue procedure in a neonate.

A newborn girl with progressive respiratory distress and cyanosis was found to have severely obstructed supracardiac total pulmonary venous return (TAPVR). Stenting of the stenosis provided immediate and effective relief of the obstruction until corrective surgery was performed. Catheter intervention should be considered in high-risk infants with obstructed supracardiac TAPVR as part of the strategy for preoperative cardiovascular stabilization.

Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease.

OBJECTIVE: To evaluate the relationship between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the occurrence of coronary artery lesions (CALs) among different age groups of patients with Kawasaki disease. METHODS: The frequencies of the genotypes, defined as mutations in codons 52, 54, and 57, and the functional promoter variants of the MBL2 gene were determined in 88 patients with acute Kawasaki disease (median age at onset 1.9 years). The possible influence of the MBL2 genotype on the development and progression of CALs in Kawasaki disease was assessed according to age categories and MBL genotypes in univariate and multivariate analyses. RESULTS: In patients younger than age 1 year, we found an increased risk of developing CALs in the presence of a variant MBL2 genotype (P = 0.008). In contrast, in patients older than age 1 year, we found an increased risk of CALs in those patients with the wild-type genotype (P = 0.005). CONCLUSION: Our findings indicate that MBL has an ambiguous role in Kawasaki disease and contributes differently to the pathophysiologic development of CALs, being protective in infants but potentially harmful in patients of older age. The data also imply that the standard treatment of intravenous immunoglobulins to reduce the development of lesions may not be as effective in the very young as it is in the older patients. For the very young, alternative or adjuvant treatment may be indicated, particularly in infants who are MBL-deficient.

Development of the cardiac conduction system in atrioventricular septal defect in human trisomy 21.

In patients with atrioventricular septal defect (AVSD), the occurrence of nonsurgical AV block has been reported. We have looked for an explanation in the development of the AV conduction system. Human embryos with AVSD and trisomy 21 and normal embryos were examined (age 5-16 wk gestation). Antibodies to human natural killer cell-1 (HNK-1), muscle actin (HHF-35), and collagen VI were used to delineate the conduction system. As in normal hearts, HNK-1 transiently stains the AV conduction system, the sinoatrial node, and parts of the sinus venosus in AVSD. A large distance is present between the superior and inferior node-like part of the right AV ring bundle, comparable to 6-wk-old normal hearts. The definitive inferior AV node remains in dorsal position from 7 wk onward and does not appose to the superior node-like part as seen in normal hearts. Furthermore, in AVSD, a transient third HNK-1-positive "middle bundle" branch that is continuous with the retroaortic root branch and the superior node-like part can be identified, and thus the AV conduction system forms a figure-of-eight loop. At later stages, the AV node remains in dorsal position close to the coronary sinus ostium with a long nonbranching bundle that runs through thin fibrous tissue toward the ventricular septum. The formation of the AV node and the ventricular conduction system in AVSD and Down syndrome differs from normal development, which can be a causative factor in the development of AV conduction disturbances.

Management of asymptomatic anthracycline-induced cardiac damage after treatment for childhood cancer: a postal survey among Dutch adult and pediatric cardiologists.

Asymptomatic anthracycline-induced cardiac damage (A-CD) is a serious problem among young childhood cancer survivors. The aim of this survey was to assess the current treatment policy in these patients in the Netherlands. A questionnaire was sent to all 136 departments of adult or pediatric cardiology in the Netherlands. It was returned by 61% of the departments. Sixty-six percent of the respondents started medical treatment (ie, an ACE inhibitor and/or a beta-blocker) in childhood cancer survivors with asymptomatic A-CD. Fifty-eight percent of the respondents indicated that their treatment decision was based on published findings in the literature, but none of them referred to studies evaluating the treatment of asymptomatic A-CD. A majority of adult and pediatric cardiologists started medical treatment in childhood cancer survivors with asymptomatic A-CD without knowledge of the benefits and risks of treatment in this patient group. Before ACE inhibitors and/or beta-blockers can be recommended as routine practice in childhood cancer survivors with asymptomatic A-CD, randomized controlled trials should be performed. Until then, the authors recommend centralizing the treatment of childhood cancer survivors with asymptomatic A-CD in a specialized center to cluster the available knowledge and experience.

Results of the Ross operation in a pediatric population.

OBJECTIVE: To analyse the results of the mid-term clinical and echocardiographic follow-up of the pediatric Ross operation. METHODS: Echo-Doppler follow-up of 53 consecutive pediatric Ross procedures performed between 1994 and 2003. Median age was 9.7 years at time of operation (2 weeks-17.7 years). Six patients were younger than 3 months. Median age at follow-up was 15.6 years. Aortic valve/left ventricular outflow tract (LVOT) anomalies were congenital in 49 (92%). Seventy percent had previous surgery or balloon valvuloplasty. Root replacement was used in all. Thirteen patients (25%) had LVOT enlargement. Mean cross-clamp time was 113 (69-189) minutes. RESULTS: Early mortality occurred in 3 patients after emergency surgery following balloon failure (n=1) and extended Ross following interrupted arch/VSD repair (n=2). Late mortality was due to LV fibroelastosis in 2 patients and complicated pulmonary artery stenting in another. RVOT reoperations were required because of late homograft obstruction in 2 patients and because of pulmonary artery stenosis in another. Five patients (9.4%) were reoperated for pulmonary autograft dilatation (n=3) and for leaflet fibrosis or perforation (n=2). Autografts were repaired in two patients, while a mechanical valve was inserted in 3 cases. At 9 years the actuarial survival and event free survival were 89 and 74%, respectively. At last follow-up 90% of autograft diameters indexed to body surface area was above the 90th percentile of normal aortic root diameters. LVOT and RVOT gradients were low and autograft insufficiency was trivial to mild in 84% and mild to moderate in 16%. Autograft stenosis was not noticed. CONCLUSIONS: The pediatric Ross procedure remains an important tool but autograft dilatation also occurs in the pediatric population. The significance of this finding has yet to be determined.