Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification.

BACKGROUND: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis. METHODS: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017. RESULTS: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower (P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups. CONCLUSIONS: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis.

Predicting outcome in children with dilated cardiomyopathy: the use of repeated measurements of risk factors for outcome.

AIMS: We aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome. METHODS AND RESULTS: Of 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all-cause death or HTx), 15 (11%) died at a median of 0.09 years [inter-quartile range (IQR) 0.03-0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8-6.1] after diagnosis. Median follow-up was 2.1 years [IQR 0.8-4.3]. Twenty-three children recovered at a median of 0.6 years [IQR 0.5-1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (-0.42 vs. -0.02 length Z-score per year, P < 0.001), less decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (-0.26 vs. -1.06 2log pg/mL/year, P < 0.01), no decrease in left ventricular internal diastolic dimension (LVIDd; 0.24 vs. -0.60 Boston Z-score per year, P < 0.01), and increase in New York University Pediatric Heart Failure Index (NYU PHFI; 0.49 vs. -1.16 per year, P < 0.001). When we compared children who reached the SE with those with ongoing disease (leaving out the children who recovered), we found similar results, although the effects were smaller. In univariate analysis, NT-proBNP, length Z-score, LVIDd Z-score, global longitudinal strain (%), NYU PHFI, and age >6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT-proBNP appeared the only independent predictor for adverse outcome, a two-fold higher NT-proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81-3.94, P < 0.001). CONCLUSIONS: The evolution over time of NT-proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT-proBNP was the strongest independent predictor for adverse outcome.

Emotional and behavioral problems in children with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) in children is an important cause of severe heart failure and carries a poor prognosis. Adults with heart failure are at increased risk of anxiety and depression and such symptoms predict adverse clinical outcomes such as mortality. In children with DCM, studies examining these associations are scarce. AIMS: We studied whether in children with DCM: (1) the level of emotional and behavioral problems was increased as compared to normative data, and (2) depressive and anxiety problems were associated with the combined risk of death or cardiac transplantation. METHODS: To assess emotional and behavioral problems in children with DCM, parents of 68 children, aged 1.5-18 years (6.9±5.7 years), completed the Child Behavior Checklist. RESULTS: Compared to normative data, more young children (1.5-5 years) with DCM had somatic complaints (24.3% vs. 8.0%; p < .001), but fewer had externalizing problems (5.4% vs. 17.0%; p = .049). Overall internalizing problems did not reach significance. Compared to normative data, more older children (6-18 years) showed internalizing problems (38.7% vs. 17.0%; p = .001), including depressive (29.0% vs. 8.0%; p < .001) and anxiety problems (19.4% vs. 8.0%; p = .023), and somatic complaints (29.0% vs. 8.0%; p < .001). Anxiety and depressive problems, corrected for heart failure severity, did not predict the risk of death or cardiac transplantation. CONCLUSION: Children of 6 years and older showed more depressive and anxiety problems than the normative population. Moreover, in both age groups, somatic problems were common. No association with outcome could be demonstrated.

Does Repeated Measurement of a 6-Min Walk Test Contribute to Risk Prediction in Children with Dilated Cardiomyopathy?

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients ≥ 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2-6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5-5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p < 0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test.

Long-term follow-up after transatrial-transpulmonary repair of tetralogy of Fallot: influence of timing on outcome.

OBJECTIVES: Our goal was to report the long-term serial follow-up after transatrial-transpulmonary repair of tetralogy of Fallot (TOF) and to describe the influence of the timing of the repair on outcome. METHODS: We included all patients with TOF who had undergone transatrial-transpulmonary repair between 1970 and 2012. Records were reviewed for patient demographics, operative details and events during the follow-up period (death, pulmonary valve replacement, cardiac reinterventions and hospitalization/intervention for arrhythmias). In patients with elective early primary repair of TOF after 1990, a subanalysis of the optimal timing of TOF repair was performed. RESULTS: A total of 453 patients were included (63% male patients; 65% had transannular patch); 261 patients underwent primary elective repair after 1990. The median age at TOF repair was 0.7 years (25th-75th percentile 0.3-1.3) and decreased from 1.7 to 0.4 years from before 1990 to after 2000, respectively (P < 0.001). The median follow-up duration after TOF repair was 16.8 years (9.6-24.7). Events developed in 182 (40%) patients. In multivariable analysis, early repair of TOF (<6 months) [hazard ratio (HR) 3.06; P < 0.001] and complications after TOF repair (HR 2.18; P = 0.006) were found to be predictive for an event. In a subanalysis of the primary repair of TOF after 1990, the patients (n = 125) with elective early repair (<6 months) experienced significantly worse event-free survival compared to patients who had elective repair later (n = 136). In multivariable analysis, early repair (HR 3.00; P = 0.001) and postoperative complications (HR 2.12; P = 0.010) were associated with events in electively repaired patients with TOF. CONCLUSIONS: Transatrial-transpulmonary repair of TOF before the age of 6 months may be associated with more events during the long-term follow-up period.

Transient left bundle branch block and left ventricular dysfunction in a patient with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome.

The NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome is a rare novel autoinflammatory disorder. Cardiac involvement has not been previously reported. We present a 12-year-old girl with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome who was diagnosed with severely impaired left ventricular function and complete left bundle branch block during an exacerbation of the disease. Cardiac dysfunction proved to be rapidly reversible after initiation of high-dose methylprednisolone.

Distribution of strain patterns in children with dilated cardiomyopathy.

OBJECTIVES: This study aimed to evaluate the predicting value of quantitative and qualitative dyssynchrony parameters as assessed by two-dimensional speckle tracking echocardiography (STE) on outcome in children with dilated cardiomyopathy (DCM). Furthermore, the reproducibility of these parameters was investigated. BACKGROUND: In previous studies in adults with heart failure, several dyssynchrony parameters have been shown to be a valuable predictor of clinical outcome. METHODS: This multicenter, prospective study included 75 children with DCM and 75 healthy age-matched controls. Using STE, quantitative (time to global peak strain and parameters describing intraventricular time differences) and qualitative dyssynchrony parameters (pattern analysis) of the apical four-chamber, three-chamber, two-chamber views, and the short axis of the left ventricle were assessed. Cox regression was used to identify risk factors for the primary endpoints of death or heart transplantation. Inter-observer and intra-observer variability were described. RESULTS: During a median of 21 months follow-up, 10 patients (13%) reached an endpoint. Although quantitative dyssynchrony measures were higher in patients as compared to controls, the inter-observer and intra-observer variability were high. Pattern analysis showed mainly reduced strain, instead of dyssynchronous patterns. CONCLUSIONS: In this study, quantitative dyssynchrony parameters were not reproducible, precluding their use in children. Qualitative pattern analysis showed predominantly reduced strain, suggesting that in children with DCM dyssynchrony may be a minor problem.

Parent reports of health-related quality of life and heart failure severity score independently predict outcome in children with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents' sense of their child's functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome. Methods and results In this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0-4 years) or Child Health Questionnaire-Parent Form 50 (4-18 years) at 3-6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9-12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0-4 years: 7/10 subscales and 4-18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (p<0.05). After a median follow-up of 3 years (IQR 2-4), 15 patients underwent transplantation. Using multivariable time-dependent Cox regression, "physical functioning" subscale and the Heart Failure Index were independently predictive of the risk of death and heart transplantation (hazard ratio 1.24 per 10% decrease of predicted, 95% confidence interval (CI) 1.06-1.47 and hazard ratio 1.38 per unit, 95% CI 1.19-1.61, respectively). CONCLUSION: Physical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.

Six-Minute Walk Test as a Predictor for Outcome in Children with Dilated Cardiomyopathy and Chronic Stable Heart Failure.

Cardiopulmonary exercise testing is an important tool to predict prognosis in children and adults with heart failure. A much less sophisticated exercise test is the 6 min walk test, which has been shown an independent predictor for morbidity and mortality in adults with heart failure. Therefore, we hypothesized that the 6 min walk test could be predictive for outcome in children with dilated cardiomyopathy. We prospectively included 49 children with dilated cardiomyopathy ≥6 years who performed a 6 min walk test. Median age was 11.9 years (interquartile range [IQR] 7.4-15.1), median time after diagnosis was 3.6 years (IQR 0.6-7.4). The 6 min walk distance was transformed to a percentage of predicted, using age- and gender-specific norm values (6MWD%). For all patients, mean 6MWD% was 70 ± 21%. Median follow-up was 33 months (IQR 14-50). Ten patients reached the combined endpoint of death or heart transplantation. Using univariable Cox regression, a higher 6MWD% resulted in a lower risk of death or transplantation (hazard ratio 0.95 per percentage increase, p = 0.006). A receiver operating characteristic curve was generated to define the optimal threshold to identify patients at highest risk for an endpoint. Patients with a 6MWD% < 63% had a 2 year transplant-free survival of 73%, in contrast to a transplant-free survival of 92% in patients with a 6MWD% ≥ 63% (p = 0.003). In children with dilated cardiomyopathy, the 6 min walk test is a simple and feasible tool to identify children with a higher risk of death or heart transplantation.

Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.

Impaired longitudinal deformation measured by speckle-tracking echocardiography in children with end-stage renal disease.

BACKGROUND: Left ventricular dysfunction is an important co-morbidity of end-stage renal disease (ESRD) and is associated with a poor prognosis in the adult population. In pediatric ESRD, left ventricular function is generally well preserved, but limited information is available on early changes in myocardial function. The aim of this study was to investigate myocardial mechanics in pediatric patients with ESRD using speckle-tracking echocardiography (STE). METHODS: Echocardiographic studies, including M-mode, tissue Doppler imaging (TDI) and STE, were performed in 19 children on dialysis, 17 transplant patients and 33 age-matched controls. Strain measurements were performed from the apical four-chamber and the short axis view, respectively. RESULTS: The interventricular and left ventricular posterior wall thickness was significantly increased in dialysis and transplant patients compared to healthy controls. No significant differences were found in shortening fraction, ejection fraction and systolic tissue Doppler velocities. Dialysis and transplant patients had a decreased mean longitudinal strain compared to healthy controls, with a mean difference of 3.1 [95 % confidence interval (CI) 2.0-4.4] and 2.7 (95 % CI 1.2-4.2), respectively. No differences were found for radial and circumferential strain. CONCLUSIONS: Speckle-tracking echocardiography may reveal early myocardial dysfunction in the absence of systolic dysfunction measured by conventional ultrasound or TDI in children with ESRD.

Prospective Evaluation of Sleep Apnea as Manifestation of Heart Failure in Children.

In adults with heart failure, central sleep apnea (CSA), often manifested as Cheyne-Stokes respiration, is common, and has been associated with adverse outcome. Heart failure in children is commonly caused by dilated cardiomyopathy (DCM). It is unknown whether children with heart failure secondary to DCM have CSA, and whether CSA is related to the severity of heart failure. In this prospective observational study, 37 patients (<18 year) with heart failure secondary to DCM were included. They underwent polysomnography, clinical and laboratory evaluation and echocardiographic assessment. After a median follow-up time of 2 years, eight patients underwent heart transplantation. CSA (apnea-hypopnea index [AHI] ≥1) was found in 19 % of the patients. AHI ranged from 1.2 to 4.5/h. The occurrence of CSA was not related to the severity of heart failure. Three older patients showed a breathing pattern mimicking Cheyne-Stokes respiration, two of whom required heart transplantation. CSA was found in 19 % of the children with heart failure secondary to DCM. No relation was found with the severity of heart failure. In a small subset of children with severe DCM, a pattern mimicking Cheyne-Stokes respiration was registered.

Management of children with dilated cardiomyopathy in The Netherlands: Implications of a low early transplantation rate.

BACKGROUND: The policy for listing and transplant for children with dilated cardiomyopathy (DCM) in The Netherlands has been conservative because of low donor availability. The effects of this policy on outcome are reported. METHODS: This was a multicenter, nationwide study performed in 148 children with DCM. The primary outcome was death or heart transplant. RESULTS: Overall, 43 patients (29%) died or were transplanted. Within 1 year of diagnosis, 21 patients died, and only 4 underwent transplantation (3 on mechanical circulatory support). The 1-year survival was 85% (95% confidence interval [CI] = 79-91), and 5-year survival was 84% (95% CI = 78-90). Transplantation-free survival at 1 year was 82% (95% CI = 75-88) and at 5 years was 72% (95% CI = 64-80). Within 1 year of diagnosis, with death as the main end-point (21 of 25, 84%), intensive care unit admission (hazard ratio = 2.6, p = 0.05) and mechanical circulatory support (hazard ratio = 3.2, p = 0.03) were risk factors (multivariable Cox analysis); inotropic support was longer in patients reaching an end-point. At >1 year after diagnosis, with transplantation as the main end-point (15 of 18, 83%), age >6 years (hazard ratio = 6.1, p = 0.02) was a risk factor. There were 56 (38%) children who recovered, 50% within 1 year of diagnosis. Recovery was associated with younger age; was similar in patients with myocarditis (43%) and idiopathic disease (41%); and was similar in patients initially admitted to the intensive care unit, admitted to the ward, or treated as outpatients. CONCLUSIONS: The transplantation rate in our cohort in the first year was low, with 1-year and 5-year survival rates similar to other cohorts. Our results suggest that a conservative approach to list children for transplantation early after presentation may be justifiable except for patients with prolonged intensive care unit or mechanical circulatory support.

Long-term outcomes of transatrial-transpulmonary repair of tetralogy of Fallot.

OBJECTIVES: The surgical approach to repair of tetralogy of Fallot (ToF) has shifted over the years. We aimed to report the long-term follow-up after ToF repair with the transatrial-transpulmonary approach and to determine predictors of long-term outcomes. METHODS: Retrospective analysis of patients operated on in two tertiary referral centres. Primary outcome measures were: death, pulmonary valve replacement (PVR), reintervention for other reasons, internal cardiodefibrillator and/or pacemaker placement. Kaplan-Meier assessment of overall and event-free survival as well as uni- and multivariate analyses of risk factors for outcomes were performed. RESULTS: Four hundred and fifty-three patients were included. Median age at operation was: 0.6 years (range 0-19.6) and median age at the last follow-up was 14.3 years (range 0.1-42.1). Median age at repair decreased from 1.2 years (range 0.6-5.8) (1970-80) to 0.3 years (range 0-4.7) (2000-12). A transannular patch (TP) was used in 65% of all patients. The use of a TP showed a decline from 89% in the initial years of the cohort to 64% in 2000-12. Early mortality was 1.1% (5 patients) for the entire cohort and late mortality 2.4% (11 patients). Overall survival for the entire cohort was 97.3% (95% CI 95.7-98.8) and 91.8% (95% CI 85.9-97.7) at 10 and 25 years, respectively. For patients with a TP (n = 294) vs non-TP (n = 159), this was 97.2% (95% CI 95.2-99.2) vs 97.5% (95% CI 95.1-99.9) at 10-year and 91.0% (95% CI 83.9-98.1) vs 96.3% (95% CI 93.0-99.6) at 25-year follow-up (P = 0.958). Fifty-two patients underwent PVR, and in 5 a pacemaker was inserted. Event-free survival for TP versus non-TP patients was 80.2% (95 CI% 75.5-84.9) vs 81.7% (95% CI 75.2-88.2) at 10-year and 27.9% (95% CI 17.7-38.1) vs 78.5% (95% CI 71.4-85.6) at 25-year follow-up (P = 0.016). In multivariate analysis, both the use of a TP (HR 1.705, 95% CI 1.023-2.842) and the year of surgical repair of tetralogy of Fallot (HR 1.039, 95% CI 1.006-1.073) were associated with a higher probability of an event. CONCLUSIONS: ToF patients corrected with the transatrial-transpulmonary approach have good long-term survival. PVR is a frequent event at longer follow-up, and other events are limited. The use of a TP is a predictor for poorer event-free outcomes, increasing the risk of the composite endpoint 1.7 times.

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.

Clinical recognition of mid-aortic syndrome in children.

Mid-aortic syndrome is characterized by narrowing of the abdominal aorta, usually with the involvement of renal arteries and other visceral branches. The combination of the presence of an abdominal bruit, diminished or absent pulsations of the lower extremities, and a blood pressure discrepancy between upper and lower extremities is the classic triad associated with mid-aortic syndrome. However, it has a wide variety of clinical symptoms, and awareness of the variable presentation can lead to early diagnosis of the vascular anomaly. We report three cases presenting at three different stages of this disease, such as hydrops fetalis, refractory hypertension, and intracerebral bleeding. In conclusion, these cases highlight the importance of blood pressure measurements in all patients and accurate physical examination for early recognition of a mid-aortic syndrome.

Results of balloon dilatation of stenotic homografts in pulmonary position in children and young adults.

OBJECTIVES: To evaluate the results of balloon dilatation of stenotic homografts in children, adolescents, and young adults and to identify factors that might influence or predict the effect of the dilatation. BACKGROUND: Homografts are widely used in congenital cardiac surgery; however, the longevity remains a problem mostly because of stenosis in the homograft. The effect of treatment by balloon dilatation is unclear. METHODS: In a retrospective study, the effect of balloon dilatation was determined by the percentage of reduction of the peak systolic pressure gradient over the homograft during catheterisation and the postponement of re-intervention or replacement of the homograft in months. Successful dilatations - defined in this study as a reduction of more than 33% and postponement of more than 18 months - were compared with unsuccessful dilatations in search of factors influencing or predicting the results. RESULTS: The mean reduction of the peak systolic pressure gradient was 30% in 40 procedures. Re-intervention or replacement of the homograft was postponed by a mean of 19 months. In all, 14 balloon dilatations (35%) were successful; the mean reduction was 49% and the mean postponement was 34 months. The time since homograft implantation, the presence of calcification, the homograft/balloon ratio, and the pressure applied during dilatation all tended to correlate with outcome, but were not statistically significant. CONCLUSIONS: Balloon dilatation is able to reduce the peak systolic pressure gradient over homografts in a subgroup of patients and can be of clinical significance to postpone re-intervention or pulmonary valve replacement.

Persistent reduction in left ventricular strain using two-dimensional speckle-tracking echocardiography after balloon valvuloplasty in children with congenital valvular aortic stenosis.

BACKGROUND: The aim of this study was to investige serial changes of myocardial deformation using two-dimensional speckle-tracking echocardiographic (2DSTE) imaging in children undergoing balloon valvuloplasty for congenital valvular aortic stenosis (VAS). METHODS: Thirty-seven children with isolated congenital VAS were enrolled in this study prospectively. Patients underwent echocardiographic evaluation at three instances: before balloon valvuloplasty, 6 months after intervention, and 3 years after intervention. Longitudinal, circumferential, and radial peak systolic strain values were determined, as well as systolic strain rate and the time to peak global systolic strain. Linear mixed statistical models were used to assess changes in 2DSTE parameters after balloon intervention. Using one-way analysis of variance, 2DSTE results at 3-year follow-up were compared with 2DSTE measurements in 74 healthy age-matched children and 76 children with uncorrected VAS whose severity of stenosis corresponded to residual stenosis of study subjects at 3-year follow-up. RESULTS: Global peak strain and strain rate measurements in all three directions were decreased before intervention compared with healthy children. Global peak strain and strain rate measurements increased significantly (P < .001) several months after balloon valvuloplasty and continued to increase at 3-year follow-up. However, at 3-year follow-up, global peak strain and strain rate in the longitudinal and circumferential directions were significantly lower (P < .001) compared with both control groups. Measurements of time to peak global systolic strain were significantly shorter at early follow-up compared with measurements before intervention (P < .05). CONCLUSIONS: Shortly after balloon valvuloplasty for severe congenital VAS, there is an improvement in systolic myocardial deformation. However, 2DSTE parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation.

Exercise capacity in children with isolated congenital complete atrioventricular block: does pacing make a difference?

The management of patients with isolated congenital complete atrioventricular block (CCAVB) has changed during the last decades. The current policy is to pace the majority of patients based on a variety of criteria, among which is limited exercise capacity. Data regarding exercise capacity in this population stems from previous publications reporting small case series of unpaced patients. Therefore, we have investigated the exercise capacity of a group of contemporary children with CCAVB. Sixteen children (mean age 11.5 ± 4; seven boys, nine girls) with CCAVB were tested. In 13 patients, a median number of three pacemakers were implanted, whereas in three patients no pacemaker was given. All patients had an echocardiogram and completed a cardiopulmonary cycle exercise test. Exercise parameters were determined and compared with reference values obtained from healthy Dutch peers. The peak oxygen uptake/body mass was reduced to 34.4 ± 9.5 ml kg(-1) min(-1) (79 ± 24% of predicted) and the ventilatory threshold was reduced to 52 ± 17% of peak oxygen uptake (78 ± 21% of predicted), whereas the peak work load/body mass was 2.8 ± 0.6 W/kg (91 ± 24% of predicted), which was similar to controls. Importantly, 25% of the paced patients showed upper rate restriction by the pacemaker. In conclusion, children with CCAVB show a reduced peak oxygen uptake and ventilatory threshold, whereas they show normal peak work rates. This indicates that they generate more energy during exercise from anaerobic energy sources. Paced children with CCAVB do not perform better than unpaced children.