Gestational hypertensive disorders and blood pressure and childhood cardiac outcomes: A prospective cohort study.

OBJECTIVE: To assess whether gestational hypertensive disorders and higher gestational blood pressure were associated with subclinical changes in offspring cardiac structure and function during childhood. DESIGN: Population-based prospective cohort study. SETTING: Rotterdam, the Netherlands. POPULATION: A cohort of 2502 mother-offspring pairs. METHODS: Maternal blood pressure was measured in early, mid and late pregnancy, and information on gestational disorders were obtained from medical records. Offspring cardiac measurements were assessed by Cardiovascular Magnetic Resonance at 10 years. MAIN OUTCOME MEASURES: Left and right ventricular end-diastolic volumes (LVEDVs and RVEDVs), and ejection fractions, and left ventricular mass (LVM). RESULTS: Offspring exposed to pre-eclampsia had a lower right ventricular ejection fraction (RVEF) (difference, -0.31 SDS; 95% CI -0.60, -0.02); however, no associations with other cardiac outcomes were present. Higher maternal diastolic blood pressure (DBP) in early and late pregnancy was associated with lower LVEDVs and RVEDVs (p < 0.05), with the strongest effect in early pregnancy. No associations of systolic blood pressure (SBP) with offspring outcomes were present. These associations persisted after additional adjustment for birth and child factors. Paternal SBP and DBP were not associated with offspring cardiac outcomes. CONCLUSIONS: No consistent associations of gestational hypertensive disorder status with childhood cardiac outcomes were present. Higher maternal DBP throughout pregnancy was associated with lower childhood LVEDVs and RVEDVs. Stronger maternal-offspring rather than paternal-offspring associations were present, which may suggest that suboptimal maternal gestational haemodynamic adaptations affects offspring cardiac structure through direct intrauterine effects. Further studies are needed to replicate these findings and examine the underlying mechanisms.

NPHP4 variants are associated with pleiotropic heart malformations.

RATIONALE: Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. OBJECTIVE: To identify genetic mutations causing cardiac laterality defects. METHODS AND RESULTS: We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry. CONCLUSIONS: NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning.

Long term outcome after surgical ASD-closure at young age: Longitudinal follow-up up to 50 years after surgery.

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia). METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years. RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified. CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.

Clinical Course of TGA After Arterial Switch Operation in the Current Era.

Background: The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era. Objectives: The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events. Methods: A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined. Results: At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2). Conclusions: TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.

Mucopolysaccharidosis: cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI.

We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme-replacement therapy (ERT) on cardiac disease. Twenty-four children aged 1-18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme-replacement therapy up to 6 years of treatment. At start of therapy, 66% had abnormal cardiac geometric features. Left-ventricular mass index (LVMI) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI. Regurgitation was most severe in a subgroup of young MPS VI patients (<5 years) at the mitral valve. At baseline, all patients had abnormal valves. The ECG showed no clear rhythm or conduction abnormalities; neither, in most patients, did it reflect the hypertrophy. After ERT, the LVMI Z-score normalized in 70% of the patients who had a Z-score > 2. LVMI Z-scores decreased significantly in patients with MPS I and MPS II (p = 0.04 and p = 0.032). Despite ERT, valve regurgitation increased in 60% of the patients. We conclude that all our MPS patients have cardiac abnormalities. The most severe cardiac disease was observed in a subgroup of young MPS VI patients. While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation.

Disturbance of glucose homeostasis after pediatric cardiac surgery.

This study aimed to evaluate the time course of perioperative blood glucose levels of children undergoing cardiac surgery for congenital heart disease in relation to endogenous stress hormones, inflammatory mediators, and exogenous factors such as caloric intake and glucocorticoid use. The study prospectively included 49 children undergoing cardiac surgery. Blood glucose levels, hormonal alterations, and inflammatory responses were investigated before and at the end of surgery, then 12 and 24 h afterward. In general, blood glucose levels were highest at the end of surgery. Hyperglycemia, defined as a glucose level higher than 8.3 mmol/l (>150 mg/dl) was present in 52% of the children at the end of surgery. Spontaneous normalization of blood glucose occurred in 94% of the children within 24 h. During surgery, glucocorticoids were administered to 65% of the children, and this was the main factor associated with hyperglycemia at the end of surgery (determined by univariate analysis of variance). Hyperglycemia disappeared spontaneously without insulin therapy after 12-24 h for the majority of the children. Postoperative morbidity was low in the study group, so the presumed positive effects of glucocorticoids seemed to outweigh the adverse effects of iatrogenic hyperglycemia.

Physical exercise training in patients with a Fontan circulation: A systematic review.

BACKGROUND: Patients with a Fontan circulation have a reduced exercise capacity, which is an important prognostic predictor of morbidity and mortality. A way to increase exercise capacity in Fontan patients might be exercise training. This systematic review assesses the effects of exercise training investigated in Fontan patients in order to provide an overview of current insights. DESIGN AND METHODS: Studies evaluating an exercise training intervention in Fontan patients published up to February 2020 were included in this systematic review. RESULTS: From 3000 potential studies, 16 studies reported in 22 publications met the inclusion criteria. In total, 264 Fontan patients with mean age range 8.7-31 years, were included. Different training types including inspiratory muscle training, resistance training and aerobic training were investigated. Main outcome measures reported were peak oxygen uptake, cardiac function, lung function, physical activity levels and quality of life. Peak oxygen uptake increased significantly in 56% of the studies after training with an overall mean increase of +1.72 ml/kg/min (+6.3%). None of the studies reported negative outcome measures related to the exercise programme. In four studies an adverse event was reported, most likely unrelated to the training intervention. CONCLUSIONS: Exercise training in Fontan patients is most likely safe and has positive effects on exercise capacity, cardiac function and quality of life. Therefore exercise training in Fontan patients should be encouraged. Further studies are required to assess the optimal training type, intensity, duration and long-term effects.

Outcome after surgical repair of tetralogy of Fallot: A systematic review and meta-analysis.

INTRODUCTION: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Intracardiac correction was pioneered by Walton Lillehei in 1955 and has since then gone through major developments. The aim of this study was to provide a systematic literature review of published results on the long-term outcome of complete surgical correction of TOF. METHODS: MEDLINE, PubMed, Embase, Web of Science, Cochrane, and Google Scholar were systematically searched for literature published between January 2000 and July 2018. Pooled estimates with a random effects model after log-transformation were calculated for mortality and reintervention. Potential heterogeneity was assessed by subgroup analyses and meta-regression. RESULTS: A total of 143 papers of 137 distinct cohorts comprising 21,427 patients and total follow-up duration of 147,430 patient-years were included. Overall mean age at correction was 3.7 ± 5.6 years, but excluding papers exclusively focusing on correction in adults yielded a mean age of 0.5 ± 2.5 years at correction. Previous palliative shunts (107 studies), a transventricular approach (81 studies), and a transannular patch (124 studies) were used in 16% (range 0%-78%), 39% (range 0%-100%), and 49% (range 0%-100%) of the patients. respectively. In case a transannular patch was used, monocusp reconstruction was applied in 15% (range 0%-100%) (49 studies). The most common genetic abnormality was Down syndrome, with a pooled estimated prevalence of 4.6% (range 0%-12.3%). The pooled estimates of early and late mortality were 2.84% (95% confidence interval [CI], 2.34-3.45) and 0.42%/year (95% CI, 0.33-0.54), respectively. The pooled estimate of late cardiac mortality was 0.26%/year (95% CI, 0.21-0.34). Valve-related mortality and non-valve-related mortality had pooled estimates of 0.20%/year (95% CI, 0.15-0.26) and 0.17%/year (95% CI, 0.12-0.22), respectively. The pooled estimate of reintervention was 2.26%/year (95% CI, 1.86-2.75). CONCLUSIONS: TOF can be surgically corrected at a young age with low perioperative and long-term mortality. Life-long intensive follow-up and substantial reintervention rates characterize the clinical course.

EMDR for children with medically related subthreshold PTSD: short-term effects on PTSD, blood-injection-injury phobia, depression and sleep.

Background: Paediatric illness, injury and medical procedures are potentially traumatic experiences with a range of possible negative psychosocial consequences. To prevent psychosocial impairment and improve medical adherence, evidence-based psychotherapy should be offered if indicated. Eye movement desensitization and reprocessing (EMDR) has been found to reduce symptoms of posttraumatic stress disorder (PTSD) in adults. The evidence for the use with children is promising. Furthermore, recent studies indicate its effectiveness for the treatment of other psychological symptomatology. However, the effectiveness of EMDR in children with subthreshold PTSD after medically related trauma has not yet been investigated. Objective: Investigating the short-term effectiveness of EMDR on posttraumatic stress, anxiety, depression and sleep problems in children with subthreshold PTSD after hospitalization through a randomized controlled trial (RCT). Method: Following baseline screening of 420 children from various Dutch hospitals, 74 children (4-15 years old) with medically related subthreshold PTSD were randomized to EMDR (n = 37) or care-as-usual (CAU; n = 37). Follow-up assessment took place after M = 9.7 weeks. Generalized Estimating Equation (GEE) analyses were performed to examine the effectiveness of EMDR compared to CAU. Results: Children in both groups improved significantly over time on all outcomes. However, the EMDR group improved significantly more as to child-reported symptoms of blood-injection-injury (BII) phobia and depression, and child-, and parent-reported sleep problems of the child. There was no superior effect of EMDR compared to CAU on subthreshold PTSD symptom reduction. Conclusions: EMDR did not perform better than CAU in reducing PTSD symptoms in a paediatric sample of children with subthreshold PTSD after hospitalization. However, the study results indicate that EMDR might be superior in reducing symptoms of blood-injection-injury phobia, depression and sleep problems.

Antecedentes: La enfermedad pediátrica, injuria y procedimientos médicos son experiencias potencialmente traumáticas con un rango de posibles consecuencias psicosociales negativas. Para prevenir el deterioro psicosocial y mejorar la adherencia médica, se debe ofrecer psicoterapia basada en evidencia si está indicada. Se ha observado que la Desensibilización y Reprocesamiento por Movimientos Oculares (EMDR) reduce los síntomas del Trastorno de Estrés Postraumático (TEPT) en adultos. La evidencia para su uso en niños es promisoria. Asimismo, estudios recientes indican su efectividad para el tratamiento de otra sintomatología psicológica. No obstante, la efectividad de la EMDR en niños con TEPT subumbral posterior a trauma médicamente relacionado aún no ha sido estudiada.Objetivo: Investigar la efectividad a corto plazo de la EMDR en estrés postraumático, ansiedad, depresión y alteraciones del sueño en niños con TEPT subumbral posterior a hospitalización, a través de un ensayo controlado aleatorizado (ECA).Método: Seguimiento de una muestra de 420 niños provenientes de varios hospitales holandeses, 74 niños (4­15 años de edad) con TEPT subumbral médicamente relacionado fueron aleatorizados a EMDR (n=37) o tratamiento habitual (TH, n=37). La evaluación posterior tuvo lugar tras M=9,7 semanas. Se realizó un análisis de ecuaciones de estimación generalizadas (EEG) para examinar la efectividad de EMDR comparado con TH.Resultados: Los niños en ambos grupos mejoraron significativamente a lo largo del tiempo en todas las variables. No obstante, el grupo EMDR mejoró significativamente más en los síntomas reportados por los niños respecto a belonefobia y depresión, y en alteraciones del sueño de los niños reportadas tanto por ellos como por sus padres. No hubo efecto superior de EMDR comparado con TH en la reducción de síntomas de TEPT subumbral.Conclusiones: EMDR no actuó mejor que TH en la reducción de síntomas de TEPT en niños en una muestra pediátrica de niños con TEPT subumbral posterior a hospitalización. Sin embargo, los resultados del estudio indican que EMDR podría ser superior en la reducción de síntomas de belonefobia, depresión y alteraciones del sueño.

Tetralogy of Fallot in the Current Era.

Only few studies have reported long-term outcome of the transatrial-transpulmonary approach in the current era of management of tetralogy of Fallot (ToF). We investigated 15-year outcome of correction via a transatrial-transpulmonary approach in a large cohort of successive patients operated in the 21st century. All infant ToF patients undergoing transatrial-transpulmonary ToF correction between 2000 and 2015 were included (N = 177, 106 male, median follow-up 7.1 (interquartile range 3.0-10.9) years. Data regarding postoperative complications, reinterventions, development of atrial and ventricular arrhythmia, cardiac function, and survival were evaluated. Prior shunting was performed in 10 patients (6%). The transatrial-transpulmonary approach resulted in valve-sparing surgery in 57 patients (32%). Postoperative surgical complications included junctional ectopic tachycardia (N = 12, 7%), pericardial (N = 10, 6%) or pleural effusion (N = 7, 3%), chylothorax (N = 7, 4%), bleeding requiring reoperation (N = 4, 3%), and superficial wound infection (N = 1). Fifty-one patients underwent 68 reinterventions, mainly due to pulmonary restenosis (PS) (N = 57). ToF correction at age <2 months and double outlet or double-chambered right ventricle variants of the ToF spectrum were independent predictors for reintervention. Patients undergoing valve-sparing ToF correction had a significant longer PR-free survival than those with a transannular patch (8.5 [95% confidence interval 6.8-10.3] years vs 1.1 [95% confidence interval 0.8-1.5] years; P < 0.001). Overall mortality was 2.8%; mortality rates were higher in premature/dysmature newborns (0.7% vs 9.5%; P < 0.001). Although the 15-year outcome of the transatrial-transpulmonary approach in terms of postoperative complications and mortality rates is excellent, the high incidence of moderate and severe PR is worrisome. Valve-sparing surgery was associated with a substantially lower incidence of PR, yet was surgically not possible in the majority of patients.

Cardiac outcome in classic infantile Pompe disease after 13 years of treatment with recombinant human acid alpha-glucosidase.

BACKGROUND: Cardiac failure is the main cause of death in untreated classic infantile Pompe disease, an inheritable metabolic myopathy characterized by progressive hypertrophic cardiomyopathy. Since the introduction of enzyme replacement therapy (ERT), survival has increased significantly due to reduced cardiac hypertrophy and improved cardiac function. However, little is known about ERT's long-term effects on the heart. METHODS: Fourteen patients were included in this prospective study. Cardiac dimensions, function, conduction and rhythm disturbances were evaluated at baseline and at regular intervals thereafter. RESULTS: Treatment duration ranged from 1.1 to 13.9 years (median 4.8 years). At baseline, all patients had increased left ventricular mass index (LVMI) (median LVMI 226 g/m2, range 98 to 599 g/m2, Z-score median 7, range 2.4-12.4). During the first four weeks, LVMI continued to increase in six patients. Normalization of LVMI was observed in 13 patients (median 30 weeks; range 3 to 660 weeks). After clinical deterioration, LVMI increased again slightly in one patient. At baseline, PR interval was shortened in all patients; it normalized in only three. A delta-wave pattern on ECG was seen in six patients and resulted in documented periods of supraventricular tachycardias (SVTs) in three patients, two of whom required medication and/or ablation. One patient had severe bradycardia (35 beats/min). CONCLUSION: This study shows that ERT significantly reduced LVMI, and sustained this effect over a period of 13.9 years. The risk for rhythm disturbances remains. Regular cardiac evaluations should be continued, also after initially good response to ERT.

Eye movement desensitization and reprocessing (EMDR) in children and adolescents with subthreshold PTSD after medically related trauma: design of a randomized controlled trial.

Background: Three in every 10 children and adolescents admitted to a hospital or undergoing medical treatment develop subthreshold symptoms of posttraumatic stress disorder (PTSD). When untreated, subthreshold PTSD can have a serious impact on psychosocial functioning, quality of life and long-term psychopathology. However, research investigating subthreshold PTSD and its treatment following paediatric medical interventions and/or hospitalization is scarce. Eye Movement Desensitization and Reprocessing (EMDR) is a fast and non-invasive psychosocial treatment for posttraumatic stress complaints. However, the effectiveness of EMDR in paediatric patients with subthreshold PTSD has not previously been systematically investigated. Objective: Describing the design of a randomized controlled trial (RCT) set up to evaluate the effectiveness of EMDR in children with subthreshold PTSD after hospitalization. Method: Children aged 4-15 years who have undergone a one-time (trauma type I) or repeated (trauma type II) hospitalization up to five years ago will be included. Participating children will be first screened with a standardized questionnaire for PTSD-symptoms. Subsequently, children with subthreshold PTSD will be randomly assigned to (1) approximately six sessions of standardized EMDR or (2) care as usual (CAU). Children with full diagnostic PTSD do not participate in the RCT, but are referred for direct treatment. Follow-up measurements will take place after eight weeks and eight months. Discussion: Considering the scarce evidence for the effectiveness of EMDR in children with medically related trauma, clinicans, researchers and children treated in hospitals can benefit from this study. Potential strengths and limitations of this study are discussed. Trial Registration: Netherlands Trial Register NTR5801.

Antecedentes: Alrededor de 3 de cada 10 niños y adolescentes ingresados en un hospital o sometidos a tratamiento médico desarrollan síntomas subumbrales de trastorno de estrés postraumático (TEPT). Cuando no se trata, el TEPT subumbral puede tener un impacto grave en el funcionamiento psicosocial, la calidad de vida, y la psicopatología a largo plazo. Sin embargo, la investigación sobre el TEPT subumbral y su tratamiento después de las intervenciones médicas pediátricas y/o la hospitalización es escasa. La desensibilización y reprocesamiento por movimientos oculares (EMDR) es un tratamiento psicosocial rápido y no invasivo para las quejas de estrés postraumático. Sin embargo, la efectividad del EMDR en pacientes pediátricos con TEPT subumbral no ha sido previamente investigada de manera sistemática.Objetivo: Describir el diseño de un ensayo controlado aleatorizado (RCT, en sus siglas en inglés) establecido para evaluar la efectividad de EMDR en niños con TEPT subumbral después de una hospitalización.Método: Se incluirán niños de 4 a 15 años que hayan sido sometidos a una hospitalización única (trauma tipo I) o repetida (trauma tipo II) hasta en los 5 años previos. Los niños participantes serán evaluados inicialmente con un cuestionario estandarizado para síntomas de TEPT. Posteriormente, los niños con TEPT subumbral serán asignados aleatoriamente a (1) seis sesiones de EMDR estandarizado o (2) cuidados usuales (CAU, por sus siglas en inglés). Los niños con diagnóstico completo de TEPT no participan en el RCT, pero serán derivados para tratamiento directo. Las mediciones de seguimiento se llevarán a cabo después de ocho semanas y ocho meses.Discusión: Teniendo en cuenta la escasa evidencia de la efectividad de EMDR en niños con trauma médico, los clínicos, los investigadores y los niños tratados en hospitales pueden beneficiarse de este estudio. Se discuten las fortalezas y limitaciones potenciales de este estudio.

Comparison of real-time three-dimensional echocardiography to magnetic resonance imaging for assessment of left ventricular mass.

This is the first study to assess the feasibility and accuracy of real-time 3-dimensional echocardiography (RT-3DE) for the measurements of left ventricular (LV) mass in patients with congenital heart disease (CHD) compared with magnetic resonance imaging (MRI). Twenty patients (60% men) with CHD were evaluated by MRI and RT-3DE on the same day. Their mean age was 29 +/- 8 years (range 19 to 49). RT-3DE was performed with a Philips Sonos 7500 echocardiographic system and LV mass analyses with the assistance of TomTec software. The results for LV mass obtained by manual tracing were compared with Signa 1.5-T MRI data. The acquisition of RT-3DE data sets was feasible in all 20 patients. Nine patients (45%) had good, 5 patients (25%) moderate, and 6 patients (30%) poor image quality of the 3-dimensional data set. The time of 3-dimensional data acquisition was 4 +/- 2 minutes. Off-line image processing and tracing required approximately 11 +/- 3 minutes. A very good correlation was observed between RT-3DE data with sufficient image quality and MRI (r = 0.98, y = 0.96x + 4.1, SEE 9.8 g), with a mean difference of 2.0 +/- 20 g. Interobserver agreement was excellent (r = 0.99, y = 0.97x + 3.81), with a mean difference of -1 +/- 11 g. In conclusion, the assessment of LV mass from RT-3DE data is feasible in patients with CHD. The mass of an abnormally shaped left ventricle can be determined with high accuracy and low interobserver variability in patients with good or moderate echocardiographic image quality.

Sudden unexpected death in children with a previously diagnosed cardiovascular disorder.

BACKGROUND: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. OBJECTIVE: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death (SUD), and to identify the possible cause of death. DESIGN: Retrospective, cross-sectional study. PATIENTS AND SETTING: All children (<19 years) with a previously diagnosed heart defect and SUD between January 1990 and June 2001 in seven out of eight tertiary centres in the Netherlands were identified using the hospital databases. We excluded patients receiving compassionate care. Diagnoses, clinical status and circumstances of death were sought from case notes and post mortem reports. Deaths were classified as of cardiac or non-cardiac origin. RESULTS: We identified 150 cases of SUD (89 male) at a median age of 2.3 years (range 18 days-18.9 years); 49/150 patients (33%) were

Effect of exercise training on sports enjoyment and leisure-time spending in adolescents with complex congenital heart disease: the moderating effect of health behavior and disease knowledge.

OBJECTIVE: The aim of this study was to evaluate the effects of a standardized exercise program on sports enjoyment and leisure-time spending in adolescents with congenital heart disease and to know what the moderating impact of their baseline health behavior and disease knowledge is. METHODS: Included were 93 patients, aged 10 to 25, with surgical repair for tetralogy of Fallot or with a Fontan circulation for single-ventricle physiology, of 5 participating centers of pediatric cardiology in The Netherlands. They were randomly allocated, stratified for age, gender, and type of congenital heart disease to a 12-week period with either: (1) three times per week standardized exercise training or (2) care as usual (randomization ratio 2:1). At baseline and after 12 weeks, participants completed Web-based questionnaires and were interviewed by phone. OUTCOME MEASURES: Primary analyses tested changes from baseline to follow-up in sports enjoyment and leisure-time spending in the exercise group vs. control group. Secondary analyses concerned the moderating influence of baseline health behavior and disease knowledge on changes from baseline to follow-up, and comparison with normative data. RESULTS: At follow-up, the exercise group reported a decrease in passive leisure-time spending (watching television and computer usage) compared with controls. Exercise training had no effect on sports enjoyment and active leisure-time spending. Disease knowledge had a moderating effect on improvement in sports enjoyment, whereas health behavior did not. Compared with normative data, patients obtained similar leisure time scores and lower frequencies as to drinking alcohol and smoking. CONCLUSIONS: Exercise training decreased passive, but not active, leisure-time spending. It did not influence sports enjoyment.

The unnatural history of an atrial septal defect: longitudinal 35 year follow up after surgical closure at young age.

OBJECTIVE: To describe the very long-term outcome after surgical closure of an atrial septal defect (ASD). DESIGN: Longitudinal cohort study of 135 consecutive patients who underwent surgical ASD repair at age <15 years between 1968 and 1980. The study protocol included ECG, echocardiography, exercise testing, N-terminal prohormone of brain natriuretic hormone, Holter monitoring and cardiac MRI. MAIN OUTCOME MEASURES: Survival, major events (cardiac reinterventions, stroke, symptomatic arrhythmia or heart failure) and ventricular function. RESULTS: After 35 years (range 30-41), survival status was obtained in 131 of 135 patients (97%): five died (4%), including two sudden deaths in the last decade. Fourteen patients (16%) had symptomatic supraventricular tachyarrhythmias and six (6%) had a pacemaker implanted which was predicted by early postoperative arrhythmias. Two reoperations were performed. One ischaemic stroke occurred. Left ventricular (LV) and right ventricular (RV) ejection fractions (EF) were 58 ± 7% and 51 ± 6%, respectively. RVEF was diminished in 17 patients (31%) and in 11 (20%) the RV was dilated. Exercise capacity and quality of life were comparable to the normal population. No clear differences were found between ASD-II or sinus venosus type ASD. CONCLUSIONS: Very long-term outcome after surgical ASD closure in childhood shows good survival and low morbidity. Early surgical closure prevents pulmonary hypertension and reduces the occurrence of supraventricular arrhythmias. Early postoperative arrhythmias are predictive for the need for pacemaker implantation during early follow-up, but the rate of late pacemaker implantation remains low. Although RVEF was unexpectedly found to be decreased in one-third of patients, the functional status remains excellent.

Real-time transthoracic three-dimensional echocardiographic assessment of left ventricular volume and ejection fraction in congenital heart disease.

OBJECTIVE: The purpose of this study was to assess the (1) feasibility of real-time three-dimensional echocardiography (RT-3DE) data acquisition and (2) volumes and function of the abnormal left ventricle (LV) in adult patients with congenital heart disease (CHD), compared with magnetic resonance imaging (MRI) data. METHODS: Thirty-two patients (59% were male) with CHD were evaluated on the same day by MRI and RT-3DE. Acquisition of RT-3DE data sets was feasible in 29 of the 32 patients (91%). The time of 3D data acquisition was 4 +/- 2 minutes, and LV analysis was 17 +/- 5 minutes per patient for manual border tracing. RESULTS: A good correlation was observed between RT-3DE with manual border detection and MRI for LV end-diastolic volume (r = 0.97), LV end-systolic volume (r = 0.98), and LV ejection fraction (r = 0.94). CONCLUSION: RT-3DE is feasible for volumetric analysis of the abnormal LV allowing accurate determination of LV volume and ejection fraction compared with MRI in adult patients with CHD.

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.