The development and validation of a health-related quality of life questionnaire for pre-school children with a chronic heart disease.

PURPOSE: Heart diseases are often associated with residual injuries, persisting functional restrictions, and long-term sequelae for psychosocial development. Currently, there are no disease-specific instruments to assess the health-related quality of life (HrQoL) of pre-school children. The aims of this study were to develop a parent proxy instrument to measure the HrQoL of children aged 3-7 years with a heart disease and to confirm its validity and reliability. METHODS: Items from the Preschool Pediatric Cardiac Quality of Life Inventory (P-PCQLI) were generated through focus groups of caregivers. In a pilot study, comprehensibility and feasibility were tested. Five subdimensions were defined theoretically. Psychometric properties were analysed within a multicentre study with 167 parental caregivers. RESULTS: The final 52-item instrument contains a total score covering five moderately inter-correlated dimensions. The total score of the questionnaire showed a very high internal consistency (Cronbachs' α = 0.95). Test-retest correlation was at r tt = 0.96. External validity was indicated by higher correlations (r = 0.24-0.68) with a generic paediatric quality of life questionnaire (KINDL) compared to the Strengths and Difficulties Questionnaire (r = 0.17 to 0.59). Low P-PCQLI total scores were significantly associated with inpatient as opposed to outpatient treatment (t = 6.04, p < .001), with at least moderate disease severity ((t = 5.05, p < .001) NYHA classification) and with poorer prognosis (t = 5.53, p < .001) as estimated by the physician. CONCLUSIONS: The P-PCQLI is reliable and valid for pre-school children with a heart disease. It could be used as a screening instrument in routine care, and for evaluation of HrQoL outcomes in clinical trials and intervention research.

Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease: a report from the Exercise, Basic & Translational Research Section of the European Association of Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and Lung Exercise Group, and the Association for European Paediatric Cardiology.

All children have a natural need to move, play, and perform activities. Physical activity is necessary for optimal physical, emotional, and psychosocial development for healthy children as well as children with congenital heart disease (CHD). In this paper we provide recommendations for physical activity, recreational sport, and exercise training in children and adolescents with CHD. In general, children with CHD should be advised to comply with public health recommendations of daily participation in 60 min or more of moderate-to-vigorous physical activity that is developmentally appropriate and enjoyable and involves a variety of activities. While all patients with CHD can participate and benefit from physical activity and exercise, those with specific lesions or complications may require counselling regarding precautions and recommendations.

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis]. / Neurologische und psychomotorische Entwicklung von Feten und Neugeborenen mit angeborenen Herzfehlern--Ursachen und Prävalenz von Störungen im Langzeitverlauf.

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population.

Long-term behavior and quality of life after corrective cardiac surgery in infancy for tetralogy of Fallot or ventricular septal defect.

The objective of this study was to evaluate behavior and quality of life in children after corrective cardiac surgery in infancy. Twenty cyanotic (tetralogy of Fallot) and 20 acyanotic children (ventricular septal defect), operated at a mean age of 0.7 years with deep hypothermic circulatory arrest (DHCA) and low-flow cardiopulmonary bypass (CPB), were assessed at a mean age of 7.4 years by the Child Behavior Checklist (CBCL) and the German KINDL. Test results were related to perioperative and neurodevelopmental outcome. Compared to healthy children and not significantly different between the groups, internalizing and externalizing problems were elevated, school performance and total competence were reduced, and self- and parent-reported quality of life was not reduced. Parent-reported problems and reduced physical status were correlated with longer durations of DHCA and CPB. Internalizing and externalizing problems, reduced school competence, and reduced self-esteem were associated with reduced endurance capacity. Externalizing problems were related to reduced gross motor function. Poor school competence was related to reduced intelligence and academic achievement. Children with preoperative hypoxemia in infancy due to cyanotic cardiac defects are not at significantly higher risk for behavioral problems and reduced quality of life than those with acyanotic heart defects. The risk of long-term psychosocial maladjustment after corrective surgery in infancy is increased compared to that for normal children and related to the presence of neurodevelopmental dysfunction.

Results of exercise testing at a mean age of 10 years after neonatal arterial switch operation.

AIM: This prospective follow-up study investigated long-term exercise capacity at a mean age of 10 y after neonatal arterial switch operation for transposition of the great arteries in a large group of homogeneous unselected children. METHODS: 56 asymptomatic children, aged 7.9-14.3 y (10.5 +/- 1.6, mean +/- SD), were examined with respect to exercise tolerance, electrocardiographic (ECG) response and activity of biochemical markers for myocardial injury. The protocol included standard electrocardiography, M-mode and two-dimensional echocardiography at rest, a Bruce walking treadmill test to voluntary exhaustion, and determination of cardiac troponin I and T, creatine kinase and myoglobin from venous blood samples at rest and 4 h after exercise. Heart rate, blood-pressure response to exercise stress and endurance time were compared with published results of age-matched normal children. RESULTS: 54 patients (96.4%) had normal exercise capacity; a reduction in 2 patients was not due to cardiac disease. Heart rate and systolic blood pressure rose significantly between rest and peak exercise and did not differ from normal controls, whereas diastolic blood pressure was lower. ECG remained normal at rest and on exercise in 54 children (96.4%). Serum values of cardiac troponin I and T, creatine kinase and myoglobin were normal at rest and after exercise in all patients. CONCLUSION: The study demonstrates excellent long-term exercise capacity after neonatal arterial switch operation. Exercise testing is a useful and non-invasive screening method to detect patients with clinically relevant exercise-induced myocardial ischaemia and should be routinely performed in growing patients.

Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries.

AIMS: To evaluate behavioural outcome and quality of life in children aged 8-14 years after neonatal arterial switch operation for transposition of the great arteries. METHODS: Sixty children operated as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were evaluated at age 7.9-14.3 years by the Child Behaviour Checklist (CBCL) and the Inventory for the Assessment of the Quality of Life in Children and Adolescents (IQCL). RESULTS: Parent reported behavioural outcome on all CBCL problem and competence scores was worse, whereas quality of life on self reported IQCL scores was not reduced compared to the normal population. On multivariate analysis, severe preoperative hypoxia was related to parent reported social problems; peri- and postoperative cardiocirculatory insufficiency was associated with internalizing, externalizing, attention, and total behavioural problems. Reduced expressive language was associated with total behavioural problems, and poor academic achievement was related to parent reported deficits in school performance. Impaired neurological status and reduced endurance capacity both predicted self reported stress by illness. CONCLUSIONS: The neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with parent reported long term behavioural impairment, but not with self reported general reduction in quality of life. This discrepancy may be a result of different perception of illness. In our experience, increased risk of long term psychosocial maladjustment after neonatal corrective cardiac surgery is related to the presence of neurological impairment and reduced endurance capacity.

Time course of cranial ultrasound abnormalities after arterial switch operation in neonates.

BACKGROUND: The object of this study was to investigate the time course and fate of abnormal findings in cranial ultrasound after performing an arterial switch operation in neonates with transposition of the great arteries, and to analyze the relationship to cerebral cell damage. METHODS: Cranial ultrasound was performed prospectively in 35 neonates with transposition of the great arteries before the operation as well as 4 hours, 1, 2, and 3 days, and 1 and 2 weeks postoperatively. Blood levels of neuron-specific enolase, a marker of cerebral cell damage, were determined before, during, and 4 and 24 hours postoperatively. RESULTS: In 17 of 35 neonates (49%), early postoperative cranial ultrasound revealed abnormalities indistinguishable from intraventricular hemorrhage. In 11 neonates findings were transient and were normalized 2 weeks postoperatively, whereas in the remaining 6 neonates there was evidence of resolving hemorrhage. In all neonates there was a rise in neuron-specific enolase blood concentrations during and 4 hours after extracorporal circulation without correlation to sonographic findings. CONCLUSIONS: Enhanced echogenicity of the choroid plexus or dilatation of the cerebral ventricular system is a frequent early postoperative finding that may be caused by transient plexus edema rather than intraventricular hemorrhage and is not related to cerebral cell damage.

Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation.

BACKGROUND: Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospective assessment. METHODS: A group of 33 unselected children (3.0 to 4.6 years) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children (3.0 to 4.8 years) underwent evaluation of socioeconomic and clinical neurological status and a standardized test comprising all areas of child development. Results of patients were related to those of the control group, to population norms, and to preoperative, perioperative, and postoperative cerebral risk factors. RESULTS: Clinical neurological status was normal in 26 patients (78.8%) and reduced in 7 (21.2%). Complete developmental score and the subscores for motor function, visual perception, learning and memory, cognitive function, language, and socioemotional functions were not different compared to population norms. Compared to the patients, the children of the control group scored higher on tests of complete development, cognition, and language, but also on socioeconomic status. Complete developmental score and the scores for motor, cognitive, and language functions were weakly inversely related to the duration of circulatory arrest, but not to the duration of bypass. Cerebral risk factors such as serum levels of the neuron-specific enolase, perinatal acidosis, perinatal asphyxia, peri- and postoperative cardiocirculatory insufficiency, or clinical seizures were not correlated to the test results. CONCLUSIONS: Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment, but not with reduced development as assessed by formal testing of motor, cognitive, language, and behavioral functions. Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment.

Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. There is a remarkable degree of clinical variability both within and between families with Marfan syndrome as well as in individuals with related disorders of connective tissue caused by FBN1 mutations and collectively termed type-1 fibrillinopathies. The so-called neonatal region in FBN1 exons 24-32 comprises one of the few generally accepted genotype-phenotype correlations described to date. In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders. The data reported here, together with other published reports, document a significant clustering of mutations in exons 24-32. Although all reported mutations associated with neonatal Marfan syndrome and the majority of point mutations associated with atypically severe presentations have been found in exons 24-32, mutations associated with classic Marfan syndrome occur in this region as well. It is not possible to predict whether a given mutation in exons 24-32 will be associated with classic, atypically severe, or neonatal Marfan syndrome.

Cardiac myxoma in a 6-year-old child--constitutional symptoms mimicking rheumatic disease and the role of interleukin-6.

A 6-y-old girl with right atrial myxoma presented with remittent fever attacks, general arthralgia and laboratory investigations mimicking rheumatic or autoimmune disease. Interleukin-6 (IL-6) serum concentration was markedly elevated before and normal after tumour resection, whereas myxoma cells stained negatively for IL-6. IL-6 should be considered a myxoma marker: overproduction by myxoma cells and consecutive systemic passage are assumed to cause immunological features.

Results of the Bruce treadmill test in children after arterial switch operation for simple transposition of the great arteries.

Children who underwent arterial switch operation for simple transposition of the great arteries in the neonatal period are now reaching an age when exercise testing becomes feasible. This study was conducted to assess exercise tolerance and electrocardiographic response to exercise stress in 50 asymptomatic children, aged 4 to 9 years, using the Bruce walking treadmill protocol to voluntary exhaustion. Heart rate and blood pressure response to exercise stress, endurance time, and electrocardiographic changes were analyzed and compared with those of age-matched normal children. Forty-seven patients had normal exercise capacity and parameters. One patient, whose coronary angiogram showed occlusion of the left main coronary artery, developed electrocardiographic signs of myocardial ischemia during exercise. In 1 patient with a single right coronary artery ostium and in another, who underwent a neonatal internal mammary bypass graft for obstruction of the right coronary artery, the resting electrocardiogram showed ventricular premature complexes and exercise stress-induced salvos of ventricular tachycardia. We conclude that most of the children who underwent the neonatal arterial switch operation for simple transposition of the great arteries have a normal exercise capacity. Exercise testing appears to be useful in detecting ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve.

Cardiological and general health status in preschool- and school-age children after neonatal arterial switch operation.

OBJECTIVE: Cardiological and general health status 3-9 years after neonatal arterial switch operation for transposition of the great arteries should be evaluated by non-invasive methods. METHODS: A total of 77 unselected children with intact ventricular septum (75.3%) or ventricular septal defect (24.7%) without or with aortic isthmic stenosis (5.2%) were prospectively examined 3.2-9.4 years (5.4 +/- 1.6) after neonatal switch. Clinical pediatric and cardiological examination, standard and 24 h Holter electrocardiogram, M-mode, 2D-, Doppler and colour Doppler echocardiography were performed. Outcome data were compared to published normals. RESULTS: Reoperation rate was 2.6%, 96.1% were without limitation of physical activity and 98.7% without medication. Compared to normals, growth was adequate, weight and head circumference were slightly reduced. After median sternotomy, 23.4% had abnormal thoracic configuration (16.9% asymmetry, 6.5% funnel chest). ECG and Holter: 93.5% were in sinus, 6.5% in ectopic atrial or junctional rhythm. Incidence of complete right bundle branch block was 15.8% in patients with ventricular septal defect and 5.2% in those without. Ischemic ST-T changes during exercise due to coronary artery occlusion and evidence of old myocardial infarction were found in 1 patient (1.3%) each. Occasional atrial ectopy was found in 27.4%, ventricular ectopy in 15.3%: occasional in 12.5% and frequent (> 30/h) in 2.8% presenting bigemini, couplets and short runs of ventricular tachycardia at rest and during exercise. Echocardiography: Left ventricular function was normal in all. Endsystolic diameter of neoaortic valve annulus was beyond 90% confidence interval for controls in 79.2%, neoaortic root diameter in 100%. Mild aortic insufficiency was seen in 10.4%. No correlation was found between aortic insufficiency and aortic dilatation. Neoaortic stenosis was not seen, mild residual coarctation after end-to-end-anastomosis was found in 2.6%, native coarctation corrected later on in 1.3%. Supravalvular pulmonary stenosis was seen in 29.9% (19.5% trivial, 7.8% mild, 2.6% moderate), mild subvalvular pulmonary stenosis in 1.3%, pulmonary insufficiency in 2.6%. CONCLUSION: The study confirms good midterm results after neonatal arterial switch operation for transposition with or without ventricular septal defect. Long-term observation is necessary to assess rhythm, coronary artery and myocardial function as well as development of neo-aorta and pulmonary artery system.

Cognitive and motor development in preschool and school-aged children after neonatal arterial switch operation.

OBJECTIVE: The developmental status of children beyond 3 years of age after the neonatal arterial switch operation has not yet been systematically evaluated and is the topic of the present work. METHODS: Seventy-seven unselected children operated on as neonates with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass were examined at an age of 3.2 to 9.4 years (5.4 +/- 1.6 years, mean +/- standard deviation). Clinical neurologic status, standard scores of intelligence, acquired abilities and vocabulary, and standardized tests on gross motor and fine motor functions were carried out, and the results were related to preoperative, perioperative, and postoperative status and management. RESULTS: Neurologic impairment was more frequent (9.1%) than in the normal population. Intelligence was not different in these patients compared with normal children (p = 0.11), but motor function, vocabulary, and acquired abilities were poorer. Reduced intelligence was found in 9.1%, fine motor dysfunction in 22.1%, and gross motor dysfunction in 23.4% of the children. Intelligence was weakly but significantly inversely related to the duration of bypass (Spearman correlation coefficient -0.25, p = 0.03) and tended to be inversely related to the duration of circulatory arrest (-0.21, p = 0.07), but not to core cooling time on bypass or degree of hypothermia. Gross motor function, vocabulary, and acquired abilities were not significantly related to any of the perioperative parameters considered. No correlation was found between the test results and the variables perinatal asphyxia, perioperative and postoperative cardiocirculatory insufficiency, resuscitation events, and plexal or intraventricular cerebral hemorrhage. CONCLUSIONS: The neonatal arterial switch operation with combined circulatory arrest and low-flow bypass in our experience is associated with neurologic as well as fine and gross motor impairment but appears to be well tolerated concerning cognitive functions as based on formal intelligence testing.

["Primary" pulmonary hypertension and systemic lupus erythematosus in adolescence]. / "Primäre" pulmonale Hypertension und systemischer Lupus erythematodes im Jugendalter.

Report is given on a 15 years old girl suffering from severe "primary" pulmonary hypertension (PPH) of the plexogenic type without underlying pulmonary parenchymal or cardiac disease. Diagnosis was established by cardiac catheterization and lung biopsy. At the same time she had clinical symptoms and laboratory signs of systemic lupus erythematosus (SLE). Looking back there had been for some years symptoms suggestive of both diseases. PPH is characterized by several histopathological criteria whereas its aetiology is unknown. A causal connexion between PPH and connective tissue diseases, especially SLE, is probable because of their repeatedly observed coincidence. Raynauds phenomenon, sometimes included in some connective tissue syndrome, and vascular alterations in PPH could be explained by sustained vasoconstrictive mechanisms caused by hyperractive pulmonary vessels. Another possible pathogenetic role relates to immune complexes causing vascular changes. It is assumed that, besides the classical pulmonary involvement, vascular changes of "primary" pulmonary hypertension themselves may represent a typical albeit rare pulmonary manifestation of SLE or other connective tissue disease.

[Skeletal side effects of treatment with prostaglandin E1]. / Nebenwirkungen am Skelettsystem bei Behandlung mit Prostaglandin E.

The effects on the skeleton of the treatment of childhood ductus with prostaglandin E1 and E2 are described. Prolonged prostaglandin therapy leads to cortical hyperostosis of the diaphyses of long tubular bones, ribs, scapulae, and clavicles. There is also delay in ossification of the skull vault and widening of the sutures. After cessation of treatment, cortical hyperostosis in the long bones remains, whereas the widening of the skull sutures regresses completely.