Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005.

BACKGROUND: Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. METHODS AND RESULTS: Two registries were used to retrospectively identify children (0-17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently. CONCLUSIONS: Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses.

Normal values for cardiopulmonary exercise testing in children.

BACKGROUND: A reference set of data of normal values of newly developed cardiopulmonary parameters of exercise testing in an 8-18-year-old population is lacking. PATIENTS AND METHODS: Cardiopulmonary exercise testing was performed in 175 healthy school children (8-18 years old). Continuous electrocardiography was performed, and minute ventilation, oxygen uptake (VO2), and carbon dioxide (CO2) production were measured continuously with a respiratory gas analysis system. RESULTS: Peak VO2/kg did not change with age, whereas the ventilation to carbon dioxide exhalation slope was lower in the older children. The decline in heart rate during recovery was much faster in the youngest children. Linear regression analysis showed a significant effect of age on: peak work rate (WRpeak) and WRpeak/kg, ventilation to carbon dioxide exhalation slope, heart rate recovery, and VO2peak (boys only) (All P < 0.001). The ΔVO2/ΔWR slope remained constant throughout all age groups. CONCLUSION: This study comprehensively provides a reference set of data for the most important cardiopulmonary variables that can be obtained during exercise testing in children.

Outcome of pediatric patients with pulmonary arterial hypertension in the era of new medical therapies.

Little is known about the effects of "second-generation drugs" (prostanoids, endothelin receptor antagonists, 5-phosphodiesterase inhibitors) in children with pulmonary arterial hypertension (PAH). This study describes the outcome of a national cohort of children with PAH in an era when these drugs became available. From 1993 to 2008, 52 consecutive children with idiopathic PAH (n = 29) or systemic-to-pulmonary shunt-associated PAH (n = 23) underwent baseline and follow-up assessments. Treatment was initiated depending on functional class, acute pulmonary vasoreactivity response, and drug availability. Observed survival was evaluated depending on time of diagnosis in relation to second-generation drug availability and subsequently compared to calculated predicted survival. Children for whom second-generation drugs were available had improved survival compared to their predicted survival (1-, 3-, and 5-year survival rates 93%, 83%, and 66% vs 79%, 61%, and 50%, respectively). However, this improved survival was observed only in patients for whom second-generation drugs became available during their disease course. No improved survival was observed in patients for whom drugs were available already at diagnosis. Baseline variables associated with decreased survival included higher functional class, higher pulmonary-to-systemic arterial pressure ratio, lower cardiac index, and higher serum levels of N-terminal pro-brain natriuretic peptide and uric acid. After start of second-generation drugs, functional class, 6-minute walking distance, and N-terminal pro-brain natriuretic peptide improved but gradually decreased after longer follow-up. In conclusion, survival of pediatric PAH seemed improved since the introduction of second-generation drugs only in selected patients for whom these drugs became available during their disease course. Start of second-generation drugs initially induced clinical improvements, but these effects decreased after longer follow-up.

Clinical characterization of pediatric pulmonary hypertension: complex presentation and diagnosis.

OBJECTIVES: To describe the clinical presentation of pediatric pulmonary arterial hypertension (PAH) and the intricacies of how to classify pediatric PAH according to the Venice classification. STUDY DESIGN: Children (n = 63) seen at a national referral center for pediatric PAH underwent a diagnostic work-up for diagnosis of pulmonary hypertension (PH) and associated conditions and for assessment of the explanatory role of associated conditions for the PH. Subsequently, PH was classified. RESULTS: In 18 patients (29%), no associated conditions were identified; they were classified as having idiopathic PAH. In 45 patients (71%), > or = 1 associated conditions were detected: congenital heart defects (CHD, n = 40), connective tissue disease (CTD, n = 2), disorders of respiratory system and/or hypoxemia (RSH, n = 17), and chronic thromboembolic disease (CTE, n = 1). Patients were classified according to the condition judged to be primarily explanatory for the PH. In 11 of 45 patients with associated conditions, the PH was not sufficiently explained by these conditions; these patients were classified as having idiopathic-like PAH. In 17 of 40 cases of CHD and 9 of 17 cases of RSH, these conditions were not sufficiently explanatory for the PH. Syndromal abnormalities were frequent (43%). Ultimately, classification revealed idiopathic (-like) PAH (n = 29; 46%), PAH-CHD (n = 23; 37%), PAH-CTD (n = 2; 3%), PH-RSH (n = 8; 12%), and CTE-PH (n = 1; 2%). CONCLUSION: Pediatric PH frequently presents with associated conditions and syndromal abnormalities. However, detailed evaluation of this complex presentation reveals that associated conditions are not always explanatory for the PH.

Diastolic dysfunction in paediatric patients on peritoneal dialysis and after renal transplantation.

BACKGROUND: Cardiovascular disease is the leading cause of death in children with end-stage renal disease. We investigated the presence of cardiac systolic and diastolic dysfunction in patients on peritoneal dialysis or after renal transplantation. Methods and results. Fourteen patients on peritoneal dialysis for a mean of 1.4 years (range 0.1-5.3) and 39 patients with a functioning kidney transplant for a median time of 3.3 years (range 1.2-14.5) were studied. These patients were compared to 153 age-matched healthy controls. As assessed by echocardiography, both dialysis and transplant patients showed left ventricular dysfunction. Systolic tissue Doppler values were lower as compared to controls. Mitral E/A ratios were significantly lower as well, indicating diastolic dysfunction (transplant 1.82 +/- 0.58 versus 2.15 +/- 0.63, P < 0.01; dialysis patients 1.57 +/- 0.73 versus 2.31 +/- 0.52, P < 0.01). Also, tissue Doppler values were different, showing an increased E/E' ratio in the patients, indicating diastolic dysfunction (transplant 9.49 +/- 1.71 versus 7.50 +/- 1.60, P < 0.01; dialysis patients 11.90 +/- 2.11 versus 8.10 +/- 1.24, P < 0.01). The left ventricular mass index was increased in the transplant patients (controls 25 +/- 7 g/m(2.7); transplant 59 +/- 64 g/m(2.7); P < 0.01), as well as in the dialysis patients (controls 28 +/- 7 g/m(2.7); dialysis 43 +/- 11 g/m(2.7); P < 0.01) and was associated with systolic hypertension (R = 0.46, P < 0.05). High parathyroid hormone (PTH) levels, more prevalent in dialysis patients, were associated with abnormal E/A and E/E' ratios. CONCLUSIONS: Abnormalities in diastolic function are present in both peritoneal dialysis and renal transplanted patients. In the dialysis group, abnormalities in calcium-phosphate metabolism are associated with diastolic dysfunction. Cardiac hypertrophy was noted in both patient groups and was associated with systolic hypertension.

Follow-up outcomes 10 years after arterial switch operation for transposition of the great arteries: comparison of cardiological health status and health-related quality of life to those of the a normal reference population.

The purpose of this study was to investigate the cardiological health status and health-related quality of life after the arterial switch operation (ASO) for transposition of the great arteries (TGA) in comparison with a normative reference group. Chart review and cross-sectional systematic follow-up, including echocardiography, exercise testing, and electrocardiography, were performed on all survivors of ASO for TGA between 1990 and 1995. Health-related quality of life (HRQOL) was assessed using a standardized questionnaire. A normative reference group was included. Forty-nine survivors [median age at operation 13 days, mean age at follow-up 11 +/- 2 years (37/49 with intact ventricular septum] were identified. Thirty-three of 49 patients (67%) [22/33 TGA with intact ventricular septum (IVS)] participated in cross-sectional follow-up. Cumulative 10-year event-free survival was 88% and the re-intervention rate 6%. Aortic root dilatation occurred in 70% of patients; none had severe aortic regurgitation. Left ventricular function was normal. Exercise performance (85% of reference capacity, p = 0.02), maximal oxygen uptake (85%, p < 0.01) and peak heart rate (95%, p < 0.01) were decreased. Exercise electrocardiogram was normal as was rhythm status. Unfavourable outcomes on HRQOL were found for motor functioning and positive emotional functioning. Overall there were no significant differences between TGA/IVS and TGA/VSD. We conclude that at mid- to long-term follow-up after ASO, major events and re-interventions (6%) occur infrequently. Exercise capacity and maximal oxygen uptake are lower than those in a reference population, which could not be related to diminished ventricular function. Aortic root dilatation is frequent, irrespective of the anatomical subgroup. Severe aortic regurgitation or left ventricular dilatation was not found. The unfavourable health-related quality of life deserves further attention.