Summary Background Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in ...Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about demographics, treatment, and outcomes in paediatric pulmonary hypertension. Methods Consecutive patients aged 18 years or younger at diagnosis with pulmonary hypertension and increased pulmonary vascular resistance were enrolled in TOPP at 31 centres in 19 countries from Jan 31, 2008, to Feb 15, 2010. Patient and disease characteristics, including age at diagnosis and at enrolment, sex, ethnicity, presenting symptoms, pulmonary hypertension classification, comorbid disorders, medical and family history, haemodynamic indices, and functional class were recorded. Follow-up was decided by the patients' physicians according to the individual's health-care needs. Findings 362 of 456 consecutive patients had confirmed pulmonary hypertension (defined as mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤12 mm Hg, and pulmonary vascular resistance index ≥3 WU/m−2 ). 317 (88%) patients had pulmonary arterial hypertension (PAH), which was idiopathic IPAH or familial FPAH in 182 (57%), and associated with other disorders in 135 (43%), of which 115 (85%) cases were associated with congenital heart disease. 42 patients (12%) had pulmonary hypertension associated with respiratory disease or hypoxaemia, with bronchopulmonary dysplasia most frequent. Finally, only three patients had either chronic thromboembolic pulmonary hypertension or miscellaneous causes of pulmonary hypertension. Chromosomal anomalies, mainly trisomy 21, were reported in 47 (13%) of patients with confirmed disease. Median age at diagnosis was 7 years (IQR 3–12); 59% (268 of 456) were female. Although dyspnoea and fatigue were the most frequent symptoms, syncope occurred in 31% (57 of 182) of patients with IPAH or FPAH and in 18% (eight of 45) of those with repaired congenital heart disease; no children with unrepaired congenital systemic-to-pulmonary shunts had syncope. Despite severe pulmonary hypertension, functional class was I or II in 230 of 362 (64%) patients, which is consistent with preserved right-heart function. Interpretation TOPP identifies important clinical features specific to the care of paediatric pulmonary hypertension, which draw attention to the need for paediatric data rather than extrapolation from adult studies. Funding Actelion Pharmaceuticals.
Abstract Objectives The goal of this study was to delineate outcomes of children weighing <10 kg supported with the Berlin Heart EXCOR Pediatric Ventricular Assist Device (EXCOR Pediatric, Berlin ...Heart Inc., The Woodlands, Texas) and to identify factors that increased the risk of all-cause mortality in this population. Background Ventricular assist devices have been shown to be an effective bridge to transplant, with improved outcomes compared with use of extracorporeal membrane oxygenation. Smaller patients may be at greatest risk for poor outcomes, but it remains unclear if mortality is uniform across all smaller candidates. Methods Patients included in the analysis were part of a multicenter prospective cohort study examining the use of the Berlin Heart EXCOR Pediatric Ventricular Assist Device as a bridge to transplant. All children who received the device between May 9, 2007 and December 31, 2010, and who were enrolled in the sponsor’s U.S. regulatory database, were identified and analyzed. Multivariable analysis was performed to determine risk factors associated with mortality. Results A total of 97 children weighing <10 kg were included (median age 6.2 months; median weight 6.2 kg; median duration of support 26 days). Successful outcomes were achieved in 56.7% of patients. Independent risk factors for mortality in smaller children included pre-existing congenital heart disease (odds ratio: 4.8 95% confidence interval: 1.5 to 15.0; p = 0.007) and an elevated bilirubin level (odds ratio: 5.3 95% confidence interval: 2.0 to 14.3; p = 0.001). Conclusions Overall results for children weighing <10 kg were inferior to those of their larger counterparts. This outcome was primarily influenced by congenital heart disease and presence of elevated pre-implant bilirubin levels. These factors should be taken into consideration at decision making because reasonable outcomes can be achieved in a select population of children weighing <10 kg.
BACKGROUND Pulmonary venoocclusive disease (PVOD) is a rare lung disease, diagnosed in 5% to 10% of patients with pulmonary hypertension (PH). The incidence, prevalence, and etiology of PVOD in ...children are not well defined. The mortality remains high, related, at least partly, to the limited treatment options. METHODS This retrospective analysis (1985-2011) summarizes symptoms, associated factors, treatment, and outcomes of nine pediatric patients (five girls, four boys) with histologic confirmation of PVOD. RESULTS PH was diagnosed at a mean age of 13.5 years (range, 8-16 years), followed by the definitive diagnosis of PVOD at a mean age of 14.3 years (range, 10-16 years). Symptoms such as decreased exercise tolerance (n = 6) and/or shortness of breath (n = 9) preceded the diagnosis by 21 months on average; the mean survival time after diagnosis was 14 months (range, 0-47 months). CT scans of the lungs showed typical radiologic features. Treatment included supplemental home oxygen (n = 5), diuretics (n = 9), warfarin (n = 4), and pulmonary vasodilators (n = 4). Four children were listed for lung transplantation, and three have undergone transplantation. Eight patients died, including two after lung transplantation. One patient with lung transplant survived with good quality of life. CONCLUSIONS PVOD is an important differential diagnosis for pediatric patients with PH. CT scanning is a valuable tool to image lung abnormalities; the definitive diagnosis can only be made by examination of lung biopsy specimens, which subjects the patient to additional risk. Early listing for lung transplantation is essential, as the mean survival time is only 14 months.
Background Biventricular assist device (BiVAD) support was a strong predictor of early mortality in the Berlin Heart EXCOR Pediatric investigational device exemption (IDE) study (Assess Safety and ...Probable Benefit of the EXCOR Pediatric Ventricular Assist Device VAD). In adults, it has been identified that 5% to 10% of the VAD population is benefited by BiVAD support over left ventricular assist device (LVAD) support. An analysis of the Berlin Heart study cohort was performed to characterize patients supported with BiVAD, examine risk factors of mortality in this group, and identify subsets of patients in whom BiVAD is associated with survival. Methods All EXCOR Pediatric devices (Berlin Heart, Inc, The Woodlands, TX) placed in North America between May 2007 and December 2010 comprised the study cohort of 204 patients (128 63% LVADs and 76 37% BiVADs). The following patient cohorts were analyzed to determine the effect of BiVAD use on survival: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients, patients with abnormal bilirubin levels, patients who received previous extracorporeal membrane oxygenation (ECMO), and patients with a 10-mL pump size. Results There were more patients with BiVADs in INTERMACS profile 1 (63% compared with 46%; p = 0.018). The incidence of major bleeding, neurologic and renal dysfunction, and infection was similar between BiVAD and LVAD groups. White race, abnormal glomerular filtration rate (GFR), sites with experience of less than 5 implantations, and use of 10-mL pumps were predictors of mortality in patients who received BiVADs. BiVADs were not associated with improved survival in any patient cohort; however, they were associated with increased mortality in patients who had undergone ECMO before receiving a VAD. Conclusions BiVAD support was not associated with improved survival in any identified subset of patients. Although not randomized, these results (which were corrected for multiple possible risk factors) suggest that some children supported with BiVADs might have done better with LVADs alone. Further prospective studies will be needed to identify patient cohorts that will be better served with BIVAD support.
The objective of this study was to investigate the systolic to diastolic duration ratio (S:D ratio) in children with pulmonary arterial hypertension (PAH) and its association with right ventricular ...(RV) performance, hemodynamics, 6-minute walk test, clinical outcomes, and survival. We reviewed 503 serial echocardiograms in 47 children with PAH (mean pulmonary artery pressure ≥25 mm Hg) and compared the S:D ratio, assessed from Doppler flow of tricuspid valve regurgitation, to that in 47 age-matched controls. We reviewed echocardiograms, catheterization data, 6-minute walk tests, clinical data, lung transplantation, and death and used univariate linear regression models with a maximum likelihood algorithm for parameter estimation to investigate associations between S:D ratio and RV function, hemodynamics, functional capacity, and clinical outcomes. The S:D ratio was significantly higher in patients than in controls (1.38 ± 0.61 vs 0.72 ± 0.16, p <0.001). A higher S:D ratio was associated with worse echocardiographic RV fractional area of change, worse catheterization hemodynamics, shorter 6-minute walk distance, and worse clinical outcomes independent of pulmonary resistance or pressures. An increase of 0.1 in the S:D ratio was associated with a 13% increase in yearly risk for lung transplantation or death (hazard ratio 1.13, p <0.001). An S:D ratio 1.00 to 1.40 was associated with a moderate risk and an S:D ratio >1.40 was associated with a high risk of a negative outcome. In conclusion, in children with PAH, an increased S:D ratio is temporally associated with worse RV function, hemodynamics, exercise capability, clinical status, and survival.
Objectives Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function ...in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Methods Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Results Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor β genes. Conclusions Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV.
Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North ...America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation.
Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available.
Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR.
This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.
Abstract The updated American Heart Association/American Stroke Association guidelines include recommendation for thrombectomy in certain adult stroke cases. The safety and efficacy of thrombectomy ...in children are unknown. An 8-year-old girl experienced acute stroke symptoms on two occasions while therapeutically anticoagulated on Novalung. Computed tomography scans showed proximal vessel thrombi, which were retrieved using a Trevo device without hemorrhagic complications. Postprocedural assessment found respective decreases in the National Institutes of Health Stroke Scale score from 10 to 4 and 12 to 7. The indications for treatment and early benefits observed in our case are consistent with other pediatric thrombectomy cases reported. However, publication bias and the heterogeneity of reported cases prevent drawing conclusions about the safety and efficacy of thrombectomy in children. Anticipating that updates to adult stroke guidelines would likely incite stroke providers to consider thrombectomy in children, our institution developed guidelines for thrombectomy before the index patient. Establishing institutional guidelines before considering thrombectomy in children may optimize patient safety.
PDF
