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1.
Pediatr Res ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32521539

RESUMO

Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient.We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions.We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.

3.
Hepatology ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32407592

RESUMO

OBJECTIVES: Portopulmonary hypertension (POPH) was previously associated with a single nucleotide polymorphism (SNP) rs7175922 in aromatase (CYP19A1). We sought to determine if genetic variants and metabolites in the estrogen signaling pathway are associated with POPH. METHODS: We performed a multicenter case-control study. POPH patients had mean pulmonary artery pressure > 25 mmHg, pulmonary vascular resistance > 240 dynes•s•cm-5 , and pulmonary artery wedge pressure ≤ 15 mmHg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure < 40 mmHg and normal RV function by echocardiography. We genotyped three SNPs in CYP19A1 and CYP1B1 using TaqMan and imputed SNPs in ESR1 using genome-wide markers. Estrogen metabolites were measured in blood and urine samples. MAIN RESULTS: There were 37 patients with POPH and 290 controls. The mean age was 57 years and 36% were female. The risk allele rs7175922 in CYP19A1 was significantly associated with higher levels of estradiol (p = 0.02) and an increased risk of POPH (OR 2.36, 95% CI 1.12-4.91, p = 0.02) whereas other SNPs were not. Higher urinary 2-hydroxyestrogen/16-α-hydroxyestrone (2-OHE/16α-OHE1) (OR per 1 ln increase = 2.04, 95%CI 1.16-3.57, p = 0.01), lower plasma levels of dehydroepiandrosterone-sulfate (DHEA-S) (OR per 1 ln decrease = 2.38, 95%CI 1.56-3.85, p < 0.001) and higher plasma levels of 16-α-hydroxyestradiol (16α-OHE2) (OR per 1 ln increase = 2.16, 95%CI 1.61-2.98, p < 0.001) were associated with POPH. CONCLUSIONS: Genetic variation in aromatase and changes in estrogen metabolites were associated with POPH.

4.
J Cardiovasc Pharmacol ; 76(1): 94-100, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32398473

RESUMO

As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7-17 years), and the median weight was 42.2 kg (range 19.3-78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32255665

RESUMO

Mutations in the gene encoding the bone morphogenetic protein type 2 receptor, BMPR2, are the major cause of heritable pulmonary arterial hypertension (HPAH). Point mutations in the BMPR2 ligand binding domain involving cysteine residues (such as C118W) are causative of PAH and predicted to cause protein misfolding. Using heterologous overexpression systems, we showed previously that these mutations lead to retention of BMPR2 in the endoplasmic reticulum, but are partially rescued by chemical chaperones. Here we determine whether the chemical chaperone, 4-PBA, restores BMPR2 signalling in primary cells and in a knock-in mouse harbouring a C118W mutation. First, we confirmed dysfunctional BMP signalling in dermal fibroblasts isolated from a PAH family segregating the BMPR2 C118W mutation. Following BMP4 treatment, the induction of downstream signalling targets, Smad1/5, ID1 and ID2, was significantly reduced in C118W mutant cells. Treatment with 4-PBA significantly rescued Smad1/5, ID1 and ID2 expression. Pulmonary artery smooth muscle cells (PASMCs) isolated from the lungs of heterozygous mice harbouring the Bmpr2 C118W mutation exhibited significantly increased proliferation. In the presence of 4-PBA, hyperproliferation was dramatically reduced. Furthermore, in vivo, 4-PBA treatment of Bmpr2 C118W mice partially rescued Bmpr2 expression, restored downstream signalling and improved vascular remodelling. These findings demonstrate in primary cells and in a knock-in mouse that the repurposed small molecule chemical chaperone, 4-PBA, might be a promising precision medicine approach to treat PAH in patients with specific subtypes of BMPR2 mutation involving cysteine substitutions in the ligand binding domain.

6.
JRSM Cardiovasc Dis ; 9: 2048004020906994, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110389

RESUMO

Purpose: Chronic thromboembolic pulmonary hypertension is characterized by incomplete thrombus resolution following acute pulmonary embolism, leading to pulmonary hypertension and right ventricular dysfunction. Conditions such as thrombophilias, dysfibrinogenemias, and inflammatory states have been associated with chronic thromboembolic pulmonary hypertension, but molecular mechanisms underlying this disease are poorly understood. We sought to characterize the molecular and functional features associated with chronic thromboembolic pulmonary hypertension using a multifaceted approach. Methods: We utilized functional assays to compare clot lysis times between chronic thromboembolic pulmonary hypertension patients and multiple controls. We then performed immunohistochemical characterization of tissue from chronic thromboembolic pulmonary hypertension, pulmonary arterial hypertension, and healthy controls, and examined RNA expression patterns of cultured lymphocytes and pulmonary arterial specimens. We then confirmed RNA expression changes using immunohistochemistry, immunofluorescence, and Western blotting in pulmonary arterial tissue. Results: Clot lysis times in chronic thromboembolic pulmonary hypertension patients are similar to multiple controls. Chronic thromboembolic pulmonary hypertension endarterectomized tissue has reduced expression of both smooth muscle and endothelial cell markers. RNA expression profiles in pulmonary arteries and peripheral blood lymphocytes identified differences in RNA transcript levels related to inflammation and growth factor signaling, which we confirmed using immunohistochemistry. Gene expression data also suggested significant alterations in metabolic pathways, and immunofluorescence and Western blot experiments confirmed that unglycosylated CD36 and adiponectin expression were increased in chronic thromboembolic pulmonary hypertension versus controls. Conclusions: Our data do not support impaired clot lysis underlying chronic thromboembolic pulmonary hypertension, but did demonstrate distinct molecular patterns present both in peripheral blood and in pathologic specimens of chronic thromboembolic pulmonary hypertension patients suggesting that altered metabolism may play a role in chronic thromboembolic pulmonary hypertension pathogenesis.

7.
Am J Respir Crit Care Med ; 201(11): 1329-1331, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32053755
8.
Eur Respir J ; 55(4)2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32029443

RESUMO

The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort.IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models.Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08-1.38; p<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease.IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.

9.
Chest ; 157(6): 1606-1616, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31987881

RESUMO

BACKGROUND: Three biomarkers, soluble suppression of tumorigenicity 2 (ST2), galectin 3 (Gal3), and N-terminal brain natriuretic peptide prohormone (NT-proBNP), are approved for noninvasive risk assessment in left-sided heart failure, and small observational studies have shown their prognostic usefulness in heterogeneous pulmonary hypertension cohorts. We examined associations between these biomarkers and disease severity and survival in a large cohort of patients with pulmonary arterial hypertension (PAH) (ie, group 1 pulmonary hypertension). We hypothesized that additive use of biomarkers in combination would improve the prognostic value of survival models. METHODS: Biomarker measurements and clinical data were obtained from 2,017 adults with group 1 PAH. Associations among biomarker levels and clinical variables, including survival times, were examined with multivariable regression models. Likelihood ratio tests and the Akaike information criterion were used to compare survival models. RESULTS: Higher ST2 and NT-proBNP were associated with higher pulmonary pressures and vascular resistance and lower 6-min walk distance. Higher ST2 and NT-proBNP levels were associated with increased risk of death (hazard ratios: 2.79; 95% CI, 2.21-3.53; P < .001 and 1.84; 95% CI, 1.62-2.10; P < .001, respectively). The addition of ST2 to survival models composed of other predictors of survival, including NT-proBNP, significantly improved model fit and predictive capacity. CONCLUSIONS: ST2 and NT-proBNP are strong, noninvasive prognostic biomarkers in PAH. Despite its prognostic value in left-sided heart failure, Gal3 was not predictive in PAH. Adding ST2 to survival models significantly improves model predictive capacity. Future studies are needed to develop multimarker assays that improve noninvasive risk stratification in PAH.

10.
Pediatr Pulmonol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917901

RESUMO

Emerging data from studies of pediatric-onset pulmonary arterial hypertension (PAH) indicate that the genomics of pediatric PAH is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 35% of pediatric-onset idiopathic PAH (IPAH) compared with ~11% of adult-onset IPAH. De novo variants are the most frequent genetic cause of PAH in children, likely contributing to ~15% of all cases. Rare deleterious variants in bone morphogenetic protein receptor 2 (BMPR2) contribute to pediatric-onset familial PAH and IPAH with similar frequency as adult-onset. While likely gene-disrupting (LGD) variants in BMPR2 contribute across the lifespan, damaging missense variants are more frequent in early-onset PAH. Rare deleterious variants in T-box 4-containing protein (TBX4) are more common in pediatric-compared with adult-onset PAH, explaining ~8% of pediatric IPAH. PAH associated with congenital heart disease (APAH-CHD) and other developmental disorders account for a large proportion of pediatric PAH. SRY-related HMG box transcription factor (SOX17) was recently identified as an APAH-CHD risk gene, contributing less frequently to IPAH, with a greater prevalence of rare deleterious variants in children compared with adults. The differences in genetic burden and genes underlying pediatric- vs adult-onset PAH indicate that genetic information relevant to pediatric PAH cannot be extrapolated from adult studies. Large cohorts of pediatric-onset PAH are necessary to identify the unique etiological differences of PAH in children, as well as the natural history and response to therapy.

11.
Am J Respir Crit Care Med ; 201(2): 148-157, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31513751

RESUMO

Pulmonary arterial hypertension (PAH) is a disease characterized by progressive loss and remodeling of the pulmonary arteries, resulting in right heart failure and death. Until recently, PAH was seen as a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Although some of these anomalies are partially due to right ventricular insufficiency, recent data support a mechanistic link to the genetic and molecular events behind PAH pathogenesis. This review serves as an introduction to the major systemic findings in PAH and the evidence that supports a common mechanistic link with PAH pathophysiology. In addition, it discusses recent studies describing morphological changes in systemic vessels and the possible role of bronchopulmonary anastomoses in the development of plexogenic arteriopathy. On the basis of available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to systemic manifestations in PAH. This concept not only opens exciting research possibilities but also encourages clinicians to consider extrapulmonary manifestations in their management of patients with PAH.

12.
J Heart Lung Transplant ; 38(9): 879-901, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31495407

RESUMO

The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term "pulmonary hypertension" and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.

13.
Eur Respir J ; 54(2)2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31151956

RESUMO

Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated with TBX4 variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carrying TBX4 rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entire TBX4 locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4 mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

14.
Pulm Circ ; 9(3): 2045894019856471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215336

RESUMO

Treprostinil, a prostacyclin analogue, is approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Transition from parenteral to oral treprostinil has been successfully accomplished in adults with PAH but not in children. In this multicenter study, pediatric patients treated with parenteral (Cohort 1) or inhaled (Cohort 2) treprostinil were transitioned to oral treprostinil. Prostacyclin-naïve individuals on background oral PAH therapy received oral treprostinil as add-on therapy (Cohort 3). Successful transition was oral treprostinil dose maintenance through week 24. Patients were monitored for adverse events (AEs), 6-min walk distance (6MWD), PAH symptoms, World Health Organization (WHO) Functional Class (FC), cardiac magnetic resonance imaging (cMRI), cardiopulmonary exercise testing (CPET), and quality of life through 24 weeks. A total of 32 patients were enrolled in the study; 23 (72%) were girls (mean age = 12.2 years). All patients were on background oral PAH therapy. Overall, patients (96.9%) maintained transition to oral treprostinil; one patient (Cohort 1) transitioned to oral treprostinil, then back to parenteral after experiencing syncope and WHO FC change from II to III. Cohorts 1, 2, and 3 received a final mean oral treprostinil dose of 5.6, 3.3, and 4.5 mg t.i.d., respectively. All cohorts had variable changes in 6MWD, cMRI, and CPET. Overall, 12 serious AEs were reported. All patients had drug-related AEs including headache (81%), diarrhea (69%), nausea (66%), vomiting (66%), and flushing (56%). Pediatric patients maintained transition to oral treprostinil with preservation of exercise capacity and WHO FC. Prostanoid-related AEs were most common and similar to those reported in adults.

15.
J Pediatr ; 211: 63-71.e6, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31176455

RESUMO

OBJECTIVE: To investigate racial and ethnic differences in pulmonary hypertension subtypes and survival differences in a pediatric population. STUDY DESIGN: This was a retrospective analysis of a cohort of patients with pulmonary hypertension (aged ≤18 years) enrolled in the Pediatric Pulmonary Hypertension Network registry between 2014 and 2018, comprising patients at eight Pediatric Centers throughout North America (n = 1417). RESULTS: Among children diagnosed after the neonatal period, pulmonary arterial hypertension was more prevalent among Asians (OR, 1.83; 95% CI, 1.21-2.79; P = .0045), lung disease-associated pulmonary hypertension among blacks (OR, 2.09; 95% CI, 1.48-2.95; P < .0001), idiopathic pulmonary arterial hypertension among whites (OR, 1.58; 95% CI, 1.06-2.41; P = .0289), and pulmonary veno-occlusive disease among Hispanics (OR, 6.11; 95% CI, 1.34-31.3; P = .0184). Among neonates, persistent pulmonary hypertension of the newborn (OR, 4.07; 95% CI, 1.54-10.0; P = .0029) and bronchopulmonary dysplasia (OR, 8.11; 95% CI, 3.28-19.8; P < .0001) were more prevalent among blacks, and congenital diaphragmatic hernia was more prevalent among whites (OR, 2.29; 95% CI, 1.25-4.18; P = .0070). An increased mortality risk was observed among blacks (HR, 1.99; 95% CI, 1.03-3.84; P = .0396), driven primarily by the heightened mortality risk among those with lung disease-associated pulmonary hypertension (HR, 2.84; 95% CI, 1.15-7.04; P = .0241). CONCLUSIONS: We found significant racial variability in the prevalence of pulmonary hypertension subtypes and survival outcomes among children with pulmonary hypertension. Given the substantial burden of this disease, further studies to validate phenotypic differences and to understand the underlying causes of survival disparities between racial and ethnic groups are warranted.


Assuntos
Pediatria/métodos , Hipertensão Arterial Pulmonar/etnologia , Sistema de Registros , Adolescente , Afro-Americanos , Criança , Pré-Escolar , Grupos de Populações Continentais , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Lactente , Recém-Nascido , Masculino , América do Norte/epidemiologia , Prevalência , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/mortalidade , Análise de Regressão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
16.
Circulation ; 140(1): e9-e68, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31132865

RESUMO

In this scientific statement from the American Heart Association, experts in the field of cardiomyopathy (heart muscle disease) in children address 2 issues: the most current understanding of the causes of cardiomyopathy in children and the optimal approaches to diagnosis cardiomyopathy in children. Cardiomyopathies result in some of the worst pediatric cardiology outcomes; nearly 40% of children who present with symptomatic cardiomyopathy undergo a heart transplantation or die within the first 2 years after diagnosis. The percentage of children with cardiomyopathy who underwent a heart transplantation has not declined over the past 10 years, and cardiomyopathy remains the leading cause of transplantation for children >1 year of age. Studies from the National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry have shown that causes are established in very few children with cardiomyopathy, yet genetic causes are likely to be present in most. The incidence of pediatric cardiomyopathy is ≈1 per 100 000 children. This is comparable to the incidence of such childhood cancers as lymphoma, Wilms tumor, and neuroblastoma. However, the published research and scientific conferences focused on pediatric cardiomyopathy are sparcer than for those cancers. The aim of the statement is to focus on the diagnosis and classification of cardiomyopathy. We anticipate that this report will help shape the future research priorities in this set of diseases to achieve earlier diagnosis, improved clinical outcomes, and better quality of life for these children and their families.


Assuntos
American Heart Association , Cardiomiopatias/classificação , Cardiomiopatias/diagnóstico , Adolescente , Cardiomiopatias/epidemiologia , Cardiomiopatias/genética , Criança , Testes Genéticos/normas , Humanos , Sistema de Registros/normas , Estados Unidos/epidemiologia
17.
Pulm Circ ; 9(2): 2045894019851696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31099303

RESUMO

Diagnostic World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) and Diagnostic Group 1' pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) are progressive and fatal disorders. Past registries provided important insights into these disorders, but did not include hormonal exposures or genomic data. The United States Pulmonary Hypertension Scientific Registry (USPHSR) will provide demographic, physiologic, anorexigen and hormone exposure, genomic, and survival data in the current therapeutic era for 499 patients diagnosed with PAH, PVOD, or PCH. The USPHSR also will explore the relationship between pharmacologic, non-pharmacologic, and dietary hormonal exposures and the increased risk for women to develop idiopathic or heritable PAH.

18.
Pulm Circ ; 9(2): 2045894019845615, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880574

RESUMO

The role of perinatal insults in the development of adult onset pulmonary hypertension (PH) is unclear. We surveyed patients with and without PH for a history of early life risk factors, and identified prematurity, oxygen use, and respiratory illness each as risk predictors for development of adult PH.

20.
Pulm Circ ; 9(2): 2045894018824564, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30632900

RESUMO

Low-grade albuminuria, determined by the urinary albumin to creatinine ratio, has been linked to systemic vascular dysfunction and is associated with cardiovascular mortality. Pulmonary arterial hypertension is related to mutations in the bone morphogenetic protein receptor type 2, pulmonary vascular dysfunction and is increasingly recognized as a systemic disease. In a total of 283 patients (two independent cohorts) diagnosed with pulmonary arterial hypertension, 18 unaffected BMPR2 mutation carriers and 68 healthy controls, spot urinary albumin to creatinine ratio and its relationship to demographic, functional, hemodynamic and outcome data were analyzed. Pulmonary arterial hypertension patients and unaffected BMPR2 mutation carriers had significantly elevated urinary albumin to creatinine ratios compared with healthy controls ( P < 0.01; P = 0.04). In pulmonary arterial hypertension patients, the urinary albumin to creatinine ratio was associated with older age, lower six-minute walking distance, elevated levels of C-reactive protein and hemoglobin A1c, but there was no correlation between the urinary albumin to creatinine ratio and hemodynamic variables. Pulmonary arterial hypertension patients with a urinary albumin to creatinine ratio above 10 µg/mg had significantly higher rates of poor outcome ( P < 0.001). This study shows that low-grade albuminuria is prevalent in pulmonary arterial hypertension patients and is associated with poor outcome. This study shows that albuminuria in pulmonary arterial hypertension is associated with systemic inflammation and insulin resistance.

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