scholarly journals EXPRESS: Application of [18F]FLT-PET in Pulmonary Arterial Hypertension (PAH): A clinical study in PAH patients and unaffected BMPR2 mutation carriers

2021 ◽  
pp. 204589402110280
Author(s):  
liza botros ◽  
Samara M.A. Jansen ◽  
Ali Ashek ◽  
Onno A. Spruijt ◽  
Jelco Tramper ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Regional Distribution ◽  
Small Sample ◽  
Healthy Controls ◽  
Vascular Cell ◽  
Flt Pet ◽  
Mutation Carriers ◽  
Pet Scanning ◽  
Pulmonary Arterial

Background: Pulmonary arterial hypertension (PAH) is a heterogeneous group of diseases characterized by vascular cell proliferation leading to pulmonary vascular remodelling and ultimately right heart failure. Previous data indicated that 3'-deoxy-3'-[18F]-fluorothymidine (18FLT) positron emission tomography (PET) scanning was increased in PAH patients, hence providing a possible biomarker for PAH as it reflects vascular cell hyperproliferation in the lung. This study sought to validate 18FLT-PET in an expanded cohort of PAH patients in comparison to matched healthy controls and unaffected bone morphogenetic protein receptor type 2 (BMPR2) mutation carriers. Methods and Results: 18FLT-PET scanning was performed in 21 PAH patients (15 hereditary PAH and 6 idiopathic PAH), 11 unaffected mutation carriers and 9 healthy control subjects. In-depth kinetic analysis indicated that there were no differences in lung 18FLT k3 phosphorylation among PAH patients, unaffected BMPR2 mutation carriers and healthy controls. Lung 18FLT uptake did not correlate with hemodynamic or clinical parameters in PAH patients. Sequential 18FLT-PET scanning in three patients demonstrated uneven regional distribution in 18FLT uptake by 3D parametric mapping of the lung, although this did not follow the clinical course of the patient. Conclusion: We did not detect significantly increased lung 18FLT uptake in PAH patients, nor in the unaffected BMPR2 mutation carriers, as compared to healthy subjects. The conflicting results with our preliminary human 18FLT report may be explained by a small sample size previously and we observed large variation of lung 18FLT signals between patients, challenging the application of 18FLT-PET as a biomarker in the PAH clinic.

scholarly journals Low-grade albuminuria in pulmonary arterial hypertension

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401882456 ◽  
Author(s):  
Nils P. Nickel ◽  
Vinicio A. de Jesus Perez ◽  
Roham T. Zamanian ◽  
Joshua P. Fessel ◽  
Joy D. Cogan ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Dysfunction ◽  
Urinary Albumin ◽  
Low Grade ◽  
Healthy Controls ◽  
Creatinine Ratio ◽  
Poor Outcome ◽  
Mutation Carriers ◽  
Pulmonary Arterial

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.

scholarly journals Meta-analysis of blood genome-wide expression profiling studies in pulmonary arterial hypertension

2020 ◽  
Vol 318 (1) ◽  
pp. L98-L111 ◽  
Author(s):  
Jason M. Elinoff ◽  
Adrien J. Mazer ◽  
Rongman Cai ◽  
Mengyun Lu ◽  
Grace Graninger ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Expression Profiling ◽  
Meta Analysis ◽  
Small Sample ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Genome Wide ◽  
Transcriptomic Signature ◽  
Pulmonary Arterial

Inflammatory cell infiltrates are a prominent feature of aberrant vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that immune effector cells contribute to disease progression. Genome-wide blood expression profiling studies have attempted to better define this inflammatory component of PAH pathobiology but have been hampered by small sample sizes, methodological differences, and very little gene-level reproducibility. The current meta-analysis (seven studies; 156 PAH patients/110 healthy controls) was performed to assess the comparability of data across studies and to possibly derive a generalizable transcriptomic signature. Idiopathic (IPAH) compared with disease-associated PAH (APAH) displayed highly similar expression profiles with no differentially expressed genes, even after substantially relaxing selection stringency. In contrast, using a false discovery rate of ≤1% and I2 < 40% (low-to-moderate heterogeneity across studies) both IPAH and APAH differed markedly from healthy controls with the combined PAH cohort yielding 1,269 differentially expressed, unique gene transcripts. Bioinformatic analyses, including gene-set enrichment, which uses all available data independent of gene selection thresholds, identified interferon, mammalian target of rapamycin/p70S6K, stress kinase, and Toll-like receptor signaling as enriched mechanisms within the PAH gene signature. Enriched biological functions and diseases included tumorigenesis, autoimmunity, antiviral response, and cell death consistent with prevailing theories of PAH pathogenesis. Although otherwise indistinguishable, APAH (predominantly PAH due to systemic sclerosis) had a somewhat stronger interferon profile than IPAH. Meta-analysis defined a robust and generalizable transcriptomic signature in the blood of PAH patients that can help inform the identification of biomarkers and therapeutic targets.

scholarly journals Nailfold capillary density is associated with the presence and severity of pulmonary arterial hypertension in systemic sclerosis

2008 ◽  
Vol 68 (2) ◽  
pp. 191-195 ◽  
Author(s):  
H M A Hofstee ◽  
A Vonk Noordegraaf ◽  
A E Voskuyl ◽  
B A C Dijkmans ◽  
P E Postmus ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Capillary Density ◽  
Total Width ◽  
Healthy Controls ◽  
Mean Pulmonary Arterial Pressure ◽  
Microvascular Changes ◽  
Pulmonary Arterial ◽  
Disease Specificity

Objective:The aim of this study was to investigate whether there are differences in capillary nailfold changes in patients with systemic sclerosis (SSc) with and without pulmonary arterial hypertension (PAH), and whether these changes are associated with PAH severity and disease specificity.Methods:Capillary density and loop dimensions were studied in 21 healthy controls, 20 patients with idiopathic PAH (IPAH) and 40 patients with SSc. Of the 40 patients with SSc, 19 had no PAH (SSc–nonPAH) and 21 had PAH (SSc–PAH), of whom eight had PAH during exercise.Results:Capillary density was lower in SSc–PAH compared with patients who had SSc–nonPAH (4.33/mm vs 6.56/mm respectively, p = 0.001), but loop dimensions were equal. In comparison with IPAH, patients with SSc–PAH had reduced capillary density (4.33/mm vs 7.86/mm, p<0.001) and larger loop dimensions (total width 101.05 µm vs 44.43 µm, p<0.001). Capillary density in healthy controls (9.87/mm) was significantly higher when compared with SSc–nonPAH (6.56/mm), SSc–PAH (4.33/mm) and with IPAH (7.86/mm). No differences in capillary dimensions were present between healthy controls and IPAH.Capillary density correlated with mean pulmonary arterial pressure (PAP) at rest in SSc–PAH at rest (r = −0.58, p = 0.039) and IPAH (r = −0.67, p = 0.001).Conclusions:Reduction of nailfold capillary density, but not capillary loop dimensions is associated with PAH, and correlates with the severity of PAH in both SSc and IPAH. This suggests that either systemic microvascular changes play a part in the development of PAH, or that PAH itself contributes to systemic microvascular changes.

scholarly journals Use of eHealth in the management of pulmonary arterial hypertension: review of the literature

2020 ◽  
Vol 27 (3) ◽  
pp. e100176
Author(s):  
Manuel C Gonzalez-Garcia ◽  
Farhad Fatehi ◽  
Marlien Varnfield ◽  
Hang Ding ◽  
Mohan Karunanithi ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Small Sample Size ◽  
Survival Rates ◽  
Poor Quality ◽  
Small Sample ◽  
Haemodynamic Monitoring ◽  
Clinical Benefits ◽  
Pulmonary Arterial ◽  
Diagnostic Technologies

BackgroundPulmonary arterial hypertension (PAH) is a severe chronic condition associated with poor quality of life and high risks of mortality and hospitalisation. The utilisation of novel diagnostic technologies has improved survival rates although the effectiveness of Electronic Health (eHealth) interventions in patients with a chronic cardiopulmonary disease remains controversial. As the effectiveness of eHealth can be established by specific evaluation for different chronic health conditions, the aim of this study was to explore and summarise the utilisation of eHealth in PAH.MethodWe searched PubMed, CINAHL and Embase for all studies reporting clinical trials on eHealth solutions for the management of PAH. No limitations in terms of study design or date of publication were imposed.Results18 studies (6 peer-reviewed journal papers and 12 conference papers) were identified. Seven studies addressed the accuracy, safety or reliability of eHealth technologies such as intra-arterial haemodynamic monitoring of the pulmonary artery pressure, self-administered 6-Minute walk test App, computerised step-pulse oximeter and ambulatory impedance cardiography. Two studies evaluated eHealth as part of the medical management and showed a reduction in hospitalisation rate.ConclusionsThe evidence of eHealth supporting the management of people with PAH is limited and only embraced through a few studies of small sample size and short-term duration. Given the proposed clinical benefits in heart failure, we postulate that the evaluation of eHealth for the clinical management of PAH is highly warranted.

scholarly journals BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension

2016 ◽  
Vol 48 (6) ◽  
pp. 1668-1681 ◽  
Author(s):  
Maria-Rosa Ghigna ◽  
Christophe Guignabert ◽  
David Montani ◽  
Barbara Girerd ◽  
Xavier Jaïs ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bronchial Artery ◽  
Gene Mutations ◽  
Systemic Circulation ◽  
Systematic Analysis ◽  
Mutation Status ◽  
Mutation Carriers ◽  
Pulmonary Arterial ◽  
The Impact

The impact of bone morphogenetic protein receptor 2 (BMPR2) gene mutations on vascular remodelling in pulmonary arterial hypertension (PAH) is unknown. We sought to identify a histological profile of BMPR2 mutation carriers.Clinical data and lung histology from 44 PAH patients were subjected to systematic analysis and morphometry.Bronchial artery hypertrophy/dilatation and bronchial angiogenesis, as well as muscular remodelling of septal veins were significantly increased in PAH lungs carrying BMPR2 mutations. We found that patients displaying increased bronchial artery remodelling and bronchial microvessel density, irrespective of the mutation status, were more likely to suffer from severe haemoptysis. History of substantial haemoptysis (>50 mL) was significantly more frequent in BMPR2 mutation carriers. 43.5% of BMPR2 mutation carriers, as opposed to 9.5% of noncarriers, displayed singular large fibrovascular lesions, which appear to be closely related to the systemic lung vasculature.Our analysis provides evidence for the involvement of the pulmonary systemic circulation in BMPR2 mutation-related PAH. We show that BMPR2 mutation carriers are more prone to haemoptysis and that haemoptysis is closely correlated to bronchial arterial remodelling and angiogenesis; in turn, pronounced changes in the systemic vasculature correlate with increased pulmonary venous remodelling, creating a distinctive profile in PAH patients harbouring a BMPR2 mutation.

scholarly journals Platelet glycolytic metabolism correlates with hemodynamic severity in pulmonary arterial hypertension

2020 ◽  
Vol 318 (3) ◽  
pp. L562-L569
Author(s):  
Ruth E. McDowell ◽  
Kulwant S. Aulak ◽  
Allaa Almoushref ◽  
Celia A. Melillo ◽  
Brittany E. Brauer ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Time Window ◽  
Healthy Controls ◽  
Metabolic Shift ◽  
Glycolytic Metabolism ◽  
Pulmonary Arterial ◽  
Group 2 ◽  
Group 1

Group 1 pulmonary hypertension (PH), i.e., pulmonary arterial hypertension (PAH), is associated with a metabolic shift favoring glycolysis in cells comprising the lung vasculature as well as skeletal muscle and right heart. We sought to determine whether this metabolic switch is also detectable in circulating platelets from PAH patients. We used Seahorse Extracellular Flux to measure bioenergetics in platelets isolated from group 1 PH (PAH), group 2 PH, patients with dyspnea and normal pulmonary artery pressures, and healthy controls. We show that platelets from group 1 PH patients exhibit enhanced basal glycolysis and lower glycolytic reserve compared with platelets from healthy controls but do not differ from platelets of group 2 PH or dyspnea patients without PH. Although we were unable to identify a glycolytic phenotype unique to platelets from PAH patients, we found that platelet glycolytic metabolism correlated with hemodynamic severity only in group 1 PH patients, supporting the known link between PAH pathology and altered glycolytic metabolism and extending this association to ex vivo platelets. Pulmonary artery pressure and pulmonary vascular resistance in patients with group 1 PH were directly associated with basal platelet glycolysis and inversely associated with maximal and reserve glycolysis, suggesting that PAH progression reduces the capacity for glycolysis even while demanding an increase in glycolytic metabolism. Therefore, platelets may provide an easy-to-harvest, real-time window into the metabolic shift occurring in the lung vasculature and represent a useful surrogate for interrogating the glycolytic shift central to PAH pathology.

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