scholarly journals EXPRESS: Plasma ADAMTS-13 and von Willebrand factor in diagnosis and prediction of prognosis in pulmonary arterial hypertension

2021 ◽  
pp. 204589402110415
Author(s):  
Abdulla Ahmed ◽  
Salaheldin Ahmed ◽  
Göran Rådegran
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Ejection Fraction ◽  
Arterial Hypertension ◽  
Von Willebrand Factor ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Healthy Controls ◽  
Pulmonary Arterial ◽  
Von Willebrand ◽  
Willebrand Factor

To improve outcome in pulmonary arterial hypertension (PAH), earlier diagnosis and better prognostic assessments are required. We aimed to investigate the diagnostic and prognostic potential of plasma proteins related to pathways recognized in PAH including coagulation, inflammation, and metabolism. Forty-two proteins were analysed with proximity extension assay from plasma of 20 healthy controls and 150 patients, including (PAH, n=48, whereof 33 also during early treatment follow-ups); chronic thromboembolic pulmonary hypertension (CTEPH, n=20); pulmonary hypertension (PH) due to heart failure (HF) with preserved ejection fraction (HFpEF-PH, n=31); PH due to HF with reduced ejection fraction (HFrEF-PH, n=36); and HF without PH (Dyspnoea/HF-non-PH, n=15). Patients’ haemodynamics were assessed by right heart catheterization. Plasma ADAMTS-13 in incident PAH was lower compared to the healthy controls (p=0.055), as well as CTEPH (p<0.0001), HFrEF-PH (p<0.0001), HFrEF-PH (p<0.0001), and Dyspnoea/HF-non-PH (p<0.0001). Adjusted for age and sex, ADAMTS-13 discriminated PAH from the other disease groups with an AUC of 0.91 (sensitivity=87.5%, and specificity=78.4%). Higher plasma von Willebrand factor (vWF) was associated with worse survival (log-rank p=0.0029), and a higher mortality rate (adjusted hazard ratio 1.002, 95% confidence interval 1-1.004: p=0.041). Adjusted for age, sex, and combined with the ESC/ERS risk score, vWF predicted mortality (median follow-up 3.6 years) in PAH with an AUC of 0.94 (sensitivity=81.3%, and specificity=93.8%). ADAMTS-13 may be a promising biomarker for early detection of PAH, and vWF as a candidate prognostic biomarker. The putative additional value of vWF to the European multiparametric risk assessment strategy remains to be elucidated.

von Willebrand Factor Independently Predicts Long-term Survival in Patients With Pulmonary Arterial Hypertension

CHEST Journal ◽  
2005 ◽  
Vol 128 (4) ◽  
pp. 2355-2362 ◽  
Author(s):  
Steven M. Kawut ◽  
Evelyn M. Horn ◽  
Ketevan K. Berekashvili ◽  
Allison C. Widlitz ◽  
Erika B. Rosenzweig ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Von Willebrand Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
Pulmonary Arterial ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Improvement of von Willebrand Factor Proteolysis After Prostacyclin Infusion in Severe Pulmonary Arterial Hypertension

Circulation ◽  
2000 ◽  
Vol 102 (20) ◽  
pp. 2460-2462 ◽  
Author(s):  
Agnès Veyradier ◽  
Toshiya Nishikubo ◽  
Marc Humbert ◽  
Martine Wolf ◽  
Olivier Sitbon ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Von Willebrand Factor ◽  
Pulmonary Arterial ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Severe Pulmonary Arterial Hypertension

scholarly journals Plasma adrenomedullin peptides and precursor levels in pulmonary arterial hypertension disease severity and risk stratification

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402093131
Author(s):  
Habib Bouzina ◽  
Göran Rådegran
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Early Treatment ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Risk Scores ◽  
Healthy Controls ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

Adrenomedullin is a potent vasodilatory peptide, linked to pulmonary arterial hypertension pathology. Proximity extension assays were utilized to study plasma biomarkers related to vasoregulation, with focus on adrenomedullin peptides and precursor levels, collectively referred to as ADM. ADM was measured in 48 treatment-naïve pulmonary arterial hypertension patients at diagnosis, and in 31 of them at an early treatment follow-up. Plasma ADM was additionally assessed in patients with chronic thromboembolic pulmonary hypertension ( n = 20) and pulmonary hypertension due to heart failure with preserved (HFpEF(PH)) ( n = 33) or reduced (HFrEF(PH)) ( n = 36) ejection fraction, as well as healthy controls ( n = 16). ADM was studied in relation to pulmonary arterial hypertension hemodynamics, risk assessment, prognosis, treatment response, and differentiation. Plasma ADM levels in pulmonary arterial hypertension patients at diagnosis were higher than in healthy controls ( p < 0.001), similar as in chronic thromboembolic pulmonary hypertension patients ( p = ns), but lower compared to HFpEF(PH) ( p < 0.03) and HFrEF(PH) ( p < 0.001). In pulmonary arterial hypertension, specifically, plasma ADM at diagnosis correlated mainly to mean right atrial pressure ( r = 0.73, p < 0.001), N-terminal prohormone of brain natriuretic peptide ( r = 0.75, p < 0.001), six-minute walking distance ( r = –0.57, p < 0.001), and venous oxygen saturation ( r = –0.57, p < 0.001). ADM also correlated to the ECS/ERS- ( r = 0.74, p < 0.001) and REVEAL risk scores ( r = 0.54, p < 0.001) at pulmonary arterial hypertension diagnosis. Plasma ADM in pulmonary arterial hypertension patients was unaltered at early treatment follow-up compared to baseline ( p = ns). Pulmonary arterial hypertension patients with supra-median ADM at diagnosis showed worse overall survival than those with infra-median levels (median survival 34 versus 66 months, p = 0.0077). In conclusion, the present results suggest that baseline plasma ADM levels mirror disease severity, correlating to both ECS/ERS- and the REVEAL risk scores.

scholarly journals Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension

2020 ◽  
Vol 10 (1) ◽  
pp. 204589401989055 ◽  
Author(s):  
Gustavo A. Heresi ◽  
Jacob T. Mey ◽  
John R. Bartholomew ◽  
Ihab S. Haddadin ◽  
Adriano R. Tonelli ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Healthy Controls ◽  
Metabolomic Profile ◽  
Plasma Metabolome ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

We aimed to characterize the plasma metabolome of chronic thromboembolic pulmonary hypertension patients using a high-throughput unbiased omics approach. We collected fasting plasma from a peripheral vein in 33 operable chronic thromboembolic pulmonary hypertension patients, 31 healthy controls, and 21 idiopathic pulmonary arterial hypertension patients matched for age, gender, and body mass index. Metabolomic analysis was performed using an untargeted approach (Metabolon Inc. Durham, NC). Of the total of 862 metabolites identified, 362 were different in chronic thromboembolic pulmonary hypertension compared to controls: 178 were higher and 184 were lower. Compared to idiopathic pulmonary arterial hypertension, 147 metabolites were different in chronic thromboembolic pulmonary hypertension: 45 were higher and 102 were lower. The plasma metabolome allowed us to distinguish subjects with chronic thromboembolic pulmonary hypertension and healthy controls with a predictive accuracy of 89%, and chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension with 80% accuracy. Compared to idiopathic pulmonary arterial hypertension and healthy controls, chronic thromboembolic pulmonary hypertension patients had higher fatty acids and glycerol; while acyl cholines and lysophospholipids were lower. Compared to healthy controls, both idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients had increased acyl carnitines, beta-hydroxybutyrate, amino sugars and modified amino acids and nucleosides. The plasma global metabolomic profile of chronic thromboembolic pulmonary hypertension suggests aberrant lipid metabolism characterized by increased lipolysis, fatty acid oxidation, and ketogenesis, concomitant with reduced acyl choline and phospholipid moieties. Future research should investigate the pathogenetic and therapeutic potential of modulating lipid metabolism in chronic thromboembolic pulmonary hypertension.

scholarly journals Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401989541 ◽  
Author(s):  
Mattias Arvidsson ◽  
Abdulla Ahmed ◽  
Habib Bouzina ◽  
Göran Rådegran
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Matrix Metalloproteinases ◽  
Ejection Fraction ◽  
Matrix Metalloproteinase ◽  
Arterial Hypertension ◽  
Healthy Controls ◽  
Matrix Metalloproteinase 7 ◽  
Pulmonary Arterial

Pulmonary arterial hypertension is a severe disease for which diagnosis often is delayed. Matrix metalloproteinases have been suggested to play a role in vascular remodeling and pulmonary hypertension development. Our aim was therefore to investigate the potential role of matrix metalloproteinases as biomarkers in diagnosis and differentiation of pulmonary arterial hypertension in relation to various causes of dyspnea and pulmonary hypertension. Using proximity extension assays, 10 matrix metalloproteinases and associated proteins were analyzed in venous plasma from healthy controls (n = 20), as well as patients diagnosed with pulmonary arterial hypertension (n = 48), chronic thromboembolic pulmonary hypertension (n = 20), pulmonary hypertension due to heart failure with preserved (n = 33) or reduced (n = 36) ejection fraction, and heart failure with reduced ejection fraction and heart failure with preserved ejection fraction without pulmonary hypertension (n = 15). Plasma levels of matrix metalloproteinase-2, -7, -9, -12 and TIMP-4 were elevated (p < 0.01) in pulmonary arterial hypertension compared to controls. Plasma levels of matrix metalloproteinase-7 were furthermore lower (p < 0.0081) in pulmonary arterial hypertension than in all the other disease groups, but higher compared to controls (p < 0.0001). Receiver operating characteristic analysis of matrix metalloproteinase-7 resulted in sensitivity of 58.7% and a specificity of 83.3% for detecting pulmonary arterial hypertension among the other disease groups. Plasma matrix metalloproteinase-7 may provide a potential new diagnostic tool to differentiate pulmonary arterial hypertension from other causes of dyspnea, including heart failure with or without pulmonary hypertension and healthy controls. Matrix metalloproteinase-7 may furthermore be involved in the development of pulmonary hypertension and pulmonary arterial hypertension. Future studies investigating the clinical usefulness of matrix metalloproteinase-7 in the differentiation and earlier diagnosis of pulmonary arterial hypertension, as well as its relationship to pulmonary arterial hypertension pathogenesis, are encouraged.

scholarly journals Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with chronic thromboembolic pulmonary hypertension (CTEPH): a qualitative interview study

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Brooke Currie ◽  
Evan Davies ◽  
Amélie Beaudet ◽  
Larissa Stassek ◽  
Leah Kleinman
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Shortness Of Breath ◽  
Response Options ◽  
Qualitative Interview Study ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
The Impact

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension caused by blood clots and scar tissue in the blood vessels of the lungs. Health-related quality of life is often significantly impaired in patients with CTEPH. However, a better understanding of how CTEPH symptoms affect patients’ lives is needed to optimally assess the impact of the disease and treatment. Objectives This qualitative study aimed to better understand the symptoms of CTEPH and how they affect patients’ lives, as well as to determine the appropriateness of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire for use in this patient population. Methods Adults diagnosed with CTEPH, recruited from two clinical sites in the US, participated in one-to-one qualitative telephone interviews. They described their experience of CTEPH symptoms and the impact these symptoms have on their lives. They also provided feedback on the comprehensibility and relevance of the PAH-SYMPACT™‘s instructions, items, and response options. Results Participants (N = 12) had a mean age of 62.5 years. Two thirds were female and most (83%) had undergone pulmonary endarterectomy and/or balloon pulmonary angioplasty. The most frequently endorsed symptoms were shortness of breath (endorsed by all 12 participants), fatigue (11 participants), and lightheadedness (10 participants). All participants identified shortness of breath as an “extremely important” symptom, and seven participants rated fatigue as “extremely important.” The most frequent impacts of CTEPH were on ability to walk quickly (endorsed by all 12 participants), ability to walk up inclines or stairs (11 participants), and ability to carry things (11 participants). The PAH-SYMPACT™ items were relevant to most participants and reflected their experience of CTEPH. All participants indicated that no important CTEPH symptoms were missing from the PAH-SYMPACT™. Overall, the instructions, items, and response options of the PAH-SYMPACT™ were clear and easy to understand. Conclusions The symptoms and impacts experienced by patients with CTEPH align with items included in the PAH-SYMPACT™. The PAH-SYMPACT™ appears to be fit for purpose for assessing disease status in patients with CTEPH.

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