scholarly journals Role of Biomarkers in the Diagnosis, Risk Assessment, and Management of Pulmonary Hypertension

2016 ◽  
Vol 11 ◽  
pp. BMI.S38323 ◽  
Author(s):  
Vanessa Rameh ◽  
Antoine Kossaify

Pulmonary hypertension is a severe and debilitating disease with no definite cure, and the domain of targeted therapies is a promising field for better management of this severe condition. The disease comprises pulmonary arterial remodeling, hypoxia, endothelial dysfunction, and inflammation, with subsequent organ damage including right heart and liver dysfunction. Biomarkers have a valuable role at different levels of the disease, from diagnosis to risk assessment and management, in order to decrease the burden of the disease in terms of both morbidity and mortality.

2015 ◽  
Vol 24 (138) ◽  
pp. 642-652 ◽  
Author(s):  
Stephan Rosenkranz ◽  
Ioana R. Preston

Right heart catheterisation (RHC) plays a central role in identifying pulmonary hypertension (PH) disorders, and is required to definitively diagnose pulmonary arterial hypertension (PAH). Despite widespread acceptance, there is a lack of guidance regarding the best practice for performing RHC in clinical practice. In order to ensure the correct evaluation of haemodynamic parameters directly measured or calculated from RHC, attention should be drawn to standardising procedures such as the position of the pressure transducer and catheter balloon inflation volume. Measurement of pulmonary arterial wedge pressure, in particular, is vulnerable to over- or under-wedging, which can give rise to false readings. In turn, errors in RHC measurement and data interpretation can complicate the differentiation of PAH from other PH disorders and lead to misdiagnosis. In addition to diagnosis, the role of RHC in conjunction with noninvasive tests is widening rapidly to encompass monitoring of treatment response and establishing prognosis of patients diagnosed with PAH. However, further standardisation of RHC is warranted to ensure optimal use in routine clinical practice.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Tanyeri ◽  
B Keskin ◽  
O Y Akbal ◽  
A Hakgor ◽  
A Karagoz ◽  
...  

Abstract Background and aim In this study we evaluated the impact of the updated pulmonary hypertension (PH) definitive criteria proposed in 6th World PH Symposium (WSPH) on numbers and frequencies of and pre- versus post-capillary PH as compared to those in European Society of Cardiology (ESC) 2015 PH Guidelines. Methods Study group comprised the retrospectively evaluated 1299 patients (pts) (age 53.1±18.8 years, female 807, 62.1%) who underwent right heart catheterisation (RHC) with different indications between 2006 and 2018. For ESC and WSPH PH definitions, pulmonary arterial mean pressure (PAMP) ≥25 mmHg (definition-A) and PAMP >20 mmHg (definition-B) RHC criteria were used, respectively. For pre-capillary PH definitions, pulmonary artery wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units criteria were included in the both definitions. Results In RHC assessments, PAMP ≥25 mmHg and >20 mmHg were noted in 891 (68.6%) and 1051 (80.9%) of overall pts, respectively. Moreover, pre-capillary PH was diagnosed in 284 (21.8%) and 298 (22.9%) with definition-A and B, respectively. Although updated WSPH definition was associated with a net 12.3% and a relative 18% increase in the overall PH diagnosis, net and relative changes in the frequency of the pre-capillary PH were only 1% and 4.9%. Increase in the overall PH with updated WSPH criterias compared to previous ESC definitions was associated with increase in the number of pre-capillary PH (n=298, 22.9%) but not in the overall frequency of post-capillary PH (688, 52.9%). Because PVR was the product of the transpulmonary gradient (PAMP minus PAWP) divided by cardiac output, this measure was found to keep specificity for distinction between pre- versus post-capillary PH even after lowering thetreshold diagnostic for PAMP from 25 to 20 mmHg. Conclusions Although updated WSPH definition was associated with net 12.3% and relative 18% increase in the overall PH diagnosis, its impact on frequencies of pre- versus post-capillary PH within overall PH population was negligible.These seem to be due to critical role of PVR ensuring specificity in pre-capillary PH diagnosis even after lowering the definitive PAMP treshold to 20 mmHg.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Pereira ◽  
J.G Santos ◽  
M.J Loureiro ◽  
F Ferreira ◽  
A.R Almeida ◽  
...  

Abstract Introduction Thermodilution (TD) and indirect Fick (IF) methods are widely used to measure cardiac output (CO). They are often used interchangeably to make critical clinical decisions, yet few studies have compared these approaches concerning agreement and comparative prognostic value as applied in medical practice. Purpose To assess agreement between TD and IF methods and to compare how well these methods predict mortality. Methods Retrospective cohort study including all consecutive right heart catheterizations performed in a referral pulmonary hypertension (PH) centre from 2010 to 2018. Cardiac index (CI) was calculated by indexed CO to body surface area. PH was classified according to the new definition of the 6st World Symposium on Pulmonary Hypertension 2018 [mean pulmonary arterial pressure (mPAP) >20 mmHg]. Patients with cardiac or extra-cardiac shunts or significant (moderate to severe or severe) tricuspid regurgitation were excluded. All-cause mortality over 1 year after right heart catheterization was recorded. Logistic regression was used to identify predictors of the adverse event. Results From a total of 569 procedures, 424 fulfilled the inclusion criteria: mean age 56.7±15.4 years, 67.3% female. Haemodynamic parameters were diagnosed of PH in 86.2% of cases: mPAP 35.3±15.3 mmHg, 83.6% pre-capillary subtype, 42.9% belonging to group 4 (chronic thromboembolic pulmonary hypertension) and 26.6% to group 1 (pulmonary arterial hypertension). Mean values of CO and CI were, respectively, 4.5±2.8 L/min and 2.5±0.8 L/min/m2 measured by TD and 4.6±2.4 L/min and 2.6±1.3 L/min/m2 measured by IF method. There was a median difference (IF minus TD) of - 0.03 / min to CO and - 0.05 L/min/m2 to CI but both meausres correlated only modestly (r=0.6 to TD and r=0.5 to IF). One-year all-cause mortality rate was 5.4% (median time to death was 50.5 days). Lower values of CO and CI assessed by TD were significantly associated with all-cause mortality occurrence (CO TD: 4.5±1.3 L/min versus 3.6±1.0 L/min, p<0.01; CI TD: 2.6±0.7 L/min/m2 versus 2.1±0.4 L/min/m2, p<0.01). No association was observed between CO (p=0.31) and CI (p=0.42) measured by IF method and the adverse event. Logistic regression identified 2 independent predictors of all-cause mortality: TD CO (OR 0.55, 95% CI 0.38–0.79, p<0.01) and TD CI (OR 0.34, 95% CI 0.17–0.67, p<0.01). Similar results were obtained when patients diagnosed with PH were independently analyzed. Conclusions There is only modest agreement between TD and IF CO and CI estimates. Despite being more time-consuming, TD measurements were predictors of all-cause mortality and present a highest prognostic value. These findings favored their used over IF in clinical practice. Funding Acknowledgement Type of funding source: None


2021 ◽  
pp. 204589402110295
Author(s):  
Hirohisa Taniguchi ◽  
Tomoya Takashima ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Asuka Furukawa ◽  
...  

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.


2015 ◽  
Vol 51 (8) ◽  
pp. 6399-6416 ◽  
Author(s):  
B. Merz ◽  
S. Vorogushyn ◽  
U. Lall ◽  
A. Viglione ◽  
G. Blöschl

2021 ◽  
Vol 7 (3) ◽  
pp. 170-183
Author(s):  
Ioan Tilea ◽  
Andreea Varga ◽  
Anca-Meda Georgescu ◽  
Bianca-Liana Grigorescu

Abstract Despite substantial advancements in diagnosis and specific medical therapy in pulmonary arterial hypertension patients’ management, this condition continues to represent a major cause of mortality worldwide. In pulmonary arterial hypertension, the continuous increase of pulmonary vascular resistance and rapid development of right heart failure determine a poor prognosis. Against targeted therapy, patients inexorable deteriorate over time. Pulmonary arterial hypertension patients with acute right heart failure who need intensive care unit admission present a complexity of the disease pathophysiology. Intensive care management challenges are multifaceted. Awareness of algorithms of right-sided heart failure monitoring in intensive care units, targeted pulmonary hypertension therapies, and recognition of precipitating factors, hemodynamic instability and progressive multisystem organ failure requires a multidisciplinary pulmonary hypertension team. This paper summarizes the management strategies of acute right-sided heart failure in pulmonary arterial hypertension adult cases based on recently available data.


2008 ◽  
Vol 42 (11) ◽  
pp. 1653-1659 ◽  
Author(s):  
Sandra L Hrometz ◽  
Kelly M Shields

Objective: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). Data Sources: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966–March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. Study Selection and Data Extraction: Abstracts and original preclinical and clinical research reports available in the English language were Identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. Data Synthesis: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan's twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. Conclusions: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH.


2012 ◽  
Vol 303 (12) ◽  
pp. C1229-C1243 ◽  
Author(s):  
Abigail S. Forrest ◽  
Talia C. Joyce ◽  
Marissa L. Huebner ◽  
Ramon J. Ayon ◽  
Michael Wiwchar ◽  
...  

Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca2+ levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca2+-activated Cl− channels (ClCa), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of ClCa channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks postinjection with a single dose of MCT (50 mg/kg ip), the animals developed right ventricular hypertrophy (heart weight measurements) and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca2+-activated Cl− current [ ICl(Ca)] density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats vs. aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in ICl(Ca) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for ClCa channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 μM), an l-type Ca2+ channel blocker, and NFA (30 or 100 μM, with or without 10 μM indomethacin to inhibit cyclooxygenases) or T16AInh-A01 (10 μM), TMEM16A/ClCa channel inhibitors, than that of control animals. In conclusion, augmented ClCa/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease.


2018 ◽  
Vol 24 (1) ◽  
pp. 37-45
Author(s):  
Jessica Yakeley ◽  
William Burbridge-James

SUMMARYRates of suicide and self-harm are rising in many countries, and it is therapeutically important to explore the personal stories and relationships that underlie this behaviour. In this article psychoanalytic and psychodynamic principles and concepts in relation to violence towards the self are introduced and the various unconscious meanings of suicide and self-harm are explored within a relational context and attachment framework. We describe how a psychodynamic approach may enhance the risk assessment and treatment of patients presenting with self-harm and suicidality, particularly examining the role of transference and countertransference within the therapeutic relationship.LEARNING OBJECTIVES•Understand historical and contemporary psychoanalytic theories and concepts regarding the aetiology of suicide and self-harm•Understand the different meanings and expressions of acts of suicide and self-harm•Understand the use of countertransference in the risk assessment and management of self-harm and suicide attemptsDECLARATION OF INTERESTNone.


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