scholarly journals The Evolution of Risk Assessment in Pulmonary Arterial Hypertension

2021 ◽  
Vol 17 (2) ◽  
pp. 134-144
Author(s):  
Sandhya Murthy ◽  
Raymond Benza
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
High Morbidity ◽  
Risk Calculation ◽  
Pulmonary Arterial ◽  
Timely Referral

Pulmonary arterial hypertension (PAH) is a chronic debilitating disease that carries an unacceptably high morbidity and mortality rate despite improved survival with modern therapies. The combination of several modifiable and nonmodifiable variables yields a robust risk assessment across various available clinical calculators. The role of risk calculation is integral to managing PAH and aids in the timely referral to expert centers and potentially lung transplantation. Studies are ongoing to determine the role of risk calculators in the framework of clinical trials and to elucidate novel markers of high risk in PAH.

P4688Additional role of unmodifiable risk factors in pulmonary arterial hypertension risk stratification according to current ESC/ERS guidelines

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zuffa ◽  
F Dardi ◽  
M Palazzini ◽  
E Gotti ◽  
A Rinaldi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Risk Stratification ◽  
Arterial Hypertension ◽  
Specific Treatment ◽  
Low Risk ◽  
P Value ◽  
Pulmonary Arterial

Abstract Background Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. Anyway, the role of unmodifiable risk factors is not taken into account. Purpose The aim of this study was to evaluate the role of unmodifiable risk factors (age, gender, PAH aetiology) in PAH risk stratification using the recently proposed simplified risk table and to test if these factors influence the response to PAH-specific treatment. Methods All patients with PAH referred to a single centre were included from 2003 to 2017. We applied a simplified risk assessment strategy using the following criteria: WHO functional class, 6-min walking distance, right atrial pressure or brain natriuretic peptide plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). The last 2 criteria were based on which parameter was available; if both were available the worst was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. Then we performed multivariate Cox analysis to evaluate what are the independent predictors of survival (age, gender, PAH aetiology together with the recently proposed simplified PAH risk table) and we tested if these factors influence the response to PAH specific therapy comparing the % improvement of hemodynamic parameters from baseline to 3–4 months after starting treatment. Wilcoxon-Mann-Whitney test was used for comparisons. Results Six hundreds and twenty-one treatment-naïve patients were enrolled. Age [HR (95% CI) = 1.022 (1.014–1.030); p-value <0.001], male gender [HR (95% CI) = 1.881 (1.479–2.392); p-value <0.001] and connective tissue disease (CTD)-PAH aetiology [HR (95% CI)= 2.278 (1.733–2.995); p-value <0.001] were all independent predictors of prognosis in patients with PAH together with the recently validated simplified PAH risk table [HR (95% CI) = 2.161 (1.783–2.618); p-value <0.001] but they didn't significantly influence the response to PAH specific treatment as shown in the Figure. Figure 1 Conclusions Age, gender and CTD-PAH aetiology significantly influence prognosis together with the recently validated simplified PAH risk table but don't significantly influence the response to PAH-specific treatment. Acknowledgement/Funding None

Single-center prognostic validation of the risk assessment of the 2015 ESC/ERS guidelines in patients with pulmonary arterial hypertension in Japan

2020 ◽  
Vol 98 (9) ◽  
pp. 653-658 ◽  
Author(s):  
Ryo Imai ◽  
Shiro Adachi ◽  
Masahiro Yoshida ◽  
Shigetake Shimokata ◽  
Yoshihisa Nakano ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Risk Group ◽  
Low Risk ◽  
World Health ◽  
Right Atrial ◽  
Walking Distance ◽  
Pulmonary Arterial

The 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension include a multidimensional risk assessment for patients with pulmonary arterial hypertension (PAH). However, prognostic validations of this risk assessment are limited, especially outside Europe. Here, we validated the risk assessment strategy in PAH patients in our institution in Japan. Eighty consecutive PAH patients who underwent right heart catheterization between November 2006 and December 2018 were analyzed. Patients were classified as low, intermediate, or high risk by using a simplified version of the risk assessment that included seven variables: World Health Organization functional class, 6-min walking distance, peak oxygen consumption, brain natriuretic peptide, right atrial pressure, mixed venous oxygen saturation, and cardiac index. The high-risk group showed significantly higher mortality than the low- or intermediate-risk group at baseline (P < 0.001 for both comparisons), and the mortalities in the intermediate- and low-risk groups were both low (P = 0.989). At follow-up, patients who improved to or maintained a low-risk status showed better survival than those who did not (P = 0.041). Our data suggest that this risk assessment can predict higher mortality risk and long-term survival in PAH patients in Japan.

scholarly journals Case report: Stepwise transition from subcutaneous treprostinil to epoprostenol in high-risk pulmonary arterial hypertension

2021 ◽  
Vol 5 (10) ◽  
Author(s):  
Ana Laura Mori ◽  
Andrea Rodríguez ◽  
Juan Alberto Gagliardi ◽  
Alejandro Stewart Harris
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Combined Treatment ◽  
Functional Class ◽  
High Morbidity ◽  
Stepwise Approach ◽  
Pulmonary Arterial ◽  
High Doses ◽  
Prostacyclin Analogues

Abstract Background Idiopathic pulmonary arterial hypertension is associated with high morbidity and mortality. In recent years, the use of targeted therapies has led to an improvement in prognosis. Prostacyclin analogues treprostinil and epoprostenol require continuous subcutaneous or intravenous infusion and are generally administered in a stepwise approach. However, there are no clear recommendations for transition in high-risk patients requiring high doses of prostacyclin analogues. Case summary In this report, we describe the case of a 20-year-old woman under combined treatment with sildenafil, macitentan, and treprostinil who required transition from subcutaneous treprostinil therapy to intravenous epoprostenol due to erratic drug absorption and functional class progression. The transition was performed over 48 h in a stepwise approach reducing treprostinil dose 4 ng/kg/min every 3 h while increasing epoprostenol infusion 2 ng/kg/min until achieving a maintenance dose of 32 ng/kg/min. There were no side effects requiring changes in the infusion rate. Discussion Patients with advanced pulmonary arterial hypertension may necessitate switching from subcutaneous treprostinil to epoprostenol. Although many protocols have been used to date, there are no guidelines to direct this process safely. This 48-h scheme based on the pharmacokinetic properties of each drug was successful and well-tolerated.

Role of vascular remodeling markers in the development of osteoporosis in idiopathic pulmonary arterial hypertension

2016 ◽  
Vol 88 (9) ◽  
pp. 65-70
Author(s):  
V A Nevzorova ◽  
E A Kochetkova ◽  
L G Ugay ◽  
Yu V Maistrovskaya ◽  
E A Khludeeva
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Cardiac Index ◽  
Arterial Hypertension ◽  
Healthy Volunteers ◽  
Vascular Remodeling ◽  
Serum Levels ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Arterial

Aim. To define the role of circulating biomarkers for the metabolism of collagen and intercellular substance and vascular remodeling in the development of osteoporosis (OP) in idiopathic pulmonary arterial hypertension (IPAH). Materials and methods. Functional hemodynamic parameters, bone mineral density (BMD) in the lumbar spine and femoral neck and the serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 complex, C-terminal telopeptide of collagen type 1 (CITP), and endothelin-1 (ET-1) were determined in 27 high-risk IPAH patients and 30 healthy volunteers. Results. OP in IPAH was detected in 50% of the examinees. The serum levels of CITP, MMP-9, TIMP-1, and ET-1 proved to be higher in the high-risk IPAH patients than in the healthy volunteers. There was a direct correlation between BMD and six-minute walk test and an inverse correlation with total pulmonary vascular resistance (TPVR). Serum TMIP-1 levels correlated with cardiac index and TPVR; ET-1 concentrations were directly related to pulmonary artery systolic pressure, cardiac index, and TPVR. Inverse relationships were found between BMD and circulating CITP, MMP-9, TMIP-1, MMP-9/TMIP-1, and ET-1. At the same time, there was only a tendency towards a positive correlation between serum CITP and ET-1 concentrations. Conclusion. The results of the investigation confirm that endothelin system dysregulation plays a leading role in the development of persistent hemodynamic disorders in high-risk IPAH and suggest that it is involved in the development of osteopenic syndrome. Enhanced ET-1 secretion initiates bone loss possibly via activation of connective tissue matrix destruction.

scholarly journals Risk assessment in patients with functional class II pulmonary arterial hypertension: Comparison of physician gestalt with ESC/ERS and the REVEAL 2.0 risk score

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241504
Author(s):  
Sandeep Sahay ◽  
Adriano R. Tonelli ◽  
Mona Selej ◽  
Zachary Watson ◽  
Raymond L. Benza
Keyword(s):  
Risk Assessment ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Functional Class ◽  
Low Risk ◽  
Assessment Tools ◽  
Patient Risk ◽  
Objective Risk ◽  
Pulmonary Arterial

Background Accurate and regular risk assessment is important for evaluation and treatment of pulmonary arterial hypertension (PAH) patients, including those with functional class (FC) II symptoms, a population considered at low risk for disease progression. Risk assessment methods include subjective and objective evaluations. Multiparametric assessments include tools based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines (COMPERA and FPHR methods, respectively) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL; REVEAL 2.0 tool). To better understand risk status determination in FC II patients, we compared physician-reported risk assessments with objective multiparameter assessment tools. Methods This retrospective chart analysis included PAH patients with FC II symptoms receiving monotherapy or dual therapy. Physicians were surveyed (via telephone) to obtain an assessment of patient risk using their typical methodology, which might have been informed by objective risk assessment. Patient risk was then calculated independently using COMPERA, FPHR and REVEAL 2.0 tools. Factors associated with incongruent risk assessment were identified. Results Of the 153 patients, 41%, 46%, and 13% were classified as low, intermediate, and high risk, respectively, by physicians. Concordance between physician gestalt and objective methods ranged from 43%–54%. Among patients considered as low risk by physician gestalt, 4%–28% were categorized as high risk using objective methods. The most common physician factor associated with incongruent risk assessment was less frequent echocardiography during follow-up (every 7–12 months vs. every 3 months; p = 0.01). Conclusions More than half of FC II PAH patients were classified as intermediate/high risk using objective multiparameter assessments. Incorporating objective risk-assessment algorithms into clinical practice may better inform risk assessment and treatment strategies.

scholarly journals Additional role of echocardiogram in pulmonary arterial hypertension risk stratification according to current ESC/ERS guidelines

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Rotunno ◽  
F Dardi ◽  
A De Lorenzis ◽  
M Palazzini ◽  
E Zuffa ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Risk Stratification ◽  
Arterial Hypertension ◽  
Likelihood Ratio ◽  
Right Atrial ◽  
P Value ◽  
Pulmonary Arterial ◽  
Additional Role

Abstract Background Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. A simplified risk table has been recently proposed and validated without including echocardiographic parameters. Purpose We evaluate the additional role of echocardiogram in PAH risk stratification using the recently proposed simplified risk table in patients with idiopathic/heritable (I/H) PAH and PAH associated with connective tissue disease (CTD) and congenital heart disease (CHD). Methods All patients with I/H-PAH, CTD-PAH and CHD-PAH referred to a single centre were included from 2003 to 2017. All patients were treated according to PH guidelines. The simplified risk assessment considered the following criteria: WHO functional class, 6-min walking distance, right atrial (RA) pressure or brain natriuretic peptide (BNP) plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). For the last 2 criteria the worst parameter was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. Then we performed a Cox analysis to evaluate the independent echocardiographic predictors of survival that were subsequently added to the simplified risk table to test their additional role in ameliorating risk stratification. Results 461 treatment-naïve patients were enrolled. Echocardiographic independent predictors of prognosis were the severity of tricuspid regurgitation [HR (95% CI) = 1.013 (1.006–1.021); p-value = 0.001], right atrial area [HR (95% CI) = 1.028 (1.012–1.045); p-value = 0.001] and the presence of pericardial effusion [HR (95% CI) = 1.533 (1.142–2.057); p-value= 0.004]. Only RA area significantly ameliorate the risk stratification power of the recently validated simplified PAH risk table (likelihood ratio chi2 increased from 63.8 to 68.1, likelihood ratio test = 0.039). Due to the significant correlation between RA area and both RA pressure (r=0.470; p&lt;0.001) and BNP (r=0.372; p=0.004), we elaborate a second risk table in which RA area (utilizing the cut-offs proposed by the current PH guidelines) was considered together within the criteria including RA pressure and BNP (the worst parameter of the 3 was considered). Considering the second risk table including RA area the risk stratification power significantly improved (likelihood ratio chi2 increased from 63.8 to 72.7, AIC/BIC decreased from 1956/1964 to 1947/1955). Conclusions Echocardiographic RA area significantly improve the risk discrimination power of the recently proposed simplified risk table for patients with PAH. Funding Acknowledgement Type of funding source: None

P4680Prognostic value of stroke volume index in patients with pulmonary arterial hypertension at intermediate risk

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Dardi ◽  
E Gotti ◽  
M Palazzini ◽  
A Rinaldi ◽  
E Zuffa ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Plasma Levels ◽  
Prognostic Value ◽  
Functional Class ◽  
P Value ◽  
Intermediate Risk ◽  
Pulmonary Arterial

Abstract Background Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. Low, intermediate and high-risk are defined by estimated 1-year mortality of <5%, 5–10% and >10%, respectively. This risk assessment has been recently validated in 3 cohorts of PAH patients and a simplified risk table for patients with idiopathic/heritable (I/H) PAH and PAH associated with connective tissue disease (CTD) and congenital heart disease (CHD) has been recently proposed and validated. However, with this method most of the patients are classified in the intermediate risk category and additional strategies are required to further stratify this group of PAH patients. Purpose To evaluate the prognostic value of SVI measured with right heart catheterization (RHC) in patients at intermediate-risk. Methods All treatment naïve patients with I/H-PAH, CTD-PAH and CHD-PAH referred to a single centre were included from 2003 to 2017. All patients were assessed at baseline and at the 1st follow-up at 3–4 months after starting PAH-specific therapy (1st F-UP) with RHC, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD) and WHO functional class. We applied a simplified risk assessment strategy using the following criteria: WHO functional class, 6MWD, right atrial pressure or BNP plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). The last 2 criteria were based on which parameter was available; if both were available the worst was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. The prognostic value of SVI was assessed using Cox regression analysis. Intermediate risk patients were further stratified in intermediate-low and intermediate-high risk taking into account the value of SVI that best discriminate prognosis (according to ROC curve analysis). Kaplan Meier curves and Log-rank test were used for survival analysis. Results Seven hundreds and twenty-five patients were enrolled. SVI is able to stratify the prognosis of PAH patients at 1st F-UP [HR 0.979 (0.964–0.994), p-value= 0.008] but not at baseline [HR 0.986 (0.970–1.002), p-value= 0.085]. The best predictive cut-off value is 38 ml/m2 (AUC= 0.66, sensitivity= 73%, specificity= 59%). Survival curves are shown in the Figure. Figure 1 Conclusions SVI assessed at 1st F-UP is predictive of prognosis and the cut off value of 38 ml/m2 is able to further stratify the survival of intermediate risk PAH patients. Acknowledgement/Funding None

scholarly journals EXPRESS: Phosphoproteomic Analysis of Lung tissue from Patients with Pulmonary Arterial Hypertension

2021 ◽  
pp. 204589402110311
Author(s):  
Ravikumar Sitapara ◽  
Tukiet Lam ◽  
Aneta Gandjeva ◽  
Rubin Tuder ◽  
Lawrence Zisman
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Tissue ◽  
Immune Regulation ◽  
Potential Role ◽  
Rho Gtpase ◽  
High Morbidity ◽  
Pulmonary Arterial

Pulmonary Arterial Hypertension (PAH) is a rare disorder associated with high morbidity and mortality despite currently available treatments. We compared the phosphoproteome of lung tissue from subjects with iPAH obtained at the time of lung transplant with control lung tissue. The mass spectrometry-based analysis found 60,428 phosphopeptide features from which 6622 proteins were identified. Within the subset of identified proteins there were 1234 phosphopeptides with q<0.05, many of which are involved in immune regulation, angiogenesis, and cell proliferation. Most notably there was a marked relative increase in phosphorylated (S378) IKZF3 (Aiolos), a zinc finger transcription factor that plays a key role in lymphocyte regulation. In vitro phosphorylation assays indicated that GSK3 alpha and/or GSK3 beta could phosphorylate IKZF3 at S378. Western blot analysis demonstrated increased pIKZF3 in iPAH lungs compared to controls. Immunohistochemistry demonstrated phosphorylated IKZF3 in lymphocytes surrounding severely hypertrophied pulmonary arterioles. In situ hybrization showed gene expression in lymphocyte aggregates in PAH samples. A BCL2 reporter assay showed that IKZF3 increased BCL2 promoter activity and demonstrated the potential role of phosphorylation of IKZF3 on the regulation of BCL mediated transcription. Kinase network analysis demonstrated potentially important regulatory roles of casein kinase 2, CDK1, MAPKs, and PRKs in iPAH. Bioinformatic analysis demonstrated enrichment of Rho GTPase signaling and the potential importance of PRKG. In conclusion, this unbiased phosphoproteomic analysis demonstrated several novel targets regulated by kinase networks in iPAH, and reinforced the potential role of immune regulation in the pathogenesis of iPAH. The identified up and down-regulated phosphoproteins have potential to serve as biomarkers for PAH and to provide new insights for therapeutic strategies.

Risk assessment in pulmonary arterial hypertension (PAH): Insights from the GRIPHON study

2019 ◽  
Author(s):  
HA Ghofrani ◽  
O Sitbon ◽  
K Chin ◽  
R Channick ◽  
L Di Scala ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arterial
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