Diagnosis Of Pulmonary Hypertension Research Articles

Pulmonary Hypertension Association's 2022 International Conference Scientific Sessions Overview.

The considerable progress made in recent years in the diagnosis, risk stratification, and treatment of pulmonary hypertension was highlighted during the most recent edition of the Pulmonary Hypertension Association Scientific Sessions, which was held in Atlanta, Georgia from June 9 to 11, 2022, with the theme: Vision for the PHuture: The Evolving Science and Management of PH. Content presented over the 3-day conference focused on scientific and management updates since the last sessions were held in 2018 and included didactic talks, debates, and roundtable discussions across a broad spectrum of topics related to pulmonary hypertension. This article aims to summarize the key messages from each of the sessiontalks.

Role of right heart catheterization in diagnosis of pulmonary arterial hypertension

Abstract Background Pulmonary hypertension (PH) presumably has an impact on 1% or less of the world’s population. Right Heart Catheterization (RHC) is essential for determining PH problems. RHC determines prognosis and offers helpful information on the degree of hemodynamic impairment. Therefore, this comparative study was carried out to determine the diagnostic role, pitfalls associated, and complications encountered during RHC in suspected cases of PAH and chronic thromboembolic pulmonary hypertension (CTEPH). Methods The observational cohort study was conducted on 75 patients with clinical suspicion of PH and CTEPH. All patients were subjected to full history taking, ECG, Echocardiography, and radiological investigations including Chest radiography (CXR), high-resolution computed tomography (HRCT), and computed tomography (CT) pulmonary angiography. Results The mean pulmonary artery mean pressure (PAMP) was 46.05 ± 9.631 mmHg, the mean Pulmonary artery dilatation (PAD) was 30.04 ± 1.082 mm the mean ejection fraction (EF%) was 63.87%, the mean right ventricular diameter was 45.83 ± 0.444 mm. The mean pulmonary artery wedge pressure (PAWP) was 10.91 ± 2.303 mmHg, and the mean cardiac output (CO) was 4.00 ± 0.773 L/min mean cardiac index (CI) was 1.94 ± 0.416 L/min/m2. Doppler echocardiographic estimated pulmonary artery systolic pressure (DE-ePASP) and estimated pulmonary, artery, end-diastolic pressure (ePADP) significantly positively correlated with RHC-PASP (P < 0.001) and mean DE-ePAP significantly positively Correlated with mean RHC-PAP (P < 0.001). Conclusions RHC is still the only method that can completely and accurately diagnose PAH. however, the combination between right cardiac catheterization and echocardiography provides a more accurate diagnosis of the diseases and their complications.

Guest Editor’s Memo

We are thrilled to bring this issue of Advances in Pulmonary Hypertension to you, which highlights some of the fruits of basic and clinical research in pulmonary hypertension. We have invited accomplished PH experts to help us navigate through some of the increasingly complex challenges in the diagnosis and treatment of PH. First, we have included all the scientific abstracts presented at the PHA 2022 International Pulmonary Hypertension Conference.Next, Drs. Jennifer Keen, Nadine Al-Naamani, and Corey Ventetuolo provide a focused review on emerging therapies for the management of pulmonary arterial hypertension (PAH). They summarize selected and most promising novel pharmaceuticals currently on the horizon and in clinical trials that are targeting new pathways in PAH.In August of 2022, the European Society of Cardiology and the European Respiratory Society published guidelines for the diagnosis and management of pulmonary hypertension (PH). This recent guideline now lowers the pulmonary vascular resistance from > 3 Wood units down to >2 Wood Units to meet the criteria for pre-capillary PH. Drs. Bradley Maron and Georgios Triantafyllou take us back to 1973, when the diagnosis of PH only required a mean PAP of >25 mmHg, and then review the subsequent literature that forms the basis for the revised definition. Dr. Robert Frantz provides a counterpoint to the lowering of the upper limit of PVR by highlighting the problems with the revised definition of pre-capillary PH, and how it might be practically implemented in clinical practice. Finally, Drs. Vallerie McLaughlin, Marc Humbert, Charles Burger, and Hilary DuBrock discuss the pros and cons of these new guidelines in-depth in a roundtable format.We immensely thank all of our contributing authors for sharing their experience and insights. We sincerely hope you enjoy reading this issue of Advances in Pulmonary Hypertension.

Bosentan Is Associated with a Reduction in Right Ventricular Systolic Pressure N-Terminal Pro-Hormone B-Type Natriuretic Peptide Levels in Young Patients with Pulmonary Hypertension

Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population; however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg; p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037; p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements; however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.

Could Impedance Cardiography be a Non-Invasive Alternative Method of Measuring Cardiac Output in Patients with Pulmonary Hypertension?

Pulmonary hypertension guidelines recommend invasive right heart catheterization for diagnosis and clinical follow-up. Our aim was to compare non-invasive impedance cardiography with invasive techniques for cardiac index measurements and mortality prediction in patients with pulmonary hypertension. Between 2008 and 2018, 284 right heart catheterizations were performed for the diagnosis of pulmonary hypertension in 215 patients with mean pulmonary artery pressure >25 mm Hg, and at least 2 methods used for cardiac output measurement were included in the study retrospectively. Patients were evaluated with Pearson's correlation in 3 groups: estimated Fick (eFick) method and thermodilution (group 1), eFick method and impedance cardiography (group 2), and thermodilution and impedance cardiography (group 3). We also compared the predictive power of cardiac index measured by different methods for 1-year overall mortality and hospitalizations. There were strong and moderate positive correlations in groups 1 and 3, respectively (r = 0.634, P <.001, r = 0.534, P =.001), and the weakest correlation was in group 2 (r = 0.390, P =.001). The mean difference (bias) between eFick method versus impedance cardiography, impedance cardiography vs. thermodilution, and eFick method vs. thermodilution was 0.6 mL/min, 0.47 mL/min, and -0.2 mL/min respectively, but limits of agreement were wide. In both groups, cardiac index <2.5 L/min/m2 as measured by thermodilution significantly predicted 1-year mortality. Also, impedance cardiography was better than eFick method in predicting mortality (P =.02). Our single-center real-life data showed that for cardiac output and cardiac index measurements, impedance cardiography provides a moderate correlation with thermodilution and is fair with eFick method methods. Moreover, thermodilution appeared superior to both eFick method and impedance cardiography, while impedance cardiography was even better than eFick method in predicting 1-year adverse events, including total mortality and hospitalization, in patients with pulmonary hypertension.

Time to diagnosis of pulmonary hypertension and diagnostic burden: A retrospective analysis of nationwide US healthcare data.

The main aim of this analysis was to investigate time from symptom onset (chronic unexplained dyspnoea [CUD]) to diagnosis of Group 1 pulmonary hypertension (PH)-pulmonary arterial hypertension (PAH)-and to characterize healthcare resource utilization leading up to diagnosis using a nationwide US claims and an electronic health record (EHR) database from Optum©. Eligible patients were ≥18 years old at first CUD diagnosis (index event) and had a PAH diagnosis on or after index date. Based on administrative codes, PAH was defined as right heart catheterization (RHC), ≥ 2 PAH diagnoses (1 within a year of RHC), and ≥1 post-RHC prescription for PAH treatment. All values are median (1st quartile-3rd quartile) unless otherwise stated. Of 854,722 patients with CUD in the claims database, 582 (0.1%) had PAH. Time from CUD to PAH diagnosis was 2.26 (0.73-4.22) years. PAH patients experienced 3 (2-4) transthoracic echocardiograms (TTEs), 6 (3-12) specialist visits, and 2 (1-4) hospitalizations during the diagnostic interval. Almost one-third of patients (29%) waited 10 months or more to have a TTE. Findings from the EHR database were broadly similar. Resource utilization during the diagnostic interval was also analyzed in an overall PH cohort: findings were generally similar to the PAH cohort (2 [1-3] TTEs, 4 [2-9] specialist visits and 2 [1-4] hospitalizations). These data indicate a delay in the diagnostic pathway for PAH, and illustrate the burden associated with PAH diagnosis.

Development conceptual of pharmacoeconomic model of technology for early diagnosis and pharmacotherapy of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare, progressive disease with a poor prognosis in the absence of timely diagnosis and appropriate therapy. Despite significant advances in the treatment of PAH, many patients remain undiagnosed years after the onset of the disease. Evaluation of the implementation of early diagnostic technologies for PAH is increasingly being used to develop economic evidence for health care at the early stages of diagnosis. The development of models of early diagnosis technology for LAH is highly relevant and can be used in the development and management of new medical technologies, as well as to reduce the perceived risks during the implementation of screening programs for LAH diagnosis.&#x0D; The objective of the paper: Conceptual development of a pharmacoeconomic model of the technology of early diagnosis and pharmacotherapy of PAH.&#x0D; Our pharmacoeconomic analysis is based on the «cost–effectiveness» model, which reflects the effectiveness and associated costs of implementing diagnostic screening for early detection of patients with PAH. The analysis of input data of the existing health care system was conducted using systematic review, documentary, informational and graphical research methods.&#x0D; The presented pharmacoeconomic model describes not only the structure of the incidence of PAH in the studied risk group or at the level of the entire population, but also takes into account the pharmacoeconomic evaluation of the complex technology of timely medical care for patients with PAH based on diagnostic screening.&#x0D; A pharmacoeconomic model of the technology of early diagnosis and pharmacotherapy of pulmonary arterial hypertension was developed, which covered a horizon of 10 years and was conducted from the point of view of the existing health care system, showed that for patients with delayed diagnosis of PAH, the modeling determined the average life expectancy at the level of 4.13 years and 2.08 QALYs.&#x0D; It has been determined that a diagnostic screening strategy for PAH would be cost–effective compared to no screening at different thresholds of diagnostic cost. However, other factors such as public awareness and acceptance of the screening programme and availability of human resources should be considered.

Right heart catherisation – a virtual reality

Abstract Introduction Right heart catheterisation (RHC) is the gold standard for assessing patients with pulmonary hypertension. Doctors require training in this procedure in a safe and friendly environment with minimal risk to patients. Due to the Covid pandemic, formal RHC teaching workshops were cancelled in our country, so we sought to develop a Virtual Reality Right Heart Catheterisation (VRRHC) training program to fulfil this area of need without the need for face to face contact. The aim was to improve training, competency and confidence in this technique with improved diagnostic skills and reduction of procedural errors. Method We approached a health technology company to design a VRRHC training module based on our current RHC simulation workshops. Phase 1 required virtual insertion of RHC via the right internal jugular vein using micro-puncture, double Seldinger technique under ultrasound guidance, followed by insertion of the RHC to the right atrium, right ventricle and pulmonary artery with pulmonary artery occlusion using real time pressure tracings and fluoroscopy. Thermodilution cardiac outputs and chamber saturations were also performed. The proprietary platform technology was delivered via a laptop and VR headset. Clinicians perform the VRRHC with imaging, monitoring and haptic feedback with the collection of real time performance tracking allowing user data (e.g. failed steps and proficiency scores) to be captured and subsequently visualised in the learning management system. We collected analytics and data on user engagement, experience and retention, targeted learning outcomes and learning curve, reduction in operating costs, reduction in procedure times due to higher proficiency, early diagnosis of pulmonary hypertension, reduced complications, improved interpretation and diagnosis. Results The program was launched in October 2021. Preliminary data shows a learning curve is associated with both using VR (10–15 minutes) and the RHC procedure itself. Initial time to completion of the RHC was 30–40 mins, reducing to 20–30 minutes with experience and 15 minutes in experts. Completion rates increase with experience from 40–50% to 100% and error rates reduce with frequency of completion. Conclusion A Virtual Reality Right Heart Catheter training program is safe, feasible and non-invasive. Increased experience results in increased completion rates, reduced procedure time and reduced errors. Using this program will potentially have beneficial effects on doctor training, outcomes, patient safety and health economics with no risk to a real patient. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Janssen Pharmaceuticals

Review of current recommendations for diagnosis and treatment of patients with pulmonary hypertension

The article based on the recommendations of the European Society of Cardiology (2022) discusses the definition, pathogenesis, classification and diagnosis of pulmonary hypertension. Particular attention is paid to the indications for conducting and interpreting the results of catheterization of the right heart cavities with the selection of groups of patients with precapillary, isolated postcapillary and combined pulmonary hypertension. The article provides a diagnostic algorithm for people with suspected pulmonary arterial hypertension, as well as risk stratification of patients with a confirmed diagnosis. Issues of prescription of specific drug therapy for patients with pulmonary arterial hypertension, escalation of therapy, including indications for transplantation of the heart-lung complex are considered.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Advances in targeted therapy for pulmonary arterial hypertension in children.

Pulmonary arterial hypertension (PAH) is a rare and devastating pulmonary vascular disease that is associated with a variety of diseases of any age in childhood onset. •Therapeutic strategies for targeted drugs for PAH in children are based almost exclusively on data from adult studies and clinical experience of pediatric specialists. •Due to the complex etiology of PAH in children and the relative lack of clinical trial data, the selection of appropriate targeted drug therapy remains difficult. •We redefine the definition of pulmonary arterial hypertension in children and summarize the progress of targeted therapy of pulmonary arterial hypertension in children in the past ten years. • The dosage and adverse reactions were summarized, and the mechanism of action was drawn according to the available targeted drugs. It can provide theoretical support for the development of guidelines and treatment strategies for the diagnosis and treatment of pulmonary arterial hypertension in children.

1021 VASODILATOR CHALLENGE TEST WITH ISOSORBIDE DINITRATE DURING RIGHT HEART CATHETERIZATION: ANY ROLE IN POST-CAPILLARY PULMONARY HYPERTENSION PHENOTYPING?

Abstract Background and aims Despite recent advances in the diagnosis and treatment of pulmonary arterial hypertension (PAH), pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF-PH) still represents a diagnostic and therapeutic dilemma. Among HFpEF-PH patients, discriminating between isolated post-capillary (IpcPH) from combined post-/pre-capillary (CpcPH) PH, and especially a better understanding of the latter, is still challenging. Such a distinction can have an important therapeutic impact, as new evidence suggests that therapy with PDE5i might be beneficial in specific CpcPH patients [Humbert M, Kovacs G, Hoeper M et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022]. Our study sought to comprehensively assess and explore the role of Isosorbide Dinitrate (ISDN) testing in HFpEF-PH phenotyping. Methods From November 2019, all patients referred to our service to investigate PH and elevated pulmonary artery wedge pressures (PAWP) at rest or after fluid challenge at the time of the right heart catheterization, had a vasodilator test with a slow IV bolus of ISDN (with a specific protocol). Clinical, echocardiographic and hemodynamic data were collected. Results 38 patients (25 CpcPH, 13 IpcPH) were included in the analysis. Baseline characteristics are shown in table 1. Based on ISDN response, patients were stratified into three groups (Table 2). Group 1 showed a lack of significant pressures reduction after ISDN (“vasodilator negative Cpc-PH”). Group 2 displayed a significant reduction of PAWP &amp;lt; 15 mmHg, but persistent PH and high Pulmonary Vascular Resistance (PVR) (“vasodilator positive Cpc-PH”). Group 3 were patients whose pulmonary pressures normalized after ISDN (Ipc-PH). Conclusions albeit on a small group of patients, our preliminary results warrant further studies on the potential role of ISDN in better phenotyping HFpEF-PH and identify subgroups of patients who might benefit from PH specific therapies (“vasodilator positive Cpc-PH”) after treatment of the underling left heart disease.

905 EVALUATION OF PULMONARY HYPERTENSION BETWEEN ECHOCARDIOGRAPHIC ESTIMATION AND CARDIAC CATHETERIZATION IN PATIENTS UNDERGOING TRICLIP IMPLANTATION: PRELIMINARY DATA

Abstract Background echocardiography is a helpful tool in patients with suspected pulmonary hypertension (PH). Data derived from echocardiographic examination allow to assign a level of probability of PH by using multiple parameters. Nevertheless, the gold standard for the diagnosis of PH remains the right heart catheterization. The evaluation of PH is important in patients undergoing transcatheter tricuspid valve repair, in fact, many trials excluded those with “severe” pulmonary hypertension. Aim the aim of this study was to examine, in the evaluation of PH, the parameters derived from echocardiographic estimation and cardiac catheterization in patients undergoing TriClip implantation. Methods a retrospective analysis of 4 patients underwent to TriClip implantation in our department was performed. Echocardiography and right heart catheterization data were collected. In the assessment of pulmonary hypertension, the analyzed echocardiographic parameters were: enlarged right ventricle in parasternal long-axis view (&amp;gt;30 mm), flattened interventricular septum leading to “D-shaped LV”, dilated inferior vena cava (&amp;gt;21 mm) with diminished inspiratory collapsibility (&amp;lt;50%), RVOT acceleration time of pulmonary ejection &amp;lt;105 msec, reduced right ventricular fractional area change (&amp;lt;35%), decreased tricuspid annular plane systolic excursion (TAPSE &amp;lt;18mm), TAPSE/sPAP ratio &amp;lt;0.55 mm/mmHg, enlarged right atrial area (&amp;gt;18 cm2), increased systolic peak tricuspid regurgitation velocity (peak TRV&amp;gt;2.8 m/s), estimated systolic pulmonary artery pressure (sPAP). Echocardiographic probability of pulmonary hypertension was defined as high: peak TRV &amp;gt;3.4 m/s or a peak TRV between 2.9-3.4 m/s and the presence of other echo PH sign; intermediate: peak TRV between 2.9-3.4 or peak TRV ≤2.8 m/sec with other echo PH signs; low: peak TRV ≤2.8 m/sec. Pulmonary hypertension, in accordance with guidelines, was defined by a mean pulmonary arterial pressure (mPAP)&amp;gt;20 mmHg at rest. Results the echocardiographic probability of pulmonary hypertension was high in three patients: 2 patients had a peak TRV&amp;gt;3.4 m/s, one patient had peak TRV 2.95 with RVOT AT 55, flattened interventricular septum, dilated inferior vena cava with diminished inspiratory collapsibility, right atrium area &amp;gt;18cm2. In one patient the probability was intermediate (peak TRV 2.40 m/s, RA area &amp;gt;18 cm2 and TAPSE/sPAP ratio &amp;lt;0.55 mm/mmHg). Right heart catheterization confirmed the diagnosis of pulmonary hypertension in two patients with high echocardiographic probability. In the other two patients (one with high probability and one with intermediate probability) there was no PH diagnosis at right heart catheterization. Conclusion in only two out of four patients with intermediate-high probability of PH the diagnosis was confirmed by right catheterization. Therefore, invasive evaluation of pulmonary pressures should be performed in patients with severe tricuspid regurgitation undergoing Triclip implantation.

426 SPECKLE-TRACKING GLOBAL LONGITUDINAL STRAIN AS A PREDICTOR OF CLINICAL OUTCOMES IN SYSTEMIC SCLEROSIS PATIENTS

Abstract Introduction Cardiac involvement in patients affected by systemic sclerosis is frequent, although mostly asymptomatic, and associated with a negative prognosis. It may be secondary to pulmonary hypertension or defined as an actual systemic-sclerosis related cardiomyopathy, a standalone entity affecting the heart primarily and globally. Speckle-tracking derived global longitudinal strain (GLS) has been proven to be a cost-effective tool in the detection of LV and RV dysfunction in patients with SSc and no overt cardiac disease. The aim of our study was to assess whether GLS can predict clinical outcomes in patients with systemic sclerosis. Methods We conducted a prospective observational study enrolling all consecutive patients referred to our “cardiology clinic for autoimmune diseases and pulmonary hypertension” between June 2016 and January 2022. All patients had a confirmed diagnosis of SSc according to the EULAR guidelines and no overt cardiac disease, pulmonary hypertension, or atrial fibrillation at the time of enrollment. For each patient, echocardiogram and GLS calculations were performed at baseline and at each follow-up. We also collected all data regarding clinical history, hospitalizations or adverse events and ECGs. Results 164 patients (148 female, 58±14 years)were enrolled. 19 (11.6%) patients died during a median follow-up of 3.2 years for mainly non-cardiovascular deaths (7.3%) while cardiovascular deaths were lower (3% non-sudden, 1.3% sudden). Left GLS at first visit was associated with all-cause death, with a 1% left GLS worsening associated with a 19% increased risk of death after adjusting for age, gender, and LVEF (adjusted HR 1.19; 95% CI 1.05-1.35; p=0.007).Similarly, right GLS at first visit was associated with all-cause death, with a 1% right GLS worsening associated with a 12% increased risk of death after adjusting for age, gender, and TAPSE (adjusted HR 1.12; 95% CI 1.03-1.21; p=0.005).Patients with a left GLS worse than -20% had a 3.5-fold increased risk of death when compared to patients with better left GLS (HR 3.55; 95% CI 1.28-9.88; p=0.015). Similarly, patients with a right GLS worse than -20% had a 4.5-fold increased risk of death when compared to patients with better left GLS (HR 4.47; 95% CI 1.4-13.74; p=0.009).Both left and right ventricular GLS were not associated with changes in risk of all-cause hospitalizations, cardiovascular hospitalizations or subsequent diagnosis of pulmonary hypertension. Conclusions GLS is a reproducible, cost effective echocardiographic based method to assess both primary heart disease and its progression. It has proven to be associated with clinical outcomes in patients with systemic sclerosis, therefore allowing a prompt intervention when needed in order to try and prolong the life expectancy of this cohort of patients.

Updated definition of exercise pulmonary hypertension.

In the recently published European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of pulmonary hypertension (PH) the haemodynamic definitions of PH were updated and a new definition for exercise PH was introduced. Accordingly, exercise PH is characterised by a mean pulmonary arterial pressure/cardiac output (CO) slope >3 Wood units (WU) from rest to exercise. This threshold is supported by several studies demonstrating prognostic and diagnostic relevance of exercise haemodynamics in various patient cohorts. From a differential diagnostic point of view, an elevated pulmonary arterial wedge pressure/CO slope >2 WU may be suitable to identify post-capillary causes of exercise PH. Right heart catheterisation remains the gold standard to assess pulmonary haemodynamics both at rest and exercise. In this review, we discuss the evidence that led to the reintroduction of exercise PH in the PH definitions.

Diagnosis and management of pulmonary hypertension in infants with bronchopulmonary dysplasia: a guide for paediatric respiratory specialists.

To identify those BPD patients most at risk of developing PH.To be aware of detection, multidisciplinary management, pharmacological treatment and monitoring strategies for BPD-PH patients.To understand the potential clinical course for patients with BPD-PH and that evidence on efficacy and safety of PH-targeted pharmacotherapy in BPD-PH is limited.

Diagnosis and management of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that is characterised by elevated pressures within the pulmonary vascular tree. Recent decades have witnessed a dramatic expansion in our understanding of the pathobiology and the epidemiology of PAH, and improvements in treatment options and outcomes. The prevalence of PAH is estimated to be between 48 and 55 cases per million adults. The definition was recently amended and a diagnosis of PAH now requires evidence of a mean pulmonary artery pressure >20 mmHg, a pulmonary vascular resistance >2 Wood units and a pulmonary artery wedge pressure ≤15 mmHg at right heart catheterisation. Detailed clinical assessment and a number of additional diagnostic tests are required to assign a clinical group. Biochemistry, echocardiography, lung imaging and pulmonary function tests provide valuable information to assist in the assignment of a clinical group. Risk assessment tools have been refined, and these greatly facilitate risk stratification and enhance treatment decisions and prognostication. Current therapies target three therapeutic pathways: the nitric oxide, prostacyclin and endothelin pathways. While lung transplantation remains the only curative intervention for PAH, there are a number of promising therapies under investigation which may further reduce morbidity and improve outcomes. This review describes the epidemiology, pathology and pathobiology of PAH and introduces important concepts regarding the diagnosis and risk stratification of PAH. The management of PAH is also discussed, with a special focus on PAH specific therapy and key supportive measures.

A signal recognition particle-related joint model of LASSO regression, SVM-RFE and artificial neural network for the diagnosis of systemic sclerosis-associated pulmonary hypertension.

Background: Systemic sclerosis-associated pulmonary hypertension (SSc-PH) is one of the most common causes of death in patients with systemic sclerosis (SSc). The complexity of SSc-PH and the heterogeneity of clinical features in SSc-PH patients contribute to the difficulty of diagnosis. Therefore, there is a pressing need to develop and optimize models for the diagnosis of SSc-PH. Signal recognition particle (SRP) deficiency has been found to promote the progression of multiple cancers, but the relationship between SRP and SSc-PH has not been explored. Methods: First, we obtained the GSE19617 and GSE33463 datasets from the Gene Expression Omnibus (GEO) database as the training set, GSE22356 as the test set, and the SRP-related gene set from the MSigDB database. Next, we identified differentially expressed SRP-related genes (DE-SRPGs) and performed unsupervised clustering and gene enrichment analyses. Then, we used least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) to identify SRP-related diagnostic genes (SRP-DGs). We constructed an SRP scoring system and a nomogram model based on the SRP-DGs and established an artificial neural network (ANN) for diagnosis. We used receiver operating characteristic (ROC) curves to identify the SRP-related signature in the training and test sets. Finally, we analyzed immune features, signaling pathways, and drugs associated with SRP and investigated SRP-DGs' functions using single gene batch correlation analysis-based GSEA. Results: We obtained 30 DE-SRPGs and found that they were enriched in functions and pathways such as "protein targeting to ER," "cytosolic ribosome," and "coronavirus disease-COVID-19". Subsequently, we identified seven SRP-DGs whose expression levels and diagnostic efficacy were validated in the test set. As one signature, the area under the ROC curve (AUC) values for seven SRP-DGs were 0.769 and 1.000 in the training and test sets, respectively. Predictions made using the nomogram model are likely beneficial for SSc-PH patients. The AUC values of the ANN were 0.999 and 0.860 in the training and test sets, respectively. Finally, we discovered that some immune cells and pathways, such as activated dendritic cells, complement activation, and heme metabolism, were significantly associated with SRP-DGs and identified ten drugs targeting SRP-DGs. Conclusion: We constructed a reliable SRP-related ANN model for the diagnosis of SSc-PH and investigated the possible role of SRP in the etiopathogenesis of SSc-PH by bioinformatics methods to provide a basis for precision and personalized medicine.

Maternal and Fetal Outcomes in Pregnant Women with Pulmonary Arterial Hypertension: A Single-Center Experience and Review of Current Literature.

Although pregnancy in women with pulmonary arterial hypertension has been considered a high-risk condition, current data regarding pregnancy with pulmonary arterial hypertension are scarce. In this study, we aimed to evaluate our single-center data on maternal and fetal outcomes in pregnant women with PAH and review currently available risk-based management strategies. Our single-center study group comprised 35 women who became pregnant after the diagnosis of pulmonary arterial hypertension or in whom pulmonary arterial hypertension was diagnosed within early post-partum period. Clinical, laboratory, echocardiographic, and hemodynamic characteristics of pregnant and non-pregnant productive women with pulmonary arterial hypertension were compared, and similar comparison was also repeated for survivors and non-survivors in pregnant patient group. Pregnancy was noted in 15% of the 228 females with pulmonary arterial hypertension who were of hormonally productive ages, generally well-tolerated until delivery. Elective abortion and pre-term delivery were documented in 1 (2.8%) and 12 (35.3%) pregnant women, respectively. Switching to sildenafil was the standard medication during pregnancy. Cesarian section was the preferred method of delivery in all pregnant women with pulmonary arterial hypertension and was performed without any complication. Clinic deteoriation within the first week of delivery was observed in 5 (41.6%) patients. Maternal mortality was noted in 13 (37.1%) patients and was documented to cumulate within the first month of delivery. However, any sign predicting post-partum clinical deterioration was not found. No fetal mortality was observed. Despite the development of advanced therapies, pregnancy in pulmonary arterial hypertension still carries a high mortality risk and requires multi-disciplinary expert center care with more proactive management strategies.

Comments on the 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension

Comments on the 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension