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Background: Pulmonary arterial hypertension (PAH) is a common complication among patients with congenital heart disease (CHD). Despite advances in PAH treatment, evidence for the benefits of PAH therapies in CHD-PAH is limited. Objectives: This analysis aimed to evaluate outcomes in patients with repaired PAH-CHD receiving an approved PAH drug. Methods: This was a pooled analysis including CHD-PAH patients whose CHD was repaired ≥1 year prior from 3 randomized, placebo-controlled, event-driven studies: GRIPHON (NCT01106014), SERAPHIN (NCT00660179), and COMPASS-2 (NCT00303459). The primary endpoint was time to first confirmed morbidity/mortality (M/M) event. HRs with 95% CIs were determined with random effects models. Results: The analysis included 1,982 patients with PAH, 177 (8.9%) with CHD-PAH. In the overall PAH cohort, the mean age was 48 and 49 years in treatment and placebo groups; 80% and 77% were female. In the CHD-PAH cohort, the mean age was 41 and 39 years; 70% and 66% were female. Overall, ≥98% in each group were World Health Organization functional class II and III at baseline. There was a significant reduction in risk of M/M events vs placebo in the overall PAH and CHD-PAH cohorts: 37% reduction in the overall PAH cohort (HR: 0.63; 95% CI: 0.52-0.77) and 50% reduction in the CHD-PAH population (HR: 0.50; 95% CI: 0.26-0.94). Conclusions: Treatment with approved PAH drugs provided a similar reduction in M/M risk in patients with repaired CHD-PAH when compared with the overall PAH population. This pooled analysis provides important evidence to guide medical management in this patient population.

BACKGROUND: Age affects disease severity and patient outcomes in pulmonary arterial hypertension. This post-hoc analysis identified prognostic age groups and associated macitentan/selexipag treatment effects. METHODS: Randomized trials evaluated macitentan (SERAPHIN; NCT00660179) and selexipag (GRIPHON; NCT01106014) versus placebo (primary endpoint: time to morbidity/mortality [M/M]). This analysis defined age thresholds differentiating M/M risk in patients randomized to placebo (Cox regression determining treatment effect by age). RESULTS: Three age groups (< 35, 35–64, ≥ 65 years) showed good M/M risk discrimination (c-statistic 0.69, SERAPHIN; 0.66, GRIPHON). M/M risk was higher in placebo patients < 35 versus 35–64 years (SERAPHIN: hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10–2.72, p = 0.02; GRIPHON: HR 1.81, 95% CI 1.28–2.56, p < 0.001). M/M risk trended higher in patients ≥ 65 versus 35–64 years (SERAPHIN: HR 1.55, 95% CI 0.89–2.69, p = 0.12; GRIPHON (HR 1.08, 95% CI 0.75–1.55, p = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25–0.78; p = 0.005), 35–64 (HR 0.50, 95% CI 0.33–0.76; p < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30–1.58; p = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32–0.78; p = 0.002), 35–64 (HR 0.72, 95% CI 0.54–0.96; p = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33–0.91; p = 0.02). Adverse-event discontinuations were similar. CONCLUSIONS: The benefit (vs placebo) of macitentan/selexipag on reducing risk of M/M events was consistent across all ages, including the younger group where significant treatment effects were observed.

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment.

Abstract Introduction The aim of this sub-study was to evaluate the relationship between echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) variables and to utilize echo to assess the effect of macitentan on right ventricle (RV) structure and function. Methods REPAIR (NCT02310672) was a prospective, multicenter, single-arm, open-label, 52-week, phase 4 study in pulmonary arterial hypertension (PAH) patients, which investigated the effect of macitentan 10 mg as monotherapy, or in combination with a phosphodiesterase 5 inhibitor, on RV structure, function, and hemodynamics using cMRI and right heart catheterization. In this sub-study, patients were also assessed by echo at screening and at weeks 26 and/or 52. Post hoc correlation analyses between echo and cMRI variables were performed using Pearson’s correlation coefficient, Spearman's correlation coefficient, and Bland–Altman analyses. Results The Echo sub-study included 45 patients. Improvements in echo-assessed RV stroke volume (RVSV), left ventricular SV (LVSV), LV end-diastolic volume (LVEDV), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and in 2D global longitudinal RV strain (2D GLRVS) were observed at weeks 26 and 52 compared to baseline. There was a strong correlation between echo (LVSV, 2D GLRVS, and LVEDV) and cMRI variables, with a moderate correlation for RVSV. Bland–Altman analyses showed a good agreement for LVSV measured by echo versus cMRI, whereas an overestimation in echo-assessed RVSV was observed compared to cMRI (bias of − 15 mL). Hemodynamic and functional variables, as well as safety, were comparable between the Echo sub-study and REPAIR. Conclusions A good relationship between relevant echo and cMRI parameters was shown. Improvements in RV structure and function with macitentan treatment was observed by echo, consistent with results observed by cMRI in the primary analysis of the REPAIR study. Echo is a valuable complementary method to cMRI, with the potential to non-invasively monitor treatment response at follow-up. Trial registration number REPAIR NCT02310672. Graphical Abstract

Background Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 European Society of Cardiology/European Respiratory Society guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (cMRI) comparable with functional and haemodynamic variables? Methods REPAIR (ClinicalTrials.gov: NCT02310672) was a prospective, multicentre, single-arm, open-label, 52-week phase 4 study evaluating the effect of macitentan 10 mg, with or without a phosphodiesterase 5 inhibitor (PDE5i), on right ventricular (RV) remodelling, cardiac function and cardiopulmonary haemodynamics. Both cMRI and functional assessments were performed at screening and at weeks 26 and 52; haemodynamic measurements were conducted at screening and week 26. In this post hoc analysis, STES were estimated using the parametric Cohen's d and non-parametric Cliff's delta tests. Results At week 26, large STES (Cohen's d) were observed for 10 of the 20 cMRI variables assessed, including the prognostic measures of RV and left ventricular stroke volume and RV ejection fraction and the haemodynamic trial end-point, pulmonary vascular resistance; medium STES were observed for 6-min walk distance (6MWD). The STES were consistent in treatment-naïve patients and those escalating therapy and maintained at week 52. Similar results were obtained using the non-parametric Cliff's delta method. Conclusions The treatment effect of macitentan, alone or in combination with a PDE5i, was comparable for several cMRI and haemodynamic variables with prognostic value in PAH, and greater than that of 6MWD in patients with PAH, highlighting the emerging relevance of cMRI in PAH.

Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long‐Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long‐term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double‐blind clinical trial comparing high‐dose and low‐dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high‐dose arm vs. 8.6 in low‐dose arm), but mean RRS change from baseline to Week 24 was greater in the high‐dose treprostinil group than in the low‐dose treprostinil group (−0.88 vs. −0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of −0.70 (95% confidence interval: −1.36 to −0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N‐terminal pro‐brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

Abstract Background Little attention has been paid to chest high resolution computed tomography (HRCT) findings in idiopathic pulmonary arterial hypertension (IPAH) patients so far, while a couple of small studies suggested that presence of centrilobular ground-glass opacifications (GGO) on lung scans could have a significant negative prognostic value. Therefore, the aims of the present study were: to assess frequency and clinical significance of GGO in IPAH, and to verify if it carries an add-on prognostic value in reference to multidimensional risk assessment tool recommended by the 2015 European pulmonary hypertension guidelines. Methods Chest HRCT scans of 110 IPAH patients were retrospectively analysed. Patients were divided into three groups: with panlobular (p)GGO, centrilobular (c)GGO, and normal lung pattern. Association of different GGO patterns with demographic, functional, haemodynamic, and biochemical parameters was tested. Survival analysis was also performed. Results GGO were found in 46% of the IPAH patients: pGGO in 24% and cGGO in 22%. Independent predictors of pGGO were: positive history of haemoptysis, higher number of low-risk factors, and lower cardiac output. Independent predictors of cGGO were: positive history of haemoptysis, younger age, higher right atrial pressure, and higher mixed venous blood oxygen saturation. CGGO had a negative prognostic value for outcome in a 2-year perspective. This effect was not seen in the longer term, probably due to short survival of cGGO patients. Conclusions Lung HRCT carries a significant independent prognostic information in IPAH, and in patients with cGGO present on the scans an early referral to lung transplantation centres should be considered.

Abstract Pulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO2) in PH are lacking. We hypothesized that RV hypoxia occurs in monocrotaline-induced PH in rats and that myo-inositol trispyrophosphate (ITPP), facilitating oxygen dissociation from hemoglobin, can relieve it. Rats received monocrotaline (PH) or saline (control) and 24 days later echocardiograms, pressure–volume loops were obtained and myocardial pO2 was measured using a fluorescent probe. In PH mean pulmonary artery pressure more than doubled (35 ± 5 vs. 15 ± 2 in control), RV was hypertrophied, though its contractility was augmented. RV and LV pO2 was 32 ± 5 and 15 ± 8 mmHg, respectively, in control rats. In PH RV pO2 was reduced to 18 ± 9 mmHg, while LV pO2 was unchanged. RV pO2 correlated with RV diastolic wall stress (negatively) and LV systolic pressure (positively). Acute ITPP administration did not affect RV or LV pO2 in control animals, but increased RV pO2 to 26 ± 5 mmHg without affecting LV pO2 in PH. RV oxygen balance is impaired in PH and as such can be an important target for PH therapy. ITPP may be one of such potential therapies.

Introduction Non-invasive tests that may improve clinical evaluation of pulmonary hypertension (PH) are needed. The purpose of this study was to assess the role of soluble ST2 (sST2) in patients with PH. Material and methods A total of 57 patients with chronic thromboembolic PH and 43 patients with idiopathic arterial PH were enrolled in this study. All patients were evaluated for World Health Organization (WHO) functional class (FC), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), troponin T (TnT), and hemodynamics. Plasma sST2 was assessed by an immu­nofluorescent in vitro diagnostic assay. All patients were followed up from the date of blood sampling. The endpoint was all-cause death. Results The median sST2 concentration was 32.8 ng/ml (IQR: 21.6–48.5 ng/ml) in the whole study population. Significant differences were found between median sST2 in successive WHO FCs (FC II vs. FC III, p = 0.002; FC III vs. FC IV, p = 0.12; FC II vs. FC IV, p = 0.008). Significant correlations were found between sST2 and hemodynamic parameters: mean right atrial pressure (r = 0.56; p

Abstract A 46‐year‐old man 1 year after left‐sided pneumonectomy for squamous cell lung cancer presented with severely limited exercise tolerance and dyspnea corresponding to World Health Organization functional class IV (WHO Class IV). After right heart catheterization (RHC), mean pulmonary artery pressure (mPAP) was 43 mmHg and pulmonary vascular resistance (PVR) was 10.2 Wood units (WU). Arteriography revealed organized clots located at the proximal level of the right pulmonary artery, leading to a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). The CTEPH team disqualified the patient from surgical treatment due to high perioperative risk and referred him for balloon pulmonary angioplasty (BPA) together with pulmonary hypertension‐specific pharmacotherapy (sildenafil). The patient underwent a cycle of nine BPA sessions and completed treatment without complications. Follow‐up showed sustained hemodynamic improvement in RHC (mPAP 23 mmHg, PVR 2.6 WU), improved physical capacity (WHO Class II), and relief of dyspnea symptoms.

Pulmonary hypertension (PH) is a common finding that can result from many different pathological conditions. Depending on the etiology, treatment may be quite different, but early diagnosis and correct classification of PH is difficult. With an aging population and recently suggested decreased pulmonary arterial pressure threshold defining PH, we are facing even more diagnostic uncertainties. A new approach to patients' phenotyping is needed. Here we present available data and future perspectives on employing an in-depth analysis of the omics cascade to allow an earlier and more reliable diagnosis and classification of PH. Indeed, with the help of super-fast computing, it became possible to simultaneously consider the levels of thousands of potential biomarkers to find patterns specific for clinically suspected disease. The omics cascade is an invaluable source of information. However, while the genome can be perceived as providing possibilities, transcriptome–as carving them this is metabolome that may tell us 'what is really going on' in an individual living organism. Metabolomics research requires blinded search for characteristic patterns of discreet changes in the levels of detectable metabolites. Since as many as 40,000 various substances are produced as a 'side effect of staying alive', metabolite profiling can be compared to fishing up for organized signals in a universe of chaos. Although difficult, such search for metabolic patterns that might lead to replacing the term biomarker by metabolic fingerprinting in the area of pulmonary circulation has already begun.

Abstract Background Systemic artery to pulmonary artery fistulas (SA-PAFs), are extremely rare in people without congenital heart disease. In this group of patients pulmonary arterial hypertension was reported in the single case. Then, we describe a case of multiple SA-PAFs, which were the cause of severe nonreversible arterial pulmonary hypertension in a patient who had a right-sided pneumothorax 35 years earlier. Case presentation 52-year-old male Caucasian patient with echocardiographically confirmed pulmonary hypertension (PH) was admitted to cardiology department due to exertional dyspnea and signs of right ventricle failure. Routine screening for causes of secondary PH was negative. Right heart catheterization (RHC) confirmed a high degree arterial PH [mean pulmonary artery pressure (mPAP); 50,6 mmHg, pulmonary wedge pressure (PWP); 11,3 mmHg, pulmonary vascular resistance (PVR); 11,9 Wood’s units (WU)] irreversible in the test with inhaled nitric oxide. Oxygen saturation (SaO2) of blood samples obtained during the first RHC ranged from 69.3 to 73.2%. Idiopathic pulmonary arterial hypertension was diagnosed. Treatment with inhaled iloprost and sildenafil was initiated. Control RHC, performed 5 months later showed values of mPAP (59,7 mmHg) and PVR (13,4 WU) higher in comparison to the initial measurement, SaO2 of blood obtained during RHC from upper lobe artery of the right lung was elevated and amounted 89.7%. Then, pulmonary arteriography was performed. Lack of contrast in the right upper lobe artery with the evidence of retrograde blood flow visible as a negative contrast in the right pulmonary artery was found. Afterwards, right subclavian artery arteriography detected a huge vascular malformation communicating with right upper lobe artery. Following computed tomography angiogram (angio-CT) additionally revealed the enlargement of bronchial arteries originated fistulas to pulmonary artery of right upper lobe. In spite of intensive pharmacological treatment, including the therapy of pulmonary hypertension and percutaneous embolisation of the fistulas, the patient’s condition continued to deteriorate further. He died three months after embolisation due to severe heart failure complicated by pneumonia. Conclusion Non-congenital SA-PAFs are extremely rare, however, they should be excluded in patients with pulmonary arterial hypertension and history of inflammatory or infectious disease of the lung and pleura, pneumothorax, cancer or Takayashu’s disease and after chest trauma.

Background: Significant achievements in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) have provided effective therapeutic options for most patients. However, the true impact of the changed landscape of CTEPH therapies on patients’ management and outcomes is poorly known. We aimed to characterize the incidence, clinical characteristics, and outcomes of CTEPH patients in the modern era of CTEPH therapies. Methods: We analyzed the data of CTEPH adults enrolled in the prospective multicenter registry. Results: We enrolled 516 patients aged 63.8 ± 15.4 years. The incidence rate of CTEPH was 3.96 per million adults per year. The group was burdened with several comorbidities. New oral anticoagulants ( n = 301; 58.3%) were preferred over vitamin K antagonists ( n = 159; 30.8%). Pulmonary endarterectomy (PEA) was performed in 120 (23.3%) patients and balloon pulmonary angioplasty (BPA) in 258 (50%) patients. PEA was pretreated with targeted pharmacotherapy in 19 (15.8%) patients, and BPA in 124 (48.1%) patients. Persistent CTEPH was present in 46% of PEA patients and in 65% of patients after completion of BPA. Persistent CTEPH after PEA was treated with targeted pharmacotherapy in 72% and with BPA in 27.7% of patients. At a mean time period of 14.3 ± 5.8 months, 26 patients had died. The use of PEA or BPA was associated with better survival than the use of solely medical treatment. Conclusions: The modern population of CTEPH patients comprises mostly elderly people significantly burdened with comorbid conditions. This calls for treatment decisions that are tailored individually for every patient. The combination of two or three methods is currently a frequent approach in the treatment of CTEPH. Clinical Trial Registration: clinicaltrials.gov/ct2/show/NCT03959748

Pulmonary arterial compliance is a measure of the pulsatile afterload of the right ventricle. Lower pulmonary arterial compliance is associated with reduced right ventricular function and worse prognosis in pulmonary hypertension. The effect of pulmonary vasodilators on pulmonary arterial compliance has not been evaluated in detail in pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In this post hoc analysis of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the PATENT and CHEST studies, we evaluated the change in pulmonary arterial compliance with riociguat versus placebo. Association of pulmonary arterial compliance with clinical outcomes was assessed using Kaplan–Meier and Cox proportional hazards analyses. Compared with placebo, riociguat significantly improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline was associated with survival and clinical worsening-free survival in pulmonary arterial hypertension but only with clinical worsening-free survival in chronic thromboembolic pulmonary hypertension. In patients with pulmonary arterial hypertension, pulmonary arterial compliance at follow-up ≥1.6 mL/mmHg was associated with better outcomes than pulmonary arterial compliance

Abstract Background The remodeling of the right heart in patients with chronic pulmonary hypertension (cPH) is associated with the appearance of electrocardiographic (ECG) abnormalities. We investigated the resolution of ECG markers of right ventricular hypertrophy (RVH) caused by acute and long‐term hemodynamic improvement. Methods Twenty‐nine (29) patients with chronic thromboembolic pulmonary hypertension (CTEPH) and seven patients with pulmonary arterial hypertension (PAH) were included in the analysis. Patients with CTEPH achieved a significant long‐term hemodynamic improvement following the treatment with balloon pulmonary angioplasty (BPA); all the patients with PAH reported significant acute hemodynamic relief after a single inhalation of iloprost, fulfilling the criteria of responder. Standard 12‐lead ECG was performed before and after intervention. Results The interval between baseline and control ECG in CTEPH and PAH groups was 28 (IQR: 17–36) months and 15 min (IQR: 11–17), respectively. Despite similar hemodynamic improvement in both groups, only the CTEPH group presented significant changes in most analyzed ECG parameters: T‐wave axis (p = .002), QRS‐wave axis (p = .012), P‐wave amplitude (p

Abstract Background Subcutaneous treprostinil is a prostacyclin analogue used to treat pulmonary arterial hypertension (PAH). Due to local pain it can cause a deterioration of heart related quality of life (HRQoL) or even abandonment of treatment. The aim of this paper was to assess the feasibility of treatment with intravenous treprostinil administered by means of the Lenus Pro® implantable pump. Methods This was a retrospective, multi-center study involving 12 patients (8 females) with PAH treated with a subcutaneous infusion of treprostinil with intolerable pain at the infusion site. Clinical evaluation, including HRQoL assessment with SF-36 questionnaire was performed, before pump implantation and 2–9 months after. The median time of follow-up time was 14 months (4–29 months). Results After implantation of the Lenus Pro® pump, no statistically significant changes were observed in the 6-min walking distance and NT-proBNP. After implantation 50% of patients were in II WHO functional class (33% before, p = 0,59). There was a significant improvement in HRQoL within the Physical Component Score (28 ± 7 vs 38 ± 8 pts., p

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) may be treated with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapy (MT). Assessment in a multidisciplinary team of experts (CTEPH team) is currently recommended for treatment decision making. The aim of the present study was to report the effects of such an interdisciplinary concept. Methods and results: A total of 160 patients were consulted by the CTEPH team between December 2015 and September 2018. Patient baseline characteristics, CTEPH team decisions and implementation rates of diagnostic and therapeutic procedures were analysed. Change in World Health Organization (WHO) functional class and survival rates were evaluated by treatment strategy. A total of 51 (32%) patients were assessed as operable and 109 (68%) were deemed inoperable. Thirty-one (61% of operable patients) underwent PEA. Patients treated with PEA, BPA(+MT) and MT alone were 50.9 ± 14.7, 62.9 ± 15.1 and 68.9 ± 12.7 years old, respectively. At the follow-up, PEA patients had the highest WHO functional class improvement. Patients treated with BPA(+MT) had significantly better survival than PEA ( p = 0.04) and MT patients ( p = 0.04; 2-year survival of 92%, 79% and 79%, respectively). Conclusions: The CTEPH team ensures that necessary diagnostic procedures are performed. A relatively low proportion of patients was assessed by the CTEPH team as operable and underwent surgery, which in survivors resulted in the best functional improvement. Although patients undergoing BPA(+MT) were older than patients treated with PEA, their survival was better than patients subjected to PEA or MT alone. The reviews of this paper are available via the supplemental material section.

With great satisfaction, we now share with you the contents of this Special Issue of Diagnostics dedicated to Diagnosis and Treatment of Pulmonary Hypertension (PH) [...]

The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)

Human pulmonary circulation is as full of mysteries and surprises as is the history of attempts to uncover and understand them. The Special Issue of Diagnostics, appearing after 2020 immobilized the world, give us an opportunity, space and momentum to remind to our medical community at least the main milestones which mark the progress that was made before our times. This review’s aim is to remind about pioneers and their ideas which now are considered as if they were always with us—which is not the case…

Background: The aim of the study was to assess soluble ST2 (sST2) concentration and its dynamic changes in the periprocedural period in patients with chronic thromboembolic pulmonary hypertension (CTEPH) treated with balloon pulmonary angioplasty (BPA). Methods: We prospectively analyzed 57 procedures of BPA performed in 37 patients with CTEPH. Biomarkers, such as N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T (TnT), and sST2 were assessed at four time points: Before the BPA procedure, 24 h and 48 h after the procedure, and at the discharge from hospital. Each postprocedural period was assessed for complications. Results: Before the BPA procedure, median sST2 concentration was 26.56 ng/mL (IQR: 16.66–40.83 ng/mL). sST2 concentration was significantly higher 24 h and 48 h after the BPA compared to the baseline measurements (33.31 ng/mL (IQR: 20.81–62.56), p = 0.000 and 27.45 ng/mL (IQR: 17.66–54.45), p = 0.028, respectively). sST2 level 24 h after the BPA procedure was significantly higher in the group with complications compared to the group without complications in the postprocedural period (97.66 ng/mL (IQR: 53.07–126.18) vs. 26.86 ng/mL (IQR: 19.10–40.12), p = 0.000). Conclusions: sST2 concentration in patients with CTEPH treated with BPA changes significantly in the postprocedural period and is significantly higher in the group with complications in postprocedural period.

Effective targeted therapy of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) requires regular risk stratification. Among many prognostic parameters, three hemodynamic indices: right atrial pressure, cardiac index, and mixed venous saturation are considered critically important for correct risk classification. All of them are measured invasively and require right heart catheterization (RHC). The study was aimed to verify assumption that a model based on non-invasive parameters is able to predict hemodynamic profile described by the mentioned invasive indices. A group of 330 patients with pulmonary hypertension was used for the selection of the best predictors from the set of 17 functional, biochemical, and echocardiographic parameters. Multivariable logistic regression models for the prediction of low-risk and high-risk profiles were created. The cut-off points were determined and subsequent validation of the models was conducted prospectively on another group of 136 patients. The ROC curve analysis showed the very good discrimination power of the models (AUC 0.80–0.99) in the prediction of the hemodynamic profile in the total validation group and subgroups: PAH and CTEPH. The models indicated the risk profiles with moderate sensitivity (57–60%) and high specificity (87–93%). The method enables estimation of the hemodynamic indices when RHC cannot be performed.

We present a case of a 67-year-old female with proximal chronic thromboembolic pulmonary hypertension (CTEPH), disqualified from pulmonary endarterectomy due to multiple comorbidities and high risk-to-benefit ratio as assessed by multidisciplinary CTEPH team. She was referred for balloon pulmonary angioplasty (BPA) and underwent three sessions with balloon catheters up to 8 mm diameter. During the second procedure, the elastic recoil phenomenon was observed in the treated post-thrombotic lesion of the right lower lobe artery, which made the balloon angioplasty ineffective. It was decided to implant a self-expanding stent for the prevention of restenosis. The procedure resulted in significant improvement of regional perfusion, as confirmed by control angiography. We feel that it contributed to the significant improvement of hemodynamic parameters and exercise capacity, as assessed three months after the last BPA procedure. In conclusion, pulmonary artery stenting may be an option in proximal CTEPH when elastic recoil phenomenon makes balloon angioplasty of a large vessel ineffective.

Guidelines on the diagnosis and management of acute pulmonary embolism.

Right ventricular failure is a leading cause of mortality in patients with pulmonary arterial hypertension (PAH). However, up to 25% of such patients die unexpectedly, without warning signs of hemodynamical decompensation. We previously documented that pulmonary artery (PA) dilatation significantly increases the risk of those deaths. Some of them may be due to dissection of PA resulting in cardiac tamponade. However, direct confirmation of this mechanism is difficult as most of such deaths occur outside hospitals. We present 4 patients with severe PAH and PA dilatation in whom PA dissection has been confirmed. Three patients had IPAH, one had PAH associated with congenital heart disease. All patients had mean pulmonary artery pressure (PAP) > 50 mmHg at diagnosis and dissection occurred late in the course of apparently well controlled disease (6 to 14 years). Several clinical elements were common to our patients - high systolic PAP, long lasting PH, progressive dilatation of PA to more than 50 mm with chest pain prior to dissection. However, clinical course followed three different patterns: sudden death due to cardiac tamponade, hemopericarditis caused by blood leaking from dissected aneurysm with imminent but not immediate cardiac tamponade, or chronic asymptomatic PA dissection. Indeed, two of our patients are alive and on lung transplantation waiting list for more than 2 years now. Further research is needed to suggest optimal management strategies for patients with stable PAH but significantly dilated proximal pulmonary arteries or confirmed PA dissection depending on the clinical presentation and expected outcome.

Patients with pulmonary arterial hypertension who achieve a six-minute walk distance of 380-440 m may have improved prognosis. Using the randomized controlled trial of macitentan in pulmonary arterial hypertension (SERAPHIN), the association between six-minute walk distance and long-term outcomes was explored.Patients with six-minute walk distance data at Month 6 were dichotomized as above or below the median six-minute walk distance (400 m) and assessed for future risk of pulmonary arterial hypertension-related death or hospitalization and all-cause death. Additionally, six-minute walk distance values at baseline, Month 6 and the change from baseline to Month 6 were categorized by quartiles. All associations were analyzed by the Kaplan-Meier method using a log-rank test and Cox regression models.Patients with a six-minute walk distance >400 m vs. ≤400 m at Month 6 have a reduced risk of pulmonary arterial hypertension-related death or hospitalization (hazard ratio 0.48; 95% confidence interval 0.33-0.69). The risk was also lower for patients with higher quartiles of six-minute walk distance at baseline or Month 6 (baseline: hazard ratio [Q4 (>430 m) vs. Q1 (≤300 m)] 0.23; 95% confidence interval 0.15-0.36; Month 6: hazard ratio [Q4 (>455 m) vs. Q1 (≤348 m)] 0.33; 95% confidence interval 0.19-0.55). In contrast, six-minute walk distance changes at Month 6 were not associated with the risk of pulmonary arterial hypertension-related death or hospitalization (p = 0.477). These findings were consistent when adjusted for known confounders. Similar results were observed for the risk of all-cause death up to end of study.Patients with pulmonary arterial hypertension walking >400 m had better long-term prognosis. Although changes in six-minute walk distance were not associated with long-term outcomes, assessing absolute six-minute walk distance values remains important in the clinical management of patients with pulmonary arterial hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres.