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Objectives Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. Methods We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. Results This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n  = 390) were 85%, 59% and 42%; for SLE-PAH (n  = 34) they were 97%, 77% and 61%; for MCTD-PAH (n  = 33) they were 97%, 70% and 59%; for UCTD-PAH (n  = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n  = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P  = 0.001). In these patients, the survival estimates were significantly better with initial ERA–PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P  = 0.016 and P  = 0.012, respectively). Conclusions Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA–PDE5i combination therapy compared with initial monotherapy. [ABSTRACT FROM AUTHOR]

Background The gold standard treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). Little is known about the influence of advanced age on surgical outcome. Therefore, the aim of this study was to investigate the impact of patient's age on postoperative morbidity, mortality, and quality of life in a German referral center. Methods Prospectively collected data from 386 consecutive patients undergoing PEA between 01/2014 and 12/2016 were analyzed. Patients were divided into three groups according to their age: group 1: ≤ 50 years, group 2: > 50 ≤ 70 years, group 3: > 70 years. Results After PEA, distinct improvements in pulmonary hemodynamics, physical capacity (World Health Organization [WHO] functional class and 6-minute walking distance) and quality of life were found in all groups. There were more complications in elderly patients with longer time of invasive ventilation, intensive care, and in-hospital stay. However, the in-hospital mortality was comparable (0% in group 1, 2.6% in group 2, and 2.1% in group 3 [ p = 0.326]). Furthermore, the all-cause mortality at 1 year was 1.1% in group 1, 3.2% in group 2, and 6.3% in group 3 (p = 0.122). Conclusions PEA is an effective treatment for CTEPH patients of all ages accompanied by low perioperative and 1-year mortality. CTEPH patients in advanced age carefully selected by thorough preoperative evaluation should be offered PEA in expert centers to improve quality of life, symptoms, and pulmonary hemodynamics. [ABSTRACT FROM AUTHOR]

Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. Objectives: To quantify and analyze the plasma proteome of patients with PAH using inherited genetic variation to inform on underlying molecular drivers. Methods: An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers, and 23 relatives of patients with PAH. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared, and the relationship to transplantation-free survival in PAH was determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomization (MR) analysis. Measurements and Main Results: From 4,152 annotated plasma proteins, levels of 208 differed between patients with PAH and healthy subjects, and 49 predicted long-term survival. MR based on cis-pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR, 0.83; 95% CI, 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset. Conclusions: Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition.Research Question: Which factors determine the outcome of PH in COPD?Study Design and Methods: We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH).Results: The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes.Interpretation: Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further.Trial Registry: ClinicalTrials.gov; No.: NCT01347216; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Renal congestion is becoming recognized as a potential contributor to cardiorenal syndromes. Adequate control of congestion with simultaneous preservation of renal function has been proposed as a central goal of the management of heart failure. We report our care of a 48-year-old woman suffering from right heart failure and massive fluid overload due to severe pulmonary hypertension secondary to a combination of left-heart disease and status after recurrent pulmonary embolisms. Alterations in Doppler-derived intrarenal venous flow patterns and a novel renal venous stasis index were used to evaluate improvement in renal venous congestion during recompensation. Due to refractory congestion despite optimal medical treatment and continuous veno-venous hemodialysis, a peritoneal dialysis catheter was placed to relieve the massive ascites. The paracentesis of ascites led to a significant loss of weight, normalization of hydration status with subsequent termination of continuous veno-venous hemodialysis, and a significant improvement in clinical and echocardiographic parameters. Renal Doppler ultrasonography showed continuous improvement in intrarenal venous flow patterns and the renal venous stasis index indicative of effective decongestion up to a normal intrarenal venous flow pattern and renal venous stasis index. Furthermore, residual renal function increased during follow-up. This case demonstrates the feasibility of renal Doppler ultrasonography as a simple, non-invasive, and integrative measure of renal congestion. The renal venous stasis index and intrarenal venous flow patterns may be useful to evaluate the treatment response and to guide therapy in patients with right heart failure. [ABSTRACT FROM AUTHOR]

BACKROUND Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension. METHODS We conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro—B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension—Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit. RESULTS A total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, —0.3 to 3.5) in the placebo group. The Hodges—Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, in-creased hemoglobin levels, thrombocytopenia, and increased blood pressure. CONCLUSIONS In patients with pulmonary arterial hypertension who were receiving stable back-ground therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988.) [ABSTRACT FROM AUTHOR]

Background: Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease. Methods: In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers. Results: Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost. Conclusions: Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on the study entitled, "Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy," by H. A. Ghofrani, N. W. Morrell, and M. M. Hoeper, which looks into the effectiveness of imatinib in the treatment of patients with pulmonary arterial hypertension.

Abstract: The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations on the diagnosis of pulmonary hypertension (PH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the treatment of pulmonary arterial hypertension (PAH). This commentary describes in detail the results and recommendations of the working group on treatment of PAH which were last updated in October 2011. [Copyright &y& Elsevier]