Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy.

Background: The European Chronic Thromboembolic Pulmonary Hypertension (CTEPH) registry, conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context.

Asymmetric Dimethylarginine and NT-proBNP Levels Provide Synergistic Information in Pulmonary Arterial Hypertension.

Background: Plasma asymmetric dimethylarginine (ADMA) is elevated in pulmonary arterial hypertension (PAH) and is associated with unfavorable outcomes.

Objectives: The aim of this study was to assess changes in ADMA plasma levels for monitoring disease progression and outcomes during PAH-specific therapy.

Methods: ADMA was measured at baseline and after at least 6 months of follow-up using enzyme-linked immunosorbent assay and high-performance liquid chromatography.

The risk profile change in patients with severe chronic thromboembolic pulmonary hypertension treated with subcutaneous treprostinil.

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.

Pulmonary pressure recovery in idiopathic, hereditary and drug and toxin-induced pulmonary arterial hypertension: determinants and clinical impact.

Background: Over the past two decades randomized controlled trials of combination treatments for Pulmonary Arterial Hypertension (PAH) have demonstrated improvements of clinical status but only modest reductions in mean pulmonary arterial pressure (mPAP). Recent experiences with upfront combination treatments including parenteral prostacyclins have shown more substantial mPAP reductions, and have provided grounds for reconsiderations of treatment.

Objectives: To evaluate the possibility of achieving mPAP <25 mmHg with current treatments, its determinants and the prognostic impact of mPAP reduction.

Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry.

Background: Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context.

Methods: 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016.

Efficacy and Safety of Percutaneous Pulmonary Artery Subtotal Occlusion and Chronic Total Occlusion Intervention in Chronic Thromboembolic Pulmonary Hypertension.

[Figure: see text].

Chronic Thromboembolic Disease and Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary vascular disease (CTED) are rare manifestations of venous thromboembolism. Presumably, CTEPH and CTED are variants of the same pathophysiological mechanism. CTEPH and CTED can be near-cured by pulmonary endarterectomy, balloon pulmonary angioplasty, and medical treatment with Riociguat or subcutaneous treprostinil, which are the approved drugs.

Neutrophil extracellular traps and monocyte subsets at the culprit lesion site of myocardial infarction patients.

Neutrophils release their chromatin into the extracellular space upon activation. These web-like structures are called neutrophil extracellular traps (NETs) and have potent prothrombotic and proinflammatory properties. In ST-elevation myocardial infarction (STEMI), NETs correlate with increased infarct size.

Treprostinil for the treatment of chronic thromboembolic pulmonary hypertension.

: Parenteral treprostinil for patients with pulmonary arterial hypertension has resulted in improvement of exercise capacity, functional class, hemodynamics, and survival. Recently, a first randomized trial performed in patients with chronic thromboembolic pulmonary hypertension confirmed the efficacy of subcutaneous treprostinil in this subset of pulmonary hypertension. : Treprostinil sodium is a prostacyclin analog produced synthetically.

Chronic thromboembolic pulmonary hypertension in Austria and Japan.

Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by one or more of the following features: intraluminal thrombus organization, fibrous stenosis, and complete obliteration of major pulmonary arteries, amenable to significant improvement by pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty, and medical treatments with vasodilators. Because treatment practices and outcomes differ in Europe versus Japan, we hypothesized that population-based characteristics of pulmonary vascular phenotypes may exist in Austria compared with Japan. The objectives of this study were to analyze clinical characteristics, hemodynamics, and PEA specimens in consecutive patients with CTEPH undergoing PEA in Austria and Japan.

Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial.

Background: Treprostinil, a prostacyclin analogue, is effective for the treatment of pulmonary arterial hypertension. However, information is scarce regarding treprostinil for treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the efficacy and safety of subcutaneous treprostinil in this setting.

Usefulness of thrombosis and inflammation biomarkers in chronic thromboembolic pulmonary hypertension-sampling plasma and surgical specimens.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) results from persistent pulmonary vascular obstructions, presumably due to inflammatory thrombosis. Because estimates of thrombus volume at diagnosis have no predictive value, we investigated the role of the thrombosis marker, D-dimer, and the inflammation marker, C-reactive protein (CRP), for predicting outcomes in CTEPH.

Methods: A total 289 consecutive patients with CTEPH were followed for 57 (median 45 to 69) months.

Subcutaneous treprostinil in congenital heart disease-related pulmonary arterial hypertension.

Objective: To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment.

Methods: Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study.

Results: Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13).

Hemodynamic Thresholds for Precapillary Pulmonary Hypertension.

Background: Hemodynamic differentiation between pulmonary arterial hypertension (PAH) and postcapillary pulmonary hypertension (PH) is important because treatment options are strikingly different for the two disease subsets. Whereas patients with PAH can be treated effectively with targeted therapies, their use in postcapillary PH is currently not recommended. Our aim was to establish an algorithm to identify patients who are likely to experience a significant hemodynamic treatment response.

Prognostic Significance and Determinants of the 6-Min Walk Test in Patients With Heart Failure and Preserved Ejection Fraction.

Objectives: This study sought to define the prognostic significance and clinical determinants of the 6-min walk distance (6-MWD) in affected patients.

Background: Symptoms of exertional fatigue and dyspnea, as well as a reduced exercise tolerance, are cardinal features of pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF). Mechanisms limiting exercise capacity in this specific entity remain incompletely understood.

Local and systemic RAGE axis changes in pulmonary hypertension: CTEPH and iPAH.

Objective: The molecular determinants of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) remain poorly understood. The receptor for advanced glycation endproducts (RAGE) and its ligands: HMGB1 and S100A9 are involved in inflammatory disorders. We sought to investigate the role of the RAGE axis in patients with CTEPH undergoing pulmonary endarterectomy (PEA), iPAH undergoing lung transplantation (LuTX).

Surgical specimens, haemodynamics and long-term outcomes after pulmonary endarterectomy.

Background: Chronic thromboembolic pulmonary hypertension is surgically curable by pulmonary endarterectomy (PEA). It is unclear whether PEA impacts primarily steady state right ventricular afterload (ie, pulmonary vascular resistance (PVR)) or pulsatile right ventricular afterload (ie, pulmonary arterial compliance (C(PA))). Our objectives were to (1) quantify PEA specimens and measure the impact of PEA on PVR and C(PA) in a structure/function study and (2) analyse the effects of haemodynamic changes on long-term survival/freedom of lung transplantation in an outcome study.

Long-term treatment, tolerability, and survival with sub-cutaneous treprostinil for severe pulmonary hypertension.

Background: Randomized controlled trials have resulted in improved outcomes in pulmonary arterial hypertension; however, they are biased by stringent inclusion criteria, pre-specified patient sub-sets, and study durations. In addition, common practice is to start oral therapies ahead of the more potent and titratable prostanoid therapies, despite advanced disease states at diagnosis. The objectives of our prospective registry were to evaluate long-term effects on functional class, 6-minute walking distance, hemodynamics, and survival, and also long-term tolerability of first-line sub-cutaneous treprostinil, a prostacyclin analog, in patients with severe pulmonary hypertension.

Imaging in pulmonary hypertension.

Pulmonary hypertension is defined as an increase in mean pulmonary arterial pressure ≥25 mm Hg at rest and occurs in a majority of patients with heart failure. Diagnostic imaging targets the right ventricle and the pulmonary vasculature. Although echocardiography is cost-effective for screening and follow-up, right heart catheterization is still mandatory to differentiate pre- from post-capillary disease and to directly measure pressure and flow.

Pulmonary vascular reactivity and prognosis in patients with chronic thromboembolic pulmonary hypertension: a pilot study.

Background: Surgical pulmonary endarterectomy is the preferred treatment for chronic thromboembolic pulmonary hypertension. Persistent pulmonary hypertension after pulmonary endarterectomy has been recognized as a major determinant of poor outcome. We tested whether acute vasoreactivity identifies chronic thromboembolic pulmonary hypertension patients prone to develop persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and whether the degree of acute vasoreactivity affects survival or freedom from lung transplantation.