Predicting Response to Switching From Phosphodiesterase Type 5 Inhibitor to Riociguat in Patients With Pulmonary Arterial Hypertension: Biomarker and Responder Analysis of the RESPITE and REPLACE Studies.

This exploratory analysis assessed whether plasma biomarkers predict the response to switching from phosphodiesterase type 5 inhibitors (PDE5is) to the soluble guanylate cyclase stimulator riociguat in patients with pulmonary arterial hypertension. Selected biomarkers at baseline and their changes to Week 24 were evaluated in patients with and without a favorable response to riociguat in two trials: RESPITE, in which patients with an inadequate response to PDE5i were switched to riociguat; and REPLACE, in which patients at intermediate risk of 1-year mortality despite a PDE5i were randomized to remain on PDE5i or were switched to riociguat. A response was defined as absence of clinical worsening and at least two of the following criteria: 6-min walk distance increase by 10% or ≥ 30 m, World Health Organization functional class I/II, or -terminal prohormone of brain natriuretic peptide reduction of ≥ 30% at Week 24.

Inflammation and Obesity Correlate in Pulmonary Hypertension but Associate with Diverging Outcomes.

Rationale & Objectives: Inflammation is associated with all types of Pulmonary Hypertension (PH) both as a known cause and/or a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informed clinical endotyping and outcomes.

Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study.

Introduction: Seralutinib is an inhaled tyrosine kinase inhibitor targeting platelet-derived growth factor receptor (PDGFR) α/β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) kinases. TORREY, a phase 2, double-blind, randomized, placebo-controlled study of seralutinib in pulmonary arterial hypertension (PAH), met its primary endpoint, demonstrating a significant reduction in pulmonary vascular resistance (PVR) over placebo after 24 weeks (NCT04456998; EudraCT 2019-002669-37). We present results (as of December 5, 2024) from an open-label extension (OLE) study evaluating long-term safety, tolerability, and efficacy of seralutinib in adults with PAH (NCT04816604).

Exercise haemodynamics in pulmonary hypertension - a prospective pressure-volume loop study on right ventricular adaptation and prognosis.

Aims: The haemodynamic response to exercise is prognostic in pulmonary hypertension (PH). However, little is known about right ventricular (RV) adaptation in this context. We analysed the patterns and prognostic relevance of RV adaptation to exercise in PH.

Hemodynamics and Phosphodiesterase-5 Inhibitor Treatment Associated with Survival in ILD-PH: A PVRI GoDeep Meta-Registry Analysis.

Background: Pulmonary hypertension (PH) in interstitial lung disease (ILD) lacks approved therapies. The PVRI GoDeep meta-registry collects real-world data of PH patients from international PH referral centers.

Methods: ILD-PH patients and relevant subgroups (IIP, IPF) were stratified by pulmonary vascular resistance (PVR).

Evaluation of the Safety of Percutaneous Dilatational Tracheostomies in Patients with Antiplatelet Therapy-A Comparison of Two Single-Step Percutaneous Dilatational Techniques.

Antiplatelet therapy (APT) increases bleeding risk and is frequently used in patients who undergo percutaneous dilatational tracheostomy (PDT). However, there are different techniques for single-step PDTs, which can be differently invasive. The aim of the present study was to investigate complications in patients undergoing PDT while being on APT, especially with regard to bleeding and the influence of different PDT techniques.

Survival Outcomes and Impact of Targeted PAH Therapy in Portopulmonary Hypertension in the PVRI GoDeep Meta-Registry.

Portopulmonary hypertension (PoPH), a type of pulmonary arterial hypertension (PAH) in patients with liver disease, is associated with high morbidity and mortality. The relationship between cardiopulmonary hemodynamics, PAH therapy, and survival in PoPH remains unclear. We performed a retrospective cohort study of PoPH patients from the international pulmonary hypertension (PH) meta-registry, PVRI GoDeep.

Changes in Renal Venous Flow and Liberation from Renal Replacement Therapy in Patients with Acute Heart Failure.

Introduction: In acute heart failure (AHF), the factors associated with successful renal replacement therapy (RRT) discontinuation are largely undefined. We hypothesized that improvements in Doppler-derived renal venous flow (RVF) waveforms may serve as indicators of recovering cardiorenal function associated with successful liberation from RRT.

Methods: We performed a post hoc analysis of a prospective cohort study involving inpatients with AHF undergoing serial renal Doppler evaluations.

Bradycardias in Patients with Pulmonary Hypertension-Prevalence, Pathophysiology and Clinical Relevance.

Introduction: Arrhythmias are a frequent complication of pulmonary hypertension (PH). Supraventricular tachycardias (SVT) are predominantly reported and are associated with clinical deterioration and an increased mortality. In contrast, the prevalence and clinical relevance of bradycardias is largely unclear.

A simple electrocardiographic model for an improved detection of chronic thromboembolic pulmonary hypertension after pulmonary embolism.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a late sequelae of a preceding pulmonary embolism (PE). There is reasonable suspicion that the majority of CTEPH patients are currently not detected. The aim of the present study was to evaluate the potential utility of a simple electrocardiographic (ECG) model for an improved detection of CTEPH after PE.

Association of pulmonary hypertension-targeted therapy and survival in precapillary pulmonary hypertension with mean pulmonary arterial pressure between 21 and 24 mmHg.

Introduction: The definition of pulmonary hypertension (PH) was recently changed and led to a new subset of PH patients with mildly impaired pulmonary haemodynamics, characterised by a mean pulmonary artery pressure (mPAP) of 21-24 mmHg and with a pulmonary vascular resistance (PVR) >2 WU. We evaluated the association of PH-targeted therapy and outcome in mild precapillary PH using the PVRI GoDeep meta-registry.

Methods: All patients with mild precapillary PH (mPAP 21-24 mmHg, pulmonary arterial wedge pressure ≤15 mmHg and PVR >2 WU) diagnosed with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) were enrolled.

A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA.

Background: SOTERIA (ClinicalTrials.gov: NCT04796337) is an ongoing open-label study evaluating long-term safety, tolerability and efficacy of sotatercept in participants with pulmonary arterial hypertension (PAH).

Methods: Eligible adults with PAH on stable background therapy who completed a prior sotatercept study without early discontinuation were enrolled.

The Diagnostic Accuracy of an Electrocardiogram in Pulmonary Hypertension and the Role of "R V1, V2 + S I, aVL - S V1".

: Pulmonary hypertension (PH) can cause characteristic electrocardiographic (ECG) changes due to right ventricular hypertrophy and/or strain. The aims of the present study were to explore the diagnostic accuracy of ECG parameters for the diagnosis of PH, applying the recently adjusted mean pulmonary artery pressure (mPAP) threshold of >20 mmHg, and to determine the role of "R V1, V2 + S I, aVL - S V1". : Between July 2012 and November 2023, 100 patients without PH, with pulmonary arterial hypertension, or with chronic thromboembolic pulmonary hypertension were retrospectively enrolled.

Cryoablation for the Treatment of Post-Tracheostomy Tracheal Stenosis in Neurological Patients.

Introduction: Post-tracheostomy tracheal stenosis is a clinically relevant late complication of tracheostomy. To date, there is no standardized treatment strategy for post-tracheostomy tracheal stenosis. Contact cryoablation is one of the applicable methods.

Riociguat in pulmonary arterial hypertension: Application of the 4-strata COMPERA 2.0 risk assessment tool in the PATENT studies.

Background: Risk stratification is an essential part of evaluating disease severity in patients with pulmonary arterial hypertension (PAH). This study applied the 4-strata COMPERA 2.0 risk model to the Phase 3 PATENT-1/2 studies of riociguat.

Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension.

Introduction: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.

Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial).

Background: SELECT was the first global randomised controlled trial of selexipag with standard of care in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension.

Methods: SELECT was a multicentre, randomised, double-blind, placebo-controlled, parallel-group, group-sequential, phase 3 study (ClinicalTrials.gov: NCT03689244).

Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial.

Background: The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results.

Methods: ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America.

Safety and efficacy of riociguat in patients with pulmonary arterial hypertension and cardiometabolic comorbidities: Data from interventional clinical trials.

Background: There is limited evidence to support treatment recommendations in patients with pulmonary arterial hypertension (PAH) and comorbidities. To investigate the impact of riociguat treatment in this patient population, we analyzed pooled data from randomized controlled trials of riociguat.

Methods: This post hoc analysis included data from the PATENT-1, PATENT-2, PATENT PLUS, and REPLACE studies.

Pulmonary hypertension associated with lung diseases.

Pulmonary hypertension (PH) associated with chronic lung disease (CLD) is both common and underrecognised. The presence of PH in the setting of lung disease has been consistently shown to be associated with worse outcomes. Recent epidemiological studies have advanced understanding of the heterogeneity of this patient population and shown that defining both the specific type of CLD as well as the severity of PH ( deeper phenotyping) is necessary to inform natural history and prognosis.

Association of Phosphodiesterase-5 Inhibitor Treatment With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry.

Background: Patients with COPD frequently demonstrate pulmonary hypertension (PH). Severe PH in patients with COPD, identified by pulmonary vascular resistance (PVR) of > 5 Wood units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear.