Treatment with Oral or Inhaled Treprostinil in Patients with Pulmonary Arterial Hypertension and Cardiovascular Comorbidities.

Background: An increasing number of patients with pulmonary arterial hypertension (PAH) have cardiovascular comorbidities. However, the effects of comorbidities on responses to PAH treatment are not well understood.

Research Question: Do cardiovascular comorbidities in patients with PAH influence the efficacy and tolerability of inhaled or oral treprostinil?

Study Design And Methods: All patients from phase 3 studies TRIUMPH (N = 235) and FREEDOM-EV (N = 690) were included in this post hoc analysis and were classified as having 0, ≥1, or ≥2 cardiovascular comorbidities of interest based on patients' medical histories.

Health-related quality of life and symptom concordance between patients and physicians in pulmonary arterial hypertension in the United States, Europe, and Japan.

This study involved analysis of a real world, cross-sectional survey of physicians and their patients with pulmonary arterial hypertension (PAH). Physician and patient symptom concordance was assessed and patients self-reported Health-Related Quality of Life (HRQoL). Data were drawn from the Adelphi PAH Disease Specific Programme (DSP)™ in the United States, France, Germany, Italy, Spain, United Kingdom, and Japan, between March and August 2022.

Utility of factor D and other alternative complement factors as biomarkers in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH).

Background: Activation of the complement cascade is thought to play a role in scleroderma vasculopathy. We previously showed that complement factor D was elevated in patients with limited cutaneous SSc and pulmonary arterial hypertension (PAH). In this study, we sought to assess multiple relevant components of the complement cascade to determine if they are altered in SSc-PAH, as well as their potential utility as biomarkers of disease severity and progression.

Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus.

Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy.

Application of REVEAL Lite 2 and COMPERA 2.0 risk scores to patients with pulmonary arterial hypertension switching to riociguat in the REPLACE study.

In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement.

Cardiac effort and 6-min walk distance correlate with stroke volume measured by cardiac magnetic resonance imaging.

Right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) is associated with poor outcomes. Cardiac magnetic resonance imaging (cMRI) is the gold standard for volumetric assessment, and few reports have correlated 6-min walk distance (6MWD) and cMRI parameters in PAH. Cardiac Effort, (the number of heart beats used during 6-min walk test)/(6MWD), incorporates physiologic changes into walk distance and has been associated with stroke volume (SV) measured by nuclear imaging and indirect Fick.

Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension.

Introduction: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable.

Peak steps: Capacity for activity improves after adding approved therapy in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) patients have low activity. Activity intensity or duration could be a measure of clinical status or improvement. We aimed to determine whether standard or novel actigraphy measures could detect increases in activity after adding therapy.

Regional Variation in Pulmonary Arterial Hypertension in the United States: The Pulmonary Hypertension Association Registry.

Pulmonary arterial hypertension (PAH) is a heterogeneous disease within a complex diagnostic and treatment environment. Other complex heart and lung diseases have substantial regional variation in characteristics and outcomes; however, this has not been previously described in PAH. To identify baseline differences between U.

Contemporary risk scores predict clinical worsening in pulmonary arterial hypertension - An analysis of FREEDOM-EV.

Background: Risk scores integrate clinical variables emphasizing symptoms, exercise capacity, and measures of cardiac strain to predict clinical outcome better than any single value in pulmonary arterial hypertension (PAH). Risk scores have demonstrated prognostic utility for outcomes in registries, and recent studies have suggested that they are also therapy-responsive in controlled trials.

Methods: FREEDOM-EV, a global, placebo-controlled, event-driven study, randomized 690 PAH participants 1:1 to oral treprostinil (TRE) or placebo.

Cardiac Effort to Compare Clinic and Remote 6-Minute Walk Testing in Pulmonary Arterial Hypertension.

Background: The SARS-CoV-2 pandemic has limited objective physiologic assessments. A standardized remote alternative is not currently available. "Cardiac effort" (CE), that is, the total number of heart beats divided by the 6-min walk test (6MWT) distance (beats/m), has improved reproducibility in the 6MWT and correlated with right ventricular function in pulmonary arterial hypertension.

Delphi consensus recommendation for optimization of pulmonary hypertension therapy focusing on switching from a phosphodiesterase 5 inhibitor to riociguat.

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined.

Transitioning selexipag to oral treprostinil in patients with pulmonary artery hypertension.

There are no prospective studies or guidelines describing transition between selexipag and oral treprostinil. We present two different transition strategies from selexipag to oral treprostinil, one started inpatient and then completed at home, and one completely under outpatient settings. Neither patient experienced worsening prostacyclin-type adverse effects; both were rigorous in their attention to a 7-8 hour administration schedule for oral treprostinil, and both experienced objective clinical benefit at follow-up.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival.

Reduced Notch1 Cleavage Promotes the Development of Pulmonary Hypertension.

Clinical trials of Dll4 (Delta-like 4) neutralizing antibodies (Dll4nAbs) in cancer patients are ongoing. Surprisingly, pulmonary hypertension (PH) occurs in 14% to 18% of patients treated with Dll4nAbs, but the mechanisms have not been studied. Here, PH progression was measured in mice treated with Dll4nAbs.

Comparison of chest- and wrist-based actigraphy in pulmonary arterial hypertension.

Aims: Activity trackers for clinical trials and remote monitoring are appealing as they provide objective data outside of the clinic setting. Algorithms determine physical activity intensity and count steps. Multiple studies show physical inactivity in pulmonary arterial hypertension (PAH).

An untapped resource: characteristics of thrombus recovered from intermediate or high risk pulmonary embolus patients.

Introduction: Response to anticoagulation varies during management of acute hospitalized pulmonary embolism. We aimed to study thrombus histology in pulmonary embolism samples removed during acute surgical embolectomy to evaluate whether thrombus morphology was similar between patients and whether there was an association with duration of symptoms and/or resolution on follow up imaging.

Methods: This was a retrospective observational single center study at the University of Rochester Medical Center.

Vasodilator use in precapillary pulmonary hypertension with end stage kidney disease: A single center experience.

Background And Objectives: Pulmonary hypertension is commonly seen in end stage kidney disease and is most commonly due to elevated left heart pressures. There is limited data about vasodilator use during the management of Group 1 pulmonary arterial hypertension in the context of those who also have or later developed end stage kidney disease. The objective of this study was to determine safety and efficacy of vasodilator therapy in precapillary pulmonary hypertension requiring renal replacement therapy.

Selonsertib in adults with pulmonary arterial hypertension (ARROW): a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Data obtained in human lung tissue and preclinical models suggest that oxidative stress and increased apoptosis signal-regulating kinase 1 (ASK1) activity might have a prominent role in the pathobiology of pulmonary arterial hypertension (PAH). The purpose of this study was to determine the efficacy, safety, and tolerability of the ASK1 inhibitor selonsertib compared with placebo in patients with PAH.

Methods: We did a randomised, double-blind, placebo-controlled, phase 2 trial at 46 centres located in Canada, France, Germany, Italy, the Netherlands, Spain, the UK, and the USA.

Evaluation of Clinical Recovery After Surgical Treatment for Hand Ischemia From Vasospastic and Occlusive Disease Using PROMIS.

Background: There is a paucity of literature describing the recovery trajectory after surgery for upper extremity ischemia. Using Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Upper Extremity (UE), Pain Interference (PI), and Depression domains, we aimed to describe the postoperative recovery of such patients.

Methods: We queried our PROMIS database for patients undergoing surgery for vasospastic or occlusive disease over a 4.