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).

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).

Ground Glass Opacities in Pulmonary Arterial Hypertension-Results from the PVDOMICS Study.

Rationale And Objectives: Pulmonary Hypertension (PH) is associated with significant morbidity and mortality. Ground glass opacities (GGOs) are common in Group 1 PH, but their clinical significance is unclear. We sought to characterise the clinical features and outcomes of Group 1 PH patients with and without GGOs in the PVDOMICS study, a prospective multicentre cohort study aimed at deep phenotyping PH.

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.

Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension.

A subset of patients with group 1 pulmonary hypertension (PH) have superimposed left heart abnormalities with unclear metabolic implications. To compare serum/transpulmonary metabolome between group 1 PH stratified by heart failure with preserved ejection fraction (HFpEF) probability. Patients with group 1 PH were stratified into low (<25%) and high (⩾75%) HFpEF-ABA (age, body mass index, and atrial fibrillation) probability, with healthy control subjects and subjects with clinical HFpEF used for comparison of venous and transpulmonary metabolomics.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Results of an International Multicenter Prospective Registry.

Background: Chronic thromboembolic pulmonary hypertension results from mechanical obstruction of major pulmonary artery lumina with fibrotic tissue. Main treatment has been pulmonary endarterectomy, a complex surgical procedure removing vascular obstruction. However, at least 40% of patients are not candidates for pulmonary endarterectomy because of technical inoperability, comorbidities, or limited access to surgery.

Left Heart Abnormalities in Patients With Lung Disease, OSA, and Chronic Thromboemboli at Risk for or With Known Pulmonary Hypertension.

Background: Patients with lung disease, sleep apnea, and chronic thromboemboli can develop pulmonary hypertension, currently classified as group 3 or 4. Many of these patients also have risk factors for heart failure with preserved ejection fraction (HFpEF), but the optimal approach to identify the disease overlap remains unclear.

Methods: Pretest probability for HFpEF was determined using the HFpEF-ABA (age, body mass index, atrial fibrillation) algorithm among adjudicated group 3 or 4 patients at risk for pulmonary hypertension in the PVDOMICS study (Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics).

Characteristics of Daily Walking Bouts as Valid and Reliable Indicators of Exercise Capacity in Pulmonary Arterial Hypertension: Insights From the Randomized Controlled Study With Selexipag (TRACE).

Unlabelled: There is a need for objective, continuous and remote assessment of exercise capacity in patients with pulmonary arterial hypertension (PAH). Using data from the TRACE study, in which 108 adult patients with PAH were continuously monitored with a wrist-worn accelerometer, we evaluated whether actigraphy can facilitate continuous monitoring of exercise capacity. Distributions of step rate, distance and duration of patient's walking bouts were estimated at baseline, Week 16 and Week 24 using 2-week periods of actigraphy data.

Daratumumab monotherapy as a desensitization strategy prior to cardiac transplantation.

Background: Human leukocyte antigen (HLA) sensitization is a significant barrier to transplantation for many patients. Daratumumab has proven safety and tolerability in multiple myeloma. We hypothesized that daratumumab monotherapy could be an effective and safe desensitization strategy in highly sensitized patients awaiting cardiac transplantation.

Dysregulated Tricarboxylic Acid Cycle Metabolism Is Associated With Right Ventricular Maladaptation in Pulmonary Vascular Disease.

Background: Right ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood.

Methods: We performed global untargeted metabolomics on plasma from 55 patients who underwent gold-standard RV-PA coupling measurements using multibeat pressure volume loop assessment in a single-center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex-adjusted linear regression was performed to identify associations between metabolites and coupling metrics.

Disentangling the Impact of Adiposity From Insulin Resistance in Heart Failure With Preserved Ejection Fraction.

Background: Obesity, insulin resistance (IR), and diabetes are common in heart failure with preserved ejection fraction (HFpEF) and are associated with worsening heart failure, but their independent contributions remain unknown.

Objectives: In this study, we sought to determine the contribution of diabetes vs obesity to left heart abnormalities in HFpEF METHODS: Indices of adiposity (body mass index [BMI], bioimpedance fat mass, waist circumference) and IR (homeostasis-model assessment [HOMA]) were measured among PVDOMICS study participants with HFpEF. Rest and exercise pulmonary capillary wedge pressure (PCWP) responses were compared, stratified by obesity (BMI ≥30 kg/m), IR status (HOMA-IR ≥2.

The Frequency and Predictors of Pulmonary Rehabilitation Referrals Among Patients With Pulmonary Arterial Hypertension: An Analysis of the Pulmonary Hypertension Association Registry.

Background: Pulmonary arterial hypertension (PAH) is a complex cardiopulmonary disease associated with exertional dyspnea and impaired health-related quality of life (HRQOL) despite medical therapy. Pulmonary rehabilitation (PR), a supervised exercise program for patients with chronic lung disease, improves symptoms, HRQOL, and exercise capacity. Despite these benefits, there is a paucity of data regarding PR in PAH.

Physical Activity, Sleep, and Quality of Life in Pulmonary Arterial Hypertension: Novel Insights From Wearable Devices.

Reduced functional capacity and poor sleep quality are common in pulmonary arterial hypertension (PAH). Wearable devices are an emerging, user-friendly tool to capture activity and sleep information. We aimed to determine whether Fitbit-derived activity and sleep trends provide clinically meaningful information in patients with PAH.

Echocardiographic Parameters and Risk Prediction in Pulmonary Arterial Hypertension: Insights From the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Network.

Background: Echocardiographic metrics of right ventricular (RV) chamber size and function enhance prognostication, risk stratification, and measurement of therapeutic response in patients with pulmonary arterial hypertension (PAH), though the most effective metrics remain unclear.

Research Question: In a well-phenotyped cohort of patients with incident and prevalent PAH, can qualitative grades of RV echocardiographic function be established based on their association with functional outcomes, and do they demonstrate prognostic value beyond traditional risk scores?

Study Design And Methods: In the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) program, 405 (prevalent, n = 336; incident, n = 69) participants were investigated. Multivariable linear regression examined associations with 6-minute walk distance and the Comparative Prospective Registry for Newly Initiated Therapies (COMPERA) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.

Cardiopulmonary Exercise Testing With Forehead and Popliteal Oximetry in Evaluating Efficacy of Reverse Potts Shunt.

Reverse Potts shunt (rPS) is a surgical procedure that creates an anastomosis between the left pulmonary artery and descending aorta to decompress the right ventricle in suprasystemic pulmonary arterial hypertension (PAH). In this paper, we introduce a unique procedure combining cardiopulmonary exercise testing with forehead and popliteal oximetry to evaluate the efficacy of the rPS. Our study involved tests on 4 patients with PAH who had the shunt in place.

Future treatment paradigms in pulmonary arterial hypertension: a personal view from physicians, health authorities, and patients.

Novel treatments in pulmonary arterial hypertension (PAH) with significant pathophysiological and clinical responses have generated renewed interest in changing the course of the disease and achieving long-term disease control. Historically, the term disease modification was coined in rheumatological conditions with therapies that managed to treat the underlying condition as opposed to just alleviating symptoms. With the advent of novel therapies, the term disease modification was introduced in our discussions.

Defining Echocardiographic Degrees of Right Heart Size and Function in Pulmonary Vascular Disease from the PVDOMICS Study.

Background: Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function.

Methods: We investigated 1053 study participants in the Redefining Pulmonary Hypertension through PVD Phenomics program (PVDOMICS) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance (PVR) severity.

Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.

Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status.

SOPRANO: Macitentan in patients with pulmonary hypertension following left ventricular assist device implantation.

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study.

Association of Male Sex With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort.

Background: Sex-based differences are important in the development and progression of pulmonary arterial hypertension. However, it is not established whether these differences are generalizable to all forms of pulmonary hypertension (PH).

Research Question: What are the sex-based differences in right ventricle (RV) function and transplant-free survival in patients with PH from the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort?

Study Design And Methods: Patients with PH enrolled in the PVDOMICS cohort study underwent right heart catheterization, cardiac MRI, and echocardiography.

Post-Pulmonary Embolism Syndrome-A Diagnostic Dilemma and Challenging Management.

Historically, research on pulmonary embolism (PE) management has focused on short-term outcomes, such as acute cardiovascular collapse, change in right ventricular function, and in-hospital mortality. However, long-standing functional impairments from acute PE occur in up to half of all patients. This chronic syndrome has been termed the post-PE syndrome, which describes patients who have persistent or worsening symptoms, functional limitations, and cardiorespiratory impairment not explained by a comorbid condition.

Clinical Implications of Pretest Probability of HFpEF on Outcomes in Precapillary Pulmonary Hypertension.

Background: Patients with group 1 pulmonary hypertension (PH) and risk factors for heart failure with preserved ejection fraction (HFpEF) demonstrate worse response to pulmonary vasodilator therapy. The mechanisms and optimal diagnostic approach to identify such patients remain unclear.

Objectives: The purpose of this study was to compare exercise capacity, cardiac function, and hemodynamic responses to provocative maneuvers among patients with group 1 PH based upon pretest probability of HFpEF.

Risk stratification and treatment goals in pulmonary arterial hypertension.

Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all currently validated risk stratification tools. However, suffering from limitations mainly related to reduced specificity of PAH severity, these variables may not always be adequate in isolation for guiding individualised treatment decisions.