Transplantation, bridging, and support technologies in pulmonary hypertension.

Despite the progress made in medical therapies for treating pulmonary hypertension (PH), a subset of patients remain susceptible to developing a maladaptive right ventricular phenotype. The effective management of end-stage PH presents substantial challenges, necessitating a multidisciplinary approach and early identification of patients prone to acute decompensation. Identifying potential transplant candidates and assessing the feasibility of such a procedure are pivotal tasks that should be undertaken early in the treatment algorithm.

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension.

Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso-responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information.

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.

The British Transplantation Society guidelines on cardiothoracic organ transplantation from deceased donors after circulatory death.

Maximising organ utilisation from donation after circulatory death (DCD) donors could help meet some of the shortfall in organ supply, but it represents a major challenge, particularly as organ donors and transplant recipients become older and more medically complex over time. Success is dependent upon establishing common practices and accepted protocols that allow the safe sharing of DCD organs and maximise the use of the DCD donor pool. The British Transplantation Society 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population.

Prevalence, incidence, and survival of pulmonary arterial hypertension: A systematic review for the global burden of disease 2020 study.

Pulmonary arterial hypertension (PAH) is characterized by increased resistance in the pulmonary arterioles as a result of remodeled blood vessels. We sought all available epidemiologic data on population-based prevalence, incidence, and 1-year survival of PAH as part of the Global Burden of Disease Study. We performed a systematic review searching Global Index Medicus (GIM) for keywords related to PAH between 1980 and 2021 and identified population-representative sources of prevalence, incidence, and mortality for clinically diagnosed PAH.

Autoimmunity Is a Significant Feature of Idiopathic Pulmonary Arterial Hypertension.

Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or treatment significance. To study autoimmunity in IPAH using a large cross-sectional cohort.

Application of the REVEAL risk score calculator 2.0 in the CHEST study.

Background: Currently there are no risk assessment recommendations for chronic thromboembolic pulmonary hypertension (CTEPH). The Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score (RRS), developed for risk assessment in patients with pulmonary arterial hypertension, has previously predicted outcomes in CTEPH. RRS 2.

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis.

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

Background: Inflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling.

Methods: We conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg) over 6 months in patients with group 1 PAH.

Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial.

Background: Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.

Application of the REVEAL risk score calculator 2.0 in the PATENT study.

Background: Regular risk assessment is recommended in pulmonary arterial hypertension (PAH) management to improve patient outcomes. The REVEAL risk score (RRS) predicts survival in patients with PAH, including those from the PATENT study, which assessed riociguat, a soluble guanylate cyclase stimulator approved for PAH treatment. An updated version, RRS 2.

Assessment of the REPLACE study composite endpoint in riociguat-treated patients in the PATENT study.

The goal of treatment in patients with pulmonary arterial hypertension is to achieve a low risk status, indicating a favorable long-term outcome. The REPLACE study investigated the efficacy of switching to riociguat in patients with pulmonary arterial hypertension and an insufficient response to phosphodiesterase-5 inhibitors. In this post hoc analysis, we applied the REPLACE composite endpoint of clinical improvement to the placebo-controlled PATENT-1 study of riociguat in pulmonary arterial hypertension and its long-term extension, PATENT-2.

Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension.

This manuscript on endpoints incorporates the broad experience of members of Pulmonary Vascular Research Institute's Innovative Drug Development Initiative as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertension. It reviews our current understanding of endpoints used in phase 2 and 3 trials for pulmonary hypertension and discusses in detail the value of newer approaches. These include the roles of composite endpoints and how these can be developed and validated.

Clinical trial design in phase 2 and 3 trials for pulmonary hypertension.

This article on clinical trial design incorporates the broad experience of members of the Pulmonary Vascular Research Institute's (PVRI) Innovative Drug Development Initiative (IDDI) as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertension. It is increasingly clear that the design of phase 2 and 3 trials in pulmonary hypertension will have to diversify from the traditional randomised double-blind design, given the anticipated need to trial novel therapeutic approaches in the immediate future. This article reviews a wide range of differing approaches and places these into context within the field of pulmonary hypertension.

Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE.

Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement.

Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61).

Idiopathic pulmonary arterial hypertension and co-existing lung disease: is this a new phenotype?

Patients classified as idiopathic pulmonary arterial hypertension (defined as Group 1 on European Respiratory Society (ERS)/European Cardiac Society (ESC) criteria) may have evidence of minor co-existing lung disease on thoracic computed tomography. We hypothesised that these idiopathic pulmonary arterial hypertension patients ( ) are a separate subgroup of idiopathic pulmonary arterial hypertension with different phenotype and outcome compared with idiopathic pulmonary arterial hypertension patients without co-existing lung disease ( ). Patients with ' ' have been eligible for all clinical trials of Group 1 patients because they have normal clinical examination and normal spirometry but we wondered whether they responded to treatment and had similar survival to patients with ' '.

Long-term effect of azithromycin in bronchiolitis obliterans syndrome.

Introduction: Azithromycin stabilises and improves lung function forced expiratory volume in one second (FEV) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV, BOS progression and survival .

Methods: Eligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV, BOS free progression and overall survival.

Characterization of Mutations and Levels of BMP9 and BMP10 in Pulmonary Arterial Hypertension.

Recently, rare heterozygous mutations in were identified in patients with pulmonary arterial hypertension (PAH). encodes the circulating BMP (bone morphogenetic protein) type 9, which is a ligand for the BMP2 receptor. Here we determined the functional impact of mutations and characterized plasma BMP9 and BMP10 levels in patients with idiopathic PAH.