Pulmonary endarterectomy through inverted-T upper hemisternotomy.

Objective: We aimed to explore the feasibility of an inverted-T upper hemisternotomy approach for pulmonary endarterectomy (PEA) and report the results after 17 cases.

Methods: PEA was conducted through a 7-cm skin incision using an inverted-T upper hemisternotomy across the third intercostal spaces. Cardiopulmonary bypass (CPB) was established through central arterial and percutaneous femoral dual-staged venous cannulation.

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.

Angiogenesis in Chronic Thromboembolic Pulmonary Hypertension: A Janus-Faced Player?

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension characterized by the presence of organized thrombi that obstruct pulmonary arteries, ultimately leading to right heart failure and death. Among others, impaired angiogenesis and inflammatory thrombosis have been shown to contribute to the progression of CTEPH. In this review, we summarize the 2-faced nature of angiogenesis in both thrombus formation and resolution in the context of CTEPH and highlight the dual role of angiogenesis and neovascularization in resolving venous thrombi.

Pulmonary arterial hypertension drugs can partially restore altered angiogenic capacities in -silenced human lung microvascular endothelial cells.

Mutations in the () gene and signaling pathway impairment are observed in heritable and idiopathic pulmonary arterial hypertension (PAH). In PAH, endothelial dysfunction is currently handled by drugs targeting the endothelin-1 (ET-1), nitric oxide (NO), and prostacyclin (PGI) pathways. The role of angiogenesis in the disease process and the effect of PAH therapies on dysregulated angiogenesis remain inconclusive.

Machine learning to differentiate pulmonary hypertension due to left heart disease from pulmonary arterial hypertension.

Background And Aims: Pulmonary hypertension due to left heart disease (PH-LHD) is the most frequent form of PH. As differential diagnosis with pulmonary arterial hypertension (PAH) has therapeutic implications, it is important to accurately and noninvasively differentiate PH-LHD from PAH before referral to PH centres. The aim was to develop and validate a machine learning (ML) model to improve prediction of PH-LHD in a population of PAH and PH-LHD patients.

Impairment of Angiogenesis-Driven Clot Resolution Is a Key Event in the Progression to Chronic Thromboembolic Pulmonary Hypertension: Validation in a Novel Rabbit Model.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model.

A Comprehensive Assessment of Right Ventricular Function in Chronic Thromboembolic Pulmonary Hypertension.

While chronic thromboembolic pulmonary hypertension (CTEPH) results from macroscopic and microscopic obstruction of the pulmonary vascular bed, the function of the right ventricle (RV) and increased RV afterload are the main determinants of its symptoms and prognosis. In this review, we assess RV function in patients diagnosed with CTEPH with a focus on the contributions of RV afterload and dysfunction to the pathogenesis of this disease. We will also discuss changes in RV function and geometry in response to treatment, including medical therapy, pulmonary endarterectomy, and balloon pulmonary angioplasty.

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Background: Senescent cells (SCs) are involved in proliferative disorders, but their role in pulmonary hypertension remains undefined. We investigated SCs in patients with pulmonary arterial hypertension and the role of SCs in animal pulmonary hypertension models.

Methods: We investigated senescence (p16, p21) and DNA damage (γ-H2AX, 53BP1) markers in patients with pulmonary arterial hypertension and murine models.

Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH.

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members.

Incremental Experience in In Vitro Primary Culture of Human Pulmonary Arterial Endothelial Cells Harvested from Pulmonary Arterial Catheters.

Pulmonary arterial hypertension (PAH) is a devastating condition affecting the pulmonary microvascular wall and endothelium, resulting in their partial or total obstruction. Despite a combination of expensive vasodilatory therapies, mortality remains high. Personalized therapeutic approaches, based on access to patient material to unravel patient specificities, could move the field forward.

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.

PH CARE COVID survey: an international patient survey on the care for pulmonary hypertension patients during the early phase of the COVID-19 pandemic.

Background: During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic.

Kcnk3 dysfunction exaggerates the development of pulmonary hypertension induced by left ventricular pressure overload.

Aims: Pulmonary hypertension (PH) is a common complication of left heart disease (LHD, Group 2 PH) leading to right ventricular (RV) failure and death. Several loss-of-function (LOF) mutations in KCNK3 were identified in pulmonary arterial hypertension (PAH, Group 1 PH). Additionally, we found that KCNK3 dysfunction is a hallmark of PAH at pulmonary vascular and RV levels.

COVID-19 in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a reference centre survey.

https://bit.ly/3jGuBQq.

α1AMP-Activated Protein Kinase Protects against Lipopolysaccharide-Induced Endothelial Barrier Disruption via Junctional Reinforcement and Activation of the p38 MAPK/HSP27 Pathway.

Vascular hyperpermeability is a determinant factor in the pathophysiology of sepsis. While, AMP-activated protein kinase (AMPK) is known to play a role in maintaining endothelial barrier function in this condition. Therefore, we investigated the underlying molecular mechanisms of this protective effect.

Learning from registries in pulmonary arterial hypertension: pitfalls and recommendations.

Pulmonary arterial hypertension is a rare and incurable chronic disease characterised by a progressive increase in pulmonary vascular resistance and right heart failure. Patient registries collecting observational data can be of great value in the understanding of clinical problems. While clinical trials provide data in selected patient populations, registries better depict real-life practice.

Cytokines trigger disruption of endothelium barrier function and p38 MAP kinase activation in -silenced human lung microvascular endothelial cells.

The bone morphogenetic protein receptor II (BMPRII) signaling pathway is impaired in pulmonary arterial hypertension and mutations in the gene have been observed in both heritable and idiopathic pulmonary arterial hypertension. However, all mutation carriers do not develop pulmonary arterial hypertension, and inflammation could trigger the development of the disease in mutation carriers. Circulating levels and/or lung tissue expression of cytokines such as tumor necrosis factor-α or interleukin-18 are elevated in patients with pulmonary arterial hypertension and could be involved in the pathogenesis of pulmonary arterial hypertension.

CCR2/CCR5-mediated macrophage-smooth muscle cell crosstalk in pulmonary hypertension.

Macrophages are major players in the pathogenesis of pulmonary arterial hypertension (PAH).To investigate whether lung macrophages and pulmonary-artery smooth muscle cells (PASMCs) collaborate to stimulate PASMC growth and whether the CCL2-CCR2 and CCL5-CCR5 pathways inhibited macrophage-PASMC interactions and PAH development, we used human CCR5-knock-in mice and PASMCs from patients with PAH and controls.Conditioned media from murine M1 or M2 macrophages stimulated PASMC growth.

Double-lung versus heart-lung transplantation for precapillary pulmonary arterial hypertension: a 24-year single-center retrospective study.

Transplant type for end-stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart-lung (HLT) versus double-lung (DLT) transplantation. Single-center analysis (38 HLT-30 DLT; 1991-2014) for different causes of precapillary pulmonary hypertension (PH): idiopathic (22); heritable (two); drug-induced (nine); hepato-portal (one); connective tissue disease (four); congenital heart disease (CHD) (24); chronic thromboembolic PH (six).

TGFβ and BMPRII signalling pathways in the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe condition characterised by remodelling of precapillary pulmonary arteries sometimes associated with mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene. Even in the absence of BMPR2 mutations, increased transforming growth factor (TGF)β receptor signalling and decreased BMPRII signalling have been shown to contribute to PAH pathogenesis. In this Keynote, we review the potential mechanisms by which the imbalance of BMP/TGFβ signalling contributes to endothelial dysfunction, vascular remodelling, inflammation and disordered angiogenesis in PAH.