Pulmonary Hypertension Associated With Trastuzumab-Emtansine: An Analysis of French PH Registry and WHO Pharmacovigilance Database.

Background: Trastuzumab emtansine has been recently suspected to be associated with the development of pulmonary arterial hypertension (PAH).

Research Question: Is there an association between trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan and the development of PAH?.

Study Design And Methods: Characteristics of incident PAH cases treated with trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan were analyzed from the French PH Registry, the VIGIAPATH program, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization pharmacovigilance database using a broad definition of pulmonary hypertension (PH) and a narrow definition of PAH.

Exploring the Endothelin-1 pathway in chronic thromboembolic pulmonary hypertension microvasculopathy.

Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach.

Pulmonary hypertension in patients carrying FLNA loss-of-function variants.

Background: Pulmonary hypertension (PH) is an unusual complication of X-linked disease caused by loss-of-function (LOF) variants in the () gene. Patients with LOF may also present dysmorphic facial features, aortic dilation, thrombopenia, and periventricular nodular heterotopia (PVNH).

Methods: We reported clinical, functional, radiologic, and hemodynamic characteristics of patients with LOF variants and PH from the French PH Network.

Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences of Mutation.

Background: The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the gene. The incomplete penetrance of mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling.

Evidence and unresolved questions in pulmonary hypertension: Insights from the 5th French Pulmonary Hypertension Network Meeting.

Pulmonary hypertension (PH) continues to present significant challenges to the medical community, both in terms of diagnosis and treatment. The advent of the updated 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines has introduced pivotal changes that reflect the rapidly advancing understanding of this complex disease. These changes include a revised definition of PH, updates to the classification system, and treatment algorithm.

Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness.

Perivascular collagen deposition by activated fibroblasts promotes vascular stiffening and drives cardiovascular diseases such as pulmonary hypertension (PH). Whether and how vascular fibroblasts rewire their metabolism to sustain collagen biosynthesis remains unknown. Here, we found that inflammation, hypoxia, and mechanical stress converge on activating the transcriptional coactivators YAP and TAZ (WWTR1) in pulmonary arterial adventitial fibroblasts (PAAFs).

Characteristics and outcomes of patients developing pulmonary hypertension associated with proteasome inhibitors.

Background: Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PIs). Our objective was to evaluate the association between PIs and PAH.

Methods: Characteristics of incident PAH cases previously treated with carfilzomib or bortezomib were analysed from the French pulmonary hypertension registry and the VIGIAPATH programme from 2004 to 2023, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization (WHO) global database (VigiBase) and a meta-analysis of randomised controlled trials.

Pulmonary vascular phenotype identified in patients with () or variants: an international multicentre study.

Background: Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by and , respectively, play a pivotal role in pulmonary vascular regulation. variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of and carriers remains largely unexplored.

Pulmonary hypertension associated with diazoxide: the SUR1 paradox.

The ATP-sensitive potassium channels and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH).

Diagnosis and management of pulmonary veno-occlusive disease.

Introduction: Pulmonary veno-occlusive disease (PVOD) is an orphan disease and uncommon etiology of pulmonary arterial hypertension (PAH) characterized by substantial small pulmonary vein and capillary involvement.

Areas Covered: PVOD, also known as 'PAH with features of venous/capillary involvement' in the current ESC/ERS classification.

Expert Opinion: In recent years, particular risk factors for PVOD have been recognized, including genetic susceptibilities and environmental factors (such as exposure to occupational organic solvents, chemotherapy, and potentially tobacco).

Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1.

Background: Pulmonary arterial hypertension (PAH) encompasses a group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling and inflammation. Bromodomain and extra-terminal (BET) proteins are required for the expression of a subset of NF-κB-induced inflammatory genes which can be inhibited by the BET mimic JQ1+. We hypothesised that JQ+ would supress TNFα-driven inflammatory responses in human pulmonary vascular cells from PAH patients.

The thromboxane receptor antagonist promotes beneficial adaptation and preserves cardiac function in experimental models of right heart overload.

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure leading to right ventricular (RV) failure. While current PAH therapies improve patient outlook, they show limited benefit in attenuating RV dysfunction. Recent investigations demonstrated that the thromboxane (TX) A receptor (TP) antagonist attenuates experimental PAH across key hemodynamic parameters in the lungs and heart.