David Montani

Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud) · Service de Pneumologie

Aims We hypothesized that the ATP-sensitive K ⁺ channels (KATP) regulatory subunit (ABCC9) contributes to PAH pathogenesis. ABCC9 gene encodes for two regulatory subunits of KATP channels: the SUR2A and SUR2B proteins. In the KATP channel, the SUR2 subunits are associated with the K ⁺ channel Kir6.1. We investigated how the SUR2/Kir6.1 channel cont...

Introduction Risk stratification and assessment of disease progression in patients with pulmonary arterial hypertension (PAH) are challenged by the lack of accurate disease-specific and prognostic biomarkers. To date, B-type natriuretic peptide (BNP) and/or its N-terminal fragment (NT-proBNP) are the only marker for right ventricular dysfunction us...

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 2 recep...

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH) occurring in a heritable form (hPVOD) due to biallelic inactivating mutations of EIF2AK4 (encoding GCN2, general control nonderepressible 2) or in a sporadic form in older age (sPVOD), following exposure to chemotherapy or organic solvents. In contrast t...

Objectives To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment. Methods Patients with limited cutaneous SSc, no extensive interstitial lung disease and no PAH-specific therapy were included....

Objective: Psychiatric symptoms and mental disorders are common after Coronavirus Disease-19 (COVID-19). Some drugs used to treat acute COVID-19 have psychiatric side effects. We assessed the psychiatric symptoms and mental disorders of patients treated for acute COVID-19 with hydroxychloroquine (HCQ), interleukin-6 receptor antagonists (anti-IL-6...

Over the past decade recognition of the profound impact of the T-box 4 (TBX4) gene, which encodes a member of the evolutionarily conserved family of T-box-containing transcription factors, upon respiratory diseases has emerged. The developmental importance of TBX4 is emphasized by the association of TBX4 variants with congenital disorders involving...

Rationale: Pulmonary arterial hypertension (PAH) is characterized by progressive distal pulmonary artery (PA) obstruction, leading to right ventricular hypertrophy and failure. Exacerbated intracellular calcium (Ca ²⁺ ) signaling contributes to abnormalities in PA smooth muscle cells (PASMCs), including aberrant proliferation, apoptosis resistance,...

Introduction: The ATP-sensitive K+ channels (KATP) regulatory subunit ABCC8 may be considered a new therapeutic target for pulmonary arterial hypertension (PAH). Hypothesis: We hypothesised that the second KATP regulatory subunit (ABCC9) contributes to PAH pathogenesis. ABCC9 gene encodes for two regulatory subunits of KATP channels: the SUR2A and...

Résumé L’hypertension pulmonaire thromboembolique chronique (HTP-TEC) est une complication rare d’une maladie fréquente, l’embolie pulmonaire aiguë. L’occlusion des artères pulmonaires par des caillots organisés fibreux associée à une microvasculopathie secondaire intéressant les artérioles musculaires < 500µ, similaire à celle observée dans l’hype...

Résumé Les recommandations 2022 des Sociétés européennes de cardiologie (ESC) et de pneumologie (ERS) proposent une nouvelle définition hémodynamique des hypertensions pulmonaires (HTP) abaissant le seuil de pression artérielle pulmonaire moyenne (PAPm) à 20 mmHg mesurée par cathétérisme cardiaque droit pour définir l’HTP. L’HTP pré-capillaire est...

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis re...

Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complic...

Pulmonary arterial hypertension (PAH) is a rare disease, which can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, termed bone morphogenetic protein receptor 2 (BMPR2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH....

Right ventricular failure (RVF) is the most important prognostic factor for morbidity and mortality in pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) caused by left heart diseases. However, right ventricle (RV) remodeling is understudied and not targeted by specific therapies. This can be partly explained by the lack of basic...

Background Pulmonary arterial hypertension (PAH) is characterized by progressive distal pulmonary artery (PA) obstruction, leading to right ventricular hypertrophy and failure. Exacerbated intracellular calcium (Ca ²⁺ ) signaling contributes to abnormalities in PA smooth muscle cells (PASMCs), including aberrant proliferation, apoptosis resistance,...

Introduction Qualitative and quantitative hemodynamic flow indexes have been related to right ventricular (RV) function in pulmonary arterial hypertension (PAH), using 4-dimensional flow cardiac magnetic resonance (4D-flow CMR). Little is known in PAH congenital heart disease population characterized by intracardiac shunting. Methods A prospective...

Background Although ventriculoarterial coupling is associated with better survival in pulmonary arterial hypertension (PAH), existing PAH risk assessment method has not considered echocardiographic criteria of right ventricular to pulmonary artery coupling. We aimed to test the prognostic value of the echocardiographic tricuspid annular plane systo...

Background In participants with pulmonary arterial hypertension, 24 weeks of sotatercept resulted in a significantly greater reduction from baseline in pulmonary vascular resistance than placebo. This report characterises the longer-term safety and efficacy of sotatercept in the PULSAR open-label extension. We report cumulative safety, and efficacy...

Objectives Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders. Design Cross-sectional. Settings Bicêtre Hospital, France, secondary care. Participants One hundred seventy-seven...

Background Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH. Methods In thi...

Background Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. Methods Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Lung Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a r...

Introduction and objectives: Outcome in patients with congenital heart diseases and pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Two-dimensional echocardiographic parameters, such as strain imaging or RV end-systolic remodeling index (RVESRI) have emerged to quantify RV function. Methods: We prospecti...

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening pulmonary embolism's (PE) complication whose incidence and predictors are not precisely determined. Objective: To determine the frequency and predictors for CTEPH after a first unprovoked PE. Patients/methods: In a randomized trial comparing an additional 1...

Rationale: Despite the increased recognition of TBX4-associated pulmonary arterial hypertension (PAH), genotype-phenotype associations are lacking and may provide important insights. Methods: We assembled a multi-center cohort of 137 patients harboring monoallelic TBX4 variants and assessed the pathogenicity of missense variation (n = 42) usin...

Since the 1960s, several drugs have been linked to the onset or aggravation of pulmonary arterial hypertension (PAH): dasatinib, some amphetamine‐like appetite suppressants (aminorex, fenfluramine, dexfenfluramine, benfluorex) and recreational drugs (methamphetamine). Moreover, in numerous cases, the implication of other drugs with PAH have been su...

Background It is unknown whether pulmonary arterial hypertension (PAH) risk stratification instruments could be helpful to support the decision to list a patient for lung transplantation (LT). Our aim was to evaluate contemporary risk assessment tools in a cohort of PAH patients listed for LT. Methods Consecutive PAH patients (without pulmonary ve...

Immune checkpoint inhibitors (ICI) restore immune response against cancer cells that can lead to immune-related adverse effects. While cardiovascular immune-related adverse effects are known to be associated with checkpoint inhibitors, recent case reports have raised concerns about the potential association with pulmonary hypertension (PH). By usin...

Introduction The phenotype of pulmonary arterial hypertension (PAH) patients carrying SOX17 pathogenic variants remains mostly unknown. Methods We report the genetic analysis findings, characteristics and outcomes of patients with heritable PAH carrying SOX17 variants from the French Pulmonary Hypertension Network. Results Twenty patients and eig...

Right atrial pressure (RAP) is an important prognostic criterion in pulmonary hypertension (PH). The main goals were to evaluate the following: (i) the accuracy of Doppler assessment of common femoral vein flow waveform to detect elevated RAP and (ii) the diagnostic accuracy of RAP assessed by echocardiography (eRAP). Fifty-seven patients, addresse...

Rationale: SARS-Cov2 infection is associated with pulmonary endothelial dysfunction. There is limited data available on the outcomes of COVID-19 in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVI...

Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodelling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. Objectives: To quantify and analyse the plasma proteome of PAH patients using inherited genetic variation to inform on un...

Purpose During the 2018 6th PH World Symposium, it was stated that risk stratification scores may be used for the decision of lung (LT) or heart-lung transplantation (HLT) listing in patients with pulmonary arterial hypertension (PAH). The objective of our study was to evaluate risk assessment tools in a cohort of PAH patients listed for LT or HLT....

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ven...

We read with interest the manuscript entitled “BMPR2 mutations and response to inhaled or parenteral prostanoids: a case series” published in by Scelsi, et al. in a recent issue of Pulmonary Circulation¹. The authors reported a small series of 13 patients (6 with idiopathic or anorexigen-induced PAH and 7 with heritable PAH due to BMPR2 mutation) i...

Objective The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation. The aim o...

Introduction Le diagnostic de l’hypertension pulmonaire thromboembolique chronique (HTP-TEC) est un enjeu majeur car il s’agit de la seule cause curable d’hypertension pulmonaire (HTP). La scintigraphie pulmonaire de ventilation/perfusion (V/Q) est la modalité d’imagerie de choix pour le dépistage. Cependant, il n’y a pas de consensus sur les critè...

Résumé Contexte Depuis les précédentes recommandations françaises publiées en 2017, les connaissances concernant la fibrose pulmonaire idiopathique ont évolué sur de nombreux aspects. Méthodes Des recommandations pratiques ont été établies à l’initiative du Centre coordonnateur de référence des maladies pulmonaires rares, sous l’égide de la Socié...

Mutations in ABCC8 have been identified in pulmonary arterial hypertension (PAH). ABCC8 encodes SUR1, a regulatory subunit of the ATP-sensitive-potassium channel Kir6.2. However, the pathophysiological role of the SUR1/Kir6.2 channel in PAH is unknown. We hypothesized that activation of SUR1 could be a novel potential target for PAH. We analysed th...

Rationale: Despite the increasing frequency of TBX4-associated pulmonary arterial hypertension (PAH), genotype-phenotype associations are lacking and may provide important insights. Methods: We assembled a multi-center cohort of 137 patients harboring monoallelic TBX4 variants and assessed the pathogenicity of missense variation (n = 42) using a no...

Background The pathobiology of pulmonary arterial hypertension (PAH) involves pulmonary arterial smooth muscle cells (PASMCs) dysfunction leading to abnormal proliferation, apoptosis resistance and vasoconstriction. Store-operated Ca²⁺ entry (SOCE) strongly contributes to Ca²⁺ homeostasis in PASMCs, however, the role of SOCE archetype Orai1 Ca²⁺ ch...

Introduction Leflunomide (LEF) is a immunomodulator indicated in various diseases including rheumatoid arthritis. Recently, a link between this drug and pulmonary arterial hypertension (PAH) has been suggested (Lacoste Palasset et al., 2021, Ann Am Thorac Soc). Our aim was to examine the effect of LEF on pulmonary artery (PA) tone, whose abnormalit...

Background PAH is a severe cardiopulmonary disease which is defined by an elevation of the mPAP >25 mmHg. ABCC9 mutations are responsible of Cantu syndrome, a disease characterised by several cardiac disorders and for some case pulmonary hypertension. ABCC9 gene encodes for SUR2 protein, a regulatory subunit of KATP channels. We hypothesized that S...

Rationale: N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH. Objectives:...

Introduction La prévalence et les caractéristiques des symptômes respiratoires persistants après COVID-19 sont en grande partie inconnues. Les objectifs étaient de déterminer la prévalence et les caractéristiques de ces symptômes à distance du COVID-19 et les relations entre dyspnée, anomalies radiologiques et troubles fonctionnels. Méthodes Dans...

Introduction L’hypertension artérielle pulmonaire (HTAP) est une complication rare et potentiellement fatale de la maladie de Still de l’adulte (MSA). Nous rapportons ici la plus grosse série d’HTAP associées à une MSA. Méthodes Les cas ont été rétrospectivement colligés à partir du registre français des hypertensions pulmonaires. Tous les patient...

Background Although preserved right ventricular (RV) function is consistently associated with better survival in pulmonary arterial hypertension (PAH), the French risk assessment method has not yet considered echocardiographic criteria of RV function. Purpose In the present study, we tested the value of tricuspid annular plane systolic excursion (...

Pulmonary arterial hypertension (PAH) is a rare disease characterised by pulmonary vascular remodelling and elevated pulmonary pressure, which eventually leads to right heart failure and death. Registries worldwide have noted a female predominance of the disease, spurring particular interest in hormonal involvement in the disease pathobiology. Seve...

Rationale The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for COVID-19 are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. Methods In the COMEBAC cohort study, 478 hospit...

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 th...

Pulmonary arterial hypertension (PAH) is a severe and multifactorial disease. PAH pathogenesis mostly involves pulmonary arterial endothelial and pulmonary arterial smooth muscle cell (PASMC) dysfunction, leading to alterations in pulmonary arterial tone and distal pulmonary vessel obstruction and remodeling. Unfortunately, current PAH therapies ar...

Introduction: PAH is a severe and rare cardiopulmonary disease which is defined by an elevation of the mean pulmonary artery pressure >25mmHg. ABCC9 mutations are responsible of Cantu syndrome, a disease characterised by several cardiac disorders and for some case pulmonary hypertension (PH). ABCC9 gene encodes for SUR2 protein, a regulatory subuni...

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease, characterized by a progressive obstruction of distal pulmonary artery (PA) leading to right ventricular hypertrophy and failure. Exacerbated intracellular Ca ²⁺ signalling contributes to functional abnormalities in pulmonary arterial smooth muscle cells (PASMCs), includin...

IntroductionPirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF.Methods This study wa...

Introduction Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate, or high-risk. A minority of patients achieve low-risk status with most remaining intermediate-risk. Our aim was to validate a 4-strata risk assessment approach categorising patients as low, intermediate-low, intermedi...

Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Baye...

Primary Sjögren’s syndrome (pSS) is an autoimmune disease, associated with a high risk of lymphoma. Mounting evidence suggests that cardiovascular morbidity and mortality are higher in patients with pSS, although data are heterogeneous. The aim of this study was to assess whether pSS patients are at higher risk of hospitalisation for cardiovascular...

Background Although preserved right ventricular (RV) function is consistently associated with better survival in pulmonary arterial hypertension (PAH), the French risk assessment method has not yet considered echocardiographic criteria of RV function. Purpose In the present study, we tested the value of tricuspid annular plane systolic excursion (...

Purpose Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. Methods We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outco...

Cardiopulmonary exercise testing (CPET) is a frequently used tool in the differential diagnosis of dyspnoea. Ventilatory inefficiency, defined as high minute ventilation (V' E) relative to carbon dioxide output (V' CO2 ), is a hallmark characteristic of pulmonary vascular diseases, which contributes to exercise intolerance and disability in these p...