ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly.

peer reviewedPulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation

Marqueurs pronostiques et stratification du risque dans l’HTAP

Pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis that has long been considered inevitable. About ten drugs are available to treat the disease. The choice of initial treatment strategy is based on evaluation of the risk of mortality using multiparametric models. In this work, we have proposed a risk stratification method based on the number of low-risk criteria, that can be used at the time of diagnosis and follow-up. With this approach, we were able to identify patients with a good prognosis, and refine ambitious treatment goals. We have also shown that the integration of hemodynamic criteria (such as stroke volume index) or biomarkers (with the identification of new inflammatory biomarkers) improved risk stratification models. Finally, we have shown that the choice of the initial treatment strategy was strongly associated with the outcome of patients with PAH. The use of an initial triple combination therapy including parenteral prostacyclin was associated with an excellent long-term survival, especially in the youngest and most severe patients. These results underline the importance of a rigorous multiparametric approach to identify patients at high risk requiring a more aggressive approach.L’hypertension artérielle pulmonaire (HTAP) est une maladie rare dont le mauvais pronostic a longtemps été considéré comme inéluctable. Une dizaine de traitements sont aujourd’hui disponibles pour prendre en charge cette pathologie. Le choix de la stratégie thérapeutique initiale repose sur l’évaluation du risque de mortalité à l’aide de modèles multiparamétriques. Au cours de ce travail, nous avons proposé une méthode de stratification du risque basée sur le nombre de critères associés à un faible risque, utilisable au diagnostic et au cours du suivi. Avec cette approche, nous avons pu identifier les patients ayant un bon pronostic et redéfinir des objectifs thérapeutiques ambitieux. Nous avons également montré que l’intégration de certains critères hémodynamiques (tels que le volume d’éjection systolique indexé) ou biologiques (identification de nouveaux biomarqueurs de l’inflammation) permettaient d’améliorer cette évaluation du risque. Enfin, nous avons montré que le choix de la stratégie thérapeutique initiale était fortement associé au pronostic des patients atteints d’HTAP. Le recours à une trithérapie initiale incluant une prostacycline parentérale était associé à une excellente survie à long-terme, en particulier chez les patients les plus jeunes et les plus sévères au diagnostic. Ces résultats soulignent l’intérêt d’une approche multiparamétrique rigoureuse pour identifier les patients à risque nécessitant une approche plus agressive

Acute decompensated pulmonary hypertension

Acute right heart failure in chronic precapillary pulmonary hypertension is characterised by a rapidly progressive syndrome with systemic congestion resulting from impaired right ventricular filling and/or reduced right ventricular flow output. This clinical picture results from an imbalance between the afterload imposed on the right ventricle and its adaptation capacity. Acute decompensated pulmonary hypertension is associated with a very poor prognosis in the short term. Despite its major impact on survival, its optimal management remains very challenging for specialised centres, without specific recommendations. Identification of trigger factors, optimisation of fluid volume and pharmacological support to improve right ventricular function and perfusion pressure are the main therapeutic areas to consider in order to improve clinical condition. At the same time, specific management of pulmonary hypertension according to the aetiology is mandatory to reduce right ventricular afterload. Over the past decade, the development of extracorporeal life support in refractory right heart failure combined with urgent transplantation has probably contributed to a significant improvement in survival for selected patients. However, there remains a considerable need for further research in this field

The evolving landscape of pulmonary arterial hypertension clinical trials

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 remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence

Cytokines as prognostic biomarkers in pulmonary arterial hypertension

International audienceBackground 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, brain natriuretic peptide (BNP) and/or its N-terminal fragment (NT-proBNP) are the only markers for right ventricular dysfunction used in clinical practice, in association with echocardiographic and invasive haemodynamic variables to predict outcome in patients with PAH. Methods This study was designed to identify an easily measurable biomarker panel in the serum of 80 well-phenotyped PAH patients with idiopathic, heritable or drug-induced PAH at baseline and at first follow-up. The prognostic value of identified cytokines of interest was secondly analysed in an external validation cohort of 125 PAH patients. Results Among the 20 biomarkers studied with the multiplex Ella platform, we identified a three-biomarker panel composed of β-NGF, CXCL9 and TRAIL that were independently associated with prognosis both at the time of PAH diagnosis and at the first follow-up after initiation of PAH therapy. β-NGF and CXCL9 were predictors of death or transplantation, whereas high levels of TRAIL were associated with a better prognosis. Furthermore, the prognostic value of the three cytokines was more powerful for predicting survival than usual non-invasive variables (New York Heart Association Functional Class, 6-min walk distance and BNP/NT-proBNP). The results were validated in a fully independent external validation cohort. Conclusion The monitoring of β-NGF, CXCL9 and TRAIL levels in serum should be considered in the management and treatment of patients with PAH to objectively guide therapeutic options

Interest of TAPSE/sPAP ratio for noninvasive pulmonary arterial hypertension risk assessment

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