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Artificial Intelligence and Multi-Omics Approaches in the Precision Management of Pulmonary Hypertension: From Early
Sergio Ferrantelli1,2, Alessandro Del Cuore3, Giuliano Cassataro4
1Molecular and Clinical Medicine PhD Program, University of Palermo, 90127 Palermo, Italy.
Abstract:
Pulmonary hypertension (PH) is a heterogeneous clinical syndrome in which similar haemodynamic abnormalities may arise from distinct vascular, cardiac, pulmonary, thromboembolic, and molecular mechanisms. This complexity limits the ability of conventional classifications and risk scores to fully capture individual disease trajectories and treatment responses. Artificial intelligence (AI) offers a framework for integrating clinical data, electrocardiography, multimodal imaging, invasive haemodynamics, biomarkers, and multi-omics information across the PH care pathway. This review summarises current applications of machine learning and deep learning in early detection, diagnostic referral, right-ventricular and pulmonary vascular phenotyping, molecular endotyping, risk stratification, and therapeutic decision support. Available studies show promising results for AI-assisted electrocardiographic screening, automated echocardiographic and cardiac magnetic resonance analysis, computed tomography (CT)-based phenotyping, and multimodal prognostic modelling. True multi-omics integration in PH remains limited to discovery studies and has not yet yielded externally validated endotype or treatment-response classifiers. Evidence maturity is task-dependent: screening and phenotyping span several PH groups, whereas validated risk tools, molecular endotyping, and pathway-directed therapy remain predominantly PAH-based, particularly in idiopathic/heritable PAH. However, most evidence remains retrospective, derives from selected referral populations, and lacks robust external or prospective validation. No AI-based model currently supports routine drug selection or autonomous clinical decision-making. Future progress will require harmonised multicentre datasets and standardised acquisition protocols, transparent and interpretable models, and prospective studies demonstrating meaningful clinical benefit. AI should therefore be viewed as an emerging decision-support tool that may strengthen precision medicine in PH while complementing clinical expertise across diagnosis, phenotyping, risk assessment, and therapeutic stratification pathways.
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