Article Dans Une Revue EClinicalMedicine Année : 2025

Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials

Jacob C Jentzer

Résumé

Background Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).

Methods We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes. Thereafter, a simplified classifier (Euclidean distances) was used to assign the identified CS subphenotypes in three completed randomized controlled trials (RCTs) (OptimaCC, N = 57 [2011-2016, NCT01367743]; DOREMI, N = 192 [2017-2020, NCT03207165]; and CULPRIT-SHOCK, N = 434 [2013-2017, NCT01927549]) and explore heterogeneity of treatment effect with respect to 28-day mortality (primary outcome).

Findings Four biomarker-driven CS subphenotypes ('adaptive', 'non-inflammatory', 'cardiopathic', and 'inflammatory') were identified separately in the two cohorts. Patients in the inflammatory and cardiopathic subphenotypes had the highest 28-day mortality (p (log-rank test) = 0.0099 and 0.0055 in the CardShock and FROG-ICU cohorts, respectively). Subphenotype membership significantly improved risk stratification when

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hal-04894807 , version 1 (17-01-2025)

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Sabri Soussi, Tuukka Tarvasmäki, Antoine Kimmoun, Mojtaba Ahmadiankalati, Feriel Azibani, et al.. Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials. EClinicalMedicine, 2025, 79, pp.103013. ⟨10.1016/j.eclinm.2024.103013⟩. ⟨hal-04894807⟩
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