Clinical outcomes of patients in cardiogenic shock phenotypes: data from the cardiogenic shock working group registry
Authors: Zweck E , Kanwar M , Sinha S S , Garan A R , Hernandez-Montfort J , Westenfeld R , Burkhoff D , Kapur N K 
Published: November 2023

Abstract

Background
Despite therapeutic innovations in cardiogenic shock (CS), CS patients remain at high in-hospital mortality of 30-60%. Heterogeneity of CS patients has complicated clinical trial design. Recently, three CS phenotypes were identified in Version 1 (V1) of the multi-center national Cardiogenic Shock Working Group (CSWG) registry and two validation cohorts, namely phenotype I: "non-congested", II: "cardiorenal", and III: "cardiometabolic" shock. However, little is known about the clinical course of these CS phenotypes and further validation is required.

Purpose
(i) To confirm the external applicability of phenotypes in a mixed CS population, (ii) to assess the relevance of CS phenotypes for prognosis and outcomes, (iii) to confirm their compatibility with the SCAI classification system, and (iv) to assess differences in temporary mechanical circulatory support (tMCS) usage among CS phenotypes.

Methods
We included all-cause CS patients from CSWG V2 registry. Phenotypes were assigned by nearest centroid classification with the centroids from the initial CSWG V1 registry derivation cohort. Analyses were performed in all patients with complete clustering data. A sensitivity analysis in the complete dataset included cluster assignments based on random forest imputation.

Results
796 out of 1890 all-cause CS patients had complete data for retrospective phenotype assignment without imputation. Among these, mortality in phenotype I (non-congested), II (cardiorenal) and III (cardiometabolic) was 23%, 41% and 52%, respectively, closely matching the initially reported 21%, 45% and 55% in the V1 derivation cohort. In the total cohort including patients with partially imputed data, mortality was 23%, 30%, and 52%, respectively. Phenotype-related demographic, hemodynamic and metabolic features resembled the initially reported properties (Figure). In the main cohort of 796 patients, 58.8%, 45.7%, and 51.9% in phenotype I, II, and III, received tMCS, respectively (p=0.013). Receiving any tMCS was associated with higher mortality in cardiorenal (OR [95%-CI]: 1.82 [1.16-2.84; p=0.008), but not in non-congested or cardiometabolic CS (1.26 [0.64-2.47], p=0.51 & 1.39 [0.86-2.25], p=0.18, respectively). Patients in cardiometabolic CS but not cardiorenal CS at baseline were more likely to reach SCAI Stage E ("Extremis") during the hospitalization (OR [95% CI]: 5.26 [3.53-7.83], p&lt;0.001 & 1.10 [0.76-1.61], p=0.609, respectively) than patients with non-congested CS at baseline. Admission phenotype II and III as well as admission SCAI stage E were each independently associated with more than twofold increases in odds of mortality compared to phenotype I and baseline SCAI stage C in a multivariable regression (p&lt;0.001, respectively).

Conclusion
Our findings support the universal applicability of phenotypes in all-cause CS. These data may inform future clinical trial design to tailor interventions to specific CS phenotypes.Figure