Cardiogenic shock (CS) is associated with high short-term mortality, substantial morbidity and resource utilization. Despite widespread use of early coronary reperfusion, CS prevalence remains unaltered and it is the leading cause of in-hospital death. Although contemporary risk scores are available (i.e. CardShock and IABP-SHOCK II) they mostly rely on classical clinical acumen and conventional laboratory variables and more accurate risk stratification strategies are needed to guide interventions to improve patients outcome. Here we developed a circulating protein-based classifier able to predict short-term mortality risk among patients with CS.
In an initial proteomics screening, a cohort of 48 CS patients (Barcelona cohort) was used to select candidate proteins to predict short-term mortality risk. Then, 51 selected proteins were quantified by targeted proteomics (PRM) in an independent European multicenter cohort of 97 patients (CardShock cohort). Concretely, chromatographic profiles were obtained for all measured peptides and compared to their internal references for accurate relative protein quantification.
The classification power of these proteins was evaluated resulting in CS4P (Cardiogenic Shock 4 Proteins), the combination of four plasma proteins able to predict 90-day risk of mortality among CS patients (AUC=0.83). CS4P comprises the abundances of liver fatty acid-binding protein (L-FABP), beta-2-microglobulin (B2MG), fructose-bisphosphate aldolase B (ALDOB), and SerpinG1 (IC1). Moreover, the CS4P model in combination with contemporary CardShock risk score improved mortality prediction and patient reclassification compared with the CardShock risk score alone (AUC 0.84 vs. AUC 0.78). The CS4P patient classification power was confirmed by enzyme-linked immunosorbent assay (ELISA). This validation will favor its translation into routine clinical practice and ultimately guide clinicians in selecting patients for advanced therapies.