Genetic predisposition to cardiogenic shock complicating acute myocardial infarction: a systematic review.

BACKGROUND

Cardiogenic shock (CS) complicates 5-10% of acute myocardial infarctions (AMI) and remains associated with in-hospital mortality of approximately 40-50%. The clinical predictors established do not fully explain why patients with comparable infarct severity have divergent outcomes, raising the hypothesis that host genetic factors modulate susceptibility to CS. Therefore, we conducted this systematic review to synthesize published evidence describing genetic variants associated with the development of CS complicating AMI.

METHODS

PubMed, Embase, Scopus, and the Cochrane Library were searched from inception through Jun 2026, following PRISMA 2020 guidance. Eligible studies included any study type enrolling adults with AMI and reporting association of any specific genetic variants with CS.

RESULTS

Of 480 records identified, 9 studies met inclusion criteria. Reported variants clustered into five biological pathways: inflammatory/cytokine signaling (TNF-α -308G>A, IFN-γ +874T>A, RANTES/CCL5 -403G>A), lipid metabolism (APOE ε2/ε3/ε4), thrombosis and fibrinolysis (PAI-1/SERPINE1 4G/4 G, MTHFR C677T/A1298C), clonal myeloproliferative disease (JAK2 V617F), and hypercoagulable/antioxidant pathways (protein C/S-related thrombophilia, PON1 Q192R). The APOE ε3/4 genotype and the TNF-2 allele showed the most direct associations with CS incidence and survival, respectively; JAK2 V617F and combined PAI-1/MTHFR variants were reported in severe, thrombus-driven case presentations of CS. RANTES and PON1 genotypes were not associated with CS occurrence, although circulating RANTES levels correlated with CS severity.

CONCLUSIONS

The available evidence is limited, but the variants reported to date span inflammatory, lipid, thrombotic, and myeloproliferative pathways, suggesting that genetic susceptibility to CS complicating AMI is polygenic and mechanistically heterogeneous, requiring prospective genetic association studies.