Abstract 4365425: Mediation of the Relationship Between Myocardial Replacement Fibrosis and Sudden Cardiac Death by Left Ventricular Ejection Fraction Post-Myocardial Infarction

Background: We aimed to evaluate whether and to what extent left ventricular ejection fraction (LVEF) mediates the relationship between late gadolinium enhancement (LGE) and sudden cardiac death (SCD) in patients with old myocardial infarction (OMI), and to assess this mediation effect in subgroups based on LVEF≤35% and>35% according to implantable cardioverter-defibrillator (ICD) selection criterion. Methods: A retrospective analysis was conducted on 410 patients with OMI (mean age: 56.6±10.5 years, 88.2% male) who underwent cardiac MR. The endpoint for SCDs included SCD, aborted SCD, and appropriate ICD shocks. The effect of LGE on LVEF was quantified using linear regression models. The effects of both LGE and LVEF on SCDs were assessed using Cox regression models. Mediation analysis was used to decompose the total effect of LGE on SCDs into direct and indirect (mediated through LVEF) effects. Results: Over a mean follow-up of 5.8±1.8 years, 41 patients (10.0%) experienced SCDs. LGE was significantly associated with lower LVEF (β=-0.19, p<0.001). Both LGE and LVEF independently predicted SCDs (sHR=1.03, p=0.005; sHR=0.95, p=0.002, respectively). Mediation analysis showed that LVEF accounted for 24.6% of the total effect of LGE on SCDs (p=0.04). This mediation effect was 63.2% in patients with LVEF>35% (p=0.02), while no mediation was observed in patients with LVEF≤35% (p=0.64). Conclusions: LVEF partially mediated the effect of LGE on the incidence of SCDs, accounting for less than a quarter of the total effect. This highlights the critical role of LGE assessment in SCD prevention strategies, regardless of LVEF levels.