Early post-infarct fibroblast activation protein-targeted PET/CT with ⁶⁸Ga-FAPI-46 identifies STEMI patients with preserved LVEF at higher risk for adverse remodeling and cardiovascular events.

Abstract

Fibroblast activation protein (FAP)-targeted PET/CT with radiolabeled FAPIs enables noninvasive visualization of fibroblast activity following ST-segment elevation myocardial infarction (STEMI). However, the prognostic implications of myocardial FAPI uptake remain insufficiently characterized. This prospective study aimed to evaluate the prognostic value of ⁶⁸Ga-FAPI-46 PET/CT in STEMI patients treated successfully with primary percutaneous coronary intervention (PPCI). Within six days after successful PPCI, patients underwent ⁶⁸Ga-FAPI-46 PET/CT to quantify fibroblast activation volume (FAV). The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs) over three years, including stroke, recurrent myocardial infarction, heart failure readmission, target or non-target vessel revascularization, and new-onset atrial fibrillation. Left ventricular end-diastolic diameter (LVEDD) at one year was assessed as a secondary outcome. A total of 50 STEMI patients were finally included in this study. Baseline FAV showed a positive linear correlation with one-year LVEDD (r = 0.298, p = 0.036) and independently predicted LVEDD > 50 mm (OR 1.022, 95% CI 1.007-1.038, p = 0.004). In adjusted analysis, each unit increase in FAV was associated with a 1.1% higher risk of MACEs. A nonlinear relationship was observed, with FAV ≤ 81.34 corresponding to a 5% increase in MACE risk per unit rise (HR 1.05, 95% CI 1.003-1.098, p = 0.035). Using an optimal FAV cutoff of 51.6, patients with high FAV had significantly more MACEs than those with low FAV (47.22% vs. 14.29%, p = 0.031). Incorporating dichotomized FAV into a conventional clinical model was associated with improved discrimination of two-year MACEs (AUC 0.84 vs. 0.70, p = 0.021) and provided significant net reclassification (NRI 0.506, p < 0.001) and integrated discrimination improvement (IDI 0.212, p < 0.001). In STEMI patients with preserved LVEF, early fibroblast activation measured by ⁶⁸Ga FAPI 46 PET/CT is associated with subsequent left ventricular remodeling. FAV may provide incremental prognostic value beyond traditional risk factors. These findings are exploratory, and warrant validation in larger, multicenter cohorts and comparisons with other relevant imaging methods.