Cardiac Fibroblast Activation in Patients Early After Acute Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome

Abstract

After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Methods: Thirty-five patients underwent CMR, perfusion SPECT, and ⁶⁸Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI. Infarct size was determined from SPECT by comparison to a reference database. For PET, regional SUVs and isocontour volumes of interest determined the extent of cardiac FAP upregulation (FAP volume). CMR yielded functional parameters, area of injury (late gadolinium enhancement [LGE]) and T1/T2 mapping. Follow-up was available from echocardiography or CMR after 139.5 d (interquartile range, 80.5-188.25 d) (n = 14). Results: The area of FAP upregulation was significantly larger than the SPECT perfusion defect size (58% ± 15% vs. 23% ± 17%, P < 0.001) and infarct area by LGE (28% ± 11%, P < 0.001). FAP volume significantly correlated with CMR parameters at baseline (all P < 0.001): infarct area (r = 0.58), left ventricle (LV) mass (r = 0.69), end-systolic volume (r = 0.62), and end-diastolic volume (r = 0.57). Segmental analysis revealed FAP upregulation in 308 of 496 myocardial segments (62%). Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. Fourteen percent (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. Of note, FAP volume correlated only weakly with simultaneously measured LV ejection fraction at baseline (r = -0.32, P = 0.07), whereas there was a significant inverse correlation with LV ejection fraction obtained at later follow-up (r = -0.58, P = 0.007). Conclusion: Early after AMI and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves noninfarcted myocardium. The ⁶⁸Ga-FAPI PET signal does not match regional myocardial tissue characteristics as defined by CMR but is predictive of the evolution of ventricular dysfunction. FAP-targeted imaging may provide a novel biomarker of LV remodeling that is complementary to existing techniques.

Keywords: PET; fibroblast activation protein; left ventricular remodeling; myocardial infarction.