Abstract
2217
Introduction: Molecular PET-imaging of fibroblast activation protein (FAP) has recently been evaluated in patients after acute myocardial infarction (AMI). Here, the extent of FAP upregulation significantly exceeded the infarct region. We sought to obtain further insights by correlating FAP-targeted PET imaging with tissue characteristics from cardiac magnetic resonance (CMR) and functional outcome.
Methods: 35 patients underwent 68Ga-FAPI-46 PET/CT, perfusion SPECT and cardiac magnet resonane imaging (CMR) within 11 days after AMI. Infarct size was determined from SPECT, compared to reference database. Cardiac FAP-volume was determined using an isocontour VOI including all voxels above an individually determined threshold (blood-pool SUVmean+2standard deviations (SD)). Additionally, area of FAP upregulation was calculated by polar map analysis, using the threshold (mean+2SD of bloodpool SUVmean). CMR yielded functional parameters, area of injury (late gadolinium enhancement, LGE) and T1 / T2 tissue mapping. Follow up cardiac function was available from echocardiography or CMR after 139.5 (IQR 80.5-188.25) days in a subgroup of patients (n=14).
Results: In all patients the area of FAP-upregulation was significantly larger than both the SPECT perfusion defect size (58±15 vs. 23±17%, p<0.001) and infarct area defined by LGE CMR (28±11%, p<0.001; figure 1). FAP-volume significantly correlated with CMR parameters at baseline (all p<0.001): infarct area (r=0.58), LV mass (r=0.69), endsystolic (r=0.62) and enddiastolic volume (r=0.57). Segmental analysis revealed FAP-upregulation in 308/496 (62%) myocardial segments. Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. 14% (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. There was a weak correlation between myocardial FAP volume and LVEF at baseline (r= -0.32, p=0.07). However, the early myocardial PET signal exhibited a stronger correlation to LVEF at follow-up (r= -0.58, p=0.007), suggesting a relationship between the extent of fibroblast activation and more severe adverse ventricle remodeling.
Conclusions: Early after acute myocardial infarction and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves non-infarcted myocardium. A higher extent of myocardial FAP upregulation was predictive of subsequent left ventricular dysfunction. Thus, fibroblast activation in non-infarcted myocardial areas may contribute to adverse outcome. FAPI PET signal did not match established regional CMR-derived myocardial tissue characteristics, indicating that FAP imaging may be a complementary biomarker. FAP-imaging may be used to establish treatment strategies to mitigate pro-fibrotic activity outside of the primary infarct region in order to prevent adverse remodeling.