The Area of Fibroblast Activation Exceeds the Hypoperfused Infarct Region in Patients with Acute Myocardial Infarction

Introduction: Radiolabelled inhibitors of fibroblast activation protein (FAPI) have been introduced for PET imaging and may identify an early pathway leading to cardiac fibrosis. We describe molecular imaging patterns in patients early after acute myocardial infarction (AMI).

Methods: Cardiac magnetic resonance imaging (CMR), perfusion SPECT, and PET/CT with 68Ga-FAPI-46 (kindly provided by University of Heidelberg) were performed in 12 patients at 6-11 days after reperfused AMI. MRI defined cardiac function and extent of late gadolinium enhancement (LGE). SPECT polar maps were generated and compared to normal database for calculation of perfusion defect size. Regional standardized uptake values (SUV) were determined for FAPI, and quantitative polar maps defined the area of FAPI upregulation significantly elevated above blood pool (+ 2 standard deviations). Segmental analysis of FAPI-signal and LGE transmurality was performed using AHA 17-segment model.

Results: All patients exhibited regional FAP signal enrichment at the site of the infarct relative to blood pool (SUVpeak 5.8±1.6 vs. 2.1±0.5; p<0.001). This signal was not observed in remote myocardium (1.5±0.3; p<0.001) or other peripheral organs (liver, spleen, bone marrow, lungs). The extent of elevated myocardial FAP signal encompassed 56±8% of LV, significantly larger than perfusion defect (24±16%; p<0.001). Mismatch between area of FAP upregulation and perfusion defect varied widely among individual patients (range 13-61%). Neither intensity nor extent of FAP signal correlated with available clinical variables, including measures of myocardial damage. CMR LGE was available in 10/12 patients. Expectedly, FAP signal was present in segments with transmural infarct (<75% transmural LGE; 32/32) and 25-75% non-transmural infarct (57/60). However, even half of segments without significant LGE (39/78) also exhibited significant FAP signal, suggesting fibroblast activation in non-infarcted myocardium. Conclusion: Activation of fibroblasts markedly exceeds the hypoperfused infarct region in patients after AMI and early reperfusion therapy. The extent of this regional upregulation varies significantly among individuals, and underlying mechanisms as well as clinical consequences should be the subject of future studies. Acknowledgements: Supported by the Deutsche Forschungsgemeinschaft (KFO 311, JB, FMB) and the Fondation Leducq (Transatlantic Network ,,Immunofib“,FB)