Fibroblast activation following myocardial infarction and left ventricular remodelling

Abstract Background Novel molecular positron emission tomography (PET) assessments of fibrosis are now available but have not been compared directly to cardiovascular magnetic resonance (CMR), the current reference standard for myocardial scar assessment. Using 68Gallium-fibroblast activation protein inhibitor (FAPI), a radiotracer that binds to activated fibroblasts, we compared CMR and PET assessments of myocardial scar following ST-elevation myocardial infarction. Methods Hybrid 68Ga-FAPI-46 PET/MR with gadolinium-based contrast agent was performed in 40 patients within 4 weeks of acute ST-elevation myocardial infarction (acute STEMI) with 19 returning at 12 weeks for repeat PET/MR (subacute STEMI). Scar burden (%LGE) was measured on late enhancement short axis CMR images (Circle Cardiovascular Imaging software, Canada). Volume and intensity of global myocardial 68Ga-FAPI uptake was quantified (QPET, Cedars Sinai, Los Angeles) to determine the volume myocardium with tracer uptake (%68Ga-FAPI) and intensity of PET signal (target-to-background ratio, TBRmax) after correcting for right atrial blood-pool activity. Results In acute STEMI, high intensity uptake of 68Ga-FAPI was observed localized to the infarct. The area of fibroblast activation greatly exceeded the area of scar detected by late gadolinium enhancement (LGE) (%68Ga-FAPI 26.6+-15.4% vs 14.5+-11.4%, p0.001). 68Ga-FAPI volume and intensity declined between acute and subacute STEMI (%68Ga-FAPI 26.6+-15.4% vs 12.8+-8.1%, p0.001, TBRmax 3.9+-1.1 vs 2.7+-0.7, p0.001). By week 12, there was no difference between the area of fibroblast activation detected by 68Ga-FAPI uptake and area of scar detected by LGE (%68Ga-FAPI 12.8+-8.1% vs %LGE 10.3+-6.1%, ns). Conclusion Molecular PET assessments of myocardial scar formation provide different but complementary information to structural assessments of myocardial scar. Fibroblast activation following myocardial infarction is a dynamic process that can be non-invasively measured for the first time by 68Ga-FAPI PET.