Myocardial Fibroblast Activation After Acute Myocardial Infarction

• Published in: Journal of the American College of Cardiology Vol. 85; no. 6; pp. 578 - 591
• Main Authors: Barton, Anna K., Craig, Neil J., Loganath, Krithika, Joshi, Shruti, Tsampasian, Vasiliki, Mahendran, Menaka, Lenell, Joel, Tzolos, Evangelos, Singh, Trisha, Whittington, Beth, Nash, Jennifer, Williams, Michelle C., van Beek, Edwin J.R., MacAskill, Mark G., Berkeley, Bronwyn, Vezaides, Stefan, Brittan, Mairi, Baker, Andrew H., Sellers, Stephanie, Fletcher, Alison, Clark, Tim, Waight, Clint, Slart, Riemer H.J.A., Berman, Daniel, Dey, Damini, Slomka, Piotr, Newby, David E., Dweck, Marc R.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 18.02.2025
• Subjects: Cardiovascular; fibroblast activation protein inhibitor; molecular PET; myocardial Infarction; [68Ga]FAPI-46; myocardial Infarction; FAP; SUV; TBR; fibroblast activation protein inhibitor; molecular PET; MI; PET; 68Gallium-labeled fibroblast activation protein inhibitor; standard uptake value; fibroblast activation protein; target-to-background ratio; positron emission tomography
• ISSN: 0735-1097
• DOI: 10.1016/j.jacc.2024.10.103

Myocardial fibrosis is a key healing response after myocardial infarction driven by activated fibroblasts. Gallium-68-labeled fibroblast activation protein inhibitor ([68Ga]-FAPI) is a novel positron-emitting radiotracer that binds activated fibroblasts. The aim of this study was to investigate the intensity, distribution, and time-course of fibroblast activation after acute myocardial infarction. A total of 40 patients with acute myocardial infarction underwent hybrid [68Ga]FAPI-46 positron emission tomography and cardiac magnetic resonance and were compared with matched control subjects (n = 19) and those with chronic (>2 years) myocardial infarction (n = 20). Intensity of [68Ga]FAPI-46 uptake was quantified by maximum target-to-background ratio (TBRmax). Burdens of fibroblast activation and scar were assessed by percent myocardial involvement of [68Ga]FAPI-46 uptake and late gadolinium enhancement, respectively. Myocardial [68Ga]FAPI-46 uptake was observed in the acute infarct and peri-infarct regions that exceeded the extent of late gadolinium enhancement (burden 27.8% ± 12.4% vs 15.2% ± 10.6%; P < 0.001). One-third of patients also demonstrated right ventricular involvement. Myocardial [68Ga]FAPI-46 uptake was most intense at 1 and 2 weeks before declining at 4 and 12 weeks (TBRmax 4.0 ± 1.1, 3.7 ± 1.0, 3.1 ± 0.8, and 2.7 ± 0.7; P < 0.001). In comparison with control subjects, increased [68Ga]FAPI-46 uptake was observed in chronic (7 ± 6 years ago) infarcts at lower intensity than acute infarction (TBRmax 1.2 ± 0.1 vs 1.7 ± 0.5 vs 4.0 ± 1.1; P < 0.001). Baseline [68Ga]FAPI-46 burden correlated with lower left ventricular ejection fraction (r = −0.606), higher indexed left ventricular end-diastolic volume (r = 0.572), and higher scar burden (r = 0.871) at 1 year (P < 0.001 for all). Increased remote myocardial [68Ga]FAPI-46 uptake was associated with left ventricular dilatation and systolic dysfunction. Myocardial fibroblast activation peaks within a week of acute myocardial infarction and extends beyond the infarct region. It declines slowly with time, persists for years, and is associated with subsequent left ventricular remodeling. (PROFILE-MI–The FAPI Fibrosis Study; NCT05356923) [Display omitted]