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
British Heart Foundation Centre of Research Excellence, the University of Edinburgh, Edinburgh, Scotland, United Kingdom.
British Heart Foundation Centre of Research Excellence, the University of Edinburgh, Edinburgh, Scotland, United Kingdom.
J Am Coll Cardiol. 2025 Feb 18;85(6):578-591. doi: 10.1016/j.jacc.2024.10.103. Epub 2025 Jan 8.
Myocardial fibrosis is a key healing response after myocardial infarction driven by activated fibroblasts. Gallium-68-labeled fibroblast activation protein inhibitor ([Ga]-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 [Ga]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 [Ga]FAPI-46 uptake was quantified by maximum target-to-background ratio (TBR). Burdens of fibroblast activation and scar were assessed by percent myocardial involvement of [Ga]FAPI-46 uptake and late gadolinium enhancement, respectively.
Myocardial [Ga]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 [Ga]FAPI-46 uptake was most intense at 1 and 2 weeks before declining at 4 and 12 weeks (TBR 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 [Ga]FAPI-46 uptake was observed in chronic (7 ± 6 years ago) infarcts at lower intensity than acute infarction (TBR 1.2 ± 0.1 vs 1.7 ± 0.5 vs 4.0 ± 1.1; P < 0.001). Baseline [Ga]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 [Ga]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).
心肌纤维化是心肌梗死后由活化成纤维细胞驱动的关键愈合反应。镓-68标记的成纤维细胞活化蛋白抑制剂（[Ga]-FAPI）是一种新型的正电子发射放射性示踪剂，可与活化的成纤维细胞结合。
本研究旨在调查急性心肌梗死后成纤维细胞活化的强度、分布和时间进程。
共有40例急性心肌梗死患者接受了[Ga]FAPI-46正电子发射断层扫描与心脏磁共振成像联合检查，并与匹配的对照受试者（n = 19）以及慢性（>2年）心肌梗死患者（n = 20）进行比较。通过最大靶本底比（TBR）对[Ga]FAPI-46摄取强度进行定量。分别通过[Ga]FAPI-46摄取的心肌累及百分比和延迟钆增强评估成纤维细胞活化和瘢痕的负担。
在急性梗死和梗死周边区域观察到心肌[Ga]FAPI-多摄取，其范围超过延迟钆增强的范围（负担分别为27.8%±12.4%和15.2%±10.6%；P<0.001）。三分之一的患者还表现出右心室受累。心肌[Ga]FAPI-46摄取在第1周和第2周最为强烈，随后在第4周和第12周下降（TBR分别为4.0±1.1、3.7±1.0、3.1±0.8和2.7±0.7；P<0.001）。与对照受试者相比，在慢性（7±6年前）梗死中观察到[Ga]FAPI-46摄取增加，但强度低于急性梗死（TBR分别为1.2±0.1、1.7±0.5和4.0±1.1；P<0.001）。基线[Ga]FAPI-46负担与1年后较低的左心室射血分数（r = -0.606）、较高的左心室舒张末期容积指数（r = 0.572）和较高的瘢痕负担（r = 0.871）相关（所有P<0.001）。远隔心肌[Ga]FAPI-46摄取增加与左心室扩张和收缩功能障碍相关。
急性心肌梗死后一周内心肌成纤维细胞活化达到峰值，并超出梗死区域。它随时间缓慢下降，持续数年，并与随后的左心室重构相关。（PROFILE-MI-FAPI纤维化研究；NCT05356923）
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