Projects per year
Abstract
Background
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.
Objectives
The aim of this study was to investigate the intensity, distribution, and time-course of fibroblast activation after acute myocardial infarction.
Methods
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.
Results
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.
Conclusions
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
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.
Objectives
The aim of this study was to investigate the intensity, distribution, and time-course of fibroblast activation after acute myocardial infarction.
Methods
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.
Results
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.
Conclusions
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
| Original language | English |
|---|---|
| Journal | Journal of the American College of Cardiology |
| Early online date | 8 Jan 2025 |
| DOIs | |
| Publication status | E-pub ahead of print - 8 Jan 2025 |
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Research Excellence (round 4)
Newby, D. (Principal Investigator), Newby, D. (Principal Investigator), Baker, A. (Co-investigator), Mills, N. (Co-investigator) & Reynolds, R. (Co-investigator)
1/10/24 → 30/09/29
Project: Research
-
The Role of Valvular and Myocardial Fibrosis in Patients with Aortic Stenosis
Craig, N. (Principal Investigator)
17/12/23 → 16/12/25
Project: Research
-
Finding a Cure for Aortic Stenosis
Newby, D. (Principal Investigator), Baker, A. (Co-investigator), Henderson, N. (Co-investigator), Mills, N. (Co-investigator), Tavares, A. (Co-investigator) & Williams, M. (Co-investigator)
1/04/23 → 31/03/28
Project: Research
Equipment
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Edinburgh Imaging Facility
Grant, A. (Manager), van Beek, E. (Manager) & Semple, S. (Manager)
Deanery of Clinical SciencesFacility/equipment: Facility