Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study

Anna K. Barton; Neil J. Craig; Krithika Loganath; Shruti Joshi; Vasiliki Tsampasian; Menaka Mahendran; Joel Lenell; Evangelos Tzolos; Trisha Singh; Beth Whittington; Jennifer Nash; Michelle C. Williams; Edwin J. R. van Beek; Mark G. MacAskill; Bronwyn Berkeley; Stefan Vezaides; Mairi Brittan; Andrew H. Baker; Stephanie Sellers; Alison Fletcher; Tim Clark; Clint Waight; Riemer H. J. A. Slart; Daniel Berman; Damini Dey; Piotr Slomka; David E. Newby; Marc R. Dweck

doi:10.1016/j.jacc.2024.10.103

Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study

Anna K. Barton
, Neil J. Craig
, Krithika Loganath
, Shruti Joshi
, Vasiliki Tsampasian
, Menaka Mahendran
, Joel Lenell
, Evangelos Tzolos
, Trisha Singh
, Beth Whittington
, Jennifer Nash
, Michelle C. Williams
, Edwin J. R. van Beek
, Mark G. MacAskill
, Bronwyn Berkeley
, Stefan Vezaides
, Mairi Brittan
, Andrew H. Baker
, Stephanie Sellers
, Alison Fletcher

Tim Clark, Clint Waight, Riemer H. J. A. Slart, Daniel Berman, Damini Dey, Piotr Slomka, David E. Newby, Marc R. Dweck

Research output: Contribution to journal › Article › peer-review

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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)

Original language	English
Pages (from-to)	578-591
Number of pages	14
Journal	Journal of the American College of Cardiology
Volume	85
Issue number	6
Early online date	8 Jan 2025
DOIs	https://doi.org/10.1016/j.jacc.2024.10.103
Publication status	Published - 18 Feb 2025

Keywords

fibroblast activation protein inhibitor
molecular PET
myocardial Infarction

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Barton, A. K., Craig, N. J., Loganath, K., Joshi, S., Tsampasian, V., Mahendran, M., Lenell, J., Tzolos, E., Singh, T., Whittington, B., Nash, J., Williams, M. C., van Beek, E. J. R., MacAskill, M. G., Berkeley, B., Vezaides, S., Brittan, M., Baker, A. H., Sellers, S., ... Dweck, M. R. (2025). Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study. Journal of the American College of Cardiology, 85(6), 578-591. https://doi.org/10.1016/j.jacc.2024.10.103

@article{accf96d798554bfca4f0d437717e4871,

title = "Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study",

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{\textendash}The FAPI Fibrosis Study; NCT05356923)",

keywords = "fibroblast activation protein inhibitor, molecular PET, myocardial Infarction",

author = "Barton, \{Anna K.\} and Craig, \{Neil J.\} and Krithika Loganath and Shruti Joshi and Vasiliki Tsampasian and Menaka Mahendran and Joel Lenell and Evangelos Tzolos and Trisha Singh and Beth Whittington and Jennifer Nash and Williams, \{Michelle C.\} and \{van Beek\}, \{Edwin J. R.\} and MacAskill, \{Mark G.\} and Bronwyn Berkeley and Stefan Vezaides and Mairi Brittan and Baker, \{Andrew H.\} and Stephanie Sellers and Alison Fletcher and Tim Clark and Clint Waight and Slart, \{Riemer H. J. A.\} and Daniel Berman and Damini Dey and Piotr Slomka and Newby, \{David E.\} and Dweck, \{Marc R.\}",

year = "2025",

month = feb,

day = "18",

doi = "10.1016/j.jacc.2024.10.103",

language = "English",

volume = "85",

pages = "578--591",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "6",

}

Barton, AK, Craig, NJ, Loganath, K, Joshi, S, Tsampasian, V, Mahendran, M, Lenell, J, Tzolos, E, Singh, T, Whittington, B, Nash, J, Williams, MC, van Beek, EJR, MacAskill, MG, Berkeley, B, Vezaides, S, Brittan, M, Baker, AH, Sellers, S, Fletcher, A, Clark, T, Waight, C, Slart, RHJA, Berman, D, Dey, D, Slomka, P, Newby, DE & Dweck, MR 2025, 'Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study', Journal of the American College of Cardiology, vol. 85, no. 6, pp. 578-591. https://doi.org/10.1016/j.jacc.2024.10.103

TY - JOUR

T1 - Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study

AU - Barton, Anna K.

AU - Craig, Neil J.

AU - Loganath, Krithika

AU - Joshi, Shruti

AU - Tsampasian, Vasiliki

AU - Mahendran, Menaka

AU - Lenell, Joel

AU - Tzolos, Evangelos

AU - Singh, Trisha

AU - Whittington, Beth

AU - Nash, Jennifer

AU - Williams, Michelle C.

AU - van Beek, Edwin J. R.

AU - MacAskill, Mark G.

AU - Berkeley, Bronwyn

AU - Vezaides, Stefan

AU - Brittan, Mairi

AU - Baker, Andrew H.

AU - Sellers, Stephanie

AU - Fletcher, Alison

AU - Clark, Tim

AU - Waight, Clint

AU - Slart, Riemer H. J. A.

AU - Berman, Daniel

AU - Dey, Damini

AU - Slomka, Piotr

AU - Newby, David E.

AU - Dweck, Marc R.

PY - 2025/2/18

Y1 - 2025/2/18

N2 - 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)

AB - 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)

KW - fibroblast activation protein inhibitor

KW - molecular PET

KW - myocardial Infarction

UR - https://www.scopus.com/pages/publications/85216524755

U2 - 10.1016/j.jacc.2024.10.103

DO - 10.1016/j.jacc.2024.10.103

M3 - Article

SN - 0735-1097

VL - 85

SP - 578

EP - 591

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 6

ER -

Myocardial fibroblast activation after acute myocardial infarction: A positron emission tomography and magnetic resonance study

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Keywords

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