Fibroblast activation protein imaging in reperfused ST-elevation myocardial infarction: comparison with cardiac magnetic resonance imaging.

Boqia Xie,Bi-Xi Chen,Xiaojuan Guo,Shihua Zhao,Cuncun Hua,Lina Li,Xiao-Ying Xi,Mulei Chen,Min-Fu Yang,Pixiong Su,Jiaxin Wang

doi:10.1007/s00259-021-05674-9

Abstract

The aim of this study was to explore the correlation of 18F-labeled fibroblast activation protein inhibitor (FAPI) and cardiovascular magnetic resonance (CMR) parameters in ST-elevation myocardial infarction (STEMI) patients with successful primary percutaneous coronary intervention (PPCI) and to investigate the value of FAPI imaging in predicting cardiac functional recovery, as well as the correlation between FAPI activity and circulating fibroblast activation protein (FAP) and inflammatory biomarkers. Fourteen first-time STEMI patients (11 men, mean age: 62 ± 11years) after PPCI and 14 gender-matched healthy volunteers (10 men, mean age: 50 ± 14years) who had completed FAPI imaging and blood sample collection were prospectively recruited. All patients underwent baseline FAPI imaging (6 ± 2days post-MI) and CMR (8 ± 2days post-MI). Ten patients had follow-up CMR (84 ± 4days post-MI). Myocardial FAPI activity was analyzed for extent (the percentage of FAPI uptake volume over the left ventricular volume, FAPI%), intensity (target-to-background uptake ratio, TBRmax), and amount (FAPI% × TBRmax). Late gadolinium enhancement (LGE), T2-weighted imaging (T2WI), extracellular volume (ECV), microvascular obstruction (MVO), and cardiac function from CMR imaging were analyzed. Blood samples obtained on the day of FAPI imaging were used to assess circulating FAP, TGF-β1, TNF-α, IL-6, and hsCRP in STEMI patients and controls. Localized but inhomogeneous FAPI uptake was observed in STEMI patients, which was larger than the edematous and infarcted myocardium, whereas no uptake was detected in controls. The MVO area showed lower FAPI uptake compared with the surrounding myocardium. FAPI activity was associated with the myocardial injury biomarkers T2WI, LGE, and ECV at both per-patient and per-segment levels (all p < 0.05), but was not associated with circulating FAP, TGF-β1, TNF-α, IL-6, or hsCRP. Among the CMR parameters, T2WI had the greatest correlation coefficient with both FAPI% and FAPI% × TBRmax. Baseline TBRmax was inversely correlated with the follow-up left ventricular ejection fraction (LVEF) (r = - 0.73, p = 0.02). FAPI imaging detects more involved myocardium than CMR in reperfused STEMI, and is associated with myocardial damage and follow-up LVEF.

Highlights

ST-elevation myocardial infarction (STEMI) triggers an orchestrated and complicated series of events from the initial sterile inflammation to the subsequentfibroblast proliferation and scar formation [1]
The microvascular obstruction (MVO) area showed lower Fibroblast activation protein (FAP) inhibitor (FAPI) uptake compared with the surrounding myocardium
FAPI activity was associated with myocardial injury biomarkers, T2-weighted imaging (T2WI), late gadolinium enhancement (LGE), and extracellular volume (ECV) at both per-patient and per-segment levels

Summary

Introduction

ST-elevation myocardial infarction (STEMI) triggers an orchestrated and complicated series of events from the initial sterile inflammation to the subsequent (myo)fibroblast proliferation and scar formation [1]. Cardiac magnetic resonance (CMR) is a reliable technique for the evaluation of pathological changes of post-MI myocardium using different sequences and modalities: late gadolinium enhancement (LGE) for scar and focal fibrosis [2, 3], T2-weighted imaging (T2WI) and T2 mapping for edema, and extracellular volume (ECV) derived from T1-weighted imaging for the total interstitial space [2] These imaging sequences reflects the increase of extracellular matrix components but not the central cellular effectors of fibrosis–the fibroblasts. Fibroblasts undergo dramatic phenotypic changes following MI, in addition to its traditional role as the main source of extracellular matrix proteins, recent evidence has suggested that activated fibroblasts may regulate inflammation, modulate cardiomyocyte survival, and mediate angiogenesis [4,5,6] These features made fibroblast the crucial cell in both repair and pathogenesis of adverse remodeling. Several pre-clinical and clinical studies reported that MI would induce enhanced FAPI uptake, which extended over the culprit territory and the LGE area [11,12,13,14], these findings suggested FAPI imaging may have unique advantage in detecting the affected myocardium

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Results

Conclusion