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Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension

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Abstract

Purpose

The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured.

Results

Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r =  − 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r =  − 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters.

Conclusion

Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

This work was supported by Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (ZYLX202105) and the National Natural Science Foundation of China (81871380 and 82071967).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Beijing Chaoyang Hospital, Capital Medical University, 8th Gongtinanlu Rd, Chaoyang District, Beijing, 100020, China

    Bi-Xi Chen, Xiao-Ying Xi & Min-Fu Yang

  2. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China

    Hai-Qun Xing & Li Huo

  3. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, 100730, China

    Hai-Qun Xing & Li Huo

  4. Department of Respiratory and Critical Care, Beijing Chaoyang Hospital, Capital Medical University, 8th Gongtinanlu Rd, Chaoyang District, Beijing, 100020, China

    Juan-Ni Gong & Yuan-Hua Yang

  5. Beijing Institute of Respiratory Medicine, Beijing, 100020, China

    Juan-Ni Gong & Yuan-Hua Yang

  6. Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China

    Xiao-Juan Guo

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Contributions

Bi-Xi Chen wrote the draft of the manuscript; Bi-Xi Chen and Juan-Ni Gong collected and analysed the clinical data; Hai-Qun Xing and Xiao-Ying Xi analysed the PET/CT data; Bi-Xi Chen and Xiao-Juan Guo analysed the CMR data; Min-Fu Yang, Yuan-Hua Yang, and Li Huo conceived the study and interpreted the results; Min-Fu Yang makes critical revision of the manuscript for important intellectual content. All authors contributed to the article’s revision, agreed to its submission, and had full access to original data.

Corresponding author

Correspondence to Min-Fu Yang.

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All procedures involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Bi-Xi Chen, Hai-Qun Xing, and Juan-Ni Gong contributed equally to this work and are co-first authors.

This article is part of the Topical Collection on Cardiology

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Chen, BX., Xing, HQ., Gong, JN. et al. Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension. Eur J Nucl Med Mol Imaging 49, 1211–1222 (2022). https://doi.org/10.1007/s00259-021-05577-9

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