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

Abstract

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). 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 (SUV_max) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBR_RV) 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. 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 (TBR_RV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBR_RV 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. 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.