Myocardial fibroblast imaging with 68GA-FAPI-46 PET/CT in patients with aortic stenosis and preserved left ventricular ejection fraction undergoing aortic valve replacement

Abstract Introduction Gallium-labeled fibroblast activation protein inhibitor (68GA-FAPI-46) positron emission tomography/computed tomography (PET/CT) is a novel molecular imaging technique that has been shown to detect fibroblast activation in patients with aortic stenosis 1. Purpose The aim of our study was to analyze myocardial fibroblast activity by 68GA-FAPI-46 PET/CT and compare it to established markers of myocardial fibrosis on cardiovascular magnetic resonance (CMR). Our hypothesis was that 68GA-FAPI-46 PET/CT can detect stages of fibrosis development that are related to, but distinct from, replacement fibrosis and diffuse fibrosis on CMR. Methods 11 patients with preserved left ventricular ejection fraction (LV-EF) and aortic stenosis meeting the criteria for valve replacement underwent 68GA-FAPI-46 PET/CT and CMR on a 1.5 T scanner prior to valve replacement. Myocardial FAPI volume was calculated by outlining the myocardium and including all voxels with a FAPI signal above a set threshold of the patient’s blood pool SUVmean + 2 SD, excluding the aortic valve area. CMR was used for global assessment of left ventricular (LV) volumes, mass, LV-EF, stroke volume, global longitudinal strain (GLS), T1 mapping, extracellular volume fraction (ECV) mapping and volume of LGE in the left ventricular myocardium. Short-axis images were manually segmented to obtain the myocardial volume on CMR. To quantify the volume of LGE enhancement a threshold of 5 SD above the signal in remote myocardium was used. Results Baseline characteristics are summarized in table 1. The mean myocardial volume of increased FAPI-signal was 37.5 ml, corresponding to 26.8% of the total myocardial volume calculated from CMR. The range was 0.0 to 133 ml, showing substantial variation between patients in the extent of fibroblast activation prior to valve replacement. The mean myocardial volume of LGE was 4.0 ml, corresponding to 3.0% of the total myocardial volume. The volume of increased FAPI signal was strongly correlated with the volume of LGE in the myocardium (r = 0.89, p 0.001), but the extent of fibroblast activity considerably exceeded the LGE burden (mean volume of 37.5 ml vs. 4.0 ml, p = 0.023). FAPI volume was also significantly correlated to native T1 values (r = 0.64, p = 0.032), LV mass index (r = 0.84, p = ) and GLS (r = -0.88, = p 0.001), but not to ECV (r = 0.2, p = 0.57) and LV-EF (r = -0.56, p = 0.068). Conclusion The extent of activated fibroblasts varies substantially between patients with aortic stenosis and is correlated to several CMR markers of fibrosis as well as LV mass index and GLS. The myocardial volume of elevated FAPI signal is strongly correlated to, but exceeds, the extent of replacement fibrosis on CMR. This finding suggest there is ongoing profibrotic activity without replacement fibrosis in significant parts of the left ventricular myocardium prior to valve replacement in patients with aortic stenosis.Baseline characteristics