[68Ga]Ga-FAPI PET to detect early myocardial fibrotic activity in patients with severe aortic stenosis undergoing TAVR
K Hamzaraj, A Lazarevic, R Sciagra, C Nitsche, C Dona, P Binder, T Nakuz, T Abd El-Aal, C Demirel, R Hemetsberger, P E Bartko, E Kretschmer-Chott, C Hengstenberg, M Hacker, R CalabrettaAbstract
Background
Aortic stenosis (AS) causes ongoing pressure overload on the left ventricle and leads to progressive myocardial remodeling. Early diffuse interstitial fibrosis often remains difficult to detect with conventional imaging techniques. Fibroblast activation protein (FAP)–targeted positron emission tomography (PET) can visualize activated fibroblasts and profibrotic activity. However, the usefulness of [⁶⁸Ga]Ga-FAPI PET in evaluating myocardial remodeling in patients with severe AS has not yet been determined.
Methods
This post-hoc analysis involved 18 patients with severe aortic stenosis who underwent [⁶⁸⁻Ga]Ga-FAPI PET/CT scans before transcatheter aortic valve replacement. Myocardial tracer uptake was measured as the tracer retention fraction through dynamic PET imaging, evaluated both globally and segmentally. The study also examined correlations between tracer retention and clinical data, cardiac magnetic resonance parameters, and invasive hemodynamics using correlation and receiver operating characteristic analyses.
Results
All patients showed widespread myocardial [⁶⁸Ga]Ga-FAPI uptake throughout the heart without focal hotspots, indicating diffuse tracer retention. Segmental retention was inversely related to age at both, 60 and 120 minutes post-injection, especially in basal, mid-ventricular, and apical regions at 120 minutes. Uptake in the mid-septal region was also inversely associated with mean transaortic gradients. ROC analysis showed the tracer could effectively distinguish hemodynamic severity in mid-septal segments, with AUC values up to 0.89.
Conclusion
In patients with severe aortic stenosis, [⁶⁸Ga]Ga-FAPI PET/CT demonstrated diffuse left ventricular fibroblast activation, with higher tracer retention in mid-septal segments and in younger individuals. These findings suggest that FAPI-PET may serve as a non-invasive biomarker of early myocardial fibrotic remodeling prior to transcatheter aortic valve replacement.Figure 1.Scatter PlotFigure 2.Tracer uptake patterns