Time-robust myocardial [⁶⁸Ga]Ga-FAPI PET biomarker reflects aortic stenosis severity and predicts post-TAVI outcomes

Area of Science:

• Cardiovascular Imaging
• Nuclear Medicine
• Fibrosis Biomarkers

Background:

• Aortic stenosis (AS) causes myocardial remodeling and fibroblast activation, but lacks reliable biomarkers for fibrogenesis and post-TAVI recovery prediction.
• Fibroblast activation protein (FAP)-targeted PET imaging offers noninvasive visualization of activated fibroblasts in vivo.
• This study evaluates a novel, time-robust, blood-pool-normalized myocardial [⁶⁸Ga]Ga-FAPI PET imaging biomarker for AS assessment.

Purpose of the Study:

• To assess a time-robust, blood-pool-normalized myocardial [⁶⁸Ga]Ga-FAPI PET imaging biomarker in patients with severe symptomatic AS.
• To determine if this biomarker reflects AS burden and predicts outcomes following transcatheter aortic valve implantation (TAVI).
• To correlate the biomarker with established clinical markers like NT-proBNP and LVEF.

Main Methods:

• Nineteen patients with severe symptomatic AS underwent [⁶⁸Ga]Ga-FAPI-04 PET/CT scans at 60, 70, and 120 minutes.
• A semi-automatic pipeline segmented the left ventricular (LV) myocardium to delineate regions of elevated fibroblast activity (EFM).
• Myocardial and blood-pool SUV_mean were quantified, alongside a normalized myocardium-to-blood index, TBR(EFM), and correlated with NT-proBNP and LVEF.

Main Results:

• The TBR(EFM) remained stable across imaging time points, unlike myocardial SUV_mean which decreased significantly.
• TBR(EFM) showed significant correlations with NT-proBNP at all time points, while myocardial SUV_mean did not.
• Baseline TBR(EFM) was significantly lower in patients who responded to TAVI after one year, predicting better clinical outcomes.

Conclusions:

• Myocardial [⁶⁸Ga]Ga-FAPI TBR(EFM) serves as a time-robust index of active fibroblast signaling in AS, reflecting hemodynamic stress.
• This biomarker effectively stratifies one-year clinical response after TAVI, suggesting a 60-minute acquisition may suffice.
• Further validation in larger, multicenter cohorts is warranted for these hypothesis-generating findings.