Imaging of active bioprosthetic valve degeneration using 68GA-FAPI-04 PET/CT: a pilot study of pathophysiological mechanisms and diagnostic value

Structural valve deterioration (SVD) remains the major limitation of bioprosthetic heart valves (BHV). Current imaging modalities (Echocardiography, CT) detect SVD at late stages of irreversible damage. This study aimed to evaluate the potential of 68Ga-FAPI-04 PET/CT, a marker of fibroblast activation, for the early visualization of active BHV remodeling and to assess its correlation with hemodynamic dysfunction. We performed a cross-sectional analysis of 30 patients with implanted aortic BHVs. All patients underwent transthoracic echocardiography and 68Ga-FAPI-04 PET/CT. Tracer uptake was quantified using the Differential Uptake Ratio (DUR). Statistical analysis included Spearman’s rank correlation, partial correlation to adjust for confounders, bootstrap analysis (5,000 resamples) for verification, and ROC analysis to determine diagnostic accuracy. DUR demonstrated a statistically significant positive correlation with peak transprosthetic pressure gradient (rs = 0.404, p = 0.027). Notably, an inverse correlation was observed between DUR and Left Ventricular Ejection Fraction (rs =–0.411, p = 0.024). Partial correlation analysis confirmed that the association between DUR and prosthetic gradients remained significant (rpartial = 0.385, p = 0.036) even after adjusting for LVEF, indicating that tracer uptake reflects intrinsic valve pathology rather than systemic heart failure. The intensity of FAP-targeted signal did not correlate with patient age or time since implantation (p >0.05). Specificity analysis showed no association between DUR and comorbidities (diabetes, renal failure) or gender. ROC analysis yielded an AUC of 0.682 (95 % CI: 0.478–0.887) for detecting severe dysfunction, with an optimal cut-off value of DUR > 2.35. The method visualizes active fibroblast-mediated remodeling in bioprosthetic valves, which correlates with hemodynamic deterioration but occurs independently of chronologic valve age and provides a specific molecular signal of SVD that is distinct from systemic factors or cardiac performance artifacts.