Molecular Stratification of Light-Chain Cardiac Amyloidosis With 18F-Florbetapir and 68Ga-FAPI-04 for Enhanced Prognostic Precision.

BACKGROUND

Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.

OBJECTIVES

This prospective study aimed to delineate the molecular phenotypes of AL-cardiac amyloidosis (CA) by characterizing fibro-amyloid deposition using 18F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI)-04 positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.

METHODS

Patients with confirmed AL-CA underwent echocardiography and 18F-florbetapir and 68Ga-FAPI-04 PET/CT imaging. Cardiac amyloid burden was quantified as 18F-florbetapir cardiac amyloid volume and total cardiac amyloid. Meanwhile, cardiac fibroblast activation protein (FAP) was quantified as 68Ga-FAPI-04 cardiac fibroblast activation protein volume (CFV) and total cardiac fibroblast activation protein (TCF). PET/CT metrics were calculated in correlation to clinical and echocardiographic markers and their association with overall survival (OS) evaluated.

RESULTS

Among the 38 patients enrolled (median age: 58 years; 76.3% male), all patients exhibited amyloid deposition, and 86.8% (33 of 38) patients exhibited cardiac fibroblast activation. Cardiac amyloid burden was correlated with Mayo stage and several echocardiography metrics (P < 0.05). In addition, there was a correlation between CFV and N-terminal pro-B-type natriuretic peptide level (P < 0.05). Thirteen deaths occurred over a median follow-up of 24.8 months. Higher CFV and TCF were associated with shortened OS, particularly in Mayo stage III. In multivariable analysis, higher TCF was a primary determinant for shortened OS.

CONCLUSIONS

The study underscores that higher TCF on 68Ga-FAPI-04 PET/CT imaging might be a correlated factor of worse clinical outcome in newly diagnosed AL-CA, and this metric seems to be a molecular imaging tool complementary to 18F-florbetapir imaging. The combination might offer a holistic understanding of molecular attributes, assisting in clinical decision-making.