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

Abstract

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.

Keywords: (18)F-florbetapir; (68)Ga-FAPI-04; PET/CT; amyloid light chain cardiac amyloidosis; prognosis; risk stratification.