Prognostic Value of Left Ventricular 18F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis

JACC Cardiovasc Imaging. 2024 Aug;17(8):911-922. doi: 10.1016/j.jcmg.2024.05.002. Epub 2024 Jul 10.

Abstract

Background: Positron emission tomography/computed tomography (PET/CT) with 18F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known.

Objectives: The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes.

Methods: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months.

Results: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage.

Conclusions: In this first study to link cardiac 18F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE.

Keywords: (18)F-florbetapir; adverse outcomes; cardiomyopathy; light-chain (AL) amyloidosis; mediation analysis; positron emission tomography (PET).

MeSH terms

  • Aged
  • Aniline Compounds*
  • Biomarkers / blood
  • Cardiomyopathies / diagnostic imaging
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / mortality
  • Ethylene Glycols*
  • Female
  • Heart Failure / diagnostic imaging
  • Heart Failure / metabolism
  • Heart Transplantation / adverse effects
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / metabolism
  • Humans
  • Immunoglobulin Light Chains / metabolism
  • Immunoglobulin Light-chain Amyloidosis* / diagnostic imaging
  • Immunoglobulin Light-chain Amyloidosis* / metabolism
  • Immunoglobulin Light-chain Amyloidosis* / mortality
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain* / blood
  • Peptide Fragments* / blood
  • Peptide Fragments* / metabolism
  • Positron Emission Tomography Computed Tomography*
  • Predictive Value of Tests*
  • Prognosis
  • Radiopharmaceuticals* / administration & dosage
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Ventricular Function, Left

Substances

  • Radiopharmaceuticals
  • florbetapir
  • Ethylene Glycols
  • Aniline Compounds
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Biomarkers
  • Immunoglobulin Light Chains