Independent Prognostic Utility of 11C-Pittsburgh Compound B Positron Emission Tomography in Light-Chain Cardiac Amyloidosis Patients

Abstract

11C-Pittsburgh compound B positron emission tomography/computed tomography (11C-PiB PET/CT) visualizes the amount of myocardial amyloid deposit and can be used to prognosticate patients with light-chain (AL) cardiac amyloidosis (CA). However, whether 11C-PiB PET/CT has any independent additional prognostic value beyond the commonly used biomarkers remains unknown. Methods: This was a prospective cohort of 58 consecutive patients with ALCA who underwent 11C-PiB PET/CT. Patients were stratified into 2 groups based on a visual assessment on whether there was a myocardial 11C-PiB uptake or not on PET/CT. The primary endpoint was 1-year overall mortality. The independent prognostic utility of 11C-PiB PET/CT was analyzed using net reclassification improvement and integrated discrimination improvement. Results: Among the 58 patients enrolled, 35 patients had a positive myocardial 11C-PiB uptake on PET/CT. Patients with a positive myocardial 11C-PiB PET uptake had a worse 1-year overall survival rate than those with a negative uptake (81.8% vs. 45.5%, P=0.003 by log-rank test). In the multivariate analysis, a positive myocardial 11C-PiB uptake on PET/CT was an independent predictor of 1-year mortality (adjusted hazard ratio 3.382, 95% confidence interval 1.011–11.316, P=0.048). In each subgroup analysis of patients with troponin I ≥0.1 ng/mL, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥1,800 pg/mL, and the difference between free light chains (dFLC) ≥180 mg/mL, the three commonly used biomarkers and its thresholds for staging in AL amyloidosis, Kaplan-Meier curves showed that the patients with a positive myocardial 11C-PiB uptake on PET/CT had a worse prognosis than those with a negative myocardial 11C-PiB uptake, respectively. Additionally, when the result of 11C-PiB PET/CT was added to these three biomarkers, the performance of 1-year mortality prediction significantly improved by net reclassification improvement (11C-PiB PET/CT added to troponin I, 0.861; NT-proBNP, 0.914; dFLC, 0.987) and by integrated discrimination improvement (0.200, 0.156, and 0.108, respectively). Conclusion: 11C-PiB PET/CT is a strong independent predictor of 1-year overall mortality and provides incremental prognostic benefits beyond the three commonly used biomarkers of AL amyloidosis staging. Considering the recent developments of numerous amyloid-targeting molecular imaging agents, further investigations are warranted on whether PET/CT should be included in the risk stratification for patients with ALCA.