Abstract
BACKGROUND: Current therapies for light chain (AL) amyloidosis target the plasma cell dyscrasia, but their effect on myocardial amyloid fibril burden remains poorly defined. OBJECTIVES: The authors aimed to assess longitudinal changes in myocardial amyloid burden after plasma cell-directed chemotherapy. METHODS: This prospective study included 81 patients (58 with AL amyloid cardiomyopathy and 23 with AL amyloidosis without cardiomyopathy) with recently diagnosed, biopsy-proven AL amyloidosis, who underwent serial (18)F-florbetapir positron emission tomography/computed tomography and cardiac magnetic resonance (including extracellular volume [ECV]) at baseline, 6 months (n = 52), and/or 12 months (n = 37). Molecular amyloid burden was estimated as (18)F-florbetapir percentage injected dose (%ID), and changes are presented as absolute and relative %ID changes. Cardiac biomarker response was defined as a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) >30% and >300 ng/L when baseline NT-proBNP ≥650 ng/L. All change comparisons were paired within patients. RESULTS: In AL amyloid cardiomyopathy, amyloid burden decreased significantly at 6 and 12 months after therapy initiation (median absolute [relative] change %ID: -0.3% [-13%]; P = 0.002; and -0.3% [15%]; P = 0.003). Changes in %ID correlated moderately with changes in NT-proBNP at 12 months (ρ = 0.531). Of note, %ID decreased significantly among biomarker responders (P < 0.001), whereas there was no change in nonresponders (P = 0.542). In contrast, ECV did not change in biomarker responders (P = 0.193) or nonresponders (P = 0.695). In AL amyloidosis without cardiomyopathy, %ID did not change (P = 0.523), whereas ECV increased (P = 0.011). CONCLUSIONS: Myocardial AL amyloid burden estimated by (18)F-florbetapir %ID decreases in participants undergoing plasma cell therapy and is detectable at 6 months. Molecular amyloid and ECV changes probably reflect distinct aspects of myocardial remodeling in AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]: NCT02641145).