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Olivier Clerc

Pronouns

He/Him/His

Job Title

Research Fellow

Academic Rank

Research Fellow

Department

Radiology

Authors

Clerc OF, Datar Y, Cuddy SAM, Bianchi G, Canseco Neri J, Taylor A, Benz DC, Robertson M, Kijewski MF, Jerosch-Herold M, Kwong RY, Ruberg FL, Liao R, Di Carli MF, Falk RH, Dorbala S

Principal Investigator

Sharmila Dorbala

Research Category: Cardiovascular, Diabetes, and Metabolic Disorders

Tags

Cardiomyocyte stretch mediates the relation between left ventricular amyloid burden and adverse outcomes in light chain amyloidosis: A 18F-florbetapir positron emission tomography study

Scientific Abstract

Background: In light chain (AL) amyloidosis, risk stratification is performed using Mayo stage, based on NT-proBNP, troponin, and free light chains.

Purpose: We assessed whether myocardial amyloid quantification with 18F-florbetapir positron emission tomography (PET) independently predicts outcomes and whether cardiomyocyte stretch (NTproBNP) and cardiac injury (troponin) mediate this prediction.

Methods: We performed 18F-florbetapir PET (median dose 9.05 mCi) in participants with new AL amyloidosis. Left ventricular retention index (LVRI) was calculated to adjust for tracer dose. LVRI was categorized as normal (0.12/min; log-rank statistic maximization). Adverse outcomes were death or heart failure hospitalization.

Results: We studied 79 subjects with median age 61 years, 58% men, 76% cardiomyopathy, and median LVRI 0.10/min (IQR 0.06-0.16). After a median follow-up of 16 months, adverse outcomes occurred in 35 subjects (44%). Incidence increased across LVRI levels from 29% to 57% (log-rank p=0.027). In multivariable Cox regression, only Mayo stage was independently predictive (HR 1.87 [95%CI 1.29-2.70], p

Lay Abstract

In patients with light chain (AL) amyloidosis, we researched whether a new tracer dye called 18F-florbetapir for heart imaging using positron emission tomography (PET) is able to predict adverse outcomes, when compared with the usual prediction score (Mayo stage). Patients with newly diagnosed AL amyloidosis were enrolled and underwent 18F-florbetapir PET. We defined categories of 18F-florbetapir in the heart using previous results from controls and statistical analysis. As adverse outcomes, we studied death or hospitalization for cardiac disease. In 79 participants, average age was 61 years, 58% were men, and 76% had heart disease form AL amyloidosis. Adverse events occurred in 35 participants (44%) over an average duration of 16 months. Participants with higher 18F-florbetapir in the heart had clearly more adverse events in our analyses. But when we assessed the ability of 18F-florbetapir PET and Mayo stage to predict adverse events together, only Mayo stage was really predictive. Actually, 18F-florbetapir was good at predicting a marker of heart disease, which was predictive of adverse outcomes, but which is also a component of Mayo stage. Thus, although 18F-florbetapir PET can predict heart disease and adverse outcomes in AL amyloidosis, it does not improve the prediction over the usual Mayo stage.

Clinical Implications

Although LVRI measured from 18F-florbetapir PET can predict adverse outcomes in AL amyloidosis, it does not improve prediction over Mayo stage. This is due to strong mediation by NT-proBNP, a marker of cardiomyocyte stretch, and a component of Mayo stage.