Subtyping of cardiac amyloidosis by mass spectrometry-based proteomics of endomyocardial biopsies
Fredrik Noborn, Christer Thomsen, Egor Vorontsov, Emanuele Bobbio, Carina Sihlbom, Jonas A. Nilsson, Christian L. Polte, Entela Bollano, Kristina Vukušić, Joakim Sandstedt, Göran Dellgren, Kristjan Karason, Anders Oldfors, Göran Larson
Abstract
BACKGROUND: Cardiac amyloidosis is a severe condition leading to restrictive cardiomyopathy and heart failure. Mass spectrometry-based methods for cardiac amyloid subtyping have become important diagnostic tools but are currently used only in a few reference laboratories. Such methods include laser-capture microdissection to ensure the specific analysis of amyloid deposits. Here we introduce a direct proteomics-based method for subtyping of cardiac amyloidosis. METHODS: Endomyocardial biopsies were retrospectively analysed from fresh frozen material of 78 patients with cardiac amyloidosis and from 12 biopsies of unused donor heart explants. Cryostat sections were digested with trypsin and analysed with liquid chromatography - mass spectrometry, and data were evaluated by proteomic software. RESULTS: < 0.001) for all assigned cases compared with controls. CONCLUSION: Cardiac amyloidosis can be successfully subtyped without the prior enrichment of amyloid deposits with laser microdissection.