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Subtyping of cardiac amyloidosis by mass spectrometry-based proteomics of endomyocardial biopsies

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TAYLOR & FRANCIS LTD
DOI: 10.1080/13506129.2022.2127088

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Cardiac amyloidosis; endomyocardial biopsies; mass spectrometry; proteomics; subtyping

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A proteomics-based method for subtyping cardiac amyloidosis was introduced in this study, successfully diagnosing and confirming the majority of cases. Liquid chromatography-mass spectrometry was used for analysis, and significantly higher intensities of amyloid signature proteins were observed in affected cases compared to controls.
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 With a diagnostic threshold set to 70% for each of the four most common amyloid proteins affecting the heart (LC kappa, LC lambda, TTR and SAA), 65 of the cases (87%) could be diagnosed, and of these, 61 cases (94%) were in concordance with the original diagnoses. The specimens were also analysed for the summed intensities of the amyloid signature proteins (ApoE, ApoA-IV and SAP). The intensities were significantly higher (p < 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.

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