Background: Proper identification of cardiac amyloid type is essential for patient management, and has historically relied upon immunohistochemical- or immunofluorescence-based methods, often correlated with serum and urine protein electrophoresis (SPEP and UPEP) with immunofixation electrophoresis (IFE), and/or free light chain immunoassay (FLC). The recent implementation of mass spectrometry-based proteomic analysis for clinical amyloid typing allows us to determine the validity of these tests to predict amyloid type. Validity of SPEP/UPEP/IFE and FLC assays in cardiac amyloid prediction was examined. Methods: Retrospective analysis of two tertiary care populations (n=143, 2001-2010), of cardiac biopsy-proven amyloidosis, was performed. Results: Amyloid of transthyretin (ATTR) type was found in 81 (57%) of 143 patients and immunoglobulin light chain amyloid was found in the remaining 62 (43%). SPEP/UPEP/IFE detected a monoclonal gammopathy in 76 individuals, 56 with AL and 20 with ATTR amyloid and was overall a poor predictor of AL amyloid in this patient population: specificity (75%; 95% CI, 65-83%) and positive predictive value (PPV 74%; 95% CI, 63-82%). The FLC assay detected an abnormal kappa/lambda ratio in 61 patients, 53 with AL and 8 with ATTR amyloid and was a better predictor of AL amyloid type in this patient population: specificity (90%, 95% CI, 82-95%) and PPV (87%, 95% CI, 76-93%). Conclusions: ATTR was the predominant amyloid type in this large cohort of endomyocardial biopsies characterized by mass spectrometry. Although FLC performs better than SPEP/UPEP/IFE, the performance of blood and urine studies for monoclonal proteins are not adequate to classify amyloid type. Summary: This large-scale retrospective analysis of cardiac amyloidosis shows that blood and urine monoclonal protein studies are not, by themselves, robust predictors of cardiac amyloid type in patients undergoing endomyocardial biopsy.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Pathology and Forensic Medicine