TY - JOUR
T1 - Relationship between monoclonal gammopathy and cardiac amyloid type
AU - Maleszewski, Joseph J.
AU - Murray, David L.
AU - Dispenzieri, Angela
AU - Grogan, Martha
AU - Pereira, Naveen L.
AU - Jenkins, Sarah M.
AU - Judge, Daniel P.
AU - Caturegli, Patrizio
AU - Vrana, Julie A.
AU - Theis, Jason D.
AU - Dogan, Ahmet
AU - Halushka, Marc K.
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
KW - Amyloid
KW - Cardiomyopathy
KW - Diagnosis
UR - http://www.scopus.com/inward/record.url?scp=84877720344&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877720344&partnerID=8YFLogxK
U2 - 10.1016/j.carpath.2012.09.001
DO - 10.1016/j.carpath.2012.09.001
M3 - Article
C2 - 23102805
AN - SCOPUS:84877720344
SN - 1054-8807
VL - 22
SP - 189
EP - 194
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
IS - 3
ER -