Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: A staging system for primary systemic amyloidosis

Background: Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system for AL, making comparisons between studies and treatment centers difficult. Our group previously identified elevated serum cardiac troponin T (cTnT) as the most powerful predictor of overall survival. Others have reported that N-terminal pronatriuretic peptide (NT-proBNP) is a valuable prognostic marker. Objective: To develop a staging system for patients with AL. Methods: 242 patients with newly diagnosed AL seen at the Mayo Clinic between April 1979 and November 2000, who had echocardiograms and stored serum samples at presentation. NT-proBNP measurements were performed on 242 patients in whom cTnT and troponin I (cTnI) had been previously run; overall survival. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT <0.035 µg/L and cTnI <0.1 µg/L). Depending on whether NT-proBNP and troponin levels were both low, both high, or only one high, patients were classified as Stage I, III, or II, respectively. Results: Using the cTnT/NT-proBNP model 33, 30, and 37% were Stages I, II, and III with median survivals of 26.4, 10.5, and 3.5 months, respectively. The alternate cTnI/NT-proBNP model predicted median survivals of 27.2, 11.1, and 4.1 months, respectively. Conclusions: Stratification of AL patients into 3 stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes. Supported in part by CA 62242(R.A.K), CA 91561(A.D) from the National Cancer Institute, and the Robert A. Kyle Hematology Malignancies Fund, Mayo Foundation.