Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.
OBJECTIVE
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 pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL.


METHODS
Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who had echocardiograms and stored serum samples at presentation were eligible for this retrospective review. NT-proBNP measurements were performed on 242 patients in whom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 microg/L, and cTnI < 0.1 microg/L). Depending on whether NT-proBNP and troponin levels were both low, were high for only one level, or were both high, patients were classified as stage I, II, or III, respectively.


RESULTS
Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stages I, II, and III, respectively, 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 three stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes.
Dispenzieri
Angela
A
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
Gertz
Morie A
MA
Kyle
Robert A
RA
Lacy
Martha Q
MQ
Burritt
Mary F
MF
Therneau
Terry M
TM
Greipp
Philip R
PR
Witzig
Thomas E
TE
Lust
John A
JA
Rajkumar
S Vincent
SV
Fonseca
Rafael
R
Zeldenrust
Steven R
SR
McGregor
Christopher G A
CG
Jaffe
Allan S
AS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000145:classification* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011498:Protein Precursors; D016019:Survival Analysis; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood*
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D014336:Troponin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain