Staging System for Cardiac Transthyretin Amyloidosis

Study Questions:

Can a new prognostic staging system applicable to patients with both wild-type ATTR (ATTRwt) and hereditary variant ATTR (ATTRv) amyloid cardiomyopathy be established and validated?


Using two biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP] and estimated glomerular filtration rate [eGFR]), the investigators stratified 869 patients with cardiac ATTR amyloidosis (553 with ATTRwt and 316 with ATTRv) into three disease stages at baseline. They defined stage I as NT-proBNP ≤3000 ng/L and eGFR ≥45 ml/min. Stage III was defined as NT-proBNP >3000 ng/L and eGFR <45 ml/min, and the remainder were Stage II. They validated the staging system in a cohort of 318 patients with cardiac ATTR amyloidosis from France. They defined the mortality endpoint as time to death from baseline for all deceased patients and time to censor date, May 18, 2017, from baseline among the remainder. Two-sided tests were used for all analyses, and p < 0.05 was considered significant.


Seven hundred and thirty-five (85%) patients were male, and median age at baseline was 77 years. The majority of the patients with ATTRwt and non-V122I-associated ATTRv amyloidosis were Caucasian, and nearly all of those with V122I-associated ATTR amyloidosis were of African ancestry. Median follow-up in the whole test cohort using a reversed survival model was 32.2 months (range 0.1-116 months), and median survival from baseline by the Kaplan-Meier analysis was 57 months (95% confidence interval [CI], 49.1-60.4 months). A total of 281 patients died during follow-up. The study investigators found that median survival among 393 (45%) Stage I patients was 69.2 months, 334 (38%) Stage II patients was 46.7 months, and 142 (16%) Stage III patients was 24.1 months (log rank test, p < 0.0001). After adjusting for age, compared with Stage I, the hazard ratio (HR) for death for Stage II was 2.05 (confidence interval [CI], 1.54–2.72; p < 0.001) and for Stage III was 3.80 (CI, 2.73-5.28; p < 0.001). HRs and statistical significance were little altered by TTR genotype.


The authors concluded that a simple, universally applicable staging system stratifies patients with both ATTRwt and ATTRv amyloid cardiomyopathy into prognostic categories and should be of value in the design of forthcoming therapeutic trials of amyloidosis.


This is an important study because it demonstrates that by utilizing two universally available markers, ATTR amyloid patients can be risk stratified. It would be interesting to see whether novel therapies are effective in all risk categories or only in one or two of the categories.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Amyloid, Amyloid Neuropathies, Familial, Biological Markers, Cardiomyopathies, Genotype, Geriatrics, Glomerular Filtration Rate, Heart Failure, Natriuretic Peptide, Brain, Peptide Fragments, Prealbumin

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