Accuracy of Established Prognostic Staging Systems for Cardiac Transthyretin Amyloidosis in the Tafamidis Era.

Background: Biomarker-based prognostic staging systems, including the National Amyloidosis Centre (NAC) and the Mayo staging systems, are widely-used but have only been validated for treatment-naive patients with cardiac transthyretin amyloidosis (ATTR-CA).

Objectives: The purpose of this study was to assess the accuracy of the NAC and Mayo staging systems in patients with ATTR-CA treated with tafamidis.

Methods: A retrospective observational study following patients with ATTR-CA from initiation of tafamidis (baseline) to time of all-cause death was conducted. Patients were stratified according to the NAC and an adapted Mayo staging system incorporating high-sensitivity cardiac troponin T. Agreement was assessed using weighted Cohen's kappa. The staging systems' ability to identify subgroups with distinct overall survival was assessed using Kaplan-Meier analyses and pairwise log-rank tests.

Results: A total of 251 patients with wild-type ATTR-CA treated with tafamidis were followed for a median of 521 (IQR: 262-842) days. There was substantial agreement (weighted kappa = 0.661; P < 0.001) between the NAC and the adapted Mayo staging system. Significant differences in estimated overall survival were observed across all disease stages of the adapted Mayo staging system (I vs II: P = 0.032; I vs III: P < 0.001; II vs III: P = 0.036). Accordingly, estimated overall survival was significantly lower in NAC III compared to NAC I (P < 0.001) and NAC II (P = 0.015). However, there was no significant difference between NAC I and NAC II (P = 0.340).

Conclusions: Both staging systems identified a distinct group of patients with ATTR-CA at the highest risk of death but only the adapted Mayo staging system could accurately distinguish between low- and intermediate-risk patients in the setting of disease-modifying treatment with tafamidis.