A new staging system for hereditary transthyretin amyloidosis in the era of specific amyloidosis therapies.

Objectives: Currently, there are two prognosis staging systems validated for transthyretin amyloidosis (ATTR). We sought to develop a new staging system dedicated to hereditary transthyretin amyloidosis (ATTRv) patients on specific treatments.

Methods and results: A total of 258 patients diagnosed with ATTRv from two cardiac amyloidosis reference centres in France and Romania were stratified into three disease stages based on NT-proBNP, estimated glomerular filtration rate (eGFR) and global longitudinal strain (GLS). A staging system was created using the following criteria: GLS ≥ -11%, NT-proBNP ≥ 2000 ng/L and eGFR ≤ 65 mL/min. Stage I was defined as the presence of none of the criteria. Stage III was defined as GLS ≥ -11% and either one or both NT-proBNP and eGFR criteria, while the remaining patients were defined as Stage II. Stage I patients had a 98.5% (95% CI 94.8-100) 5-year survival rate, Stage II patients 75.1% (95% CI 64.8-87.1) and Stage III patients a 29.4% (95% CI 18.6-46.5) 5-year survival rate (Stage I vs. Stage II, P = 0.001; Stage II vs. Stage III, P < 0.001). After age is adjusted for, compared to Stage I, the hazard ratio (HR) for death was 9.9 (95% CI 1.28-76.27, P = 0.02) for Stage II and 39.75 (95% CI 5.28-299.54, P < 0.001) for Stage III patients. HRs and statistical significance were maintained across different ATTR genotypes. The staging system was validated in a cohort of 138 patients.

Conclusions: We propose a novel staging system for ATTRv patients on specific treatment, based on two biological markers and one echocardiographic parameter, common in clinical practice.