Background: For the time being, tafamidis is the only approved treatment for wild-type transthyretin cardiac amyloidosis. However, benefits on all-cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age. We searched baseline variables able to discriminate patients at risk of death within 18 months.
Methods and results: We randomly divided our prospectively maintained database in 2 cohorts, a testing (two thirds) and a validating (one third) set, respectively. We used the Eastern Cooperative Oncology Group-Performance Status as a simple scoring of frailty. We analyzed the clinical, laboratory and instrumental features of 691 consecutive wild-type transthyretin cardiac amyloidosis patients diagnosed between 2006 and 2021. Median follow-up was 43 months, and 367 patients (53%) died. Eighteen-month death was predicted by NT-proBNP (N-terminal pro-B-type natriuretic peptide; cutoff 4200 ng/L), cardiac troponin I (cutoff 92 ng/L), and age (cutoff 80 years). At multivariable analysis, Eastern Cooperative Oncology Group-Performance Status >1 along with the selected variables were independent prognostic determinants and outperformed New York Heart Association functional class. The combination of these variables identified standard- and high-risk patients (all variables above the cutoffs) with a median survival of 57 and 17 months, respectively (P<0.001). This was confirmed in the validation set.
Conclusions: A simple scoring system including age, cardiac biomarkers, and Eastern Cooperative Oncology Group-Performance Status identifies subjects with cardiac wild-type transthyretin cardiac amyloidosis at high risk of early death.
Keywords: amyloidosis; biomarkers; prognosis; staging.