Post-treatment analysis of plasma transthyretin concentration as a diagnostic and prognostic biomarker in patients with transthyretin cardiac amyloidosis treated with tafamidis

Abstract Background Transthyretin (TTR) cardiac amyloidosis (ATTR-CA) is an underdiagnosed cause of heart failure, resulting from the deposition of misfolded TTR in the myocardium. We investigated the diagnostic and prognostic value of circulating plasma TTR concentration in ATTR-CA, particularly in patients treated with tafamidis. Methods This retrospective study included 52 patients with ATTR-CA treated with tafamidis from January 2018 to September 2022, alongside 52 age- and sex-matched healthy controls. Receiver operating characteristic curves assessed the diagnostic performance of plasma TTR concentration. Patients were stratified by the baseline TTR concentration into high- (≥ 18 mg/dL) and low- (< 18 mg/dL) TTR groups for comparisons of clinical and echocardiographic characteristics. Correlation analyses assessed relationships between baseline TTR concentration and echocardiography measures. Patients were also grouped by TTR concentration after Tafamidis treatment at Month 1 to compare baseline characteristics and treatment responses. Outcomes included global longitudinal strain (GLS) improvement and a composite endpoint of all-cause death or heart failure hospitalization. Logistic and Cox regression analyses identified predictors of treatment response. Results Plasma TTR concentration demonstrated a good diagnostic performance for ATTR-CA (cut-off: 21.09 mg/dL; AUC = 0.995). Lower baseline TTR concentration was associated with worse cardiac structure and function (all P < 0.05). During a median follow-up of 0.98 (0.62–1.02) years, 13 patients (25%) experienced CVD composite events. Patients with low TTR levels showed a higher incidence of CVD composite events than those with high TTR levels, although the difference did not reach statistical significance (Log-rank P = 0.079). Conclusion Circulating TTR concentration had diagnostic utility in patients with ATTR-CA. Lower TTR concentration reflected more advanced cardiac involvement, and higher TTR concentrations post 1-month treatment was associated with a lower risk of the composite endpoint of all-cause death or heart failure hospitalization.