Background: The clinical significance of circulating serum transthyretin (sTTR) levels in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains incompletely defined, particularly in patients treated with tafamidis in real-world clinical practice. We aimed to evaluate the relationship between sTTR levels, disease severity, longitudinal changes during tafamidis therapy, and clinical outcomes. Methods: We conducted a retrospective, exploratory study based on prospectively collected data, including consecutive patients with ATTR-CM initiating tafamidis therapy at a tertiary referral center. sTTR levels were measured at baseline and after six months. Associations between sTTR, markers of disease severity, functional status, and outcomes were assessed. Cox regression, receiver operating characteristic (ROC) analysis, and Kaplan-Meier survival analysis were performed. Results: A total of 107 patients (mean age 79.6 ± 8.5 years, 84 males) were enrolled and followed for 24 ± 6 months. Tafamidis therapy was associated with a significant increase in sTTR levels at six months (from 24.7 ± 8.8 to 36.9 ± 6.4 mg/dL; p = 0.006). Baseline sTTR levels were inversely correlated with NT-proBNP (ρ = -0.349; p = 0.037) and were significantly lower in non-survivors compared with survivors (14.2 ± 3.1 vs. 23.5 ± 5.2 mg/dL; p < 0.001). Each 1 mg/dL increase in baseline sTTR was associated with a 13% reduction in all-cause mortality risk (HR 0.87, 95% CI 0.83-0.91; p < 0.001). A baseline sTTR cut-off of 20 mg/dL was associated with an increased risk of mortality (AUC 0.85), and patients with sTTR < 20 mg/dL showed significantly reduced survival. Higher on-treatment sTTR levels at six months were associated with better functional capacity (r = 0.52; p = 0.009) and, when >26 mg/dL, with lower observed mortality during follow-up. Conclusions: In a real-world cohort of patients with ATTR-CM treated with tafamidis, serum transthyretin levels were associated with disease severity, functional status, and survival. Baseline and early on-treatment sTTR measurements may represent useful biomarkers for risk stratification and treatment monitoring.
Keywords: biomarkers; prognosis; serum transthyretin; tafamidis; transthyretin amyloid cardiomyopathy.