Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease characterized by amyloid fibril deposition in the myocardium, leading to an infiltrative cardiomyopathy with a hypertrophic phenotype (1). The condition arises from the destabilization of the transthyretin (TTR) tetramer, resulting in amyloid accumulation within tissues (2). Tafamidis is an approved disease-modifying therapy for ATTR-CM and currently the most widely used treatment. It acts as a TTR tetramer stabilizer and has been shown to increase serum TTR levels (3); however, its correlation with treatment efficacy and prognosis remains unclear. Methods This prospective single-center study aimed to assess the impact of tafamidis on serum TTR levels and their clinical implications. From January 2022 to January 2023, we consecutively enrolled 107 patients diagnosed with ATTR-CM (84 males, 23 females; mean age 79.55 ± 8.47 years) and followed them for 28 ± 3 months. Serum TTR levels were measured at baseline and at six months post-treatment. The six-month time point was chosen based on previous tafamidis approval studies, which demonstrated that TTR levels experience the most significant increase within the first month after drug administration and then tend to remain stable over time (3). Associations between TTR levels and clinical/functional parameters were analyzed using Pearson’s or Spearman’s correlation coefficients. Results In the 107 ATTR-CM patients analyzed, tafamidis therapy significantly increased serum TTR levels at six months (20.63 ± 8.82 mg/dL vs. 28.05 ± 6.41 mg/dL, +49.56%, p = 0.0061) (fig 1). Lower baseline TTR levels were independently associated with 18-month all-cause mortality (r = -0.354, p = 0.0158), with each 1 mg/dL decrease increasing mortality risk by 15.2% (p = 0.0407). Baseline TTR levels were also negatively correlated with NT-proBNP (ρ = -0.349, p = 0.037). Six months post-treatment, serum TTR levels positively correlated with 6-minute walk test (6MWT) performance (r = 0.52, p = 0.009) and inversely with baseline NT-proBNP (r = -0.498, p = 0.021). The increase in TTR levels was associated with improved 6MWT performance (r = 0.49, p = 0.017) and a greater response in patients with lower baseline Cogan scores (r = -0.640, p = 0.0024) (fig2). Conclusions Serum TTR levels emerge as a promising biomarker for risk stratification in ATTR-CM, with lower baseline levels associated with increased mortality and higher NT-proBNP values. Tafamidis therapy significantly elevates serum TTR levels at six months, particularly in patients with more advanced disease, as indicated by lower Cogan scores and higher baseline NT-proBNP levels. These findings support the integration of serum TTR monitoring into risk stratification and therapeutic assessment in ATTR-CM patients. However, further studies are needed to validate these results to determine whether TTR monitoring can guide therapeutic decision-making in clinical practice.Figure 1. Figure 2.
Costantino et al. (Sat,) studied this question.