Impact of serum transthyretin levels during disease-modifying therapy with tafamidis on cardiac parameters and long-term outcomes in patients with transthyretin amyloid cardiomyopathy
Y Kubota, H Kondo, S Saito, K Yonezu, N TakahashiAbstract
Background
The ATTRIBUTE-CM trial, which evaluated the efficacy of the transthyretin (TTR) tetramer stabilizer acoramidis, demonstrated that baseline serum transthyretin (sTTR) levels and early increases in sTTR predict long-term prognosis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). These findings have highlighted the clinical importance of TTR monitoring during disease-modifying therapy.
Purpose
We aimed to investigate, in a real-world setting, whether baseline sTTR levels and the change in sTTR at 1 year after tafamidis initiation (ΔTTR) are associated with cardiac parameters and cardiovascular outcomes in patients with ATTR-CM treated with tafamidis.
Methods
In this prospective multicenter study, we evaluated 259 patients with wild-type ATTR-CM treated with tafamidis who were enrolled in the Oita ATTR-CM cohort between January 2016 and February 2026. The median follow-up duration after tafamidis initiation was 21.5 months.ΔTTR was defined as the difference between sTTR levels at 1 year after tafamidis initiation and baseline values. Baseline sTTR levels and ΔTTR were dichotomized according to their respective median values. Cardiac-related parameters and long-term outcomes, including all-cause death, cardiovascular death, hospitalization for heart failure (HHF), and new-onset atrial fibrillation (NOAF), were compared between patients below and those at or above the median values.
Results
After 1 year of tafamidis treatment, circulating sTTR levels significantly increased (22.2 ± 5.4 vs. 32.2 ± 6.3 mg/dL, P < 0.0001). The median baseline sTTR level was 21.8 mg/dL, and the median ΔTTR was 10.3 mg/dL. Patients in the low baseline sTTR group (<21.8 mg/dL) had significantly higher baseline NT-proBNP and troponin T levels compared with those in the high sTTR group (P < 0.0001 and P = 0.0038, respectively). Baseline sTTR levels were inversely correlated with NT-proBNP levels (R = −0.40). At 1 year, patients in the low ΔTTR group (<10.3 mg/dL) exhibited significantly greater increases in NT-proBNP (P = 0.0014), whereas no significant difference was observed in changes in troponin T levels (P = 0.1565) compared with the high ΔTTR group. The prevalence of persistent atrial fibrillation was significantly higher in the low baseline sTTR group (35.4% vs. 20.4%, P = 0.0182). Low baseline sTTR and low ΔTTR were associated with a higher incidence of new HHF during tafamidis therapy (Figure 1 and Figure 2). Furthermore, low baseline sTTR was associated with an increased risk of NOAF (Figure 1).
Conclusion
Baseline sTTR levels and ΔTTR during tafamidis therapy may serve as promising prognostic biomarkers in patients with ATTR-CM. Serial TTR monitoring may provide clinically meaningful information for evaluating disease progression and therapeutic response during tafamidis treatment.sTTRdelta TTR