Serum transthyretin before and after starting tafamidis as outcome predictors in ATTR cardiomyopathy
V Castiglione, A Aimo, M Franzini, A Castiglione, G Palmieri, V Musetti, A Cipriani, L De Michieli, D Tomasoni, M Merlo, M Metra, G Sinagra, C Passino, M Emdin, G VergaroAbstract
Background
Tafamidis is an approved treatment for transthyretin amyloid cardiomyopathy (ATTR-CM). By stabilizing transthyretin (TTR), it increases serum TTR (sTTR) levels. The prognostic role of sTTR before and after starting tafamidis in real-world ATTR-CM patients remains uncertain.
Purpose
To evaluate whether baseline sTTR and the 30-day change after tafamidis initiation (ΔTTR) predict clinical outcomes.
Methods
We prospectively enrolled consecutive patients with wild-type ATTR-CM starting tafamidis at three Italian centers. sTTR was measured at pre-specified time points (baseline; days 14, 30, 90, 180 and 360). Co-primary endpoints were all-cause mortality and first heart failure (HF) hospitalization. Associations were assessed using receiver-operating characteristic analyses and Cox regression models adjusted for age, sex, NYHA class and National Amyloidosis Centre stage.
Results
Among 169 patients (median age 79 years; 91% male), sTTR increased from 22.6 mg/dL [19.1–25.7] at baseline to 29.7 mg/dL [25.2–33.5] at day 30 (p<0.001), plateauing by day 180. Over a median follow-up of 19 months, 13 patients died and 24 experienced at least one HF hospitalization. Baseline sTTR independently predicted all-cause mortality (HR per 1 mg/dL increase 0.88; 95% CI 0.78–0.98; p=0.026; C-statistic=0.839), with a threshold <18 mg/dL identifying higher-risk patients. ΔTTR was primarily associated with HF hospitalization (HR per 1 mg/dL increase 0.93; 95% CI 0.86–1.00; p=0.050; C-statistic=0.683), with more HF events observed in patients with ΔTTR <7.5 mg/dL. Combined stratification by baseline sTTR and ΔTTR identified three prognostic groups, with the highest event rates in patients with both baseline TTR <18 mg/dL and ΔTTR <7.5 mg/dL, whereas no events occurred within 24 months among those with both values above these thresholds.
Conclusions
In tafamidis-treated wild-type ATTR-CM, baseline sTTR informs mortality risk, whereas early on-treatment ΔTTR is associated with HF hospitalization risk. Their combined assessment allows pragmatic risk stratification in real-world practice and may support personalized clinical monitoring.FigureFor image description, please refer to the figure legend and surrounding text.