Comprehensive assessment of disease status in ATTRwt-CM: Integrating serum transthyretin levels with clinical parameters using stabilizer therapy
K Yoshie, T Yoshinaga, M Minamisawa, H Motoki, T Aoki, K Nishikawa, S Suzuki, Y Okuma, K Kimura, Y Sekijima, K KuwaharaAbstract
Background
Wild-type transthyretin cardiomyopathy (ATTRwt-CM) arises from age-related destabilization of the transthyretin (TTR) tetramer, leading to amyloid protein deposition in various organs. The introduction of TTR stabilizers has improved patient outcomes. Early increases in circulating TTR levels have been linked to better prognoses, yet optimal TTR concentration and clinical correlations remain unclear.
Purpose
This retrospective study aimed to investigate serum TTR concentration changes following tafamidis therapy initiation in patients with ATTRwt-CM, assessing the relationship between TTR increases and clinical outcomes.
Methods
We performed an analysis of 108 ATTRwt-CM patients treated with tafamidis from September 2019 to 2024, focusing on those with baseline and 1-year serum TTR measurements. Out of these, 62 patients met the inclusion criteria. We calculated median changes in TTR (ΔTTR) and categorized patients accordingly. Additionally, we examined correlations between TTR levels and clinical parameters. Logistic regression was performed, and assessed laboratory parameters influenced by TTR changes at 6 and 12 months through mixed-effects analysis.
Results
The ΔTTR after 1 year had a median increase of 8.5 mg/dL [5.7, 10.4], categorizing patients into two groups. No difference was observed in the baseline TTR concentration (Overall: 22.2 [17.7, 25.4] mg/dL;< 8.5mg/dL group: 22.4 [17.6, 25.4] mg/dL; ≧ 8.5 mg/dL group: 21.1 [17.7, 25.7] mg/dL, p=0.894). The correlation between 1-year change in serum TTR concentration and clinical parameters, included diagnosis age (Pearson r=-0.280; 95% CI, -0.458, -0.280; p=0.027), the baseline NYHA class I (Pearson r=0.275; 95% CI, 0.278, 5.429; p=0.030), prevalence of carpal tunnel syndrome (Pearson r=0.386; 95% CI, 1.286, 5.439; p=0.002), the baseline AF (Pearson r=-0.273; 95% CI, -4.902, -0.227; p=0.032), B-type natriuretic peptide (BNP) levels (Spearman r=-0.322; 95% CI, -0.602, -0.085; p=0.012), and estimated glomerular filtration rate (eGFR) (Pearson r=0.280; 95% CI, 0.109, 0.593; p=0.028) were shown. Logistic regression confirmed these associations, highlighting the impact of baseline CTS, BNP, and eGFR on TTR outcomes (CTS; OR 5.210; 95% CI, 1.694, 16.026; p=0.004, BNP baseline per 100 pg/mL increase; OR, 0.643; 95%CI, 0.460, 0.898; p=0.010, eGFR baseline per 10 mL/min/1.73m2increase; OR, 1.552; 95%CI, 1.068, 2.256; p=0.021). Moreover, the ΔTTR≧8.5 mg/dL group showed reduced high sensitivity troponin T levels during 1 year of tafamidis treatment (p=0.025).
Conclusions
The study indicates that serum TTR concentration increases are associated with relatively mild diagnosed cases, indicating the need for early diagnosis and adequate treatment to optimize the effects of TTR stabilizers.