Clinical characteristics, patient selection and clinical outcomes of tafamidis treatment in transthyretin amyloidosis cardiomyopathy
Authors: Takashio S , Morioka M , Fujiyama A , Oike F , Hanatani S , Usuku H , Yamamoto E , Matsushita K , Tsujita K 
Published: October 2022

Abstract

Background
Tafamidis is a stabilizer of transthyretin, specifically designed to decrease or prevent amyloidogenesis, and improves prognosis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, clinical coarse, selection of appropriate patients and monitoring therapeutic effect of tafamidis remained unclear.

Purpose
The aim of this study was to clarify the patients' characteristics, clinical coarse, and clinical outcomes of tafamidis in patients with ATTR-CM and to evaluate prognostic factors and changes in clinical data over time.

Methods
We evaluated consecutive 180 patients with ATTR-CM considering tafamids treatment. A total of 107 patients had tafamidis treatment (tafamidis treatment group) and 65 patients did not treat with tafamidis (treatment naïve group). The remaining 8 patients were preclinical. Clinical data were obtained at the consideration of tafamidis treatment. We divided the following the cut-off values of high-sensitivity cardiac troponin T (hs-cTnT); &gt;0.05 ng/mL, B-type natriuretic peptide (BNP); &gt;250 pg/ml, and estimated glomerular filtration rate (eGFR); &lt;45 mL/min/1.73 m2 and calculated the score by adding 1 point if increased or decreased by more than the cut-off value. We divided patients into a low score group (0–1 point) and high score group (2–3 points).

Results
All of study patients in the tafamidis treatment group were wild-type ATTR-CM. Compared to tafamidis treatment group, tafamidis naïve group were significantly older (75.6±5.3 vs. 82.8±4.6 years; p&lt;0.01), female dominant (8% vs. 28%; p&lt;0.01), increased BNP levels (median 209 vs 306 pg/ml; p&lt;0.01), and lower haemoglobin levels (14.1±1.8 vs. 12.4±1.8 g/dl; p&lt;0.01). Tafamidis treatment group was significantly favourable clinical outcomes competed to treatment naïve group (p&lt;0.05; log rank test). According to multivariate logistic regression analysis, prior heart failure hospitalization (hazard ratio [HR]: 5.93, 95% confidence interval [CI]: 1.25–28.03, p=0.03) and high score group (HR: 1.56, 95% CI: 0.37–7.25; &lt;0.01) were the significant poor prognostic factors in tafamids treatment group. Among tafamidis treatment group, Hs-cTnT levels were significantly decreased after 12 months tafamidis treatment (0.055 [0.037–0.082] vs. 0.044 [0.033–0.077]; p&lt;0.01) instead of no significant differences in BNP and significant decline of eGFR levels. There were no significant changes over time in the echocardiographic parameters after 12 months, and native T1 and extracellular volume fraction obtained by cardiac magnetic resonance in a limited number of patients.

Conclusion
The prognosis of ATTR-CM patients treated with tafamidis was favorable compared to tafamidis naïve group. Patient stratification combined with biomarkers predicted favorable prognosis in patients with tafamidis treatment. Hs-cTnT may be a useful maker for evaluating the therapeutic effect by tafamidis.

Funding Acknowledgement
Type of funding sources: None.