Impact of Tafamidis and Optimal Background Treatment on Physical Performance in Patients With Transthyretin Amyloid Cardiomyopathy

Background: In patients with transthyretin amyloid cardiomyopathy, tafamidis was shown to slow the decline in 6-minute walking distance as compared with placebo. We aimed to define the impact of tafamidis and optimal background treatment on functional capacity as determined by cardiopulmonary exercise testing (CPET).

Methods: Seventy-eight consecutive patients were enrolled in the study. They underwent CPET at baseline, and outcome defined as death or heart failure hospitalization was obtained for a time period of up to 30 months. Fifty-four patients completed a follow-up CPET at 9±3 months (range, 4-16 months). Improvement in peak VO₂ at follow-up was defined as ∆peak VO₂≥1.0 mL/(kg·min), stable peak VO₂ was defined as 0≤∆peak VO₂<1.0 mL/(kg·min), and decline in peak VO₂ was defined by ∆peak VO₂<0 mL/(kg·min).

Results: Baseline peak VO₂>14 mL/(kg·min) as well as minute ventilation/carbon dioxide production slope≤34 were associated with a lower risk of death or heart failure hospitalization (P=0.002, P=0.007, respectively). In 54 patients, who received tafamidis and underwent repeat CPET testing, an improvement in physical performance (P=0.002) was observed at follow-up. When comparing pre and post-treatment parameters, 29 patients (54%) showed an increase in percent predicted peak VO₂ (P<0.0001), an improvement of peak VO₂ (P<0.0001), and better physical performance at follow-up (P<0.0001). Patients with stable or improved peak VO₂ had less advanced heart disease at baseline (P=0.046).

Conclusions: Our findings demonstrate that baseline peak VO₂ and baseline minute ventilation/carbon dioxide production slope predict outcomes and an improvement in physical performance as measured by CPET was observed in patients receiving tafamidis, who had less advanced disease at baseline, emphasizing the importance of early diagnosis.