A new study has observed that despite treatment with tafamidis, patients with transthyretin amyloid cardiomyopathy (ATTR-CM) experienced reduced exercise tolerance after 1 year of treatment.

The study, published in the International Heart Journal, also found that the patients’ frailty progression might influence this decrease in exercise tolerance.  

“Data on the clinical significance of cardiopulmonary exercise testing in patients with ATTR-CM are limited,” the authors wrote. “Moreover, no data exist on the effects of tafamidis on patients with ATTR-CM. Therefore, as a preliminary study, we investigated exercise tolerance and changes in cardiopulmonary function in patients with ATTR-CM after one year of tafamidis treatment using cardiopulmonary exercise testing.” 

The research team assessed 12 patients diagnosed with ATTR-CM who underwent cardiopulmonary exercise testing between September 2019 and December 2020. After diagnosis, all 12 began therapy with tafamidis, and of those who underwent cardiopulmonary exercise testing at the 1-year follow-up, 8 were ultimately included in the analysis.   

Read more about ATTR-CM therapies

Baseline and 1-year data on laboratory findings, Clinical Frailty Scale, echocardiography, medications, and complications were collected. Cardiopulmonary exercise testing was conducted at baseline and at the 1-year follow-up using a cycle ergometer with respiratory gas exchange analysis. 

The results showed that at the 1-year follow-up, oxygen uptake (V02) at the anaerobic threshold in the patients with ATTR-CM receiving tafamidis was reduced by approximately 20%. The authors speculate that the characteristic decreased vascular tone in patients with ATTR-CM could have accelerated the decline in anaerobic threshold and peak V02

An additional factor related to the decline in exercise tolerance was the progression of frailty, given that all but 1 patient experienced worsening of frailty at the 1-year follow-up, and the 1 patient with an unchanged frailty score showed an improved V02 at 1 year of tafamidis therapy. The authors hope that these data will assist clinicians with planning cardiac rehabilitation for these patients, with the aim of improving their exercise tolerance.  


Nakaya Y, Ogimoto A, Kitaoka H. Changes in exercise tolerance over time in patients with transthyretin amyloidosis cardiomyopathy treated with tafamidis. Int Heart J. Published online July 14, 2023. doi:10.1536/ihj.23-075