Cardiopulmonary Exercise Testing in Evaluating ATTR Amyloidosis

Quick Takes

  • Peak oxygen consumption was reduced to a greater extent in patients with ATTR cardiomyopathy compared to ATTR polyneuropathy and correlated with amyloid burden on cardiac MRI.
  • Chronotropic incompetence and ventilatory inefficiency were noted across all ATTR phenotypes.
  • Peak oxygen consumption and systolic blood pressure were the only predictors of survival in a multivariable model in ATTR amyloidosis.

Study Questions:

What are the functional phenotypes in patients with transthyretin (ATTR) amyloidosis, how is it associated with amyloid burden, and is there an association between functional status and prognosis?


This study used a prospective cohort of patients with confirmed ATTR in the United Kingdom from 2019–2022. All patients who underwent cardiopulmonary exercise testing (CPET) were included. ATTR was classified as causing cardiomyopathy alone (ATTR-CM), polyneuropathy alone (ATTR-PN), or a mixed phenotype (ATTR-mixed) causing both.


A total of 506 ATTR amyloidosis patients were included with a mean age of 73 years; 90% were male and 66% of patients had wild type ATTR. In patients with ATTR cardiomyopathy, mean peak oxygen consumption (peak VO2) was 14.5 mL/kg/min with a percent predicted peak VO2 of 68.5%. This was lower compared to patients with ATTR polyneuropathy. Peak heart rate and chronotropic index were abnormal in all subgroups of ATTR. Ventilatory inefficiency (VE/VCO2) was significantly higher for ATTR-CM compared to the other two subtypes. Degree of reduction in peak predicted VO2 was proportional to amyloid burden on cardiac magnetic resonance imaging (MRI). Heart rate reserve and ventilatory efficiency did not correlate with amyloid burden on cardiac MRI. Survival correlated with peak VO2 and systolic blood pressure (SBP) after multivariable adjustment.


In a cohort study of ATTR patients, impaired functional capacity was widely prevalent in all phenotypes and worse in patients with ATTR-CM. Peak VO2 and SBP independently predicted prognosis.


This is among the largest cohort studies of ATTR patients. Characteristics of CPET abnormalities varied across ATTR phenotypes. While expectedly, patients with ATTR-CM had poor functional status on CPET, abnormalities were also noted for patients with ATTR-PN including chronotropic incompetence likely due to autonomic dysfunction. Furthermore, peak VO2 correlated with amyloid burden, but other parameters including chronotropic incompetence and ventilatory inefficiency did not. This suggests that other noncardiac mechanisms may be involved, such as pulmonary involvement. Finally, peak VO2 on CPET and SBP both were the only variables that predicted prognosis in ATTR in a multivariable model. This highlights how CPET can offer a comprehensive evaluation in ATTR amyloidosis.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging

Keywords: Cardiac Amyloidosis, Exercise Test

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