Assessing functional capacity in patients with ATTR-CM: the role of CPET and 6MWT

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiac disorder leading to heart failure and reduced functional capacity. Assessment of functional capacity in these patients is challenging due to the heterogeneity of clinical presentation. While both the 6-minute walking test (6MWT) and cardio-pulmonary exercise test (CPET) have been used as functional assessments in the wider context of heart failure, their relative utility and prognostic implication remains unclear in ATTR-CM. Aim The aim of the study is to compare the relative utility and prognostic implication of the 6MWT and CPET in patients with ATTR-CM. Methods Data were collected from consecutive patients diagnosed with ATTR-CM at our centre, who underwent both 6MWT and CPET between November 2019 and March 2023. 6MWT results were expressed as percentage of the predicted value adjusted for sex and BMI. CPET derived peak VO2 was expressed as percentage predicted, adjusted for sex and BMI. Each parameter was categorised using established criteria into normal capacity, mildly impaired and moderate to severely impaired. Survival analysis was performed to assess the predictive value of the 6MWT and CPET-derived peak VO2 for mortality. Results The study population comprised 264 patients with ATTR-CM who underwent both 6MWT and CPET. The mean age was 74.2±10.1 years and 90% were men. 66% of patients had the wild genotype (wATTR) and 72% were classified as NAC stage 1. Overall, the degree of functional impairment was concordant between 6MWT and peak VO2 in 95 cases (36%). Among patients with discordant results, the severity of peak VO2 impairment was analysed within each 6MWT performance category (Figure 1). Among patients with normal 6MWT, 38% had mild peak VO2 impairment while 30% had moderate to severe impairment. However, in patients with mild or moderate to severely impaired 6MWT, the majority exhibited some degree of peak VO2 impairment. Survival analysis demonstrated that peak VO2 was a strong predictor of mortality (p 0.001), with significantly worse survival in the moderate-to-severe impairment group (HR 15.7, 95% CI 3.79–65.01, p 0.001). In contrast, 6MWT did not effectively predict survival in ATTR-CM, as neither mild impairment (HR 1.41, 95% CI 0.78–2.54, p = 0.260) nor moderate-to-severe impairment (HR 1.44, 95% CI 0.74–2.78, p = 0.280) were significantly associated with mortality (Figure 2). Conclusion Despite the simplicity and accessibility of the 6MWT, the result only partially correlates with the CPET derived peak VO2 and fails to adequately stratify survival. A notable proportion of patients with a normal 6MWT exhibited significant peak VO2 impairment, potentially under-estimating disease severity. This highlights the limitation of using 6MWT alone for the functional assessment of ATTR-CM. CPET-derived peak VO2 provides a more comprehensive assessment, including ability to effectively stratify prognosis.