6MWD may disproportionately underestimate improvement in older patients with PAH, suggesting that age-adjusted 6MWD cutoffs may be necessary to ensure accurate risk assessment.
Key Findings
Results
In the derivation cohort, patients aged 55 or older with improved RV function showed significantly smaller absolute changes in 6MWD compared to younger patients.
Derivation cohort included 294 patients total; 126 patients (42.8%) showed improvement in RV function.
Absolute change in 6MWD was 25.50 (-13.25, 79.50) meters in those aged <55, compared to 0.00 (-50.00, 45.00) meters in those ≥55 years old.
This difference was statistically significant (p-value = 0.043).
RV function improvement was determined by BNP and echocardiography.
Results
In the validation cohort, patients aged 55 or older with improved RV function also demonstrated significantly smaller absolute changes in 6MWD compared to younger patients.
Validation cohort included 763 patients; 323 patients (42.3%) showed improvement in RV function.
Absolute change in 6MWD was 53.00 m (1.50, 109.81) in patients <55 and 26.00 m (-11.00, 64.00) in those ≥55 years old.
This difference was statistically significant (p = 0.023).
The finding was consistent across both independent cohorts, supporting replication of the age-related difference.
Methods
The study analyzed two independent cohorts of PAH patients segmented by age (<55 and ≥55 years) to compare changes in WHO-FC and 6MWD relative to objective RV function measures.
A derivation cohort of 294 patients and a validation cohort of 763 patients were used.
The age cutoff of 55 years was used to segment the samples.
Changes in WHO-FC and 6MWD were compared between age groups with improvement in RV function determined by BNP and echocardiography.
The study design used two independent cohorts to allow for derivation and validation of findings.
Conclusions
The authors conclude that 6MWD may disproportionately underestimate improvement in older PAH patients, potentially limiting their ability to reach low-risk status.
WHO-FC and 6MWD are described as 'inherently subjective and influenced by multiple factors, potentially leading to misclassification of risk.'
The findings suggest older patients with objectively improved RV function show smaller gains in 6MWD than younger patients.
The authors propose that 'exploring age-adjusted 6MWD cutoffs may be necessary to ensure accurate risk assessment for all patients.'
This concern is framed in the context of an 'evolving PAH population.'
Villasmil Hernandez N, Nunez N, Tonelli A, Heresi G, Farber H, Xu J, et al.. (2026). The impact of age on six-minute walk distance, functional class, and right ventricular function in pulmonary arterial hypertension.. Respiratory medicine. https://doi.org/10.1016/j.rmed.2026.108742