The impact of age on six-minute walk distance, functional class, and right ventricular function in pulmonary arterial hypertension

RATIONALE: Management of pulmonary arterial hypertension (PAH) relies on risk stratification, which incorporates parameters like 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), and brain natriuretic peptide (BNP). However, WHO-FC and 6MWD are inherently subjective and influenced by multiple factors, potentially leading to misclassification of risk.

OBJECTIVES: To determine how does age impact WHO-FC and 6MWD, compared to objective measures of right ventricular function in patients with PAH.

METHODS: We analyzed data from two independent cohorts of patients with PAH: a derivation cohort of 294 patients and a validation cohort of 763 patients. Improvement in RV function at follow up was determined by BNP and echocardiography, and sample was segmented by age (<55 and ≥ 55). Changes in WHO-FC and 6MWD were compared between age groups.

RESULTS: In the derivation cohort, 126 patients (42.8%) showed improvement in RV function. In this group, 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 (p-value = 0.043). In the validation cohort, RV function improved in 323 patients (42.3%). Within this group, the 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 (p = 0.023).

CONCLUSIONS: Our findings suggest that 6MWD may disproportionately underestimate improvement in older patients, limiting their ability to reach low-risk status. As the PAH population evolves, exploring age-adjusted 6MWD cutoffs may be necessary to ensure accurate risk assessment for all patients.