Early decline in six-minute walk distance from the time of diagnosis predicts clinical worsening in pulmonary arterial hypertension.

BACKGROUND The six-minute walk distance (6MWD) is commonly used to assess pulmonary arterial hypertension (PAH). However, the role of 6MWD in predicting outcomes in PAH is controversial. Clinical worsening is being increasingly considered as a clinically meaningful end point in PAH. OBJECTIVES We aimed to investigate whether early longitudinal changes in 6MWD (Δ6MWD) in meters and percent predicted (%pred) from the time of diagnosis predict clinical worsening of PAH. METHODS One hundred patients with group I PAH were retrospectively assessed. 6MWD was calculated using American (%pred US) or Canadian (%pred CAN) reference equations. Δ6MWD at 6 months were recorded. Clinical worsening was defined as either: development of right heart failure, hospital admission for PAH, referral for lung transplantation or initiation of prostanoids after oral therapy failed. Optimal 6-month differences in 6MWD to detect worsening were defined with receiver operating characteristics (ROC) analysis. RESULTS Progressors, i.e. patients with clinical worsening, and nonprogressors showed significant differences in Δ6MWD. The most clinically significant declines in 6MWD at 6 months were ≥35 m, ≥8%pred US and ≥6%pred CAN. ROC and Cox proportional hazard analyses showed equivalent results for 6MWD %pred and meters. Six-month declines in 6MWD predicted worsening with a high specificity (94%) but a low sensitivity (33%). CONCLUSIONS Early declines in 6MWD (within the first 6 months) predict future clinical worsening of PAH with high specificity. Δ6MWD may still be part of a comprehensive assessment of a patient's clinical status. However, given the poor sensitivity, a decline in 6MWD should be used with other clinical tools to make an appropriate assessment of the progression of PAH.