Early Decline in Six-Minute Walk Distance from the Time of Diagnosis Predicts Clinical Worsening in Pulmonary Arterial Hypertension

Abstract

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.

Pulmonary Hypertension in a Large Cohort with Hereditary Hemorrhagic Telangiectasia

“…Pulmonary hypertension (PH) is increasingly recognized as a potential important complication of HHT, as it is associated with poor prognosis and might lead to progressive right-sided heart failure and premature death [8][9][10] .…”

The 6-Min Walk Test in Pulmonary Arterial Hypertension: Only for Bad News?

“…In the present issue of Respiration , Huang et al [1] show that an early decline in the 6-min walk distance predicts clinical worsening in pulmonary arterial hypertension (PAH). The 6-min walk distance was measured at the time of diagnosis and after 6 months of the initiation of PAH-targeted therapies in a population of 100 idiopathic PAH patients.…”

“…The 6-min walk distance was measured at the time of diagnosis and after 6 months of the initiation of PAH-targeted therapies in a population of 100 idiopathic PAH patients. Both the 6-min walk distance at baseline and its decline by more than 35 m after 6 months were predictive of clinical worsening defined by clinical features of right heart failure, admission to hospital for PAH-related respiratory or cardiac causes, initiation of intravenous prostanoids after failing oral therapy, and lung transplantation or death [1]. The fact that the 6-min walk distance predicts survival in pulmonary hypertension is no new finding, but it has been subject to controversy in recent years, though probably wrongly so [2].…”

“…Huang et al [1] show, as Farber et al [14] already did in a recent study derived from the US Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL), that the decrease , not the increase , in the 6-min walk distance is associated with survival. Prognosis under treatment stays poor in PAH with rapid degradation of patients undergoing progression of the disease.…”

“…Huang et al [1] are to be commended for their elegant study which rehabilitates the 6-min walk test as clinically meaningful in the initial evaluation and also follow-up of PAH patients. Like any other clinical test, it has limitations and must be integrated in a clinical context.…”