Early decline in 6MWT distance predicts PAH worsening

Research shows that an early decline in 6-minute walk test (6MWT) distance can predict worsening of disease in patients with pulmonary arterial hypertension (PAH).

Researcher Marco Mura (Western University, London, Ontario, Canada) and co-workers retrospectively assessed 100 patients with World Health Organization group I PAH from the time of diagnosis to an average of 40 months. Patients received PAH-targeted therapies, including endothelin receptor antagonists, phosphodiesterase type-5 inhibitors or a combination of both.

The team identified 28 patients who experienced clinical worsening within 18 months of diagnosis. This was defined by the development of features of right heart failure, admission to hospital for PAH-related respiratory or cardiac causes, initiation of intravenous prostanoids after failing oral therapy or referral for lung transplantation.

These “progressors” had significantly different baseline characteristics to “nonprogressors”, including higher mean pulmonary arterial pressure (57 vs 46 mmHg) and pulmonary vascular resistance (1027 vs 549 dyn/s per cm⁵). The mean 6MWT distance was significantly shorter among progressors at 265 m compared with 346 m in nonprogressors, as was % predicted distance using both US (55 vs 71%) and Canadian (41 vs 52%) reference equations.

And among progressors, a significant decline in 6MWT distance at 6 months was observed.

Univariate analysis showed that, at 6 months, a decline in 6MWT distance of 35 m or more was associated with increased odds of worsening, with a hazard ratio (HR) of 4.86. A 6MWT decline by at least 8% predicted (US) or 6% predicted (Canadian) also correlated with elevated odds of worsening, with HRs of 4.86 and 3.87, respectively.

Using receiver operating curve analysis, the researchers found that each of these three parameters could predict worsening with high specificity (>90%) but low sensitivity (33%).

The researchers also found significant differences in 6MWT baseline values and change in 6MWT distance with regards to transplant-free survival, with both factors significant predictors for mortality.

“Our data show that early declines in [6MWT] can predict future worsening of PAH, including death and the need for [lung transplantation],” the authors write in Respiration. They also say that theirs is the first study to use % predicted values of 6MWT distance.

The authors explain that the use of the 6MWT to predict outcomes in PAH is controversial. They suggest that because patients started on therapy would be expected to see an improved 6MWT, an early decline could identify those with more aggressive disease.

“[D]espite recognized limitations, the regular assessment of [6MWT] still provides valuable information for the clinical management of group I PAH”, they say.

But the authors add: “Outcomes can be predicted more accurately when the [6MWT] is used in conjunction with a panel of other parameters.”

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