Six-minute walk test reflects neurohormonal activation and right ventricular function in systemic sclerosis patients

Heart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths. The six-minute walk test (6MWT) is a simple and reproducible test commonly used to evaluate exercise capacity. We tried to assess a potential relationship between exercise capacity assessed by 6MWT, echocardiographic parameters of right ventricular function and serum levels of endothelin-1 and NTproBNP.

We prospectively studied 111 consecutive patients (101F, 10M, age 54.2±13.8 years) with diagnosed SSc (mean disease duration 9±12.4 years) and a group of 21 age-matched subjects (18F, 3M, age 49.3±10.5 years). In addition to routine evaluation, 6MWT and transthoracic echocardiography (Phillips iE 33) were performed. We also measured serum endothelin-1 (Human Endothelin-1 immunoassay R & D Systems) and NT-proBNP levels (Elecsys pro-BNP immunoassay; Roche Diagnostics).

The mean 6MWT distance was significantly shorter in the SSc group than in the controls (562.8±60.3 vs. 514.7±102.5 m, p=0.03). In the SSc group 6MWT distance correlated with ET-1 (r=-0.5, p<0.0001), NTproBNP (r=-0.4, p=0.0008) levels, and echocardiographic indices AcT (r=0.4, p=0.0002) and TRPG (r=-0.4, p=0.0011). Moreover, in patients with 6MWT distance <450 m NTproBNP and endotothelin-1 levels were significantly higher than in patients with distance >450 m (311.2, 31.1-17237 vs. 105.3, 5-17670 pg/ml, p=0.0138 and 2.9±2.2 vs. 1.4±0.7 pg/ml, p=0.0032).

Decreased exercise capacity significantly correlates with biochemical and echocardiographic parameters of right ventricular dysfunction and neurohormonal activation providing a potential link for neuroendocrine derangement in patients with SSc.