Systemic sclerosis (SSc) is a complex immune-mediated connective tissue disease characterized by progressive fibrosis due to collagen deposition. In the heart, all structures can be affected, with inflammation, oxidative stress, vascular damage and fibrosis. However, the main underlying mechanism seems to be microcirculation impairment, with abnormal vasoreactivity due to autonomic nervous system (ANS) dysfunction. In fact, ANS dysfunction in SSc patients is associated with a risk of arrhythmias and mortality, in addition to being an early marker of SSc progression that can help identify subclinical involvement and precede the occurrence of cardiac fibrosis. The six-minute walk test (6MWT) is a simple, inexpensive, easy-to-administer, well-tolerated, safe, non-invasive, and reliable submaximal test. In SSc, the 6MWT has been increasingly used to assess performance during exertion and as a follow-up tool and primary measure of outcome and response to therapy.

To evaluate the associations between sympathetic-vagal balance and exercise measured by the 6MWT in women with SSc without cardiac involvement.

This was a cross-sectional study in which 69 women with SS [median age 51 (40–63) years] without cardiac involvement underwent the 6MWT. Throughout the 6MWT, heart rate variability (HRV) was evaluated using specific software.

The median six-minute walk distance (6MWD) was 451 (392–498), with 29 (42%) participants not achieving 80% of the predicted value. Desaturation during the 6MWT (SpO2≤4%) was observed in 10.1% of participants. Significant correlations were observed between the 6MWD and the following HRV parameters: number of interval differences of successive NN intervals greater than 50 ms (rs=-0.397, p=0.013), low-frequency range (rs=0.374, p=0.023), high-frequency range (rs=-0.372, p=0.023), and parasympathetic nervous system index (rs=-0.342, p=0.045). No significant correlation was noted between delta peripheral oxygen saturation and HRV parameters.

In women with SSc, there is an interrelationship between the 6MWD and both vagal withdrawal and sympathetic hyperactivation. This relationship between autonomic imbalance and worse exercise performance could potentially increase cardiovascular risk, even in patients without apparent cardiac involvement.

People with SS may be involved of the cardiovascular system which, even subclinical, can potentially have an important impact on functional capacity. In this sense, HRV analysis is a powerful non-invasive tool to access the sympathetic and vagal modulations of the heart, in addition to being simple to apply and widely available. Control of the autonomic nervous system of the heart could be a potential target in the treatment of SSc patients. Thus, drug and non-drug approaches that reduce sympathetic hypertonia and prevent parasympathetic withdrawal should be considered to counteract autonomic dysfunction in Ssc.