Reference equation for the six-minute walk test and assessment of heart rate variability in women with systemic sclerosis

Abstract

Introduction: Systemic sclerosis (SSc) or scleroderma is a complex immune-mediated connective tissue disease characterized by progressive fibrosis due to collagen deposition. There is enormous concern for the need for early screening, search for new therapies and closer monitoring of patients with SSc associated with interstitial lung disease (dcSSs-ILD) before it has caused irreversible impairment of lung function. The main underlying mechanism appears to be microcirculation impairment, with abnormal vasoreactivity due to dysfunction of the autonomic nervous system (ANS), which is associated with the risk of arrhythmias and mortality, in addition to being a marker of SSc progression. As it is an independent predictor of SS-related mortality, the six-minute walk test (6MWT) is a potentially useful tool in the evaluation of outcomes with the pulmonary function testicles (PFT). Objectives: To build a reference approval for the 6MWT, considering lung and muscle function in women with SSc, and also to evaluate heart rate variability (HRV) during the 6MWT.To evaluate the association between vagal sympathetic balance and exercise performance, measured by the 6MWT, in women with SSc without cardiac involvement. Methods: This was a cross-sectional study in which 69 women with dcSSs-ILD underwent the 6MWT with HRV, Health Assessment Questionnaire-Disability Index (HAQ-DI), PFTs (including spirometry, measurement of pulmonary diffusion capacity for carbon monoxide-DLCO and strength measurement of muscle strength respiratory), handgrip strength (HGS) and quadriceps muscle strength (QMS). Results: The mean distance covered in the 6MWT (6MWT) was 447 ± 78 m, with 43.5% of the participants not reaching 80% of the predicted value. The 6MWD correlated positively with QMS (r = 0.418, P = 0.0004), forced vital capacity (r = 0.306, P = 0.011), DLCO (r = 0.360, P = 0.002), maximal inspiratory pressure (r = 0.268, P = 0.029) and maximal expiratory pressure (MEP, r = 0.288, P = 0.019) and accommodated with age (r = -0.378, P = 0.001), body mass index (BMI, r = -0.248, P = 0.039) and HAQ-DI (r = -0.438, P = 0.0001). In the multiple linear regression analysis, QMS, BMI, DLCO, age and PEmax explained 72% of the 6MWT variability. Predictive equation for women with systemicsclerosis with ILD without PH: 6MWD (m) = 441.7 + (4.552 × FMQkgf) - (5.653 × BMI kg/m²) + (0.817 × DLCO%predicted) - (1.204 × ageyears) + (0.867 × Pemax%predicted). A desaturation during the 6MWT (SpO2≤4%) was observed in 10.1% of the participants. Significant correlations were observed between the 6MWT and the following HRV parameters: number of successive NN interval differences 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). None of them were significant was noted between the peripheral O2 saturation delta and the HRV parameters. Conclusion: Our study shows that, in patients with dcSSs-ILD, in addition to the reduction in pulmonary diffusion, the inspiration of respiratory and peripheral muscle strength affected performance during the 6MWT. In women with SSc, there is an interrelation of the 6MWT with both vagal withdrawal and sympathetic hyperactivation. This relationship between autonomic balance and worse exercise performance could potentially increase cardiovascular risk, even in patients without apparent cardiac involvement. Control of the heart's autonomic nervous system could be a potential target in the treatment of SSc patients. Thus, drug and non-drug approaches that demonstrate sympathetic hypertonia and prevent parasympathetic withdrawal should be considered to counteract autonomic dysfunction in SSc.