Prognostic value of cardiopulmonary exercise testing in patients with systemic sclerosis

Abstract

Background: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO 2) and ventilation/carbon dioxide (VE/VCO 2)-slope, can predict survival in patients with SSc. Subjects and methods: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters. Results: Five-and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413 m (p = 0.003), peakVO 2 < 15.6 mL•kg − 1 •min − 1 , and VE/VCO 2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO 2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO 2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell's C = 0.95). Summary: This is the first large study with SSc patients that demonstrates the prognostic value of peakVO 2 < 15.6 mL•kg − 1 •min − 1 (< 64.5% of predicted peakVO 2) and VE/VCO 2-slope > 35.

Sine Scleroderma, Limited Cutaneous and Diffused Cutaneous Systemic Sclerosis Survival and Predictors of Mortality

“…Our overall survival rates at 1 year, 3 years, 5 years, 10 years were consistent with those reported previously [8,9,11,15,18]. In addition, we have shown a non-significant higher mortality rate from the diffuse cutaneous sub-type vs. the limited cutaneous sub type and the sine scleroderma sub type of SSc, in line with the published literature [8,11,12,16,17,[50][51][52].…”

Cardiopulmonary exercise testing in interstitial lung diseases and the value of ventilatory efficiency

“…Concerning SSc, an important German multicentric study by EWERT et al [135] retrospectively analysed the outcome of 210 patients having performed CPET. Amongst them, 74 (35%) had ILD on HRCT, rated as ILD limited to less than 20% of lung surface for 42 (20%) or extensive ILD for 32 (15%).…”

Measurement and Interpretation of Exercise Ventilatory Efficiency

“…Ventilatory inefficiency increases the ventilatory demand for a given metabolic load which results in: (1) earlier attainment of critical dynamic mechanical constraint (i.e., critically reduced inspiratory reserve volume) and (2) increased respiratory neural drive, both of which lead to heightened perceived dyspnea and exercise intolerance, even in individuals with relatively preserved airway function ( Guenette et al, 2014 ; Faisal et al, 2016 ). Multiple studies have linked ventilatory inefficiency to abnormal exertional dyspnea and poor exercise capacity in varying cardiocirculatory and respiratory diseases ( Hansen and Wasserman, 1996 ; Arena et al, 2004 ; Neder et al, 2015 , 2016 ; Elbehairy et al, 2017 ; Ewert et al, 2019 ). Additionally, the elevated V˙ E / V˙ CO 2 response to exercise is an independent predictor of poor outcomes and mortality in many diseases, including chronic heart failure (CHF), PH, and COPD ( Ponikowski et al, 2001 ; Wensel et al, 2013 ; Neder et al, 2016 ).…”