Figure 1.
Categorizing referred SSc patients with normal and reduced exercise capacity, using cardiopulmonary exercise testing.
Exercise intolerance was attributed to left ventricular dysfunction or pulmonary vascular disease. Normal is defined as either: a) normal in all cardiovascular and ventilatory aspects of exercise gas exchange, including normal ventilation-perfusion matching and normal peak VO2, or b) reduced peak VO2 with normal AT and no gas exchange abnormalities suggestive of heart, lung or pulmonary vascular disease. Diamonds (branch-points) address specific data: Branch-point 1: Right branch: If the peak VO2 is ≥75% of predicted with normal VE/VCO2 and PETCO2 @ AT and non-ventilatory limitation, the patient is considered to have normal heart and lung function. Left branch includes all with peak VO2 <75%. Branch-point 2: If the AT is normal and ventilation-perfusion matching and lung mechanics are normal (right branch), the patient is considered to be limited by poor effort and not limited by heart or lung disease. If the AT is reduced (left branch), the patient is likely to have left ventricular dysfunction or pulmonary vasculopathy. Branch-point 3: The VE/VCO2 @AT was used to assess matching of ventilation to perfusion. All patients with pulmonary vasculopathy would have ventilation/perfusion mismatching and an elevated VE/VCO2. A cut-off value of ≥34 was selected. If not elevated, they were considered to have left ventricular dysfunction. Branch point 4: PETCO2 usually increases from the beginning of exercise to the AT in patients with normal cardiopulmonary function and patients with left ventricular dysfunction (right branch). However, it usually decreases in patients with pulmonary arterial hypertension (left branch). Nine of the 11 patients classified as pulmonary vasculopathy had a decreasing PETCO2. Two had either no change or increasing PETCO2 from the start of exercise to the AT, possibly due to lung restriction. However, they hyperventilated above their AT. If the patient had moderate to severe restriction and marked decrease in DLCO, this signified interstitial lung disease with pulmonary vasculopathy.
Table 1.
Demographics for each exercise diagnosis in 30 scleroderma patients.
Figure 2.
Gas exchange response to exercise in two SSc patients.
Nine panel plots of a patient with normal exercise performance (Fig. 2a) and one with pulmonary vasculopathy (Fig. 2b). The protocol consisted of a 3-minute resting period, followed by 3 minutes of very-low-level cycle exercise, and then increasing cycle workload to the patient's maximum tolerance. Points are 20-second averages. Panel 1 is plot of ventilation against time. Panel 2 is plot of heart rate and O2-pulse against time. Panel 3 is plot of O2 uptake (VO2), CO2 output (VCO2) and work rate against time. Panel 4 is plot of minute ventilation (VE) against VCO2. Panel 5 is plot of VCO2 and HR against VO2. Panel 6 is plot of ventilatory equivalent for VO2 (VE/VO2) and VCO2 (VE/VCO2) against time. Panel 7 is plot of tidal volume against minute ventilation, with resting maximum voluntary ventilation on the X-axis and inspiratory capacity and vital capacity, measured at rest, on the Y-axis. Panel 8 is plot of gas exchange ratio (RER) against time. Panel 9 is plot of end tidal pO2 (PETO2), end tidal pCO2 (PETCO2) and pulse oximeter arterial oxyhemoglobin saturation against time. The normal subject (figure 2a) is a 59 year old female with scleroderma. Peak VO2 and AT are normal (panels 3 and 5) There are no signs of impaired oxygen flow, or ventilation/perfusion mismatching during exercise. Peripheral oxyhemoglobin saturation does not decrease during exercise. There is adequate breathing reserve. The subject with suspected pulmonary vasculopathy (figure 2b) is a 37 year old female with scleroderma. Peak VO2 and AT are reduced (panel 3, panel 5). Ventilatory equivalents are elevated and decrease only slightly during exercise (panel 6). End-tidal pCO2 is low and decreases during exercise (panel 9), consistent with reduced gas exchange efficiency rather than voluntary hyperventilation (RER is normal, panel 8). The patient stopped exercise because of leg pain. Four arrows are placed on each of Figures 2a and 2b that correspond to the branch-points described in Figure 1, Arrow 1 points to the peak VO2 in panel 3 (branch-point 1). Arrow 2 points to the AT in panel 5 (branch-point 2). Arrow 3 points to the VE/VCO2 at the AT in panel 6 (branch-point 3). Arrow 4 points to the changing PETCO2 from start of exercise to AT in panel 9.
Table 2.
Physiologic measurements related to resting lung function and gas exchange during exercise in 28 scleroderma patients.
Figure 3.
Difference between PETCO2 at AT and PETCO2 at start of exercise, plotted against AT, percent predicted, for SSc patients with normal exercise tolerance, left ventricular dysfunction, and pulmonary vasculopathy.
Figure 4.
PETCO2 as a function of VE/VCO2 at the anaerobic threshold in 28 SSc patients.
Figure 5.
FVC as a function of PETCO2at AT (Fig. 5a) and PETCO2 at the AT(Fig. 5b) in 28 SSc patients with normal exercise tolerance, left ventricular dysfunction, and pulmonary vasculopathy.