VE/VCO2 slope threshold optimization for preoperative evaluation in lung cancer surgery: identifying true high- and low-risk groups

Abstract

Background: Cardiopulmonary exercise testing (CPET) enables measurement of the slope of the increase in minute ventilation in relation to carbon dioxide elimination during exercise (the VE/VCO₂ slope). Several studies have shown that the VE/VCO₂ slope is a strong marker for postoperative complications and mortality. However, current thresholds for adverse outcomes are generated from historical data in heart failure patients.

Methods: This was a retrospective analysis of 158 patients with lung cancer who underwent lobectomy or pneumonectomy during 2008-2020. The main outcome was major pulmonary complications (MPC) or death ≤30 days of cancer surgery. Patients were first categorized using two different single threshold approaches; the traditional threshold of 35 and the highest Youden value from the receiver operating curve (ROC) analysis. Secondly, patients were categorized into three risk groups using two thresholds. These two thresholds were determined in an ROC analysis, where the VE/VCO₂ slope values generating either a 90% sensitivity (lower threshold) or a 90% specificity (upper threshold) for the main outcome were chosen. The frequency of complications was compared using Chi². The overall model quality was evaluated by an area under the curve (AUC) analysis. Positive predictive values (PPVs) and negative predictive values (NPVs) are presented.

Results: The two thresholds, <30 (90% sensitivity) and >41 (90% specificity), created three risk groups: low risk (VE/VCO₂ slope <30, n=44, 28%); intermediate risk (VE/VCO₂ slope 30-41, n=95, 60%) and high risk (VE/VCO₂ slope >41, n=19, 12%). The frequency of complications differed between groups: 5%, 16% and 47% (P<0.001). Using two thresholds compared to one threshold increased the overall model quality (reaching AUC 0.70, 95% confidence interval: 0.59-0.81), and identified a high sensitivity threshold (VE/VCO₂ slope <30) which generated a NPV of 95% but importantly, also a high specificity threshold (VE/VCO₂ slope >41) with a PPV of 47%.

Conclusions: Risk stratification based on three risk groups from the preoperative VE/VCO₂ slope increased the model quality, was more discriminative and generated better PPV and NPV compared to traditional risk stratification into two risk groups.

Keywords: Cardiopulmonary exercise testing (CPET); exercise capacity; functional capacity; ventilatory efficiency.

Figure 1

Receiver operating characteristic curves for three different approaches to using the VE/VCO₂-slope to predict major pulmonary complications. Red line and dot, single threshold of the VE/VCO₂-slope at 35; blue line and dot, single threshold of the VE/VCO₂-slope at 31; green line and dots, two threshold values at 30 and 41, respectively. AUC, area under the curve; VE/VCO₂, the increase in minute ventilation in relation to carbon dioxide elimination.