Peak VO2 and VE/VCO2 exhibit differential prognostic capacity for predicting cardiac events

Abstract Background Cardiopulmonary exercise testing (CPET) is a key tool for evaluating functional capacity and prognosis in heart failure. Peak oxygen uptake (peak VO₂) and ventilatory efficiency (VE/VCO₂) serve as important prognostic markers. However, sex-specific differences in the correlation between these parameters and echocardiographic indices remain incompletely understood. Purpose This study explored the relationship between echocardiographic parameters and CPET results during supine cycling, highlighting sex-specific differences that may refine risk stratification and prognostic assessments. Methods This retrospective study included 688 patients (male 385, female 283) who underwent simultaneous CPET and supine bicycle echocardiography (SBE). Patients were categorized into subgroups based on sex. Echocardiographic parameters, including left atrial (LA) strain, left ventricular ejection fraction (LVEF), baseline and exercise E/e', were measured. To evaluate sex-specific differences, the correlation between VO₂ peak and VE/VCO₂ slope and each echocardiographic parameter was analyzed using coefficient of determination (R²) and p-values for both sexes. Results The mean age was similar between males and females. LVEF was significantly lower in males (56.9 ± 12.4%) compared to females (61.1 ± 9.4%, p 0.001). LA strain was slightly but significantly higher in females (22.0 ± 10.2%) than in males (19.2 ± 10.5%, p = 0.001). Baseline E/e' and exercise E/e’ showed no significant difference between sexes (11.8 ± 6.6 vs. 12.1 ± 7.33, 12.5 ± 6.2 vs. 12.7 ± 5.8). Peak VE/VCO₂ did not differ between males and females (31.9 ± 9.3 vs. 32.0 ± 6.6, p = 0.917), while peak VO₂ was significantly higher in males (20.6 ± 5.3 mL/kg/min) than in females (17.8 ± 4.3 mL/kg/min, p 0.001). LVEF was inversely correlated with VE/VCO₂ in men (R² = 0.11, p 0.001) but not in women (R² = 0.00, p = 0.485). Similarly, LVEF correlated significantly with peak VO₂/kg in men (R² = 0.08, p 0.001), while the correlation in women was weak (R² = 0.01, p = 0.076). A similar sex-specific pattern was observed in the analysis of LA strain and exercise E/e' (figure). Conclusions The relationship between echocardiographic parameters and VE/VCO₂ differed by sex. In females, weaker correlations may reflect physiological differences in lung mechanics, peripheral limitations, and heart-lung interactions. These findings emphasize the need for sex-specific considerations in heart failure risk stratification and management.