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We studied the prognostic significance of the ventilatory equivalent of carbon dioxide production (VEqCO2) at different time-points of a maximal cardiopulmonary exercise test (CPET) in patients with suspected heart failure (HF).The VEqCO2 was calculated at three different time-points; VEqCO2 (rest) was calculated following 30 s of resting data immediately prior to the start of exercise; VEqCO2 (nadir) was the lowest 30-s average over the duration of the test; VEqCO2 (peak) was calculated using the mean value of the final 30 s of exercise. We included a healthy control group who had no evidence of cardiorespiratory disease. Four hundred and twenty-three patients with suspected HF (mean age 63 ± 12 years; 80% males; left ventricular ejection fraction 36 ± 6 %; peak oxygen uptake 22.3 ± 8.1 mL kg−1 min−1; VE/VCO2 slope 34 ± 8) were included in the study. Seventy-eight healthy participants (62% males; age 61 ± 11 years) were recruited as controls. One hundred and eighteen patients died during follow-up with a median follow-up of 8.6 ± 2.1 years in survivors. The strongest univariable predictors of all-cause mortality were VEqCO2 (nadir) (χ2 = 47.9), peak oxygen uptake (χ2 = 53.0), and the VE/VCO2 slope (χ2 = 31.7). In a Cox multivariable proportional hazards model, VEqCO2 (nadir) (χ2 = 8.8), peak systolic blood pressure (χ2 = 6.0), and age (χ2 = 6.6) were the most potent independent predictors of all-cause mortality.The VEqCO2 (nadir) provides greater prognostic value than other related ventilatory variables in patients with suspected HF. Further work in other populations is required to confirm our conclusions.