Ventilatory and heart rate responses to exercise - Better predictors of heart failure mortality than peak oxygen consumption

Background-An abnormally low chronotropic response and an abnormally high ventilatory response ((V)over dot E/(V)over dot CO2) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. Methods and Results-Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak (V)over dot O-2 and (V)over dot E/(V)over dot CO2 were directly measured. Chronotropic index and peak (V)over dot O-2 were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas (V)over dot E/(V)over dot CO2 was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high (V)over dot E/(V)over dot CO2, low chronotropic index, low (V)over dot O-2, low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak (V)over dot E/(V)over dot CO2 and peak (V)over dot O-2, it is possible to identify low, intermediate, and very high risk groups, In multivariate analyses, the only independent predictors of death were high (V)over dot E/(V)over dot CO2 (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). Conclusions-The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.