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 v entilatory response ((V)over dot E/(V)over dot CO2) to exercise are common in patients with severe heart failure, but their relative prognostic impact s have not been well explored. Methods and Results-Consecutive patients with heart failure referred for me tabolic stress testing who were not taking beta-blockers or intravenous ino tropes (n=470) were followed for 1.5 years. The chronotropic index was calc ulated while peak (V)over dot O-2 and (V)over dot E/(V)over dot CO2 were di rectly measured. Chronotropic index and peak (V)over dot O-2 were considere d 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 25 th percentile. For comparative purposes, a group of 17 healthy controls und erwent metabolic testing as well. Compared with controls, heart failure pat ients had markedly abnormal ventilatory and chronotropic responses to exerc ise. In the heart failure cohort, there were 71 deaths. In univariate analy ses, predictors of death included high (V)over dot E/(V)over dot CO2, low c hronotropic index, low (V)over dot O-2, low resting systolic blood pressure , and older age. Nonparametric Kaplan-Meier plots demonstrated that by divi ding the population according to peak (V)over dot E/(V)over dot CO2 and pea k (V)over dot O-2, it is possible to identify low, intermediate, and very h igh risk groups, In multivariate analyses, the only independent predictors of death were high (V)over dot E/(V)over dot CO2 (adjusted relative risk [R R] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjuste d RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). Conclusions-The ventilatory and chronotropic responses to exercise are powe rful and independent predictors of heart failure mortality.