Ventilatory and Heart Rate Responses to Exercise

Background —An abnormally low chronotropic response and an abnormally high ventilatory response (V̇ e /V̇ co 2 ) 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 β-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V̇ o 2 and V̇ e /V̇ co 2 were directly measured. Chronotropic index and peak V̇ o 2 were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V̇ e /V̇ co 2 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 V̇ e /V̇ co 2 , low chronotropic index, low V̇ o 2 , low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V̇ e /V̇ co 2 and peak V̇ 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 V̇ e /V̇ co 2 (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.