OBJECTIVES: This study sought to examine the prognostic importance of chronotropic incompetence among patients referred for stress echocardiography. BACKGROUND: Although chronotropic incompetence has been shown to be predictive of an adverse prognosis, it is not clear if this association is independent of exercise-induced myocardial ischemia. METHODS: Consecutive patients (146 men and 85 women; mean age 57 years) who were not taking beta-adrenergic blocking agents and were referred for symptom-limited exercise echocardiography were followed for a mean of 41 months. Chronotropic incompetence was assessed in two ways: (1) failure to achieve 85% of the age-predicted maximum heart rate and (2) a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate and physical fitness. RESULTS: The primary end point, a composite of death, nonfatal myocardial infarction, unstable angina and late (>3 months after the exercise test) myocardial revascularization, occurred in 41 patients. Failure to achieve 85% of the age-predicted maximum heart rate was predictive of events (relative risk [RR] 2.47, 95% confidence interval [CI] 1.28 to 4.79, p=0.007); similarly, a low chronotropic index was predictive (RR 2.44, 95% CI 1.31 to 4.55, p=0.005). Even after adjusting for myocardial ischemia and other possible confounders, failure to achieve 85% of age-predicted maximum heart rate was predictive (adjusted RR 2.20, 95% CI 1.11 to 4.37, p=0.02). A low chronotropic index also remained predictive (adjusted RR 1.85, 95% CI 0.98 to 3.47, p=0.06). CONCLUSIONS: Chronotropic incompetence is predictive of an adverse cardiovascular prognosis even after adjusting for echocardiographic myocardial ischemia.