Prognostic significance of impairment of heart rate response to exercise: Impact of left ventricular function and myocardial ischemia

Objectives The goal of this research was to study the association between heart rate (HR) response to exercise and the risk of death and myocardial infarction (MI) after adjustment for left ventricular (LV) function and myocardial ischemia. Background Chronotropic incompetence during exercise testing is associated with increased mortality. It is unknown whether LV dysfunction or ischemia accounts for this. Methods We studied 3,221 patients (age 59 ± 12 years; 1,701 men) who underwent treadmill exercise echocardiography. We considered two markers of chronotropic incompetence: 1) failure to achieve 85% of the maximal predicted HR, and 2) low (<0.8) chronotropic index. The independent association between HR response and end points was evaluated by an adjusted risk (AR) model, which included clinical parameters, ejection fraction, and the severity of ischemic wall motion abnormalities. Results Target HR was not achieved in 495 (15%) patients. Low chronotropic index was observed in 793 (25%) patients. There were 129 deaths (41 cardiac) during a median follow-up of 3.2 years. Myocardial infarction occurred in 65 patients. Low chronotropic index was associated with cardiac death (AR, 1.54; 95% confidence interval [CI], 1.18 to 2.04; p = 0.002) and MI (AR, 1.37; 95% CI, 1.09 to 1.69; p = 0.007). Failure to achieve 85% of maximal predicted HR was associated with increased mortality (AR, 1.49; 95% CI, 1.02 to 2.22; p = 0.04) and cardiac death (AR, 2.13; 95% CI, 1.10 to 4.17; p = 0.03). Conclusions Impaired chronotropic response to exercise is associated with increased mortality and cardiac events even after adjusting for LV function and the severity of exercise-induced myocardial ischemia.