Effect of Beta-Blocker use on Exercise Heart Rate Gradient and Reclassification of Mortality Risk in Patients Referred for Exercise Testing

Impairments in heart rate (HR) reserve and HR recovery are associated with mortality, and the combination of these two, termed exercise HR gradient (EHRG), is a better predictor than either alone. However, the confounding effect of beta-blockade on chronotropic impairment to exercise has not been fully explored; the aim of the present study was to evaluate the effect of beta blockade on EHRG. Participants were 2769 Veterans (58.7 ± 11.6 years) who underwent a maximal exercise test for clinical reasons. HR reserve and HR recovery were acquired and divided into quintiles and summed to provide an EHRG score. Net reclassification improvement (NRI) was performed to evaluate the impact of HR reserve, HR recovery and EHRG on all-cause mortality for patients with and without beta-blocker use. During a mean follow up of 10.9 ± 4.1 years, 657 patients died. Among patients without beta-blocker therapy, adding EHRG score to an established model including multiple baseline risk factors and exercise capacity resulted in an NRI of 14.3% (p <0.001). Adding HR recovery instead of EHRG score yielded an NRI of 11.5% (p <0.001), whereas HR reserve had no significant NRI among patients without beta-blocker therapy. In contrast, among participants on beta-blocker therapy, the addition of HR reserve, HR recovery, or EHRG score did not result in any significant reclassification. In conclusion, EHRG was superior to both HR reserve and HR recovery in predicting mortality and provides significant reclassification of risk but only among patients not taking beta-blockers.