Comparison of the chronotropic response to exercise and heart rate recovery in predicting cardiovascular mortality

BACKGROUND: Both an impaired capacity to increase heart rate during exercise testing (chronotropic incompetence), and a slowed rate of recovery following exercise (heart rate recovery) have been shown to be associated with all-cause mortality. It is, however, unknown which of these responses more powerfully predicts risk, and few data are available on their association with cardiovascular mortality or how they are influenced by beta-blockade. METHODS: Routine symptom-limited exercise treadmill tests performed on 1910 male veterans at the Palo Alto Veterans Affairs Medical Center from 1992 to 2002 were analyzed. Heart rate was determined each minute during exercise and recovery. Chronotropic incompetence was defined as the inability to achieve > or =80% of heart rate reserve, using a population-specific equation for age-predicted maximal heart rate. An abnormal heart rate recovery was considered to be a decrease of <22 beats/min at 2 min in recovery. Cox proportional hazards analyses including pretest clinical data, chronotropic incompetence, heart rate recovery, the Duke Treadmill Score (abnormal defined as <4), and other exercise test responses were performed to determine their association with cardiovascular mortality. RESULTS: Over a mean follow-up of 5.1+/-2.1 years, there were 70 deaths from cardiovascular causes. Both abnormal heart rate recovery and chronotropic incompetence were associated with higher cardiovascular mortality, a lower exercise capacity, and more frequent occurrence of angina during exercise. Both heart rate recovery and chronotropic incompetence were stronger predictors of risk than pretest clinical data and traditional risk markers. Multivariately, chronotropic incompetence was similar to the Duke Treadmill Score for predicting cardiovascular mortality, and was a stronger predictor than heart rate recovery hazard ratios 3.0 (95% confidence interval 1.9-4.9), 2.8 (95% confidence interval 1.7-4.8), and 2.0 (95% confidence interval 1.1-3.5) for abnormal Duke Treadmill Score, chronotropic incompetence, and abnormal heart rate recovery, respectively. Having both chronotropic incompetence and abnormal heart rate recovery strongly predicted cardiovascular death, resulting in a relative risk of 4.2 compared with both responses being normal. Beta-blockade had minimal impact on the prognostic power of chronotropic incompetence and heart rate recovery. CONCLUSION: Both chronotropic incompetence and heart rate recovery predict cardiovascular mortality in patients referred for exercise testing for clinical reasons. Chronotropic incompetence was a stronger predictor of cardiovascular mortality than heart rate recovery, but risk was most powerfully stratified by these two responses together. The simple application of heart rate provides powerful risk stratification for cardiovascular mortality from the exercise test, and should be routinely included in the test report.