Impaired chronotropic response to exercise stress testing as a predictor of mortality

JAMA. 1999 Feb 10;281(6):524-9. doi: 10.1001/jama.281.6.524.


Context: Chronotropic incompetence, an attenuated heart rate response to exercise, is a predictor of all-cause mortality in healthy populations. This association may be independent of exercise-induced myocardial perfusion defects.

Objective: To examine the prognostic significance of chronotropic incompetence in a low-risk cohort of patients referred for treadmill stress testing with thallium imaging.

Design: Prospective cohort study conducted between September 1990 and December 1993.

Setting: Tertiary care academic medical center.

Patients: Consecutive patients (1877 men and 1076 women; mean age, 58 years) who were not taking beta-blockers and who were referred for symptom-limited treadmill thallium testing.

Main outcome measures: Association of chronotropic incompetence, defined as either failure to achieve 85% of the age-predicted maximum heart rate or a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness, with all-cause mortality during 2 years of follow-up.

Results: Three hundred sixteen patients (11%) failed to reach 85% of the age-adjusted maximum heart rate, 762 (26%) had a low chronotropic index, and 612 (21%) had thallium perfusion defects. Ninety-one patients died during the follow-up period. After adjustment for age, sex, thallium perfusion defects, and other confounders, failure to reach 85% of the age-predicted maximum heart rate was associated with increased risk of death (adjusted relative risk [RR], 1.84; 95% confidence interval [CI], 1.13-3.00; P=.01), as was a low chronotropic index (adjusted RR, 2.19; 95% CI, 1.43-3.44; P<.001).

Conclusion: Among patients with known or suspected coronary disease, chronotropic incompetence is independently predictive of all-cause mortality, even after considering thallium perfusion defects. Incorporation of chronotropic response into the routine interpretation of stress thallium studies may improve the prognostic power of this test.

MeSH terms

  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Chronobiology Phenomena
  • Exercise Test*
  • Female
  • Heart / diagnostic imaging
  • Heart Rate*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Ischemia / diagnostic imaging*
  • Myocardial Ischemia / physiopathology*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Tomography, Emission-Computed, Single-Photon