Chronotropic Incompetence as a Predictor of Death Among Patients With Normal Electrograms Taking Beta Blockers (Metoprolol or Atenolol)

Chronotropic incompetence, or an inability to increase heart rate during exercise, independently predicts death in patients not taking β blockers. Whether it predicts death in patients taking β blockers is not known. Consecutive patients (n = 3,736; mean age 58 ± 11 years; 68% men), who were taking either metoprolol tartrate or atenolol and were referred for symptom-limited exercise testing from 1990 to 2002 at a major academic medical center, formed the prospective study cohort. None had heart failure, pacemakers, atrial fibrillation, or any electrocardiographic abnormalities. Patients were followed for a median of 4.5 years for all-cause mortality. Chronotropic response was defined as the percentage of heart rate reserve used. A value of ≤62%, which was noted in 813 patients (22%), was considered abnormal, meaning that chronotropic incompetence was present. There were 173 deaths. After adjusting for age, gender, heart rate at rest, standard risk factors, other medications, Duke treadmill score, and heart rate recovery, chronotropic incompetence predicted death (adjusted hazard ratio 1.94, 95% confidence interval 1.43 to 2.64, p <0.0001). The association of chronotropic incompetence with death was present, irrespective of which drug was taken or the number of half-lives that had elapsed since the last dose. In conclusion, in patients taking β blockers, chronotropic incompetence is independently predictive of death.