title: Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: time to pace?
abstract: BACKGROUND
  Chronotropic incompetence (CI) is often seen in subjects with chronic congestive heart failure (CHF). The prevalence of CI, its mechanisms and association with beta-blocker use as well as exercise capacity have not been clearly defined.
  
  
  RESULTS
  Cardiopulmonary exercise tolerance testing data for 278 consecutive patients with systolic CHF was analyzed. CI, defined as the inability to reach 80% of maximally predicted heart rate was present in 128 of 278 subjects (46%). The prevalence of CI was highest in those with most impaired exercise capacity (72, 48, and 24% for subjects with a VO(2) of <14.0, 14.0-20.0, and >20.0 ml/kg/min respectively; p=0.001). While subjects with CI had lower peak exercise heart rate (114 vs. 152 bpm), and lower peak VO(2) (15.4 vs. 19.9 ml/kg/min), they were equally likely to be on chronic beta-blocker therapy (74% vs. 71%; p=0.51). Heart rate and norepinephrine (NE) levels were measured during exercise in a separate cohort of 24 subjects with CHF. There was no difference in beta-blocker dose between subjects with and without CI, however, exercise induced NE release and Chronotropic Responsiveness Index, a measure of post-synaptic beta-receptor sensitivity to NE, were lower in subjects with CI (1687+/-911 vs. 2593+/-1451 pg/ml p=0.08; CRI 12.7+/-5.7 vs. 22.1+/-4.7, p=0.002).
  
  
  CONCLUSIONS
  CI occurs in >70% of subjects with advanced systolic CHF irrespective of beta-blocker use and is associated with a trend toward impaired NE release, post-synaptic beta-receptor desensitization and reduced exercise capacity.
authors: Division of Cardiology, New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, United States. upj1@columbia.edu
authors: Ulrich P
authors: UP
authors: Jorde
authors: Timothy J
authors: TJ
authors: Vittorio
authors: Michael E
authors: ME
authors: Kasper
authors: Emma
authors: E
authors: Arezzi
authors: Paolo C
authors: PC
authors: Colombo
authors: Rochelle L
authors: RL
authors: Goldsmith
authors: Kartikya
authors: K
authors: Ahuja
authors: Chi-Hong
authors: CH
authors: Tseng
authors: Francois
authors: F
authors: Haas
authors: David S
authors: DS
authors: Hirsh
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology*; D013268:Stimulation, Chemical; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D009638:Norepinephrine