title: Effect of β-blocker cessation on chronotropic incompetence and exercise tolerance in patients with advanced heart failure.
abstract: BACKGROUND
  Chronotropic incompetence is defined as the inability to reach 80% of heart rate (HR) reserve or 80% of the maximally predicted HR during exercise. The presence of chronotropic incompetence is associated with reduced peak oxygen consumption, and rate-responsive pacing therapy is under investigation to improve exercise capacity in heart failure (HF). However, uncertainty exists about whether chronotropic incompetence and reduced exercise tolerance in HF are attributable to β-blockade.
  
  
  RESULTS
  Subjects with HF and receiving long-term β-blocker therapy underwent cardiopulmonary exercise tolerance testing under 2 conditions in random sequence: (1) after a 27-hour washout period (Off-BB) and (2) 3 hours after β-blocker ingestion (On-BB). Norepinephrine levels were drawn at rest and at peak exercise. β1-response to norepinephrine was assessed using the chronotropic responsiveness index: ΔHR/Δlog norepinephrine. Nineteen patients with systolic HF (left ventricular ejection fraction, 22.8±7.7%) were enrolled. Mean age was 49.4±12.3 years. Average carvedilol equivalent dose was 29.1±17.0 mg daily. Peak HR off/on β-blockers was 62.7±18.7% and 51.4±18.2% HR reserve (P<0.01) and 79.1±11.0% and 70.3±12.3% maximally predicted HR (P<0.01). For the Off-BB and On-BB conditions, the respiratory exchange ratios were 1.05±0.06 and 1.05±0.10 (P=0.77), respectively, confirming maximal and near identical effort in both conditions. The peak oxygen consumption was 16.6±3.34 and 15.9±3.31 mL/kg/min (P=0.03), and the chronotropic responsiveness index was 19.3±7.2 and 16.2±7.1 (P=0.18).
  
  
  CONCLUSIONS
  Acute β-blocker cessation does not normalize the chronotropic response to exercise in patients with advanced HF and chronotropic incompetence.
authors.affiliation: Cardiovascular Division, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Hirsh
authors.forename: Andrea
authors.initials: A
authors.lastname: Mignatti
authors.forename: A Reshad
authors.initials: AR
authors.lastname: Garan
authors.forename: Nir
authors.initials: N
authors.lastname: Uriel
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Sims
authors.forename: Ulrich P
authors.initials: UP
authors.lastname: Jorde
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D017298:Bisoprolol / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage; D000077261:Carvedilol; D004334:Drug Administration Schedule; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage; D008875:Middle Aged; D009519:New York City; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage; D011446:Prospective Studies; D012119:Respiration / Q000187:drug effects; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol; D009638:Norepinephrine; D017298:Bisoprolol