Effect of β-blocker cessation on chronotropic incompetence and exercise tolerance in patients with advanced heart failure

Benjamin J. Hirsh, Andrea Mignatti, A. Reshad Garan, Nir Uriel, Paolo Colombo, Daniel B. Sims, Ulrich P. Jorde

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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. Methods and 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, confrming 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.

Original languageEnglish (US)
Pages (from-to)560-565
Number of pages6
JournalCirculation: Heart Failure
Issue number5
StatePublished - Sep 2012
Externally publishedYes


  • Chronotropic incompetence
  • Exercise
  • Heart failure
  • Heart rate
  • β-blocker

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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