Effect of β-Blocker Cessation on Chronotropic Incompetence and Exercise Tolerance in Patients With Advanced Heart Failure

• Published in: Circulation. Heart failure Vol. 5; no. 5; pp. 560 - 565
• Main Authors: Hirsh, Benjamin J., Mignatti, Andrea, Garan, A. Reshad, Uriel, Nir, Colombo, Paolo, Sims, Daniel B., Jorde, Ulrich P.
• Format: Journal Article
• Language: English
• Published: United States 01.09.2012
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adult; Analysis of Variance; Biomarkers - blood; Bisoprolol - administration & dosage; Carbazoles - administration & dosage; Drug Administration Schedule; Exercise Test; Exercise Tolerance - drug effects; Female; Heart Failure - blood; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart Rate - drug effects; Humans; Male; Metoprolol - administration & dosage; Middle Aged; New York City; Norepinephrine - blood; Oxygen Consumption - drug effects; Propanolamines - administration & dosage; Prospective Studies; Respiration - drug effects; Time Factors; New York City
• ISSN: 1941-3289; 1941-3297; 1941-3297
• DOI: 10.1161/CIRCHEARTFAILURE.112.967695

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. 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). Acute β-blocker cessation does not normalize the chronotropic response to exercise in patients with advanced HF and chronotropic incompetence.