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

Abstract

All patients with systolic HF, New York Heart Association class II to IV, receiving β-blocker therapy (bisoprolol, carvedilol, or metoprolol) for ≥3 months referred for cardiopulmonary exercise tolerance testing (CPETT) were screened. All patients were followed at the Columbia © 2012 American Heart Association, Inc. 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, 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. (Circ Heart Fail. 2012;5:560-565.)Key Words: heart failure ◼ chronotropic incompetence ◼ β-blocker ◼ heart rate ◼ exercise Effect of β-Blocker Hirsh et al β-Blocker Cessation and CI in CHF 561University Medical Center Heart Failure Center by HF specialists. β-blockers were routinely uptitrated by physicians or nurse practitioners unless limited by blood pressure, bradycardia, fatigue, or other symptoms, possibly attributable to β-blockers. Patients were excluded if they had any of the following: atrial fibrillation or atrial flutter, inability to exercise, hospital admission for HF or acute coronary syndrome in the past 90 days or symptoms of myocardial ischemia, or inability to undergo a treadmill exercise test (eg, severe obstructive pulmonary disease or severe osteoarthritis). CI was not a factor in enrollment. Carvedilol equivalent dose was calculated for patients treated with bisoprolol and metoprolol based on the equivalence ratios established by the Metoprolol ...

Cardiovascular mortality and chronotropic incompetence in systolic heart failure: the importance of a reappraisal of current cut‐off criteria

“…The above‐mentioned interdependency, together with the prognostic role of pVO 2 in HF patients, often raised the question about the actual independent value of exercise‐induced HR response in cardiovascular mortality stratification . Moreover, it is well known that beta‐blocker treatment might per se contribute to reduce most of the chronotropic indices even if it does not significantly affect pVO 2 values , . To our knowledge, only two studies investigated a possible significance of CI together with CPET data .…”

“…11,16 Moreover, it is well known that betablocker treatment might per se contribute to reduce most of the chronotropic indices 11,21 -23 even if it does not significantly affect pVO 2 values. 23,41,42 To our knowledge, only two studies investigated a possible significance of CI together with CPET data. 11,16 Bold characters identify the best multivariate coefficient for %pHR and %pHRR cut-off values.…”

Chronotropic Incompetence During Exercise in Type 2 Diabetes: Aetiology, Assessment Methodology, Prognostic Impact and Therapy

“…This complication arises from frequent/chronic activation of sympathetic nerves, which leads to down-regulation of b-adrenergic receptors in the sinus node. This ultimately results in post-synaptic desensitization [63][64][65][66]. As the HR response to exercise is determined by the extent of sympathetic drive to the heart and the ability of b-adrenergic receptors in the sinoatrial node to respond to circulating catecholamines, such desensitization could then result in a disturbed HR regulation/ response during exercise [64,67].…”

Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers

“…Although it has been shown that high doses of beta-blockers can cause, aggravate, or reveal latent chronotropic incompetence, 7 26 27 beta-blocker cessation did not normalize chronotropic response to exercise. 28 Our study has some limitations as this was a single-center, observational, retrospective study with a relatively small group of mostly male patients. It included a diverse group of patients with and without heart failure.…”