Effect of beta-blockade on autonomic modulation of heart rate and neurohormonal profile in decompensated heart failure.
BACKGROUND
One of the putative mechanisms for the salutary effects of beta-blockers in patients with congestive heart failure (CHF) is their ability to improve autonomic dysfunction. However, patients with profound neurohumoral abnormalities derive little survival benefit from beta-blockers. The purpose of the current study was to evaluate the effect of beta-blockers on heart rate variability (HRV) in decompensated CHF.


METHODS
Time and frequency domain HRV indices were obtained from 24-hour Holter recordings and compared to assess the role of beta-blockade in 199 patients (mean age 60 +/- 14 years) with decompensated CHF. Neurohormonal differences were assessed by measuring norepinephrine, endothelin-1, tumor necrosis factor-alpha, and interleukin-6 in a subset of 64 patients.


RESULTS
All HRV indices were markedly suppressed but were substantially higher in patients who were on beta-blockers. Time domain measures of parasympathetic cardiac activity, the percentage of R-R intervals with > 50 ms variation (4.9 +/- 0.6 vs 7.7 +/- 1.2%, P = 0.006) and the square root of mean squared differences of successive R-R intervals (22.7 +/- 2.0 vs 31.6 +/- 4.1 ms, P = 0.004), were higher in the beta-blocker group. Spectral analysis revealed that the total power and the ultra-low frequency power were significantly higher in patients on beta-blockers (82% and 59%, respectively). The high frequency power, a spectral index of parasympathetic modulation, was 41% higher in the beta-blocker group (121 +/- 25 vs 171 +/- 27 ms(2), P = 0.02). Norepinephrine and interleukin-6 levels were substantially lower in patients on beta-blockers (28% and 61%, respectively). However, these differences did not reach statistical significance.


CONCLUSIONS
Beta-blockers improve the impaired cardiac autonomic regulation during high sympathetic stress of decompensated CHF. This effect may play an important role in protecting the myocardium and preventing arrhythmias during transient increases in sympathetic activity.
Aronson
D
D
Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. aburger@caregroup.harvard.edu
Burger
A J
AJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D001341:Autonomic Nervous System / Q000187:drug effects*; D018450:Disease Progression; D015716:Electrocardiography, Ambulatory; D019332:Endothelin-1 / Q000097:blood* / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D009638:Norepinephrine / Q000097:blood*; D011446:Prospective Studies; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D019332:Endothelin-1; D015850:Interleukin-6; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine