Beta-Blockade Restores Muscle Sympathetic Rhythmicity in Human Heart Failure

Abstract

Background: Muscle sympathetic nerve firing rate increases as chronic heart failure (CHF) progresses, yet its oscillation, particularly within the frequency range encompassing 0.13 Hz, diminishes. The current study tested the hypothesis that chronic therapy with lipophilic β-adrenoceptor antagonists augments the modulation of muscle sympathetic nerve activity variability (MSNAV) at this frequency range. Methods and Results:In 21 CHF angiotensin converting enzyme (ACE) inhibitor-treated patients (age: 53±2, ejection fraction: 20±2%), MSNA was recorded before and after 4 months of β-blockade with either metoprolol (up to 50 mg b.i.d.) or carvedilol (up to 25 mg b.i.d.). Harmonic MSNAV was assessed by coarse graining spectral analysis. Both drugs lowered heart rate similarly (-13±2 beats/min; P<0.001) but neither affected MSNA burst frequency (-7±4 bursts/min, not significant). Before β-blockade, harmonic MSNA power in the region encompassing 0.13 Hz was essentially absent. Beta-blockade increased the mean values for total power (from 0.00 to 0.50 Hz; 5.2±0.8 to 6.8±1.2 U 2 ; P<0.001) and for harmonic MSNA spectral power across the 0.1-0.22 Hz frequency range (from 0.48±0.10 to 1.50±0.32 U 2 , F=12.2; P<0.001). Both carvedilol and metoprolol had a similar effect. Conclusions:In patients with CHF receiving ACE inhibitors, adding a β-adrenoceptor antagonist restores low and high frequency harmonic oscillations in MSNA. Beta-1 antagonism is sufficient to achieve this response. Augmented modulation of sympathetic outflow could contribute to the beneficial effects of β-blockade in CHF on sudden death and disease progression. (Circ J 2011; 75: 1400 - 1408

Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients

“…20 We and others showed excellent reproducibility of MSNA measurements over weeks and months. 21,22 Given a surprisingly low intraindividual variability over years, 23 MSNA is a suitable readout for longitudinal studies in small samples. Central sympathetic inhibition is associated with heart rate, blood pressure, plasma norepinephrine, and MSNA reductions.…”

Intradialysis Hypertension in End-Stage Renal Disease Patients

“…In patients with heart failure on ACEIs, β-blockers do not reduce background sympathetic nerve discharge but restore low-and high-frequency harmonic oscillations in sympathetic nerve activity. 58 Therefore, treatment with a long acting β-blocker may afford background cardiovascular protection, an issue of paramount relevance in a condition like intradialysis hypertension, characterized by background systemic hypertension.…”

Do high doses of AT1-receptor blockers attenuate central sympathetic outflow in humans with chronic heart failure?

“…CGSA extracts mathematically broadband non-harmonic, central oscillatory, components of MSNA variability [23]. MSNA harmonic power was then determined for each 0.01 increment from 0 to 0.50 Hz [14,17,18] by investigators who were unaware of the subjects' losartan dose.…”

“…Advanced heart failure is characterized, in addition, by loss of the variability of central sympathetic outflow, determined using spectral analysis [14][15][16]. MSNA spectral power within the low-frequency range can be augmented or restored by acute infusion of atrial natriuretic peptide (but not nitroglycerine) or, independently of any effect on MSNA burst frequency or incidence, by 4-6 months of treatment with the centrally acting β-adrenoreceptor antagonists carvedilol and metoprolol [17,18]. We therefore submitted the MSNA signal to spectral analysis, as an additional test of the hypothesis that the higher dose of the ARB would have greater effect on the central generation and modulation of sympathetic discharge.…”