Abstract 1867: Beta-Blockade Augments Low Frequency Muscle Sympathetic Spectral Power in Human Heart Failure
Background: Oscillations in central sympathetic discharge to muscle within the low frequency (LF) range encompassing 0.13Hz disappear as chronic heart failure (CHF) progresses. This altered central modulation of sympathetic outflow is improved by atrial natriuretic peptide infusion and by cardiac transplantation. We tested the hypothesis that chronic therapy with lipophilic β-adrenoceptor antagonists augments muscle sympathetic nerve activity variability (MSNAV) within this LF range.
Methods and results: In 21 CHF ACE inhibitor-treated patients (age: 53±2, ejection fraction: 20±2%), resting heart rate (HR), blood pressure and MSNA were recorded before and after 4 months of randomized double-blind allocation of β-blockade with either metoprolol (up to 50 mg b.i.d.) or carvedilol (up to 25 mg b.i.d.). MSNAV was assessed by coarse graining spectral analysis. Both drugs had similar effects on HR (−13±2 bpm; p<0.001). Neither affected MSNA burst frequency (−7±4 bursts/min, n.s.). Before β-blockade, harmonic MSNA power in the region encompassing 0.13 Hz was essentially absent. β-blockade increased total MSNA spectral power (p<0.001) and restored harmonic MSNAV power across the 0.1–0.22 Hz frequency range (from 0.48±0.10 to 1.50±0.32 U2/Hz, F=9.06; p<0.003). (p<0.003), with carvedilol and metoprolol having similar effect.
Conclusion: In patients with CHF receiving ACE inhibitors, the addition of lipophilic β-adrenoceptor antagonists restored harmonic oscillation in MSNA over the frequency range of 0.1–0.22 Hz. β-1 antagonism appears sufficient for this purpose. Augmented central neural modulation of sympathetic outflow could contribute to the beneficial effects of β-blockade on sudden death and disease progression in CHF. Figure Legend Figure 1 Mean values with standard errors for MSNA harmonic power derived from CGSA before (open circles) and after (closed circles) β-adrenoceptor blockade (n=21). There is a significant increase (p<0.003) in MSNA harmonic power across the frequency range of 0.1–0.22 Hz.