Selective Versus Nonselective β-Adrenergic Receptor Blockade in Chronic Heart Failure: Differential Effects on Myocardial Energy Substrate Utilization

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Abstract
Background: Non-selective and selective β-blockers have been shown to improve outcomes in chronic heart failure (CHF). Recent data suggests the non-selective β-blockers have a more favourable effect on outcomes than β1-selective agents. We sought to examine the differential effects of non-selective versus selective β-blockade on myocardial substrate utilization in patients with CHF. Methods and results: Twenty-two patients with CHF were randomised to the non-selective β-blocker carvedilol or the selective β-blocker metoprolol (double-blind). Measurement of hemodynamics, arterial and coronary sinus free fatty acid (FFA) and lactate levels, and cardiac norepinephrine spillover (CANESP) were made before and after 4 months of therapy. In the carvedilol group (n=11), there was a significant reduction in myocardial FFA uptake (0.12±0.02 to 0.1±0.02 mmol/l, P<0.03). By contrast, in the metoprolol group (n=11) there was no change in myocardial FFA extraction. Carvedilol therapy tended to increase myocardial lactate extraction (0.24±0.05 to 0.35±0.08 mmol/l, P=0.08) while metoprolol therapy resulted in a trend in the opposite direction (0.18±0.03 to 0.11±0.04 mmol/l, P=0.09). The change in lactate extraction in the carvedilol group was significantly different from that in the metoprolol group (+0.11±0.06 vs. −0.09±0.04 mmol/l, P<0.01). Carvedilol treatment caused a significant reduction in CANESP while metoprolol had a neutral effect (−95±27 vs. 25±42 pmol/min, carvedilol vs. metoprolol P<0.03). Conclusion: Carvedilol treatment caused a 20% reduction in myocardial free fatty acid extraction while metoprolol had a neutral effect. These differences are most probably related to the differential effects of these two agents on efferent cardiac sympathetic activity and may be relevant to the reported differential effects of these drugs on clinical outcomes.

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