Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients

Abstract

Background— Currently, no pharmacological treatment can modify the natural history of aortic valve stenosis (AS). This underlines the critical need to explore novel treatment strategies, which could postpone or prevent the need for aortic valve replacement in patients with asymptomatic AS. The objectives of this study were to investigate whether metoprolol reduce the hemodynamic and metabolic burden imposed by AS. Methods and Results— In a double-blinded design, 40 patients with moderate-severe asymptomatic AS (aortic valve area, 0.5±0.1 cm 2 /m 2 ; peak gradient, 53±19 mm Hg) were randomized to placebo or metoprolol treatment for 22 weeks. Patients were evaluated by echocardiography, cardiovascular magnetic resonance, and 11 C-acetate positron emission tomography. Compared with placebo, metoprolol (100±53 mg/d) decreased heart rate; mean difference (95% confidence interval) −8 minute − 1 (−13, −3; P =0.003) and increased ejection time 26 ms (2, 50; P =0.03). Furthermore, metoprolol reduced aortic valve peak −7 mm Hg (−13, 0; P =0.05) and mean −4 mm Hg (−7, −1; P =0.03) gradients, without affecting stroke volume 3 mL/m 2 (−2, 8; P =0.16). Valvuloarterial impedance (ie, global afterload) and myocardial oxygen consumption were reduced by −11% and −12% ( P =0.03 and 0.01), respectively; and decreased heart rate correlated with lower valvuloarterial impedance, myocardial oxygen consumption, and improved myocardial efficiency defined as stroke work/myocardial oxygen consumption ( r =0.63–0.65; all P <0.01). There were 2 adverse cardiovascular events in the metoprolol group and none in the placebo group. Conclusions— In patients with asymptomatic AS, metoprolol increases systolic ejection time and reduces aortic valve gradients, global afterload, and myocardial oxygen requirements. Thus, metoprolol displays favorable hemodynamic and metabolic effects and could improve outcome in patients with asymptomatic AS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02076711.

Antihypertensive Treatment in Severe Aortic Stenosis

“…The decrease in heart rate by metoprolol was significantly associated with lower valvuloarterial impedance, myocardial oxygen consumption, and improved myocardial efficiency, defined as stroke work/myocardial oxygen consumption (r = 0.63–0.65; all p < 0.01). 23) Thus, the results from the above mentioned studies suggest that β-blockers may have beneficial hemodynamic and metabolic effects and may potentially be favorable in improving the outcome of patients with asymptomatic moderate-severe AS patients ( Table 1 ).…”

“… 22) The benefit of β-blocker may be due to their potential benefits in terms of reducing hemodynamic and metabolic overload in AS. In a study by Hansson et al 23) , 40 patients with moderate-severe asymptomatic AS (aortic valve area, 0.5 ± 0.1 cm 2 /m 2 ; peak gradient, 53 ± 19 mmHg) were randomized to placebo or metoprolol treatment for 22 weeks. Metoprolol (100 ± 53 mg/d), compared with placebo, significantly decreased the heart rate by −8 beats per minute (−13, −3; p = 0.003) and increased the systolic ejection time by 26 ms (2, 50; p = 0.03).…”

A randomised, double‐blind, placebo‐controlled trial of metformin on myocardial efficiency in insulin‐resistant chronic heart failure patients without diabetes

“…11,31 Myocardial mitochondrial activity is closely coupled to MVO 2 as 95% of cardiac cellular energy demand is covered by mitochondrial oxidative phosphorylation. 2 We measured MVO 2 using a robust and validated non-invasive technique of 11 C-acetate PET, 20,21,26,32 thereby translating the experimental discoveries to humans. The present study thus implies a beneficial effect of metformin on mitochondrial function in the failing heart.…”

CT imaging prior to transcatheter aortic valve implantation in the UK

“…The use of CT-TAVI to evaluate the patency of coronary artery bypass grafts and native coronary arteries is feasible, however as periprocedural medication (beta-blocker, glyceryl trinitrate) that is routinely administered for coronary CT angiography is contraindicated in the setting of severe aortic stenosis, optimal images may not always be obtained 20. Interestingly, while selective beta-blockade has been used in the context of severe asymptomatic21 and symptomatic aortic stenoses,22 there is a paucity of evidence supporting the safety of intravenous metoprolol administration during CT-TAVI acquisition. If beta1-selective blockade is to be considered on an individual basis, the patient should be counselled on the risks of exacerbating symptoms related to aortic stenosis.…”