From the Department of Cardiology (N.H.H., W.Y.K., R.N., S.H.P., H.W.) and Department of Nuclear Medicine and PET-Center (J.S., H.J.H., L.P.T., J.F., K.B.), Aarhus University Hospital, Denmark; Department of Cardiology, Horsens Regional Hospital, Denmark (K.K.D.); and Aarhus Hjerteklinik, Denmark (I.S.).
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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 cm2/m2; 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 11C-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/m2 (−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.