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Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial.

Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial.
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Hansson NH, Sörensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frøkiær J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H,


Hansson NH, Sörensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frøkiær J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H, (click to view)

Hansson NH, Sörensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frøkiær J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H,

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Circulation. Cardiovascular imaging 10(10) pii e006557
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.

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