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

Circ Cardiovasc Imaging. 2017 Oct;10(10):e006557. doi: 10.1161/CIRCIMAGING.117.006557.

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 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.

Keywords: aortic valve stenosis; magnetic resonance imaging; metoprolol; oxygen consumption; positron-emission tomography.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / adverse effects
  • Adrenergic beta-1 Receptor Antagonists / therapeutic use*
  • Aged
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / drug effects*
  • Aortic Valve / metabolism
  • Aortic Valve / physiopathology
  • Aortic Valve Stenosis / diagnostic imaging
  • Aortic Valve Stenosis / drug therapy*
  • Aortic Valve Stenosis / metabolism
  • Aortic Valve Stenosis / physiopathology
  • Asymptomatic Diseases
  • Denmark
  • Double-Blind Method
  • Echocardiography, Doppler
  • Energy Metabolism / drug effects*
  • Female
  • Hemodynamics / drug effects*
  • Humans
  • Magnetic Resonance Imaging, Cine
  • Male
  • Metoprolol / adverse effects
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Oxygen Consumption / drug effects
  • Positron-Emission Tomography
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Metoprolol

Associated data

  • ClinicalTrials.gov/NCT02076711