A randomized controlled phase IIb trial of beta(1)-receptor blockade for chronic degenerative mitral regurgitation.

Academic Article


  • OBJECTIVES: The purpose of the study was to evaluate the effect of long-term β(1)-aderergic receptor (AR) blockade on left ventricular (LV) remodeling and function in patients with chronic, isolated, degenerative mitral regurgitation (MR). BACKGROUND: Isolated MR currently has no proven therapy that attenuates LV remodeling or preserves systolic function. METHODS: Thirty-eight asymptomatic subjects with moderate to severe, isolated MR were randomized either to placebo or β(1)-AR blockade (Toprol-XL, AstraZeneca, London, United Kingdom) for 2 years. Magnetic resonance imaging with tissue tagging and 3-dimensional analysis was performed at baseline and at 6-month intervals for 2 years. Rate of progression analysis was performed for endpoint variables for primary outcomes: LV end-diastolic volume/body surface area, LV ejection fraction, LV end-diastolic (ED) mass/ED volume ratio, LV ED 3-dimensional radius/wall thickness; LV end-systolic volume/body surface area, LV longitudinal strain rate, and LV early diastolic filling rate. RESULTS: Baseline LV magnetic resonance imaging or demographic variables did not differ between the 2 groups. Significant treatment effects were found on LV ejection fraction (p = 0.006) and LV early diastolic filling rate (p = 0.001), which decreased over time in untreated patients on an intention-to-treat analysis and remained significant after sensitivity analysis. There were no significant treatment effects found on LV ED or LV end-systolic volumes, LV ED mass/LV ED volume or LV ED 3-dimensional radius/wall thickness, or LV longitudinal strain rate. Over 2 years, 6 patients treated in the placebo group and 2 patients in the β(1)-AR blockade group required mitral valve surgery (p = 0.23). CONCLUSIONS: β(1)-AR blockade improves LV function over a 2-year follow-up in isolated MR and provides the impetus for a large-scale clinical trial with clinical outcomes. (Molecular Mechanisms of Volume Overload-Aim 1 [SCCOR in Cardiac Dysfunction and Disease]; NCT01052428).
  • Keywords

  • Adrenergic beta-Antagonists, Adult, Aged, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Metoprolol, Middle Aged, Mitral Valve Insufficiency, Treatment Outcome, Ventricular Remodeling
  • Digital Object Identifier (doi)

    Author List

  • Ahmed MI; Aban I; Lloyd SG; Gupta H; Howard G; Inusah S; Peri K; Robinson J; Smith P; McGiffin DC
  • Start Page

  • 833
  • End Page

  • 838
  • Volume

  • 60
  • Issue

  • 9