β1-Receptor Blockade for Chronic Mitral Regurgitation - β1-Receptor Blockade for Chronic Mitral Regurgitation

Description:

The goal of the trial was to evaluate treatment with beta-blockade compared with placebo among patients with moderate to severe mitral regurgitation.

Hypothesis:

Beta-blockade will attenuate left ventricular (LV) remodeling and preserve systolic function.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Patients with moderate to severe mitral regurgitation
  • LVEF >55%
  • LV end-systolic dimension <40 mm
  • Echocardiographic thickening of mitral valve leaflets and prolapse

    Number of enrollees: 38
    Duration of follow-up: 2 years
    Mean patient age: 53 years
    Percentage female: 58%
    Ejection fraction: 62%
    New York Heart Association (NYHA) class: 100% with functional class I or II

Exclusions:

  • Patients with New York Heart Association functional class III or IV symptoms
  • Prior myocardial infarction or significant coronary artery disease
  • Valvular disease other than mitral
  • Renal insufficiency
  • Hypertension

Primary Endpoints:

  • Change in LV EDV/BSA
  • Change in LV ED mass /LV EDV
  • Change in LV ED radius/wall thickness
  • Change in LV EF
  • Change in LV ESV/BSA
  • Change in peak systolic longitudinal strain rate
  • Change in peak early filling rate

Drug/Procedures Used:

Asymptomatic patients with moderate to severe mitral regurgitation were randomized to metoprolol succinate (Toprol XL) 25-100 mg daily (n = 19) versus placebo (n = 19) for 2 years. Metoprolol succinate was titrated every 2 weeks to a maximum of 100 mg daily. Cardiac magnetic resonance imaging (MRI) was performed at baseline, and 6, 12, 18, and 24 months.

Principal Findings:

Overall, 38 patients were randomized. The mean age was 53 years, 58% were women, mean blood pressure was 125/75 mm Hg, mean heart rate was 66 bpm, and mean ejection fraction (EF) was 62%. No patient had atrial fibrillation.

At 2 years, there was no change in LV end-diastolic volume/body surface area (EDV/BSA), LV ED mass/LV EDV, LV ED radius/wall thickness, LV end-systolic volume/BSA, and peak systolic longitudinal strain rate for beta-blockade versus placebo.

However, at 2 years there was a benefit favoring beta-blockade for LVEF (p = 0.0060), and peak early filling rate (p = 0.0011).

Interpretation:

In this small pilot trial, in patients with asymptomatic moderate to severe mitral regurgitation, 2 years of beta-blockade treatment prevented progressive decline in LVEF compared with placebo. However, beta-blockade did not prevent parameters of LV remodeling. A large multicenter trial appears warranted.

References:

Ahmed MI, Aban I, Lloyd SG, et al. A Randomized Controlled Phase IIb Trial of β1-Receptor Blockade for Chronic Mitral Regurgitation. J Am Coll Cardiol 2012;Jul 18:[Epub ahead of print].

Clinical Topics: Noninvasive Imaging, Valvular Heart Disease, Magnetic Resonance Imaging, Mitral Regurgitation

Keywords: Body Surface Area, Follow-Up Studies, Mitral Valve Insufficiency, Stroke Volume, Blood Pressure, Metoprolol, Heart Rate, Magnetic Resonance Imaging


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