The purpose of the study was to evaluate the effect of long-term β1-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 β1-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 β1-AR blockade group required mitral valve surgery (p = 0.23).
Conclusions
β1-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)
Key Words
beta blockade
medical therapy
mitral regurgitation
mitral valve disease
Abbreviations and Acronyms
AR
adrenergic receptor
BSA
body surface area
CI
confidence interval
3D
3-dimensional
ED
end-diastolic
EDV
end-diastolic volume
EF
ejection fraction
ESV
end-systolic volume
LV
left ventricular
MR
mitral regurgitation
MRI
magnetic resonance imaging
Cited by (0)
This study was funded by the National Heart, Lung and Blood Institute Specialized Center for Clinically Oriented Research (SCCOR) in Cardiac Dysfunction, National Institutes of Health, Bethesda, Maryland (grant no.: P50HL077100). Drugs and placebos were supplied by AstraZeneca. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.