Cardiac β-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling

Abstract

After myocardial infarction (MI), left ventricular (LV) remodelling is observed in noninfarcted LV myocardium. LV remodelling is closely associated with systolic heart failure. Since myocardial dysfunction is related to the downregulation of cardiac postsynaptic beta-adrenergic receptors (β-AR), we hypothesized that a reduction in β-AR density may be manifested in the remote noninfarcted region and such reduction may be related to myocardial systolic dysfunction. Accordingly, we assessed β-AR density with a focus on the remote noninfarcted region. Cardiac PET was performed in 15 patients with a prior MI and 10 age-matched healthy controls using (11)C-CGP 12177, a radioligand for β-receptors. The maximum number of available specific (11)C-CGP 12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method. LV regional systolic function was assessed based on peak systolic myocardial strain on the LV wall in the longitudinal direction using two-dimensional ultrasound speckle tracking imaging. LV volumes and LV ejection fraction (EF) were also measured. The LV end-diastolic volume index was significantly larger in patients than in controls (67.8 ± 16.9 vs. 49.1 ± 12.3 ml/m(2), p < 0.01). Significant differences in β-AR density were observed among three areas: the apical area in controls (where the lowest β-AR density was observed), the remote noninfarcted region of patients and LVEF ≥ 55 %, and the remote noninfarcted region of patients and LVEF <55 % (5.8 ± 2.1 vs. 4.2 ± 0.7 vs. 3.3 ± 0.7 pmol/ml, p < 0.01, ANOVA). Peak systolic myocardial strain was significantly reduced in the remote noninfarcted LV wall in patients with a prior anterior wall MI compared with that in the corresponding wall in controls (-15.5 ± 2.5 vs. -20.1 ± 2.2 %, p < 0.001). A similar finding was also observed in patients with a prior inferior wall MI. In the remote noninfarcted region in patients, β-AR downregulation was observed, which was related to deterioration of local myocardial systolic function.