Autoantibody against β1-adrenergic receptor and left ventricular remodeling changes in response to metoprolol treatment

Background Autoantibodies specific for the β 1 -adrenoceptor (β 1 -AR) have been implicated in the pathology of congestive heart failure (CHF). We hypothesized that the presence of autoantibodies against β 1 -AR (anti-β 1 -AR) is associated with left ventricular (LV) remodelling in response to metoprolol. Materials and methods Synthetic β 1 -AR peptides served as the target antigen in an ELISA (enzyme-linked immunosorbent assay) were used to screen the sera of 106 CHF patients. Patients were separated into positive (+) anti-β 1 -AR or negative (-) anti-β 1 -AR groups according to their anti-β 1 -AR reactivity. Echocardiography (ECG) was performed at baseline and after one year of metoprolol therapy in combination with standard treatment regime for CHF, that is, digoxin, diuretics and an ACEI (angiotensin-converting enzyme inhibitor). The dose of metoprolol was doubled on a biweekly basis up to 50 mg x 2 daily (b.i.d./day) or attainment of maximum tolerated dose. Results Ninety-six patients completed final data analysis. Fifty-four patients with (+) anti-β 1 -AR had greater improvements than 42 patients with (-) anti-β 1 -AR in LVEDD (left ventricular end-diastolic dimension) (P<0·01, from 69 ± 0·8 to 58·0 ± 0·5 mm vs. 69·0 ± 0·8-63·6 ± 0·9 mm) and LVESD (left ventricular end-systolic dimension) (P < 0·01, from 57·1 ± 1·4 to 43·9 ± 0·8 mm vs. 56·2 ± 0·9-48·6 ± 1·0 mm), and LVEF (left ventricular ejection fraction) (P < 0·01, from 35·4 ± 1·3 to 49·8 ± 0·6% vs. 34·4 ± 1·0-44·3 ± 1·1%) by metoprolol therapy in combination with standard treatment regime for one year. Of the CHF patients with (+) anti-β 1 -AR, 65·4% responded to target metoprolol dose as compared to 21-4% of CHF patients without anti-β 1 -AR (P < 0·01). Response to target metoprolol dose occurred more rapidly in (+) anti-β 1 -AR than (-) anti-β 1 -AR of CHF patients (67·5 ± 2·4 vs. 100·8 ± 3·0 days, P < 0·01). Conclusion These results demonstrated that CHF patients with (+) anti-β 1 -AR had greater improvements in LV remodelling and heart function by metoprolol as compared to (-) anti-β 1 -AR patients. Moreover, patients with (+) antι-β 1 -AR have better tolerance to metoprolol therapy than patients without anti-β 1 -AR.