Autoantibody against beta1-adrenergic receptor and left ventricular remodeling changes in response to metoprolol treatment.
Autoantibodies specific for the beta(1)-adrenoceptor (beta(1)-AR) have been implicated in the pathology of congestive heart failure (CHF). We hypothesized that the presence of autoantibodies against beta(1)-AR (anti-beta(1)-AR) is associated with left ventricular (LV) remodelling in response to metoprolol. Synthetic beta(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-beta(1)-AR or negative (-) anti-beta(1)-AR groups according to their anti-beta(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. Ninety-six patients completed final data analysis. Fifty-four patients with (+) anti-beta(1)-AR had greater improvements than 42 patients with (-) anti-beta(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-beta(1)-AR, 65.4% responded to target metoprolol dose as compared to 21.4% of CHF patients without anti-beta(1)-AR (P < 0.01). Response to target metoprolol dose occurred more rapidly in (+) anti-beta(1)-AR than (-) anti-beta(1)-AR of CHF patients (67.5 +/- 2.4 vs. 100.8 +/- 3.0 days, P < 0.01). These results demonstrated that CHF patients with (+) anti-beta(1)-AR had greater improvements in LV remodelling and heart function by metoprolol as compared to (-) anti-beta(1)-AR patients. Moreover, patients with (+) anti-beta(1)-AR have better tolerance to metoprolol therapy than patients without anti-beta(1)-AR.
Miao
G B
GB
Beijing Chaoyang Hospital-Affiliate of Capital University of Medical Sciences, Beijing, China.
Liu
J C
JC
Liu
M B
MB
Wu
J L
JL
Zhang
G
G
Chang
J
J
Zhang
L
L
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D001323:Autoantibodies / Q000097:blood*; D004334:Drug Administration Schedule; D005080:Exercise Test / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects*; D016138:Walking / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol