The Clinical Value Of Autoantibodies Against β₁-adrenoreceptor In Patients With Chronic Heart Failure

Background Numerous β-blockers have being used to treat patients with chronic heart failure (CHF). However, how to definite β-blockers target dose and titration speed appear to be more difficult in daily practice treatment. It was reported that autoantibodies against β₁-adrenoceptor (Anti-β₁-AR) is relative to CHF,but it was not clear if CHF treatment with a β₁-blockers would have a effect on the Anti-β₁-AR positive rate and titer. The clinic value of inspecting Anti-β₁-AR was under perspicuity. We hypothesized that selective β₁-AR blocker metoprolol may decrease the frequency and titer of Anti-β₁-AR in patients with CHF, and metoprolol might show better tolerability and quicker titration in patients with positive Anti-β₁-AR than negative patients. Objectives: This investigation objectives are to make sure that metoprolol may decrease the frequency and titer of Anti-β₁-AR in patients with CHF and show more better tolerability and quicker titration in patients with positive Anti-β₁-AR,prove that Anti-β₁-AR may be a valuable marker to direct CHF treatment and find out the clinic value of Anti-β₁-AR on CHF treatment. Methods: Synthetic peptides corresponded to the sequence of the second extracellular loop of β₁-adrenoceptors were used as antigens to screen sera from 106 patients with stable CHF by SA-ELISA. CHF patients were assigned to positive and negative group according to Anti-β₁-AR reactivity. Both groups received metoprolol for at least three years in addition to standard therapy for CHF. The initiation dosage of metoprolol was 6.25mg ×2/day,then the dosage was titrated step by step to 50mg ×2/day or the maximal tolerance dosage. During follow up period the left ventricular ejection fraction (LVEF) and cavity dimension was evaluated periodically by echocardiogram in both positive and negative group,heart function was evaluated by NYHA class,liver and renal function , electrolure, blood glucose,and plasma lipids were examinated at the same time .Results: Metoprolol significantly decreased the frequencies of Anti-β₁-AR in positive group (100%vs.55.4%,P<0.01). The average dose of metoprolol was 43.3±9.8 mg×2/day in positive group and 30.9±12.9mg×2/day in negative group. 59.0% of patients in positive group received the maximal dose 50mg ×2/day, but only 20.0% in negative group received the maximal dose. The mean time to maximum titration in positive group was 78.5±12.1 days versus 90.8±25.0 days in negative group. When follow up concluded, heart function and cavity dimensions were improved to similar degree in both positive and negative group. Conclusions The patients with positive Anti-β₁-AR could be changed to negative or the frequencies and titer of Anti-β₁-AR could be significantly decreased by long-term oral metoprolol when added with digoxin, diuretics and an ACE-inhibitor. Long-term standard treatment for CHF could improve significantly heart function and cavity dimension. Positive patients showed more better tolerability and quicker titration for metoprolol than negative patients. Anti-β₁-AR may be a valuable marker for Monitoring and directing CHF treatment with a β₁-AR blocker.