EFFECTS OF A SELECTIVE ADENOSINE-A1-RECEPTOR AGONIST ON HEART-RATE AND HEART-RATE-VARIABILITY DURING PERMANENT ATRIAL-FIBRILLATION

Background: Mean heart rate and irregularity of the rate, i.e., heart rate variability (HRV), are two aspects of heart rate during atrial fi brillation (AF). An important goal of AF therapy is to control mean he art rate during exercise; the determinants of HRV during AF remain poo rly known although its prognostic value has been established. Objectiv es: To investigate the effects of a stable, long-acting, selective AZ- adenosine receptor agonist; SDZ WAG994, on heart rate during exercise and on HRV. Methods: In a multicenter, double-blind, randomized, place bo-controlled, parallel group study, patients with permanent AF perfor med a symptom-limited exercise test and underwent 24-hour ECG monitori ng on day 1 during treatment with placebo, and on day 2 during treatme nt with either placebo or 2 mg SDZWAG994 orally. Changes in mean heart rate during exercise and changes in HRV indices between day 2 and day 2 were compared between the two groups. Results: Thirty-two patients (64 +/- 8 years; 81 % male; 25% in NYHA Class II; 38% with no structur al heart disease) were included in the study. During active treatments , heart rate remained unchanged at rest and increased significantly du ring exercise. A significant daytime increase in short-term HRV indice s (DpNN50 = 4,5% P = 0.01; DrMSSD = 6% P = 0.03; DSDNN Index = 6% P = 0.02) occurred during active treatment. Conclusions: Selective AI-aden osine receptor agonism with SDZ/WAG994 limits the increase in mean hea rt rate during exercise in patients with AF. In addition, this agonist selectively increases short-term HRV indices, suggesting that pNN50, rMSSD, and SDNN reflect vagal influences during AF.