P1468Pyridostigmine, but not ivabradine, improves autonomic function after dynamic exercise in patients with heart failure

Abstract

Background: Heart rate recovery in the first minute after exercise (HR 1 min) is a marker of parasympathetic activity and has been considered a strong prognostic marker. The expected rapid vagal tone reactivation after exercise is blunted in heart failure (HF) patients. Purpose: We sought to study the effects of long-term use of either pyridostigmine (PYR) or ivabradine (IVA) on physiologic responses to dynamic exercise in patients with HF. Methods: Patients with chronic HF who were in sinus rhythm, with resting HR>70 bpm despite optimal medical treatment, were included in a randomized, double blind study comparing IVA versus PYR. IVA initial dose was 5 mg twice daily to a target HR of 50 to 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. PYR was used in a fixed dose of 30 mg three times daily. Patients underwent maximal cardiopulmonary exercise test on treadmill at baseline and after 6 months of drug use. HR 1 min was defined as the difference between peak HR during exercise and HR measured 1 minute after exercise. Results: Resting HR was reduced with both drugs (85.6±14 vs 68±11.2 in the IVA group and 80.1±12.6 vs 66.8±6.4 in the PYR group). Peak HR during exercise did not change significantly in either group (IVA 114.4±13.4 vs 105.7±14.7, p=0.27 and PYR 116.2±18.7 vs 118.8±25.4, p=0.76). Oxygen pulse, an indirect indicator of stroke volume, improved in both groups (IVA 8.5±3.9 vs 10.8±3.6, p=0.023 and PYR 10.1±1.6 vs 11.6±1.8, p=0.003). Peak VO2 was improved with both drugs (IVA 13.1±3 vs 15.6±3.8, p=0.048; PYR 13.3±3.8 vs 16.7±5.8 ml/kg/min, p=0.032). HR 1 min improved with PYR (11.8±3.9 vs 18±6.5, p=0.046) but not with IVA (13.3±6.9 vs 14.1+8.2, p=0.70). Conclusion: Our findings indicate that PYR improves autonomic function after exercise in patients with HF. On the other hand, IVA modulates resting HR but seems not to influence peak HR during exercise nor HR recovery after exercise.