Cardiac functional benefits of ivabradine therapy in patients with severe heart failure

摘要

Ivabradine is the first I_f channel inhibitor in use in clinical practice [1 ], mainly acting specifically on the sinoatrial node to slow the heart rate (HR). The SHIFT study [2] has shown that fewer patients taking ivabradine than placebo suffered a primary endpoint event of a composite of cardiovascular death or hospital admission for worsening heart failure (HR 0.82, 95% CI 0.75-0.90, p<0.0001), and deaths due to HF were also significantly reduced (HR 0.74,0.58-0.94, p = 0.014). The data from SHIFT also suggest that the prognostic benefits of ivabradine are related to the HR lowering effects of the agent [3]. Based on these results, in Europe ivabradine prescription is currently "indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is >75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated". However, since a common feature of HF is chronotropic incompetence [4], it would seem puzzling how a purely negatively chronotropic agent such as ivabradine, liable to worsen the chronotropic incompetence, could possibly confer clinical benefits. Currently there is information gap about how HF patients could functionally benefit from ivabradine therapy. We report three empirical comparisons with and without ivabradine therapy in two patients with severe HF who showed significant cardiac and physical functional benefits from ivabradine, thereby revealing its potential mechanisms of actions.