Beneficial effect of If-channel inhibition on exercise tolerance in heart failure with preserved ejection fraction

Abstract

Effective treatments for heart failure with preserved ejection fraction (HFpEF) are elusive. As symptoms are typically exertional, heart rate control may allow optimal LV diastolic filling, thereby reducing raised filling pressures and resultant dyspnea. Ivabradine-a sinus node If channel inhibitor has been lately acknowledged as a useful treatment option of systolic heart failure. This study was designed to test the effects of ivabradine on exercise capacity and LV function, particularly in the context of LV filling pressure response to exercise, in patients with HFpEF. Methods: Sixty one patients with HFpEF were randomly assigned to ivabradine 5 mg b.i.d. (n=30) or placebo (n=31) for 7 days. Cardiopulmonary exercise testing with echocardiographic assessment of myocardial function, including measurement of E/e' ratio approximating LV filling pressure, at rest and post exercise were undertaken. Results: The ivabradine group demonstrated significant improvement in exercise capacity as assessed by METs and peak VO2, with simultaneous reduction in exercise-induced increase in E/e'. No analogous changes were seen after placebo. In addition, improvement in resting LV lusitropic function as indicated by increase in E/A ratio (0.91+0.38 at baseline vs. 1.07+0.38 at follow-up, p<0.002) and tissue e' (5.4+1.1 cm/s at baseline vs. 6.1+1.3 cm/s at follow-up, p<0.007) was found with ivabradine. Among the independent correlates of exercise capacity improvement were: for increase in METs - therapy with ivabradine (beta=0.34, p<0.04) and treatment-induced limitation in exertional increase in E/e' (beta=-0.30, p<0.02), and for increase in peak VO2 - therapy with ivabradine (beta=0.32, p<0.007). (Table presented) Conclusion: In patients with HFpEF, short-term treatment with ivabradine increased exercise capacity and a contributor to this beneficial effect was improved LV filling pressure response to exercise as reflected by E/e' ratio. Since HFpEF population is symptomatic on exertion, therapeutic treatments targeting abnormal exercise hemodynamics may prove useful.