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Effect of If-Channel Inhibition on Hemodynamic Status and Exercise Tolerance in Heart Failure With Preserved Ejection Fraction: A Randomized Trial

Citation

Kosmala, W and Holland, DJ and Rojek, A and Wright, L and Przewlocka-Kosmala, M and Marwick, TH, Effect of If-Channel Inhibition on Hemodynamic Status and Exercise Tolerance in Heart Failure With Preserved Ejection Fraction: A Randomized Trial, Journal of the American College of Cardiology, 62, (15) pp. 1330-1338. ISSN 0735-1097 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 the American College of Cardiology Foundation

DOI: doi:10.1016/j.jacc.2013.06.043

Abstract

Objectives The aim of this study was to test the effects of treatment with ivabradine on exercise capacity and left ventricular filling in patients with heart failure with preserved ejection fraction (HFpEF). Background Because symptoms of HFpEF are typically exertional, optimization of diastolic filling time by controlling heart rate may delay the onset of symptoms. Methods Sixty-one patients with HFpEF were randomly assigned to ivabradine 5 mg twice daily (n = 30) or placebo (n = 31) for 7 days in this double-blind trial. Cardiopulmonary exercise testing with echocardiographic assessment of myocardial function and left ventricular filling were undertaken at rest and after exercise. Results The ivabradine group demonstrated significant improvement between baseline and follow-up exercise capacity (4.2 ± 1.8 METs vs. 5.7 ± 1.9 METs, p = 0.001) and peak oxygen uptake (14.0 ± 6.1 ml/min/kg vs. 17.0 ± 3.3 ml/min/kg, p = 0.001), with simultaneous reduction in exercise-induced increase in the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity (3.1 ± 2.7 vs. 1.3 ± 2.0, p = 0.004). Work load-corrected chronotropic response (the difference in heart rate at the same exercise time at the baseline and follow-up tests) showed a slower increase in heart rate during exercise than in the placebo-treated group. Therapy with ivabradine (β = 0.34, p = 0.04) and change with treatment in exertional increase in the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity (β = -0.30, p = 0.02) were independent correlates of increase in exercise capacity, and therapy with ivabradine (β = 0.32, p = 0.007) was independently correlated with increase in peak oxygen uptake. Conclusions In patients with HFpEF, short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity. Because this patient population is symptomatic on exertion, therapeutic treatments targeting abnormal exercise hemodynamic status may prove useful. (Use of Exercise and Medical Therapies to Improve Cardiac Function Among Patients With Exertional Shortness of Breath Due to Lung Congestion; ACTRN12610001087044). © 2013 by the American College of Cardiology Foundation.

Item Details

Item Type:Refereed Article
Keywords:diastolic function, heart failure with preserved ejection fraction, ivabradine
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Wright, L (Ms Leah Wright)
Author:Marwick, TH (Professor Tom Marwick)
ID Code:87457
Year Published:2013
Web of Science® Times Cited:90
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-11-19
Last Modified:2014-05-02
Downloads:0

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