Effect of I-f-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction

Kosmala, Wojciech, Holland, David J., Rojek, Aleksandra, Wright, Leah, Przewlocka-Kosmala, Monika and Marwick, Thomas H. (2013) Effect of I-f-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction. Journal of the American College of Cardiology, 62 15: 1330-1338. doi:10.1016/j.jacc.2013.06.043


Author Kosmala, Wojciech
Holland, David J.
Rojek, Aleksandra
Wright, Leah
Przewlocka-Kosmala, Monika
Marwick, Thomas H.
Title Effect of I-f-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction
Formatted title
Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction
Journal name Journal of the American College of Cardiology   Check publisher's open access policy
ISSN 0735-1097
1558-3597
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.jacc.2013.06.043
Volume 62
Issue 15
Start page 1330
End page 1338
Total pages 9
Place of publication San Diego, CA, United States
Publisher Elsevier
Collection year 2014
Language eng
Formatted 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)
Keyword Diastolic function
Heart failure with preserved ejection fraction
Ivabradine
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Human Movement and Nutrition Sciences Publications
 
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