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β-Blockers and ivabradine differentially affect cardiopulmonary function and left ventricular filling index

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Abstract

Objective

Patients with left ventricular (LV) diastolic dysfunction are characterized by exertional dyspnoea. Heart rate (HR) reduction by β-blockers can improve exercise tolerance by prolonging LV filling, but their negative inotropic and lusitropic properties can be detrimental in this disease. We tested the effects of administering ivabradine, a HR-lowering drug without impact on cardiac kinetics that may favorably affect diastolic function.

Methods

Twenty-four patients with coronary artery disease (CAD) and normal LV ejection fraction on chronic β-blocker therapy were included. NT-proBNP serum levels were determined prior to and after cardiopulmonary exercise. β-Blockers were then replaced by ivabradine and patients were re-tested after 6 weeks. Patients were initially classified as having a low (E/e′ ≤ 8; n = 11) or high (E/e′ > 8; n = 13) LV filling index.

Results

E/e′ significantly decreased during ivabradine therapy in patients with high E/e′ (10.7 ± 2.9 vs. 8.9 ± 1.7; p < 0.01), whereas no difference occurred in patients with low E/e′ (6.4 ± 0.7 vs. 6.5 ± 1.1; p = ns). With ivabradine, patients with high E/e′ had an increased oxygen uptake at the anaerobic threshold (from 10.8 ± 1.4 to 11.8 ± 1.9 ml/min/kg; p < 0.05) and a steeper slope of the initial oxygen pulse curve (from 293 ± 109 to 359 ± 117 µl/beat/kg/W; p < 0.05). Moreover, patients with high E/e′ had lower NT-proBNP serum levels at rest (169 ± 207 vs. 126 ± 146 pg/ml; p < 0.05) and after exercise (190 ± 256 vs. 136 ± 162 pg/ml; p < 0.05) during ivabradine therapy.

Conclusions

In patients with CAD and elevated E/e′, switching therapy from β-blockers to ivabradine may cause a reduction in LV filling pressures and an improved stroke volume response to exercise.

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Acknowledgments

We thank Elizabeth Martinson, PhD, from the KHFI Editorial Office for excellent editorial work.

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Authors and Affiliations

  1. Department of Cardiology, Kerckhoff Heart Center, Benekestr. 2-8, 61231, Bad Nauheim, Germany

    Ulrich Fischer-Rasokat, Sebastian Wolter, Christoph Liebetrau, Helge Möllmann & Christian W. Hamm

  2. Department of Cardiology, University Hospital of the Goethe University, Theodor-Stern-Kai 7, 60596, Frankfurt/Main, Germany

    Jörg Honold, Denise Lochmann, Stephan Fichtlscherer & Ioakim Spyridopoulos

Authors
  1. Ulrich Fischer-Rasokat
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  2. Jörg Honold
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  3. Denise Lochmann
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  4. Sebastian Wolter
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Correspondence to Ulrich Fischer-Rasokat.

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Conflict of interest

U. Fischer-Rasokat, H. Möllmann and C. Hamm report receiving lecture fees from Servier. No other potential conflict of interest relevant to this article was reported.

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Fischer-Rasokat, U., Honold, J., Lochmann, D. et al. β-Blockers and ivabradine differentially affect cardiopulmonary function and left ventricular filling index. Clin Res Cardiol 105, 527–534 (2016). https://doi.org/10.1007/s00392-015-0950-0

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  • DOI: https://doi.org/10.1007/s00392-015-0950-0

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