The Effect of Selective Heart Rate Slowing in Heart Failure with Preserved Ejection Fraction

Houman Ashrafian, Nikhil Pal, Nadiya Sivaswamy, Masliza Mahmod, Arash Yavari, Amelia Rudd, Satnam Singh, Dana K Dawson, Jane M Francis, Jeremy S Dwight, Hugh Watkins, Stefan Neubauer, Michael Frenneaux

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BACKGROUND: -Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF.

METHODS AND RESULTS: -We conducted a randomised, crossover study comparing selective heart rate reduction with the If blocker, ivabradine at 7.5 mg twice daily, versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise, VO2 peak, <80% predicted for age and sex). The result was compared to 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in VO2 peak. Secondary outcomes included tissue Doppler derived E/e' at echocardiography, plasma BNP and quality of life scores. Ivabradine significantly reduced peak heart rate compared to placebo in the HFpEF (107 vs. 129 bpm, P<0.0001) and Hypertensive (127 vs. 145 bpm, P=0.003) cohorts. Ivabradine, when compared to placebo, significantly worsened the change in VO2 peak in the HFpEF cohort (-2.1 vs 0.9 mL/kg/min, P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary endpoints were discernable.

CONCLUSIONS: -Our observations question the value of heart rate reduction, using ivabradine, for improving symptoms in a HFpEF population characterised by exercise limitation. Clinical Trial Registration Identifier: NCT02354573.

Original languageEnglish
Pages (from-to)1719-1725
Number of pages7
Issue number18
Early online date2 Sept 2015
Publication statusPublished - 3 Nov 2015

Bibliographical note

Dr Ashrafian acknowledges support from the BHF Center of Research Excellence, Oxford, UK. The research was also supported by the National Institute for Health Research Oxford Biomedical Research Center Program and by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC).


  • heart failure
  • heart rate
  • exercise


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