Effect of selective heart rate slowing in heart failure with preserved ejection fraction

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 (Lead Author), Houman Ashrafian (Lead Author)

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126 Citations (Scopus)
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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 randomized, 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 [GraphicO2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in GraphicO2 peak. Secondary outcomes included tissue Doppler–derived E/e′ at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in GraphicO2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg−1·min−1; P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Conclusion Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation.
Original languageEnglish
Pages (from-to)1719-1725
Number of pages7
Issue number18
Early online date2 Sep 2015
Publication statusPublished - 3 Nov 2015


  • exercise
  • heart failure
  • heart rate

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