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

Pal, Nikhil, Sivaswamy, Nadiya, Mahmod, Masliza, Yavari, Arash, Rudd, Amelia, Singh, Satnam, Dawson, Dana K., Francis, Jane M., Dwight, Jeremy S., Watkins, Hugh, Neubauer, Stefan, Frenneaux, Michael and Ashrafian, Houman (2015) Effect of selective heart rate slowing in heart failure with preserved ejection fraction. Circulation, 132 (18). pp. 1719-1725. ISSN 0009-7322

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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.

Item Type: Article
Additional Information: Date of acceptance: 10/08/2015
Uncontrolled Keywords: exercise,heart failure,heart rate
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Related URLs:
Depositing User: Pure Connector
Date Deposited: 01 Dec 2015 16:01
Last Modified: 04 May 2023 21:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/55612
DOI: 10.1161/CIRCULATIONAHA.115.017119


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