title: Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial.
abstract: OBJECTIVE
  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).
authors.affiliation: Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kosmala
authors.forename: David J
authors.initials: DJ
authors.lastname: Holland
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rojek
authors.forename: Leah
authors.initials: L
authors.lastname: Wright
authors.forename: Monika
authors.initials: M
authors.lastname: Przewlocka-Kosmala
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Marwick
mesh_terms: D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects; D004311:Double-Blind Method; D018619:Echocardiography, Doppler, Pulsed; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008943:Mitral Valve / Q000000981:diagnostic imaging; D020097:Natriuretic Peptide, Brain / Q000032:analysis; D010101:Oxygen Consumption / Q000502:physiology; D011446:Prospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D020097:Natriuretic Peptide, Brain; D000077550:Ivabradine
keywords: A; BNP; CI; E; HFpEF; I(f); ICC; LV; MET; Vo(2); WCCR; brain natriuretic peptide; confidence interval; diastolic function; e′; heart failure with preserved ejection fraction; intraclass correlation coefficient; inward “funny”; ivabradine; late diastolic mitral flow velocity; left ventricular; metabolic equivalent; oxygen uptake; peak early diastolic mitral annular velocity; peak early diastolic mitral flow velocity; work load–corrected chronotropic response