OBJECTIVES: 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).
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OBJECTIVES: 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: Jacob P Kelly; Robert J Mentz; Alexandre Mebazaa; Adriaan A Voors; Javed Butler; Lothar Roessig; Mona Fiuzat; Faiez Zannad; Bertram Pitt; Christopher M O'Connor; Carolyn S P Lam Journal: J Am Coll Cardiol Date: 2015-04-28 Impact factor: 24.094
Authors: Santanu Guha; S Harikrishnan; Saumitra Ray; Rishi Sethi; S Ramakrishnan; Suvro Banerjee; V K Bahl; K C Goswami; Amal Kumar Banerjee; S Shanmugasundaram; P G Kerkar; Sandeep Seth; Rakesh Yadav; Aditya Kapoor; Ajaykumar U Mahajan; P P Mohanan; Sundeep Mishra; P K Deb; C Narasimhan; A K Pancholia; Ajay Sinha; Akshyaya Pradhan; R Alagesan; Ambuj Roy; Amit Vora; Anita Saxena; Arup Dasbiswas; B C Srinivas; B P Chattopadhyay; B P Singh; J Balachandar; K R Balakrishnan; Brian Pinto; C N Manjunath; Charan P Lanjewar; Dharmendra Jain; Dipak Sarma; G Justin Paul; Geevar A Zachariah; H K Chopra; I B Vijayalakshmi; J A Tharakan; J J Dalal; J P S Sawhney; Jayanta Saha; Johann Christopher; K K Talwar; K Sarat Chandra; K Venugopal; Kajal Ganguly; M S Hiremath; Milind Hot; Mrinal Kanti Das; Neil Bardolui; Niteen V Deshpande; O P Yadava; Prashant Bhardwaj; Pravesh Vishwakarma; Rajeeve Kumar Rajput; Rakesh Gupta; S Somasundaram; S N Routray; S S Iyengar; G Sanjay; Satyendra Tewari; Sengottuvelu G; Soumitra Kumar; Soura Mookerjee; Tiny Nair; Trinath Mishra; U C Samal; U Kaul; V K Chopra; V S Narain; Vimal Raj; Yash Lokhandwala Journal: Indian Heart J Date: 2018-06-08