Kosmala, W and Rojek, A and Przewlocka-Kosmala, M and Wright, L and Mysiak, A and Marwick, TH, Effect of Aldosterone Antagonism on Exercise Tolerance in Heart Failure With Preserved Ejection Fraction, Journal of the American College of Cardiology, 68, (17) pp. 1823-1834. ISSN 0735-1097 (2016) [Refereed Article]
Copyright 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
OBJECTIVES: The authors sought to identify improvement in exercise capacity with spironolactone in the subset of patients with HFpEF with exercise-induced increase in ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') reflecting elevation of left ventricular (LV) filling pressure.
METHODS: In this randomized, blinded, parallel-group, placebo-controlled trial, 150 subjects (age 67 ± 9 years) with exertional dyspnea (New York Heart Association functional class II to III, left ventricular ejection fraction >50%, diastolic dysfunction, and exertional E/e' >13), excluding those with ischemic heart disease, were recruited in a tertiary cardiology center. Patients were randomized to 6 months of oral spironolactone 25 mg/day or matching placebo. Primary outcomes were improvements in peak oxygen uptake (VO2) and exertional E/e' ratio, and secondary outcomes were improvements in exercise blood pressure response and global LV longitudinal strain.
RESULTS: At follow-up, 131 patients completed therapy-64 taking spironolactone and 67 placebo. At baseline, subjects had substantial exercise limitation (peak VO2 64 ± 17% predicted). The spironolactone group showed improvement in exercise capacity (increment in peak VO2 [2.9 ml/min/kg (95% confidence interval [CI]: 1.9 to 3.9 ml/min/kg) vs. 0.3 ml/min/kg (95% CI: -0.5 to 1.1 ml/min/kg); p < 0.001], anaerobic threshold [2.0 ml/min/kg (95% CI: 0.9 to 3.2 ml/min/kg) vs. -0.9 ml/min/kg (95% CI: -3.4 to 1.6 ml/min/kg); p = 0.03], and O2 uptake efficiency [0.19 (95% CI: 0.06 to 0.31) vs. -0.07 (95% CI: -0.17 to 0.04); p = 0.002]), with reduction in exercise-induced increase in E/e' (-3.0 [95% CI: -3.9 to -2.0] vs. 0.5 [95% CI: -0.6 to 1.6]; p < 0.001). There was a significant interaction of spironolactone and change in E/e' on VO2 (p = 0.039).
CONCLUSIONS: In patients with HFpEF and abnormal diastolic response to exertion, improvement in exercise E/e' mediates the beneficial effect of spironolactone on exercise capacity. Identification of exercise-induced increase in LV filling pressure in patients with HFpEF may define a subgroup with warranting trial of spironolactone.
|Item Type:||Refereed Article|
|Keywords:||aldosterone antagonism, echocardiography, heart failure with preserved ejection fraction, left ventricular filling pressure|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Cardiology (incl. cardiovascular diseases)|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Kosmala, W (Professor Wojciech Kosmala)|
|UTAS Author:||Wright, L (Ms Leah Wright)|
|UTAS Author:||Marwick, TH (Professor Tom Marwick)|
|Web of Science® Times Cited:||54|
|Deposited By:||Menzies Institute for Medical Research|
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