Author + information
- Received June 29, 2017
- Revision received October 3, 2017
- Accepted October 4, 2017
- Published online May 6, 2019.
- Wojciech Kosmala, MD, PhDa,b,c,
- Monika Przewlocka-Kosmala, MD, PhDa,b,c and
- Thomas H. Marwick, MD, PhDb,c,∗ ()
- aCardiology Department, Wroclaw Medical University, Wroclaw, Poland
- bBaker Heart and Diabetes Institute, Melbourne, Australia
- cMenzies Institute for Medical Research, University of Tasmania, Hobart, Australia
- ↵∗Address for correspondence:
Dr. Thomas H. Marwick, Baker Heart and Diabetes Institute, Melbourne, P.O. Box 6492, Melbourne, Victoria 3004, Australia.
Objectives This study sought to investigate the association of left ventricular (LV) untwisting rate (UT) and E/e’ ratio with the response of exercise capacity to spironolactone in heart failure with preserved ejection fraction (HFpEF).
Background In most patients with HFpEF, LV filling abnormalities represent a central component in the development of dyspnea. LV diastolic filling is determined by the interplay of passive (LV stiffness and myocardial collagen content, reflected by E/e’ ratio) and active myocardial properties (UT, a precursor to isovolumic pressure decay and contributor to diastolic suction).
Methods In 194 patients with HFpEF (64 ± 8 years), a complete echocardiogram (including assessment of myocardial deformation and rotational mechanics) was performed. Echocardiography following maximal exercise was undertaken to assess LV systolic and diastolic responses to stress. A subset of 105 patients with an exercise-induced increase in estimated LV filling pressure were randomly assigned to spironolactone 25 mg (n = 51) or placebo (n = 54) for 6 months.
Results Baseline peak Vo2 was associated with UT (β = 0.19; p = 0.01) and E/e’ (β = −0.16; p = 0.03), independent of clinical data and exercise reserve in longitudinal deformation and ventricular-arterial coupling. An increase in peak Vo2 with treatment was independently associated with changes in UT (β = 0.28; p = 0.003) and exertional increase in E/e′ (β = −0.23; p = 0.01) from baseline to follow-up. A significant interaction with the use of spironolactone on peak Vo2 was found for E/e′ (p = 0.02) but not for UT (p = 0.62).
Conclusions Both active and passive determinants of LV filling, as reflected by UT and E/e′, contribute to reduced exercise capacity in HFpEF. Improvement in functional capacity with a 6-month therapy with spironolactone is associated with improvements in both indices. However, the possible mediating effect of this medication is observed only on E/e′.
- aldosterone antagonism
- E/e′ ratio
- heart failure with preserved ejection fraction
- left ventricular filling
- untwisting rate
Funded by Wroclaw Medical University (Grant ST-678) and the Royal Hobart Hospital Foundation (Grant 13-024). Dr. Marwick has received grant support from GE Medical Systems for an unrelated study of cardiotoxicity. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Farooq Chaudhry, MD, and Sherif Nagueh, MD, served as the Guest Editors for this paper.
- Received June 29, 2017.
- Revision received October 3, 2017.
- Accepted October 4, 2017.
- 2019 American College of Cardiology Foundation
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