Myocardial effects of aldosterone antagonism in heart failure with preserved ejection fraction

McDiarmid, Adam K., Swoboda, Peter P., Erhayiem, Bara, Bounford, Katrina A., Bijsterveld, Petra, Tyndall, Keith, Fent, Graham J., Garg, Pankaj ORCID:, Dobson, Laura E., Musa, Tarique A., Foley, James R. J., Witte, Klaus K., Kearney, Mark T., Greenwood, John P. and Plein, Sven (2020) Myocardial effects of aldosterone antagonism in heart failure with preserved ejection fraction. Journal of the American Heart Association, 9 (1). ISSN 2047-9980

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Background: Spironolactone may have prognostic benefit in selected patients with heart failure with preserved ejection fraction. This study assessed the myocardial tissue effects of spironolactone in heart failure with preserved ejection fraction. Methods and Results: A 1:1 randomized controlled study of 6 months of spironolactone versus control in heart failure with preserved ejection fraction. The primary outcome was change in myocardial extracellular volume fraction by cardiovascular magnetic resonance as a surrogate of diffuse fibrosis. Of 55 randomized patients, 40 (20 women; age, 75.2±5.9 years) completed follow-up (19 treatment, 21 control). A significant change in extracellular volume over the study period was not seen (treatment, 28.7±3.7% versus 27.7±3.4% [P=0.14]; controls, 27.6±3.4% versus 28.3±4.4% [P=0.14]); however, the rate of extracellular volume expansion was decreased by spironolactone (−1.0±2.4% versus 0.8±2.2%). Indexed left ventricular mass decreased with treatment (104.4±26.6 versus 94.0±20.6 g/m 2; P=0.001) but not in controls (101.4±29.4 versus 104.0±32.8 g/m 2; P=0.111). Extracellular mass decreased by 13.8% (15.1±4.8 versus 13.0±3.4 g/m 2; P=0.003), and cellular mass decreased by 8.3% (37.6±10.0 versus 34.3±7.9 g/m 2; P=0.001) with spironolactone, but was static in controls. Conclusions: Spironolactone did not lead to significant change in extracellular volume. However, spironolactone did decrease rate of extracellular expansion, with a decrease in the mass of both cellular and extracellular myocardial compartments. These data point to the mechanism of action of spironolactone in heart failure with preserved ejection fraction, including a direct tissue effect with a reduction in rate of myocardial fibrosis.

Item Type: Article
Additional Information: Funding Information: This study and Dr McDiarmid are funded by a British Heart Foundation (BHF) Project Grant (PG/14/10/30641). Dr Swoboda is funded by a BHF Clinical Fellowship (FS/12/88/29474). Dr Plein is funded by a BHF Personal Chair (CH/16/2/32089) and Program Grant (RG/16/1/32092). Dr Witte holds a National Institute for Health Research (NIHR) Clinician Scientist award. This study was supported by the NIHR Leeds Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health.
Uncontrolled Keywords: cardiovascular magnetic resonance,extracellular volume,heart failure,heart failure with preserved ejection fraction,cardiology and cardiovascular medicine ,/dk/atira/pure/subjectarea/asjc/2700/2705
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 17 Nov 2021 04:52
Last Modified: 23 Oct 2022 03:18
DOI: 10.1161/JAHA.118.011521

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