The Role of Mineralocorticoid Receptor Antagonists in the Management of Heart Failure with Preserved Ejection Fraction

Author(s): Achilleas Papagiannis, Stelina Alkagiet, Konstantinos Tziomalos*.

Journal Name: Current Pharmaceutical Design

Volume 24 , Issue 46 , 2018


Abstract:

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with increased risk for hospitalization and all-cause mortality. Currently, there is no established treatment to improve the survival of these patients. Aldosterone appears to play a role in the pathogenesis of HFpEF.

Objective: To discuss the findings of studies that evaluated the effects of mineralocorticoid receptor (MR) antagonists on the outcome of patients with HFpEF.

Methods: PubMed was searched for relevant papers. References of retrieved articles were also evaluated for pertinent material.

Results: Accumulating data suggest that MR antagonists might be useful in the management of patients with HFpEF. However, existing evidence is limited and conflicting.

Conclusions: More studies are needed to clearly define the therapeutic potential of MR antagonists in HFpEF. Given the heterogeneity of this disease and the low specificity of the criteria used for its diagnosis, it is also important to improve the definition of HFpEF and include appropriately selected patients in these studies.

Keywords: Heart failure with preserved ejection fraction, aldosterone, mineralocorticoid receptor antagonists, spironolactone, eplerenone, pulmonary crackles.

[1]
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37(27): 2129-200.
[2]
Braunwald E. Heart failure. JACC Heart Fail 2013; 1(1): 1-20.
[3]
Lee DS, Gona P, Vasan RS, et al. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the framingham heart study of the national heart, lung, and blood institute. Circulation 2009; 119(24): 3070-7.
[4]
Haass M, Kitzman DW, Anand IS, et al. Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail 2011; 4(3): 324-31.
[5]
The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: An individual patient data meta-analysis. Eur Heart J 2012; 33(14): 1750-7.
[6]
Prasad A, Hastings JL, Shibata S, et al. Characterization of static and dynamic left ventricular diastolic function in patients with heart failure with a preserved ejection fraction. Circ Heart Fail 2010; 3(5): 617-26.
[7]
Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 2011; 32(6): 670-9.
[8]
Westermann D, Lindner D, Kasner M, et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail 2011; 4(1): 44-52.
[9]
Brilla CG, Matsubara LS, Weber KT. Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 1993; 25(5): 563-75.
[10]
Lombès M, Alfaidy N, Eugene E, Lessana A, Farman N, Bonvalet JP. Prerequisite for cardiac aldosterone action. Mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase in the human heart. Circulation 1995; 92(2): 175-82.
[11]
Bunda S, Wang Y, Mitts TF, et al. Aldosterone stimulates elastogenesis in cardiac fibroblasts via mineralocorticoid receptor-independent action involving the consecutive activation of Galpha13, c-Src, the insulin-like growth factor-I receptor, and phosphatidylinositol 3-kinase/Akt. J Biol Chem 2009; 284(24): 16633-47.
[12]
Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res 2005; 96(6): 643-50.
[13]
Rogerson FM, Fuller PJ. Mineralocorticoid action. Steroids 2000; 65(2): 61-73.
[14]
McCurley A, Pires PW, Bender SB, et al. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat Med 2012; 18(9): 1429-33.
[15]
Gavras H, Brunner HR, Laragh JH, et al. Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes. Circ Res 1975; 36(2): 300-9.
[16]
Güder G, Bauersachs J, Frantz S, et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation 2007; 115(13): 1754-61.
[17]
Girerd N, Pang PS, Swedberg K, et al. Serum aldosterone is associated with mortality and re-hospitalization in patients with reduced ejection fraction hospitalized for acute heart failure: Analysis from the EVEREST trial. Eur J Heart Fail 2013; 15(11): 1228-35.
[18]
Patel K, Fonarow GC, Kitzman DW, et al. Aldosterone antagonists and outcomes in real-world older patients with heart failure and preserved ejection fraction. JACC Heart Fail 2013; 1(1): 40-7.
[19]
Lund LH, Donal E, Oger E, et al. Association between cardiovascular vs. non-cardiovascular co-morbidities and outcomes in heart failure with preserved ejection fraction. Eur J Heart Fail 2014; 16(9): 992-1001.
[20]
Kurrelmeyer KM, Ashton Y, Xu J, Nagueh SF, Torre-Amione G, Deswal A. Effects of spironolactone treatment in elderly women with heart failure and preserved left ventricular ejection fraction. J Card Fail 2014; 20(8): 560-8.
[21]
Deswal A, Richardson P, Bozkurt B, Mann DL. Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF). J Card Fail 2011; 17(8): 634-42.
[22]
Edelmann F, Wachter R, Schmidt AG, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 2013; 309(8): 781-91.
[23]
Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370(15): 1383-92.
[24]
de Denus S, O’Meara E, Desai AS, et al. Spironolactone Metabolites in TOPCAT - New Insights into Regional Variation. N Engl J Med 2017; 376(17): 1690-2.
[25]
Faselis C, Boutari C, Doumas M, Imprialos K, Stavropoulos K, Kokkinos P. Novel Drugs for Hypertension and Heart Failure: Struggling for a Place Under the Sun. Curr Pharm Des 2017; 23(10): 1540-50.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 24
ISSUE: 46
Year: 2018
Page: [5525 - 5527]
Pages: 3
DOI: 10.2174/1381612825666190219140342
Price: $58

Article Metrics

PDF: 22
HTML: 5
EPUB: 1
PRC: 1

Special-new-year-discount