Heart Rhythm
Volume 6, Issue 6 , Pages 776-783 , June 2009

Aldosterone blockade attenuates development of an electrophysiological substrate associated with ventricular tachyarrhythmias in heart failure

  • Bruce S. Stambler, MD, FHRS

      Affiliations

    • University Hospitals Case Medical Center, Cleveland, Ohio
    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. Bruce Stambler, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106
    • ,
  • Kenneth R. Laurita, PhD

      Affiliations

    • MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio
    • ,
  • Sunil C. Shroff, MD

      Affiliations

    • University Hospitals Case Medical Center, Cleveland, Ohio
    • ,
  • Gregory Hoeker, BS

      Affiliations

    • MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio
    • ,
  • Nichole L. Martovitz

      Affiliations

    • University Hospitals Case Medical Center, Cleveland, Ohio

Received 28 November 2008 ,Accepted 2 February 2009.

References 

  1. Tomaselli GF, Zipes DP. What causes sudden death in heart failure?. Circ Res. 2004;95:754–763
  2. Pitt B, Pitt GS. Added benefit of mineralocorticoid receptor blockade in the primary prevention of sudden cardiac death. Circulation. 2007;115:2976–2982
  3. Struthers AD, MacDonald TM. Review of aldosterone and angiotensin II-induced target organ damage and prevention. Cardiovasc Res. 2004;61:663–670
  4. Benitah JP, Vassort G. Aldosterone upregulates Ca2+ current in adult rat cardiomyocytes. Circ Res. 1999;8512:1139–1145
  5. Boixel C, Gavillet B, Rougier JS, et al. Aldosterone increases voltage-gated sodium current in ventricular myocytes. Am J Physiol Heart Circ Physiol. 2006;290:H2257–H2266
  6. Benitah JP, Perrier E, Gomez AM, et al. Effects of aldosterone on transient outward K+ current density in rat ventricular myocytes. J Physiol. 2001;537:151–160
  7. Ouvrard-Pascaud A, Sainte-Marie Y, Benitah JP, et al. Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation. 2005;111:3025–3033
  8. Perrier E, Kerfant BG, Lalevee N, et al. Mineralocorticoid receptor antagonism prevents the electrical remodeling that precedes cellular hypertrophy after myocardial infarction. Circulation. 2004;110:776–783
  9. Sugiyama A, Satoh Y, Takahara A, et al. Electropharmacological effects of a spironolactone derivative, potassium canrenoate, assessed in the halothane-anesthetized canine model. J Pharmacol Sci. 2004;96:436–443
  10. Caballero R, Moreno I, Gonzalez T, et al. Spironolactone and its main metabolite, canrenoic acid, block human ether-a-go-go-related gene channels. Circulation. 2003;107:889–895
  11. Sica DA. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005;10:23–29
  12. Shroff SC, Ryu K, Martovitz NL, et al. Selective aldosterone blockade suppresses inducibility of sustained atrial tachyarrhythmias in heart failure. J Cardiovasc Electrophysiol. 2006;17:534–541
  13. Van deWater A, Verheyen J, Xhonneux R, et al. An improved method to correct the QT interval of the electrocardiogram for changes in heart rate. J Pharmacol Methods. 1989;22:207–217
  14. Laurita KR, Katra R, Wible B, et al. Transmural heterogeneity of calcium handling in canine. Circ Res. 2003;92:668–675
  15. Saumarez RC, Chojnowska L, Derksen R, et al. Sudden death in noncoronary heart disease is associated with delayed paced ventricular activation. Circulation. 2003;107:2595–2600
  16. de Bakker JM, van Capelle FJ, Janse MJ, et al. Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction. J Am Coll Cardiol. 1996;27:1071–1078
  17. Spach MS, Barr RC, Serwer GA, et al. Extracellular potentials related to intracellular action potentials in the dog Purkinje system. Circ Res. 1972;30:505–519
  18. Lesh MD, Spear JF, Simson MB. A computer model of the electrogram: what causes fractionation?. J Electrocardiol. 1988;21:S69–S73
  19. Lesh MD, Pring M, Spear JF. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. Circ Res. 1989;65:1426–1440
  20. Turner I, Huang C, Saumarez RC. Numerical simulation of paced electrogram fractionation: relating clinical observations to changes in fibrosis and action potential duration. J Cardiovasc Electrophysiol. 2005;16:151–161
  21. Kawara T, Derksen R, de Groot JR, et al. Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation. 2001;104:3069–3075
  22. Akar FG, Spragg DD, Tunin RS, et al. Mechanisms underlying conduction slowing and arrhythmogenesis in nonischemic dilated cardiomyopathy. Circ Res. 2004;95:717–725
  23. Beygui F, Collet JP, Benoliel JJ, et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation. 2006;114:2604–2610
  24. De Mello WC. Beneficial effect of eplerenone on cardiac remodelling and electrical properties of the failing heart. J Renin Angiotensin Aldosterone Syst. 2006;7:40–46
  25. Cittadini A, Monti MG, Isgaard J, et al. Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure. Cardiovasc Res. 2003;58:555–564

 Supported by research grants from Pfizer, Inc., and the American Heart Association Ohio Valley to Dr. Stambler.

PII: S1547-5271(09)00130-1

doi: 10.1016/j.hrthm.2009.02.005

Heart Rhythm
Volume 6, Issue 6 , Pages 776-783 , June 2009

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