Spironolactone improves the arrhythmogenic substrate in heart failure by preventing ventricular electrical activation delays associated with myocardial interstitial fibrosis and inflammation

Journal of Cardiovascular Electrophysiology

Volumn 24, Issue 7, 2013, Pages 806-812

  Esposito, Christine Tanaka ^a   Varahan, Subha ^a   Jeyaraj, Darwin ^a   Lu, Yuan ^a   Stambler, Bruce S ^a  

^a UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

Author keywords

aldosterone; fibrosis; heart failure; inflammatory markers; ventricular tachycardia

Indexed keywords

INTERLEUKIN 6; MESSENGER RNA; MINERALOCORTICOID RECEPTOR; PLACEBO; SPIRONOLACTONE; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARRHYTHMOGENESIS; ARTICLE; CARDIOMYOPATHY; CONTROLLED STUDY; DISEASE ASSOCIATION; DOG; DRUG EFFECT; DRUG EFFICACY; ECHOCARDIOGRAPHY; GENE EXPRESSION PROFILING; GENE OVEREXPRESSION; HEART ELECTROPHYSIOLOGY; HEART MUSCLE CONDUCTION DISTURBANCE; HEART MUSCLE FIBROSIS; HEART PACING; HEART VENTRICLE REMODELING; LEFT VENTRICULAR SYSTOLIC DYSFUNCTION; MYOCARDITIS; NONHUMAN; PRIORITY JOURNAL; SYSTOLIC HEART FAILURE; VENTRICULAR ELECTRICAL ACTIVATION DELAY;

ALDOSTERONE; FIBROSIS; HEART FAILURE; INFLAMMATORY MARKERS; VENTRICULAR TACHYCARDIA;

ANIMALS; ARRHYTHMIAS, CARDIAC; DOGS; ELECTROPHYSIOLOGICAL PROCESSES; FIBROSIS; HEART FAILURE; HEART VENTRICLES; INFLAMMATION; MINERALOCORTICOID RECEPTOR ANTAGONISTS; MYOCARDIUM; SPIRONOLACTONE; VENTRICULAR DYSFUNCTION;

EID: 84879792971     PISSN: 10453873     EISSN: 15408167     Source Type: Journal    
DOI: 10.1111/jce.12115     Document Type: Article

References (31)

1. Tomaselli GF, Zipes DP,: What causes sudden cardiac death in heart failure ? Circ Res 2004; 95: 754-63. (Pubitemid 39390577)
2. Das MK, Zipes DP,: Antiarrhythmic and nonantiarrhythmic drugs for sudden cardiac death prevention. J Cardiovasc Pharmacol 2010; 55: 438-49.
3. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J,; for The Randomized Aldactone Evaluation Study Investigators: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709-717. (Pubitemid 29407370)
4. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M,; for the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309-1321. (Pubitemid 36384098)
5. Stambler BS, Laurita KR, Shroff SC, Hoeker G, Martovitz NL,: Aldosterone blockade attenuates development of an electrophysiological substrate associated with ventricular tachyarrhythmias in heart failure. Heart Rhythm 2009; 6: 776-83.
6. Weber KT,: Aldosterone in congestive heart failure. N Engl J Med 2001; 345: 1689-97. (Pubitemid 33126826)
7. Takeda Y, Miyamori I, Yoneda T, Hatakeyama H, Inaba S, Furukawa K, Mabuchi H, Takeda R,: Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. J Clin Endocrinol Metab 1996; 81: 2797-800. (Pubitemid 26323867)
8. de Jong S, van Veen TA, van Rijen HV, de Bakker JM,: Fibrosis and cardiac arrhythmias. J Cardiovasc Pharmacol 2011; 57: 630-638.
9. Kawara T, Derksen R, de Groot JR, Coronel R, Tasseron S, Linnenbank AC, Hauer RN, Kirkels H, Janse MJ, de Bakker JM,: Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation 2001; 104: 3069-3075. (Pubitemid 34014059)
10. Anderson KP, Walker R, Urie P, Ershler PR, Lux RL, Karwandee SV,: Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy. J Clin Invest 1993; 92: 122-140. (Pubitemid 23208988)
11. Spach MS, Boineau JP,: Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias. Pacing Clin Electrophysiol 1997; 20: 397-413.
12. Turner I, Huang C, Suamarez RC,: Numerical stimulation of paced electrogram fractionation: relating clinical observations to changes in fibrosis and action potential duration. J Cardiovasc Electrophysiol 2005; 16: 151-61. (Pubitemid 40322201)
13. Weber KT, Brilla CG,: Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83: 1849-1865.
14. Weber KT,: Aldosterone and spironolactone in heart failure. N Engl J Med 1999; 341: 753-755. (Pubitemid 29407377)
15. 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: 563-575. (Pubitemid 23208145)
16. Iraqi W, Rossignol P, Angioi M, Fay R, Nuée J, Ketelslegers JM, Vincent J, Pitt B, Zannad F,: Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: Insights from the eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS). Circulation 2009; 119; 2471-2479.
17. Zannad F, Alla F, Dousset B, Perez A, Pitt B,: Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: Insights from the Randomized Aldactone Evaluation Study (RALES). Circulation 2000; 102: 2700-2706.
18. Guyonnet J, Elliott J, Kaltsatos V,: A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dogs. J Vet Pharmacol Therap 2009; 33: 260-267.
19. Starmer CF, Grant AO, Colatsky TJ,: What happens when cardiac Na channel function is compromised? 2: Numerical studies of the vulnerable period in tissue altered by drugs. Cardiovasc Res 2003; 57: 1062-1071. (Pubitemid 36324611)
20. Weber KT, Pick R, Silver MA, Moe GW, Janicki JS, Zucker IH, Armstrong PW,: Fibrillar collagen and remodeling of dilated canine left ventricle. Circulation 1990; 82: 1387-1401.
21. Kajstura J, Zhang X, Liu Y, Szoke E, Cheng W, Olivetti G, Hintze TH, Anversa P,: The cellular basis of pacing-induced dilated cardiomyopathy: Myocyte cell loss and myocyte cellular reactive hypertrophy. Circulation 1995; 92: 2306-2317.
22. Milliez P, Deangelis N, Rucker-Martin C, Leenhardt A, Vicaut E, Robidel E, Beaufils P, Delcayre C, Hatem SN,: Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction. Eur Heart J 2005; 26: 2193-2199. (Pubitemid 41408006)
23. Yoshida M, Ma J, Tomita T, Morikawa N, Tanaka N, Masamura K, Kawai Y, Miyamori I,: Mineralocorticoid receptor is overexpressed in cardiomyocytes of patients with congestive heart failure. Congest Heart Fail 2005; 11: 12-16.
24. Mizuno Y, Yoshimura M, Yasue H, Sakamoto T, Ogawa H, Kugiyama K, Harada E, Nakayama M, Nakamura S, Ito T, Shimasaki Y, Saito Y, Nakao K,: Aldosterone production is activated in failing ventricle in humans. Circulation 2001; 103: 72-77. (Pubitemid 32050438)
25. Brilla CG, Pick R, Tan LB, Janicki JS, Weber KT,: Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res 1990; 67: 1355-1364.
26. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EAG, McMahon EG, Delyani JA,: Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ 2002; 283: H1802-H1810. (Pubitemid 35217013)
27. Hedayat M, Mahmoudi MJ, Rose NR, Rezaei N,: Proinflammatory cytokines in heart failure: Double-edged swords. Heart Fail Rev 2010; 15: 543-562.
28. Brown NJ,: Aldosterone and vascular inflammation. Hypertension 2008; 51; 161-167. (Pubitemid 351159920)
29. Hanna N, Cardin S, Leung T-K, Nattel S,: Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure. Cardiovasc Res 2004; 63: 236-244. (Pubitemid 38900838)
30. Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B,; EMPHASIS-HF Study Group: Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364: 11-21.
31. Anand K, Mooss AN, Mohiuddin SM,: Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart failure. J Renin Angiotensin Aldosterone Syst 2006; 7: 15-19. (Pubitemid 43891240)