on May 5, 2003
Published online before print May 5, 2003, doi: 10.1161/01.CIR.0000068340.96506.0F
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 31, 2002
From the Department of Cardiology (M. Hayashi, A.T., T.H., Y.N., K.K., N.M.), Nagahama City Hospital, Nagahama, and Department of Cardiovascular Medicine (T. Tsutamoto, A.W., T. Tsutsui, C.I., K.O., M.F., M.O., M.K., M. Horie), Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Japan. * To whom correspondence should be addressed. E-mail: tutamoto{at}belle.shiga-med.ac.jp.
Background--Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. Methods and Results--To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non-MRA (n=69) groups after revascularization. All patients were administered angiotensin-converting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0±0.6% to 53.2±0.8% versus 46.5±0.8% to 51.0±0.8%, Pinteraction=0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5±1.0 to 90.6±2.4 versus 87.5±1.3 to 106.8±3.5 mL/m2, Pinteraction=0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (Pinteraction=0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (Pinteraction=0.002). Conclusions--These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis.
Revised on March 4, 2003
Accepted on March 5, 2003
Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial Infarction
Masaru Hayashi MD,
Key words: myocardial infarction • ventricles • remodeling • collagen
Related Article:
Circulation 2003 107: 2525-2527.
This article has been cited by other articles:
 |
|
 |
|
  T. P. Singh, L. A. Sleeper, S. Lipshultz, A. Cinar, C. Canter, S. A. Webber, D. Bernstein, E. Pahl, J. A. Alvarez, J. D. Wilkinson, et al. Association of Left Ventricular Dilation at Listing for Heart Transplant With Postlisting and Early Posttransplant Mortality in Children With Dilated Cardiomyopathy Circ Heart Fail, November 1, 2009; 2(6): 591 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Adamopoulos, A. Ahmed, R. Fay, M. Angioi, G. Filippatos, J. Vincent, B. Pitt, F. Zannad, and the EPHESUS Investigators Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial Eur J Heart Fail, November 1, 2009; 11(11): 1099 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Iraqi, P. Rossignol, M. Angioi, R. Fay, J. Nuee, J. M. Ketelslegers, J. Vincent, B. Pitt, and F. Zannad 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) Study Circulation, May 12, 2009; 119(18): 2471 - 2479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ishii, T. Amano, T. Matsubara, and T. Murohara Pharmacological Intervention for Prevention of Left Ventricular Remodeling and Improving Prognosis in Myocardial Infarction Circulation, December 16, 2008; 118(25): 2710 - 2718. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Di Zhang, A. N. D. Cat, C. Soukaseum, B. Escoubet, A. Cherfa, S. Messaoudi, C. Delcayre, J.-L. Samuel, and F. Jaisser Cross-Talk Between Mineralocorticoid and Angiotensin II Signaling for Cardiac Remodeling Hypertension, December 1, 2008; 52(6): 1060 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Palmer, A. P. Pilbrow, C. M. Frampton, T. G. Yandle, L. Skelton, M. G. Nicholls, and A. M. Richards Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction Eur. Heart J., October 2, 2008; 29(20): 2489 - 2496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pitt The measurement of plasma aldosterone in patients post-myocardial infarction Eur. Heart J., October 2, 2008; 29(20): 2451 - 2452. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tsukashita, A. Marui, T. Nishina, E. Yoshikawa, H. Kanemitsu, J. Wang, T. Ikeda, and M. Komeda Spironolactone alleviates late cardiac remodeling after left ventricular restoration surgery J. Thorac. Cardiovasc. Surg., July 1, 2008; 136(1): 58 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Braunwald Biomarkers in Heart Failure N. Engl. J. Med., May 15, 2008; 358(20): 2148 - 2159. [Full Text] [PDF]
|
|
|
|
|
|
D. Fraccarollo, P. Galuppo, S. Schraut, S. Kneitz, N. van Rooijen, G. Ertl, and J. Bauersachs Immediate Mineralocorticoid Receptor Blockade Improves Myocardial Infarct Healing by Modulation of the Inflammatory Response Hypertension, April 1, 2008; 51(4): 905 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Sartorio, D. Fraccarollo, P. Galuppo, M. Leutke, G. Ertl, I. Stefanon, and J. Bauersachs Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction Hypertension, November 1, 2007; 50(5): 919 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pitt and G. S. Pitt Added Benefit of Mineralocorticoid Receptor Blockade in the Primary Prevention of Sudden Cardiac Death Circulation, June 12, 2007; 115(23): 2976 - 2982. [Full Text] [PDF]
|
|
|
|
|
|
F. Beygui, J.-P. Collet, J.-J. Benoliel, N. Vignolles, R. Dumaine, O. Barthelemy, and G. Montalescot High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction Circulation, December 12, 2006; 114(24): 2604 - 2610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Hudson, P. W. Armstrong, W. Ruzyllo, J. Brum, L. Cusmano, P. Krzeski, R. Lyon, M. Quinones, P. Theroux, D. Sydlowski, et al. Effects of Selective Matrix Metalloproteinase Inhibitor (PG-116800) to Prevent Ventricular Remodeling After Myocardial Infarction: Results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) Trial J. Am. Coll. Cardiol., July 4, 2006; 48(1): 15 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pitt, M. Gheorghiade, F. Zannad, J. L. Anderson, D. J. van Veldhuisen, A. Parkhomenko, R. Corbalan, E. Q. Klug, R. Mukherjee, H. Solomon, et al. Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction <=30% Eur J Heart Fail, May 1, 2006; 8(3): 295 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chai, I. M. Garrelds, R. de Vries, and A.H. Jan Danser Cardioprotective Effects of Eplerenone in the Rat Heart: Interaction With Locally Synthesized or Blood-Derived Aldosterone? Hypertension, April 1, 2006; 47(4): 665 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nagata, K. Obata, J. Xu, S. Ichihara, A. Noda, H. Kimata, T. Kato, H. Izawa, T. Murohara, and M. Yokota Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Failure in Low-Aldosterone Hypertensive Rats Hypertension, April 1, 2006; 47(4): 656 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Marcy and T. L. Ripley Aldosterone antagonists in the treatment of heart failure Am. J. Health Syst. Pharm., January 1, 2006; 63(1): 49 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Enomoto, M Yoshiyama, T Omura, R Matsumoto, T Kusuyama, S Kim, Y Izumi, K Akioka, H Iwao, K Takeuchi, et al. Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction Heart, December 1, 2005; 91(12): 1595 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. W. Tang, A. C. Parameswaran, A. P. Maroo, and G. S. Francis Aldosterone Receptor Antagonists in the Medical Management of Chronic Heart Failure Mayo Clin. Proc., December 1, 2005; 80(12): 1623 - 1630. [Abstract] [PDF]
|
|
|
|
|
|
H. Su, F. G. Spinale, L. W. Dobrucki, J. Song, J. Hua, S. Sweterlitsch, D. P. Dione, P. Cavaliere, C. Chow, B. N. Bourke, et al. Noninvasive Targeted Imaging of Matrix Metalloproteinase Activation in a Murine Model of Postinfarction Remodeling Circulation, November 15, 2005; 112(20): 3157 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Karram, A. Abbasi, S. Keidar, E. Golomb, I. Hochberg, J. Winaver, A. Hoffman, and Z. Abassi Effects of spironolactone and eprosartan on cardiac remodeling and angiotensin-converting enzyme isoforms in rats with experimental heart failure Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1351 - H1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chai, I. M. Garrelds, R. de Vries, W. W. Batenburg, J. P. van Kats, and A.H. Jan Danser Nongenomic Effects of Aldosterone in the Human Heart: Interaction With Angiotensin II Hypertension, October 1, 2005; 46(4): 701 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pitt, H. White, J. Nicolau, F. Martinez, M. Gheorghiade, M. Aschermann, D. J. van Veldhuisen, F. Zannad, H. Krum, R. Mukherjee, et al. Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure J. Am. Coll. Cardiol., August 2, 2005; 46(3): 425 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fraccarollo, P. Galuppo, I. Schmidt, G. Ertl, and J. Bauersachs Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction Cardiovasc Res, July 1, 2005; 67(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fiebeler, J. Nussberger, E. Shagdarsuren, S. Rong, G. Hilfenhaus, N. Al-Saadi, R. Dechend, M. Wellner, S. Meiners, C. Maser-Gluth, et al. Aldosterone Synthase Inhibitor Ameliorates Angiotensin II-Induced Organ Damage Circulation, June 14, 2005; 111(23): 3087 - 3094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A D Struthers Pathophysiology of heart failure following myocardial infarction Heart, May 1, 2005; 91(suppl_2): ii14 - ii16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Schulze and R. T. Lee Macrophage-Mediated Cardiac Fibrosis Circ. Res., September 17, 2004; 95(6): 552 - 553. [Full Text] [PDF]
|
|
|
|
|
|
B. Pitt Aldosterone Blockade in Patients With Systolic Left Ventricular Dysfunction Circulation, October 14, 2003; 108(15): 1790 - 1794. [Full Text] [PDF]
|
|
|
|
 |
|
 D. S.H. Bell Diabetic Cardiomyopathy Diabetes Care, October 1, 2003; 26(10): 2949 - 2951. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Pitt, C. T Stier Jr, and S. Rajagopalan Mineralocorticoid receptor blockade: new insights into the mechanism of action in patients with cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 164 - 168. [Abstract] [PDF]
|
|
|
|
|
|
B. Pitt Aldosterone Blockade in Patients With Acute Myocardial Infarction Circulation, May 27, 2003; 107(20): 2525 - 2527. [Full Text] [PDF]
|
|