This Article Full Text Full Text (PDF) All Versions of this Article: 107/20/2559    most recent 01.CIR.0000068340.96506.0Fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayashi, M. Articles by Horie, M. Search for Related Content PubMed PubMed Citation Articles by Hayashi, M. Articles by Horie, M. Related Collections Cardiovascular Pharmacology Related Article

(Circulation. 2003;107:2559.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

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; Takayoshi Tsutamoto, MD; Atsuyuki Wada, MD; Takashi Tsutsui, MD; Chitose Ishii, MD; Keijin Ohno, MD; Masanori Fujii, MD; Atsushi Taniguchi, MD; Tomokazu Hamatani, MD; Yoshitaka Nozato, MD; Ken Kataoka, MD; Naoki Morigami, MD; Masato Ohnishi, MD; Masahiko Kinoshita, MD; Minoru Horie, MD

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.

Correspondence to Takayoshi Tsutamoto, MD, Department of Cardivascular Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, 520-2192, Japan. 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%, P_interaction=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, P_interaction=0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (P_interaction=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 (P_interaction=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.

Key Words: myocardial infarction • ventricles • remodeling • collagen

Related Article:

Aldosterone Blockade in Patients With Acute Myocardial Infarction

Bertram Pitt
Circulation 2003 107: 2525-2527. [Full Text]

This article has been cited by other articles:

				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]

				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]

				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 Aldosterone Blockade in Patients With Acute Myocardial Infarction Circulation, May 27, 2003; 107(20): 2525 - 2527. [Full Text] [PDF]