Published online before print May 5, 2003, doi: 10.1161/01.CIR.0000068340.96506.0F
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(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
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%, 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.
Key Words: myocardial infarction • ventricles • remodeling • collagen
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