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J Am Coll Cardiol, 2001; 37:1228-1233
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure

Takayoshi Tsutamoto, MDa, Atsuyuki Wada, MDa, Keiko Maeda, MDa, Naoko Mabuchi, MDa, Masaru Hayashi, MDa, Takashi Tsutsui, MDa, Masato Ohnishi, MDa, Masahide Sawaki, MDa, Masanori Fujii, MDa, Takehiro Matsumoto, MDa, Toshiki Matsui, MDa and Masahiko Kinoshita, MDa

a First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan

Manuscript received June 1, 2000; revised manuscript received November 14, 2000, accepted December 15, 2000.

Reprint requests and correspondence: Dr. Takayoshi Tsutamoto, First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
tutamoto{at}belle.shiga-med.ac.jp

OBJECTIVES

We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF).

BACKGROUND

Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified.

METHODS

Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis.

RESULTS

Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment.

CONCLUSIONS

These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  ANP = atrial natriuretic peptide
  ALD = aldosterone
  BNP = brain natriuretic peptide
  CHF = congestive heart failure
  EDTA = ethylenediaminetetraacetic acid
  LVEF = left ventricular ejection fraction
  NYHA = New York Heart Association
  PARC = plasma active renin concentration
  PIIINP = procollagen type III aminoterminal peptide
  RALES = Randomized Aldactone Evaluation Study




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