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 |
|
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]
|
 |
|

|
 |

|
 |
 
M. Yamaji, T. Tsutamoto, C. Kawahara, K. Nishiyama, T. Yamamoto, M. Fujii, and M. Horie
Serum Cortisol as a Useful Predictor of Cardiac Events in Patients With Chronic Heart Failure: The Impact of Oxidative Stress
Circ Heart Fail,
November 1, 2009;
2(6):
608 - 615.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Haykowsky, J. R. Mackey, R. B. Thompson, L. W. Jones, and D. I. Paterson
Adjuvant Trastuzumab Induces Ventricular Remodeling Despite Aerobic Exercise Training
Clin. Cancer Res.,
August 1, 2009;
15(15):
4963 - 4967.
[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]
|
 |
|

|
 |

|
 |
 
J. A. Ezekowitz and F. A. McAlister
Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials
Eur. Heart J.,
February 2, 2009;
30(4):
469 - 477.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Boccanelli, G. F. Mureddu, G. Cacciatore, F. Clemenza, A. Di Lenarda, A. Gavazzi, M. Porcu, R. Latini, D. Lucci, A. P. Maggioni, et al.
Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results
Eur J Heart Fail,
January 1, 2009;
11(1):
68 - 76.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Maisel, C. Mueller, K. Adams Jr., S. D. Anker, N. Aspromonte, J. G.F. Cleland, A. Cohen-Solal, U. Dahlstrom, A. DeMaria, S. Di Somma, et al.
State of the art: Using natriuretic peptide levels in clinical practice
Eur J Heart Fail,
September 1, 2008;
10(9):
824 - 839.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. F. Murphy, C. O'Loughlin, M. Ledwidge, D. McCaffrey, and K. McDonald
Improvement but no cure of left ventricular systolic dysfunction in treated heart failure patients
Eur J Heart Fail,
December 1, 2007;
9(12):
1196 - 1204.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W.H. Wilson Tang, G. S. Francis, D. A. Morrow, L. K. Newby, C. P. Cannon, R. L. Jesse, A. B. Storrow, R. H. Christenson, COMMITTEE MEMBERS, R. H. Christenson, et al.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure
Circulation,
July 31, 2007;
116(5):
e99 - e109.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Haykowsky, Y. Liang, D. Pechter, L. W. Jones, F. A. McAlister, and A. M. Clark
A Meta-Analysis of the Effect of Exercise Training on Left Ventricular Remodeling in Heart Failure Patients: The Benefit Depends on the Type of Training Performed
J. Am. Coll. Cardiol.,
June 19, 2007;
49(24):
2329 - 2336.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Jourdain, G. Jondeau, F. Funck, P. Gueffet, A. Le Helloco, E. Donal, J. F. Aupetit, M. C. Aumont, M. Galinier, J. C. Eicher, et al.
Plasma Brain Natriuretic Peptide-Guided Therapy to Improve Outcome in Heart Failure: The STARS-BNP Multicenter Study
J. Am. Coll. Cardiol.,
April 24, 2007;
49(16):
1733 - 1739.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Berry, N. Murphy, G. De Vito, S. Galloway, A. Seed, C. Fisher, N. Sattar, P. Vallance, W. S. Hillis, and J. McMurray
Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker
Eur J Heart Fail,
April 1, 2007;
9(4):
429 - 434.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Ohtani, M. Ohta, K. Yamamoto, T. Mano, Y. Sakata, M. Nishio, Y. Takeda, J. Yoshida, T. Miwa, M. Okamoto, et al.
Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker
Am J Physiol Regulatory Integrative Comp Physiol,
February 1, 2007;
292(2):
R946 - R954.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Schou, F. Gustafsson, A. Kjaer, and P. R. Hildebrandt
Long-term clinical variation of NT-proBNP in stable chronic heart failure patients
Eur. Heart J.,
January 11, 2007;
(2007)
ehl449v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Schou, F. Gustafsson, P. H. Nielsen, L. H. Madsen, A. Kjaer, and P. R. Hildebrandt
Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state
Eur J Heart Fail,
January 1, 2007;
9(1):
68 - 74.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Braunschweig, A. Fahrleitner-Pammer, M. Mangiavacchi, S. Ghio, P. Fotuhi, U. C. Hoppe, and C. Linde
Correlation between serial measurements of N-terminal pro brain natriuretic peptide and ambulatory cardiac filling pressures in outpatients with chronic heart failure
Eur J Heart Fail,
December 1, 2006;
8(8):
797 - 803.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. J. Birks, P. D. Tansley, J. Hardy, R. S. George, C. T. Bowles, M. Burke, N. R. Banner, A. Khaghani, and M. H. Yacoub
Left Ventricular Assist Device and Drug Therapy for the Reversal of Heart Failure
N. Engl. J. Med.,
November 2, 2006;
355(18):
1873 - 1884.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. M. Felker, J. W. Petersen, and D. B. Mark
Natriuretic peptides in the diagnosis and management of heart failure.
Can. Med. Assoc. J.,
September 12, 2006;
175(6):
611 - 617.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. G. Lainchbury, R. W. Troughton, C. M. Frampton, T. G. Yandle, A. Hamid, M. G. Nicholls, and A. M. Richards
NTproBNP-guided drug treatment for chronic heart failure: design and methods in the "BATTLESCARRED" trial
Eur J Heart Fail,
August 1, 2006;
8(5):
532 - 538.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G A Wright and A D Struthers
Natriuretic peptides as a prognostic marker and therapeutic target in heart failure
Heart,
February 1, 2006;
92(2):
149 - 151.
[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. Izawa, T. Murohara, K. Nagata, S. Isobe, H. Asano, T. Amano, S. Ichihara, T. Kato, S. Ohshima, Y. Murase, et al.
Mineralocorticoid Receptor Antagonism Ameliorates Left Ventricular Diastolic Dysfunction and Myocardial Fibrosis in Mildly Symptomatic Patients With Idiopathic Dilated Cardiomyopathy: A Pilot Study
Circulation,
November 8, 2005;
112(19):
2940 - 2945.
[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]
|
 |
|

|
 |

|
 |
 
D. G.A. Veliotes, A. J. Woodiwiss, D. A.J. Deftereos, D. Gray, O. Osadchii, and G. R. Norton
Aldosterone Receptor Blockade Prevents the Transition to Cardiac Pump Dysfunction Induced by {beta}-Adrenoreceptor Activation
Hypertension,
May 1, 2005;
45(5):
914 - 920.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Bruins, M. R. Fokkema, J. W.P. Romer, M. J.L. DeJongste, F. P.L. van der Dijs, J. M.W. van den Ouweland, and F. A.J. Muskiet
High Intraindividual Variation of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in Patients with Stable Chronic Heart Failure
Clin. Chem.,
November 1, 2004;
50(11):
2052 - 2058.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Hernandez
Left ventricular hypertrophy after renal transplantation: new approach to a deadly disorder
Nephrol. Dial. Transplant.,
July 1, 2004;
19(7):
1682 - 1686.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J E Macdonald, N Kennedy, and A D Struthers
Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment
Heart,
July 1, 2004;
90(7):
765 - 770.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. S. Vasan, J. C. Evans, E. J. Benjamin, D. Levy, M. G. Larson, J. Sundstrom, J. M. Murabito, F. Sam, W. S. Colucci, and P. W. F. Wilson
Relations of Serum Aldosterone to Cardiac Structure: Gender-Related Differences in the Framingham Heart Study
Hypertension,
May 1, 2004;
43(5):
957 - 962.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Hartmann, M. Packer, A. J.S. Coats, M. B. Fowler, H. Krum, P. Mohacsi, J. L. Rouleau, M. Tendera, A. Castaigne, J. Trawinski, et al.
NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy
Eur J Heart Fail,
March 15, 2004;
6(3):
343 - 350.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Bettencourt
NT-proBNP and BNP: biomarkers for heart failure management
Eur J Heart Fail,
March 15, 2004;
6(3):
359 - 363.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. de Denus, C. Pharand, and D. R. Williamson
Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone
Chest,
February 1, 2004;
125(2):
652 - 668.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Clerico and M. Emdin
Diagnostic Accuracy and Prognostic Relevance of the Measurement of Cardiac Natriuretic Peptides: A Review
Clin. Chem.,
January 1, 2004;
50(1):
33 - 50.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. M. Oestreicher, D. Martinez-Vasquez, J. R. Stone, L. Jonasson, W. Roubsanthisuk, K. Mukasa, and G. K. Adler
Aldosterone and Not Plasminogen Activator Inhibitor-1 Is a Critical Mediator of Early Angiotensin II/NG-Nitro-l-Arginine Methyl Ester-Induced Myocardial Injury
Circulation,
November 18, 2003;
108(20):
2517 - 2523.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Fraccarollo, P. Galuppo, S. Hildemann, M. Christ, G. Ertl, and J. Bauersachs
Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction
J. Am. Coll. Cardiol.,
November 5, 2003;
42(9):
1666 - 1673.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. N. Cohn, I. S. Anand, R. Latini, S. Masson, Y.-T. Chiang, and R. Glazer
Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure: Results From the Valsartan Heart Failure Trial
Circulation,
September 16, 2003;
108(11):
1306 - 1309.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. F. Hernandez and C. M. O'Connor
Sparing a little may save a lot: Lessons from the Studies of Left Ventricular Dysfunction (SOLVD)
J. Am. Coll. Cardiol.,
August 20, 2003;
42(4):
709 - 711.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Cardarelli and T. G. Lumicao Jr
B-type Natriuretic Peptide: A Review of Its Diagnostic, Prognostic, and Therapeutic Monitoring Value in Heart Failure for Primary Care Physicians
J Am Board Fam Med,
July 1, 2003;
16(4):
327 - 333.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Ruskoaho
Cardiac Hormones as Diagnostic Tools in Heart Failure
Endocr. Rev.,
June 1, 2003;
24(3):
341 - 356.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Bozkurt and D. L. Mann
Use of Biomarkers in the Management of Heart Failure: Are We There Yet?
Circulation,
March 11, 2003;
107(9):
1231 - 1233.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi
Effect of spironolactone on cardiacsympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy
J. Am. Coll. Cardiol.,
February 19, 2003;
41(4):
574 - 581.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. F. Rousseau, O. Gurne, D. Duprez, W. Van Mieghem, A. Robert, S. Ahn, L. Galanti, J.-M. Ketelslegers, and Belgian RALES Investigators
Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: Results from the RALES neurohormonal substudy
J. Am. Coll. Cardiol.,
November 6, 2002;
40(9):
1596 - 1601.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Hausmann and N. Liel-Cohen
Aldactone therapy in a peritoneal dialysis patient with decreased left ventricular function
Nephrol. Dial. Transplant.,
November 1, 2002;
17(11):
2035 - 2036.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi
Spironolactone Improves Cardiac Sympathetic Nerve Activity and Symptoms in Patients with Congestive Heart Failure
J. Nucl. Med.,
October 1, 2002;
43(10):
1279 - 1285.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Davies and A. Struthers
Review: The potential benefits of aldosterone antagonism in Type 2 diabetes mellitus
Journal of Renin-Angiotensin-Aldosterone System,
September 1, 2002;
3(3):
150 - 155.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Cicoira, L. Zanolla, A. Rossi, G. Golia, L. Franceschini, G. Brighetti, P. Marino, and P. Zardini
Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure
J. Am. Coll. Cardiol.,
July 17, 2002;
40(2):
304 - 310.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. P. Rossi, V. Di Bello, C. Ganzaroli, A. Sacchetto, M. Cesari, A. Bertini, D. Giorgi, R. Scognamiglio, M. Mariani, and A. C. Pessina
Excess ldosterone Is Associated With Alterations of Myocardial Texture in Primary Aldosteronism
Hypertension,
July 1, 2002;
40(1):
23 - 27.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Sodian, M. Loebe, C. Schmitt, E. V. Potapov, H. Siniawski, J. Muller, H. Hausmann, H. R. Zurbruegg, Y. Weng, and R. Hetzer
Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems
J. Am. Coll. Cardiol.,
December 1, 2001;
38(7):
1942 - 1949.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. R. Kalra and R. Sharma
Absolute, not relative, changes are important when interpreting trial data
J. Am. Coll. Cardiol.,
December 1, 2001;
38(7):
2132 - 2132.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Tsutamoto, A. Wada, K. Maeda, N. Mabuchi, M. Hayashi, T. Tsutsui, M. Ohnishi, M. Sawaki, M. Fujii, T. Matsumoto, et al.
Absolute, not relative, changes are important when interpreting trial data: Reply
J. Am. Coll. Cardiol.,
December 1, 2001;
38(7):
2132 - 2133.
[Full Text]
[PDF]
|
 |
|
|