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CLINICAL STUDY

Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure

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

Manuscript received December 8, 1999; revised manuscript received March 15, 2000, accepted April 26, 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

The study evaluated the transcardiac extraction or spillover of aldosterone (ALDO) in normal subjects and in patients with congestive heart failure (CHF).

BACKGROUND

Aldosterone promotes collagen synthesis and structural remodeling of target organs such as the heart. Spironolactone, an ALDO receptor antagonist, has recently been reported to reduce the mortality of patients with CHF; however, the effects of spironolactone on the transcardiac gradient of ALDO have not been clarified.

METHODS

We measured plasma ALDO in the aortic root (AO) and coronary sinus (CS) in normal subjects and 113 consecutive CHF patients and also measured plasma procollagen type III aminoterminal peptide (PIIINP) in CS, a biochemical marker of myocardial fibrosis.

RESULTS

Plasma ALDO was significantly lower in the CS than in the AO in normal subjects (n = 15; 61.2 ± 9.3 vs. 83.1 ± 11.8 pg/ml, p < 0.0001). In 96 CHF patients who did not receive spironolactone, plasma ALDO was significantly lower in the CS than in the AO (59.3 ± 3.9 vs. 73.8 ± 4.9 pg/ml, p < 0.0001). In contrast to the difference in these 96 patients, there was no significant difference in ALDO between the AO and CS in 17 patients who received spironolactone (127.4 ± 20 vs. 124.0 ± 19 pg/ml, p = 0.50). Stepwise multivariate analyses showed that spironolactone therapy had an independent and significant negative relationship with the transcardiac gradient of plasma ALDO in patients with CHF. In addition, significant positive correlations were seen between the transcardiac gradient of plasma ALDO and PIIINP (r = 0.565, p < 0.0001) and the left ventricular end-diastolic volume index (r = 0.484, p < 0.0001).

CONCLUSIONS

These results indicate that plasma ALDO is extracted through the heart in normal subjects and in CHF patients who do not receive spironolactone and that spironolactone inhibits the transcardiac extraction of ALDO in CHF patients, suggesting that spironolactone blocks the effects of ALDO on the failing heart in patients with CHF.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ALDO = aldosterone   Ang II = angiotensin II   ANP = atrial natriuretic peptide   AO = aortic root   BNP = brain natriuretic peptide   CHF = congestive heart failure   CS = coronary sinus   LVEDVI = left ventricular end-diastolic volume index   LVEF = left ventricular ejection fraction   PIIINP = procollagen type III aminoterminal peptide

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