LETTER TO THE EDITOR
Torasemide inhibits transcardiac extraction of aldosterone in patients with congestive heart failure
Takayoshi Tsutamoto, MD*,
Hiroshi Sakai, MD,
Atsuyuki Wada, MD,
Chitose Ishikawa, MD,
Keijin Ohno, MD,
Masanori Fujii, MD,
Takashi Yamamoto, MD,
Tomoyuki Takayama, MD,
Tomohiro Dohke, MD and
Minoru Horie, MD
* Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan (Email: tutamoto{at}belle.shiga-med.ac.jp).
To the Editor:
Loop diuretics such as furosemide and torasemide are important for the symptomatic treatment of congestive heart failure (CHF). Recently, in the TOrasemide In Congestive Heart Failure (TORIC) study, torasemide had a more beneficial effect on the mortality and morbidity of patients with CHF than furosemide (1). The mechanism by which torasemide provides a greater benefit than furosemide remains unknown, but experimental studies indicate that torasemide may inhibit the binding of aldosterone (ALD) to its receptor in the cytoplastic fraction of the rat kidney (2,3). Therefore, in the present study, we evaluated the transcardiac extraction of ALD, as a potential marker of ALD action in the heart (4,5), in torasemide therapy compared with furosemide therapy in the treatment of patients with CHF.
The subjects were 60 consecutive patients with CHF (left ventricular ejection fraction <45%). Patients receiving spironolactone were excluded. Informed consent was obtained from all patients before participation in the study, and the protocol was approved by the Human Investigations Committee of our institution. Sixty patients were divided randomly into two groups that were treated with either furosemide (n = 30) or torasemide (n = 30) for one month. In the furosemide group, the same dose of furosemide was continued. In the torasemide group, furosemide was changed to torasemide at a dose with comparable diuretic efficacy (furosemide 40 mg/day changed to torasemide 8 mg/day).
After one month, blood samples for measuring plasma ALD were collected simultaneously from the aortic root (AO) and coronary sinus (CS), and measurements of neurohumoral factors were performed as previously reported (4,5).
All results are expressed as mean values ± SEM. Univariate analyses were performed using the Student t test. Linear regression analysis was used to determine the relationship between continuous variables. A p value < 0.05 was regarded as significant.
There was no difference in patient characteristics between the two groups (Table 1). In the torasemide group, the mean dose of torasemide was 10.1 ± 0.7 mg/day (range, 4 to 16 mg/day).
One month after randomization, there were no differences in hemodynamic parameters. In the furosemide group, the plasma ALD level in the CS was significantly lower than that in the AO (73.1 ± 10.0 pg/ml vs. 56.9 ± 6.5 pg/ml; p < 0.001). In contrast, there was no difference in plasma ALD levels between the AO and the CS in the torasemide group (85.4 ± 10.5 pg/ml vs. 83.1 ± 11.6 pg/ml) (Fig. 1). Plasma procollagen type III aminoterminal peptide in the CS concentration was significantly lower in the torasemide group than that in the furosemide group (0.52 ± 0.03 U/ml vs. 0.67 ± 0.06 U/ml; p < 0.05). There was a significant negative correlation between the dose of torasemide and the transcardiac gradient (AO–CS) of ALD in the torasemide group (r = –0.56, p < 0.01).
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Figure 1 Plasma aldosterone (ALD) concentrations in the aortic root (AO) and coronary sinus (CS) in patients with congestive heart failure. (A) furosemide group; (B) torasemide group.
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We evaluated the transcardiac extraction of ALD as a potential marker of ALD action in the heart (4,5) in patients with CHF. In the furosemide group, the plasma ALD level in the CS was significantly lower than that in the AO. In contrast, there was no difference in plasma ALD level between the AO and the CS in the torasemide group. The transcardiac gradient (AO–CS) of ALD and the extraction ratio of ALD in the AO were significantly lower in the torasemide group than those in the furosemide group. Plasma procollagen type III aminoterminal peptide concentration, a biochemical marker of fibrosis, was significantly lower in the torasemide group than in the furosemide group. These findings may indicate that unlike furosemide, torasemide has an ALD receptor antagonist in the heart. Experimental studies indicate that torasemide inhibits the binding of ALD to its receptor in the cytoplastic fraction of rat kidney (2,3). Moreover, the serum potassium level was significantly higher in the torasemide group than in the furosemide group in a large series (i.e., TORIC study). Taken together with our results, the mechanism of the beneficial effect of torasemide in comparison with those of furosemide in the TORIC study may be due to the presence of mineralocorticoid receptor blocker in torasemide.
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References
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- Cosin J, Diez J, TORIC investigators Torasemide in chronic heart failure: results of the TORIC study(erratum in Eur J Heart Fail 2002;4:667) Eur J Heart Fail 2002;4:507-513.[CrossRef][Medline]
- Uchida T, Yamanaga K, Nishikawa M, Ohtani Y, Kido H, Watanabe M. Anti-aldosterone effect of torasemide Eur J Pharmacol 1991;205:145-150.[CrossRef][Medline]
- Uchida T, Yamanaga K, Kido H, Ohtani Y, Watanabe M. Diuretic and vasodilating actions of torasemide Cardiology 1994;84:14-17.[Medline]
- Tsutamoto T, Wada A, Maeda K, et al. Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure J Am Coll Cardiol 2000;36:838-844.[Abstract/Free Full Text]
- Hayashi M, Tsutamoto T, Wada A, et al. Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction J Am Coll Cardiol 2001;38:1375-1382.[Abstract/Free Full Text]
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