© 2001 European Society of Cardiology
Letter to the Editor
Department of Cardiology University Hospital Antwerp Antwerp, Belgium
Dear Professor Cleland,
The study of Nägele et al. [1] in the March Issue of this Journal shows an impressive amelioration of clinical (NYHA class) and echocardiographic parameters in heart failure patients treated with amiodarone and carvedilol. The value of the observed mortality reduction in the amiodarone-treated group is somewhat flawed due to the comparison with historical controls. More importantly however, in their discussion, the authors mainly focus on the role of amiodarone as an adjunctive to carvedilol in the alleviation of the neurohumoral activation, known to have a detrimental effect in these patients. Additionally, maintenance of sinus rhythm in the combined therapy group could have been beneficial. However, the role of amiodarone as a potential anti-inflammatory agent was not touched. There is now ample evidence that overt cardiac failure is characterised by a cardio-inflammatory response. The prognostic implication of elevated cytokine levels, especially of Tumor Necrosis Factor-alpha and its soluble receptors, has clearly been demonstrated. Matsumori et al. [2] reported an amiodarone induced and significant decrease in the production of TNF-alfa and interleukine-6 by lipopolysaccharide stimulated peripheral blood mononuclear cells in vitro. Moreover, Tomomi et al. [3] demonstrated the anti-oxidant effect of amiodarone in an in vitro experiment using isolated canine left ventricular myocytes. Although the beneficial role of beta-blockers in cardiac failure has largely been attributed to their interference with the vicious circle of neurohumoral activation, in vitro investigations and animal experiments suggest that carvedilol provides extra protection. Carvedilol inhibits the biosynthesis of endothelin-1 in cultured human coronary artery endothelial cells [4]. This agent has been shown to prevent lipid peroxidation, to behave both as a free radical scavenger and as an inhibitor of free oxygen radical formation [5]. Hence, its role in the preservation of endothelial function could prove invaluable.
Although it remains speculative and until now, without firm clinical confirmation, the combination of two compounds, with synergistic effects (anti-inflammatory, anti-oxidative and neurohumoral modulation), could prove to be a promising therapeutic regimen in the treatment of heart failure patients.
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- Nägele H., Bohlmann M., Eck U., Petersen B., Rödiger W. Combination therapy with carvedilol and amiodarone in patients with severe heart failure. Eur J Heart Failure (2000) 2:71–79.
[Abstract/Free Full Text] - Matsumori A., Ono K., Nishio R., Nose Y., Sasayama S. Amiodarone inhibits production of Tumor Necrosis Factor-alpha by human mononuclear cells. Circulation (1997) 96:1386–1389.
[Abstract/Free Full Text] - Tomomi I., Tsutsui H., Kinugawa S., Utsumi H., Takeshita A. Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action. Circulation (1999) 100:690–692.
[Abstract/Free Full Text] - Ohlstein E.H., Arleth A.J., Storer B., Romanic A.M. Carvedilol inhibits endothelin-1 biosynthesis in cultured human coronary artery endothelial cells. J Mol Cell Cardiol (1998) 30:167–173.[CrossRef][Web of Science][Medline]
- Feuerstein G.Z., Ruffolo R.R. Carvedilol, a novel vasodilating beta-blocker with the potential for cardiovascular organ protection. Eur Heart J. (Suppl B) (1996) 17:24–29.
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