(Circulation. 2001;104:e96.)
© 2001 American Heart Association, Inc.
Correspondence |
Endothelin Receptor Blockade in Congestive Heart Failure
Professor of Medicine, The George Washington University, Washington, DC 20037
To the Editor:
Of the many new therapeutic agents for slowing the progression of congestive heart failure (CHF), other than antagonizing the renin-angiotensin-aldosterone system, blocking the endothelin receptors seems to be most promising. The two latest reports published in Circulation1,2 render further support to this exciting concept.
Endothelin may contribute to the symptoms associated with CHF. Patients with the lowest exercise capacity, as measured objectively by maximum oxygen consumption (
O2max) were those who had the highest plasma levels of endothelin-1 at the time of maximal exercise.3 This finding suggests that endothelin may play a role in limiting the ability of the peripheral vasculature to dilate during exercise and, thus, contribute to exercise intolerance in these patients.4 Therefore, the reduced exercise capacity of patients with CHF may be more than a derangement in central hemodynamic variables, such as decreased cardiac output and increased pulmonary artery wedge pressure.
Several endothelin receptor antagonists have been developed. Tezosentan1 is being developed specifically for the short-term intravenous treatment of acute CHF. Studies with LU1352522 and bosentan5 indicate that short-term treatment with bolus intravenous or oral dosages is associated with improved systemic and pulmonary hemodynamic parameters. The short-term effects are encouraging, but these drugs are being developed to treat chronic CHF.1 Only long-term studies will determine whether the short-term effects translate into long-term benefit. Further, comparative trials with "standard" therapies for CHF, such as ACE inhibitors and ß-blockers, are needed before these agents can be introduced into clinical use.
References
1.
Torre-Amione G, Young JB, Durand J-B, et al. Hemodynamic effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with class III to IV congestive heart failure. Circulation. 2001; 103: 973–980.
2.
Berger R, Stanek B, Hülsmann M, et al. Effects of endothelin A receptor blockade on endothelial function in patients with chronic heart failure. Circulation. 2001; 103: 981–986.
3. Krum H, Goldsmith R, Wilshire-Clement M, et al. Role of endothelin in the exercise intolerance of chronic heart failure. Am J Cardiol. 1995; 75: 1282–1283.[Medline] [Order article via Infotrieve]
4. Krum H. New and emerging pharmacologic strategies in the management of chronic heart failure. Clin Cardiol. 2000; 23: 724–730.[Medline] [Order article via Infotrieve]
5. Ellahham SH, Charlon V, Abassi Z, et al. Bosentan and the endothelin system in congestive heart failure. Clin Cardiol. 2000; 23: 803–807.[Medline] [Order article via Infotrieve]
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