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Role of endothelins in congestive heart failure
Gordon W Moe1, Jean L Rouleau, Quang T Nguyen
1St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada. moegord@attglobal.net
Insights
Endothelin-1 (ET-1) plays a key role in heart failure. Endothelin receptor blockers are being studied for new heart failure therapies, with ongoing trials to determine the most effective blockade strategy.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Heart failure (HF) remains a significant cause of morbidity and mortality despite advances in conventional therapy.
- Endothelin-1 (ET-1), a potent vasoconstrictor and mitogenic peptide, is activated in HF, suggesting its involvement in the disease's pathophysiology.
Purpose of the Study:
- To elucidate the role of the endothelin-1 system in heart failure.
- To explore the therapeutic potential of endothelin receptor blockers in managing heart failure.
Main Methods:
- Review of experimental and clinical evidence regarding ET-1's role in heart failure.
- Analysis of published clinical studies on endothelin receptor blockers in heart failure patients.
- Consideration of ongoing large-scale clinical trials evaluating hard clinical outcomes.
Main Results:
- Manipulation of ET-1 activity via receptor blockers has aided in understanding the neurohormonal system's role in HF.
- Previous studies involved small patient cohorts with severe HF and short follow-up periods, focusing on surrogate endpoints.
Conclusions:
- Endothelin receptor blockers represent a novel therapeutic strategy for heart failure.
- Further large-scale trials are needed to confirm clinical benefits and determine optimal blockade (selective ETA vs. dual ETA-ETB).
Abstract:
Despite major advances in conventional medical therapy, patients with heart failure continue to experience significant morbidity and mortality. Endothelin-1 (ET-1) is a potent vasocontrictor and mitogenic peptide that is activated in heart failure. There is increasing experimental and clinical evidence in support of an important role of ET-1 in the pathophysiology of heart failure. Manipulation of the activity of ET-1, especially using endothelin receptor blockers, has allowed for the further elucidation of the role of this neurohormonal system and development of novel therapeutic strategies in heart failure. Published clinical studies of these agents to date have involved relatively small numbers of patients with severe heart failure, followed for a relatively short period of time, and have mainly examined surrogate endpoints. Large-scale trials that address to hard clinical outcomes are ongoing and their results forthcoming. A key question that remains concerns whether selective ETA or dual ETA-ETB receptor blockade will be more effective.