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Role of endothelin in heart failure with reduced ejection fraction

Flora Sam, MD
Michael M Givertz, MD
Section Editor
Wilson S Colucci, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


The pathophysiology of heart failure with reduced ejection fraction (HFrEF) remains incompletely understood. Reduced myocardial contractility and systemic and pulmonary vasoconstriction induced by neurohumoral activation (eg, increased angiotensin II, aldosterone, and norepinephrine) play important roles in the progression of disease. (See "Pathophysiology of heart failure: Neurohumoral adaptations".)

The improvement in patient survival associated with the use of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, and aldosterone antagonists provides direct evidence of the long-term deleterious effect of these neurohumoral changes. (See "Overview of the therapy of heart failure with reduced ejection fraction".)

Circulating levels of endothelin also are increased in patients with HFrEF and may contribute to the progression of left ventricular dysfunction [1] and the development of secondary pulmonary hypertension [2,3]. The possible role of endothelin in HFrEF and studies of anti-endothelin therapies will be reviewed here. Unfortunately, while the pathophysiology of HFrEF strongly implicates endothelin in the progression of disease, the promise of endothelin inhibition as a novel therapeutic strategy has not been realized in clinical trials.

The role of endothelin receptor antagonists in treatment of pulmonary arterial hypertension is discussed separately. (See "Treatment of pulmonary hypertension in adults", section on 'Endothelin receptor antagonists'.)


Endothelin (ET) is a 21 amino acid, vasoconstrictor peptide first isolated in 1988 [4]. In addition to its direct vasoconstrictor properties, ET can exert long-term effects on vascular smooth muscle cell proliferation and phenotype [5].

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Literature review current through: Nov 2017. | This topic last updated: Sep 21, 2015.
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