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Published on: August 16, 2016
Adrenomedullin and heart failure
Miriam T Rademaker1, Vicky A Cameron, Christopher J Charles
1The Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, PO Box 4345, Christchurch, New Zealand. miriam.rademaker@chmeds.ac.nz
Insights
Adrenomedullin (AM) is elevated in heart failure, predicting outcomes and identifying patients who benefit from carvedilol. AM administration improves heart function and renal function in heart failure.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Nephrology
Background:
- Adrenomedullin (AM) is implicated in heart failure pathophysiology.
- Elevated circulating AM correlates with cardiovascular disease severity and prognosticates adverse outcomes.
- Raised AM levels in heart failure patients predict benefit from carvedilol therapy.
Purpose of the Study:
- To investigate the role and therapeutic potential of adrenomedullin (AM) in heart failure.
- To assess AM's prognostic value and its interaction with existing heart failure therapies.
Main Methods:
- Analysis of circulating AM concentrations in cardiovascular disease patients.
- Administration of AM in experimental and human heart failure models.
- Evaluation of hemodynamic, renal, and hormonal responses to AM therapy.
- Assessment of combined therapy effects (AM with ACE inhibitors and natriuretic peptides).
Main Results:
- Elevated plasma AM levels in heart failure correlate with disease severity and predict adverse outcomes.
- AM administration in heart failure reduces arterial and filling pressures, improving cardiac output.
- AM inhibits aldosterone, sustains renal glomerular filtration, and promotes sodium excretion.
- Combined AM therapy with ACE inhibitors and natriuretic peptides yields superior hemodynamic and renal benefits.
Conclusions:
- The adrenomedullin system is a promising therapeutic target for cardiovascular diseases, particularly heart failure.
- AM has significant prognostic and therapeutic implications in managing heart failure patients.
- Targeting the AM system offers a novel strategy for improving cardiovascular and renal function in heart failure.
Abstract:
Evidence suggests that adrenomedullin (AM) plays a role in the pathophysiology of heart failure. Circulating concentrations of AM are elevated in cardiovascular disease in proportion to the severity of cardiac and hemodynamic impairment. Raised plasma AM levels following acute cardiac injury and in heart failure provide prognostic information on adverse outcomes. In heart failure, elevated circulating AM also identifies patients likely to receive long-term benefit from inclusion of additional anti-failure therapy (carvedilol). Administration of AM in experimental and human heart failure induces reductions in arterial pressure and cardiac filling pressures, and improves cardiac output, in association with inhibition of plasma aldosterone (despite increased renin release) and sustained (or augmented) renal glomerular filtration and sodium excretion. Furthermore, AM in combination with other therapies (angiotensin-converting enzyme inhibition and augmentation of the natriuretic peptides) results in hemodynamic and renal benefits greater than those achieved by the agents separately. Manipulation of the AM system holds promise as a therapeutic strategy in cardiac disease.
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