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Neurohumoral activation and progression of heart failure: hypothetical and clinical considerations
1Cardiology Department, Cleveland Clinic Foundation, Ohio, USA.
Insights
New understanding of heart failure focuses on neurohormones. Beta-blockers like carvedilol effectively treat heart failure by blocking sympathetic nervous system activity and preventing cardiac remodeling.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Heart failure understanding has evolved from a hemodynamic model to a complex syndrome involving neurohormones and cytokines.
- Neurohormonal pathways are key drivers of heart failure progression.
- Therapeutic strategies have shifted from contractile agents to neurohormonal blockade.
Purpose of the Study:
- To review the evolving understanding of heart failure pathophysiology.
- To highlight the therapeutic implications of targeting neurohormonal systems.
- To discuss the role of beta-adrenergic blockers, specifically carvedilol, in managing heart failure.
Main Methods:
- Review of current literature on heart failure pathophysiology and treatment.
- Analysis of clinical trial data for drugs targeting neurohormonal systems.
- Examination of carvedilol's effects on left ventricular remodeling and survival.
Main Results:
- Agents blocking the renin-angiotensin-aldosterone system are effective.
- Beta-adrenergic blockers, including carvedilol, are safe and effective, improving left ventricular function and survival in specific patient groups.
- Carvedilol demonstrates benefits in both ischemic and non-ischemic heart failure, potentially by reducing left ventricular remodeling.
Conclusions:
- Heart failure management has significantly benefited from targeting neurohormonal systems.
- Beta-adrenergic blockers like carvedilol play a crucial role in preventing disease progression by mitigating left ventricular remodeling.
- Future research may yield novel antagonists for neuroendocrine and cytokine pathways for improved hypertension and heart failure treatment.
Abstract:
The model for heart failure has changed radically over the past 20 years. No longer a simple hemodynamic paradigm of pump dysfunction, heart failure is now characterized as a complex clinical syndrome with release of many neurohormones and cytokines, which are believed to be most responsible for progression of disease. This change in our understanding of the pathophysiology of heart failure has important therapeutic implications. Drugs designed to influence the myocardial contractile state have been found over the past few decades to have either a neutral or an adverse effect on long-term survival, whereas agents designed to block the renin-angiotensin-aldosterone and other neurohormonal systems have proved to be remarkably effective treatment. Recently, drugs designed to block excessive sympathetic nervous system activity have been demonstrated in well-controlled studies to be safe and effective forms of therapy for heart failure. Carvedilol, a nonselective beta-adrenergic blocker with alpha1-blocking and antioxidant properties, is associated with prevention of progression of heart failure as manifested by improvement in left ventricular (LV) function, reduction in heart size, and improved survival in patients with New York Heart Association functional Class II and III symptoms. This improvement is observed equally in patients with ischemic and non-ischemic heart failure. It is tempting to speculate that beta-adrenergic blockers prevent the progression of heart failure by reducing LV mass and LV chamber size. In essence, carvedilol, and perhaps other beta-adrenergic blockers, appear to abrogate relentless LV remodeling which is typically associated with progression of heart failure. The combination of angiotensin-converting enzyme inhibitors and beta-adrenergic blockers may be particularly effective in this regard, although more data on beta-adrenergic blockers in patients with advanced heart failure are needed. Data from experimental heart failure animal models also suggest that endothelin (ET) subtype A (ET(A)) receptor blockers have the potential to lessen the pace of progressive LV remodeling. As our understanding of the neuroendocrine response to diminished cardiac performance improves, novel and even more imaginative neurohormonal and cytokine antagonists are likely to emerge as important new treatments for both hypertension and heart failure.