VIEWPOINT
Heart failure therapy at a crossroad: are there limits to the neurohormonal model?
Mandeep R. Mehra, MD, FACC*,*,
Patricia A. Uber, PharmD* and
Gary S. Francis, MD, FACC
* Department of Cardiovascular Medicine, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
Manuscript received October 1, 2002;
revised manuscript received November 12, 2002,
accepted November 27, 2002.
* Reprint requests and correspondence: Dr. Mandeep R. Mehra, Cardiomyopathy and Heart Transplantation Center, BH-326, 1514 Jefferson Highway, New Orleans, Louisiana 70121, USA.
mmehra{at}ochsner.org
The advent of neurohormonal blockade in heart failure (HF) has been an overwhelming success, but current evidence points to a ceiling effect as newer neurohormonal targets are exploited in an incremental manner. This has lead us to question whether the neurohormonal model of HF can be sustained by simply stacking multiple neurohormonal or cytokine blockers together as treatment. A unifying theme in some of these disparate trials relates to either a lack of efficacy or, more importantly, adversity resulting in regression of already achieved benefits. It is our contention that the available evidence has uncovered the remarkable complexity of interaction within the context of the neurohormonal construct. As we stand at a crossroad in HF and begin to fervently pursue non-neurohormonal therapeutic targets, we must also direct attention at navigating the multifaceted labyrinth of the neurohormonal model that has led to the current imbroglio.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | ARB | = angiotensin receptor antagonists | | HF | = heart failure | | NEP | = neutral endopeptidase | | NYHA | = New York Heart Association | | RAAS | = renin-angiotensin-aldosterone system | | TNF | = tumor necrosis factor |
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