doi: 10.1161/01.RES.0000105922.61310.D4
© 2003 American Heart Association, Inc.
Editorials |
Blocking Stretch-Induced Myocardial Remodeling
From Temple University School of Medicine, Philadelphia, Pa.
Correspondence to Kenneth B. Margulies, MD, Associate Professor of Medicine and Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3420 N Broad St, Room 805 MRB, Philadelphia, PA 19140. E-mail margul@temple.edu
Key Words: hypertrophy • remodeling • heart failure • calcium • device
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
It is increasingly recognized that pathological cardiac remodeling, including myocardial hypertrophy and chamber dilation, is a process that promotes progression of myocardial dysfunction and adverse clinical sequelae among patients with dilated cardiomyopathies, regardless of the pathogenesis. Accordingly, the goals of delaying progression or inducing regression of pathological cardiac hypertrophy and dilation, so-called "reverse remodeling," have emerged as important therapeutic targets in the treatment of dilated cardiomyopathies.
In recent years, some of the most dramatic examples of reverse remodeling have been observed after application of devices that reduce global or regional left ventricular loading conditions. Perhaps most striking have been the myocardial adaptations after placement of a left ventricular assist device (LVAD) in patients with medically refractory heart failure awaiting heart transplantation. In these settings, studies from multiple laboratories have demonstrated that LVAD support induces regression of many of the typical abnormalities of the failing myocardium including pathological hypertrophy,1,2 action potential prolongation,3 impaired contractility and contractile reserve,4–6 extracellular matrix abnormalities,7 and expression of genes normally associated with fetal development.8 Such studies support the hypothesis that the progression and persistence of many of the myocardial abnormalities observed in dilated failing hearts, regardless of pathogenesis, are a direct or indirect consequence of increased myocardial wall stress. Because LVADs are only used among patients with the most severe degrees of myocardial failure, studies of LVAD-supported hearts also suggest that the potential for myocardial reverse remodeling is retained across a wide spectrum of disease severity.
Indeed, recent applications of other devices, most notably multisite ventricular