Controversies in ventricular remodelling.
Ventricular remodelling describes structural changes in the left ventricle in response to chronic alterations in loading conditions, with three major patterns: concentric remodelling, when a pressure load leads to growth in cardiomyocyte thickness; eccentric hypertrophy, when a volume load produces myocyte lengthening; and myocardial infarction, an amalgam of patterns in which stretched and dilated infarcted tissue increases left-ventricular volume with a combined volume and pressure load on non-infarcted areas. Whether left-ventricular hypertrophy is adaptive or maladaptive is controversial, as suggested by patterns of signalling pathways, transgenic models, and clinical findings in aortic stenosis. The transition from apparently compensated hypertrophy to the failing heart indicates a changing balance between metalloproteinases and their inhibitors, effects of reactive oxygen species, and death-promoting and profibrotic neurohumoral responses. These processes are evasive therapeutic targets. Here, we discuss potential novel therapies for these disorders, including: sildenafil, an unexpected option for anti-transition therapy; surgery for increased sphericity caused by chronic volume overload of mitral regurgitation; an antifibrotic peptide to inhibit the fibrogenic effects of transforming growth factor beta; mechanical intervention in advanced heart failure; and stem-cell therapy.
Opie
Lionel H
LH
Hatter Institute for Heart Research, Cape Heart Centre and Department of Medicine, University of Cape Town Faculty of Health Sciences, Observatory 7925, Cape Town, South Africa. Opie@capeheart.uct.ac.za
Commerford
Patrick J
PJ
Gersh
Bernard J
BJ
Pfeffer
Marc A
MA
D000818:Animals; D001291:Attitude of Health Personnel; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008944:Mitral Valve Insufficiency / Q000150:complications / Q000503:physiopathology*; D008955:Models, Cardiovascular; D018384:Oxidative Stress; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate