title: Pathophysiology of dyssynchrony: of squirrels and broken bones.
abstract: The genesis of cardiac resynchronisation therapy (CRT) consists of 'bedside' research and 'bench' studies that are performed in series with each other. In this field, the bench studies are crucial for understanding the pathophysiology of dyssynchrony and resynchronisation. In a way, CRT started with the insight that abnormal ventricular conduction, as caused by right ventricular pacing, has adverse effects. Out of this research came the ground-breaking insight that 'simple' disturbances in impulse conduction, which were initially considered innocent, proved to result in a host of molecular and cellular derangements that lead to a vicious circle of remodelling processes that facilitate the development of heart failure. As a consequence, CRT does not only correct conduction abnormalities, but also improves myocardial properties at many levels. Interestingly, corrections by CRT do not exactly reverse the derangements, induced by dyssynchrony, but also activate novel pathways, a property that may open new avenues for the treatment of heart failure.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: R F
authors.initials: RF
authors.lastname: Wiegerinck
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Schreurs
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands. frits.prinzen@maastrichtuniversity.nl.
authors.forename: F W
authors.initials: FW
authors.lastname: Prinzen
keywords: Cardiac resynchronisation therapy; Dyssynchrony; Heart failure; Protection; Remodelling; Ventricular pacing