Pathobiology of left ventricular dyssynchrony

Research output: Chapter in Book/Report/Conference proceedingChapter


Heart failure combines multiple abnormalities, including molecular and structural cardiac remodeling, neurohormonal stimulation, excessive loading, and vascular insufficiency - all conspiring to limit cardiac pump performance. Typically, heart failure therapy has relied on moderating fluid balance, and blocking both the rennin-angiotensin-aldosterone and b-adrenergic systems (see recent reviews1,2). However, mechanical factors also play a role in the pathophysiology of heart failure, particularly those affecting the intrachamber synchrony of contraction and atrial and ventricular timing intervals. Atrial activation that occurs too close or well prior to ventricular activation results in suboptimal cardiac filling and a net fall in ejection.3-5 Initial clinical trials with pacing therapy in heart failure focused on this effect, and tried to optimize atrioventricular (AV) delay time using right ventricular (RV) single-site pacing.6 However, this was soon found to be ineffective in a majority of patients.7-9 Attention shifted to problems with dyscoordinate ventricular contraction, typically the result of disparities in timing of electrical activation between one region of the heart and another. Such dyssynchrony can be reflected by prolongation of the surface QRS complex, which has been shown to be an independent and major contributor to heart failure morbidity and mortality.10-13 In 1994, Cazeau et al14 reported on the use of multisite cardiac pacing to re-establish coordinate contraction in a patient with dilated heart failure. In the years leading up to this, there were barely a handful of studies reporting on cardiac dysynchrony or resynchronization. There are now more than a thousand. Cardiac resynchronization therapy (CRT) is now an important, approved therapy for a subset of heart failure patients, having been shown to improve overall survival, clinical symptoms, and hospitalization rates.15-20.

Original languageEnglish (US)
Title of host publicationCardiac Resynchronization Therapy
PublisherCRC Press
Number of pages14
ISBN (Electronic)9780203089965
ISBN (Print)9781841846378
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • General Medicine


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