Cardiac Resynchronization Therapy: Current State of the Art

2]3456 As noted below, CRT makes heart failure patients feel better, improves cardiac structure and function, and reduces all-cause as well as heart failure morbidity and mortality.Thus, there may be a clinical mandate for use of CRT in many patients with chronic heart failure.This notion raises important questions about the clinical application of this therapy.For example, will the availability of CRT change our current clinical approach to heart failure patients?Will it lead to new research advances?Will CRT patients also require an implantable cardioverter defibrillator (ICD) to optimize outcomes?Will the clinical benefits of these therapies justify the costs? Ventricular Dyssynchrony: A Pathophysiological Cause or Contributor to Heart FailurePatients with left ventricular (LV) systolic dysfunction and dilation, with or without clinical signs or symptoms of heart failure, frequently have ventricular conduction delays. 7In such patients, this is usually manifested as a left bundlebranch block (LBBB).This type of conduction abnormality is generally associated with delayed depolarization and contraction of the lateral LV free wall (Figure 1), whereas the interventricular septum exhibits a normal (early) contraction resulting in paradoxical septal motion.The abnormal activation sequence induced by spontaneous LBBB or by right ventricular (RV) pacing generates changes in regional ventricular loading conditions (Figure 2), possibly redistributes myocardial blood flow, 8 and creates a regional nonuniform myocardial metabolism. 9These effects of ventricular dyssynchrony might contribute to disease progression in LV systolic dysfunction patients. 10For example, studies in experimental heart failure induced by rapid ventricular pacing showed regional differences in the extent of ventricular hypertrophy with an apicobasal-and septolateral-oriented gradient. 11Moreover, experimentally induced LBBB has demonstrated a large effect on the expression of regional stress kinases and calcium-handling proteins. 12Preliminary evidence suggests that the expression of p38-MAPK (a stress kinase) is significantly elevated in the endocardium of the late-activated region, whereas phospholamban is significantly decreased. 11In addition, sarco(endo)plasmatic reticulum Ca 2ϩ -ATPase is decreased in the region of early activation. 11he meaning of such complex interactions between changes in regional loading conditions, blood flow distribution, regional myocardial metabolism, and gene and protein expression induced by an abnormal activation sequence is not fully understood.However, it is likely that these conse-