Ventricular resynchronization is the principle mechanism of benefit with cardiac resynchronization therapy

Although there is little debate over the fact that cardiac resynchronization therapy (CRT) can benefit the majority of patients selected with routine indications, the precise mechanism for improvement may be considered controversial. Among patients selected with New York Heart Association functional class III or IV symptoms, left ventricular ejection fraction ≤ 35% and electrocardiographic QRS widening of at least 120-130 ms, approximately 60-80% of patients improved depending on the definition of response used. Although a reasonable assumption is that electrocardiographic QRS widening is a surrogate for delays in regional ventricular mechanical activation, a large volume of data has demonstrated that there is a subset of patients with widened QRS complexes who have no significant mechanical dyssynchrony. The reason for dissociation of electrical dispersion and mechanical dyssynchrony is unknown presently, but many studies have demonstrated the association of dyssynchrony with favorable outcome following CRT. Perhaps more importantly, several imaging studies (principally by echocardiography) have shown the lack of baseline mechanical dyssynchrony to be as a marker for a less favorable outcome after CRT. Recently, the lack of dyssynchrony before CRT has been shown to be associated with a significantly lower long-term probability of freedom from death, heart transplantation, or left ventricular assist device placement. As further mechanistic evidence for the relationship of mechanical dyssynchrony and LV functional response to CRT, it has been suggested that patients who failed to improve their tissue Doppler measures of dyssynchrony after CRT have a lower chance of reverse remodeling. This topic has been muddled by technical difficulties in measurement of mechanical dyssynchrony by all imaging approaches, the confounding variable of scar in ischemic disease, and the widely variable definitions of response used by different investigators. However, the weight of evidence from a pathophysiological basis to the recent long-term patient outcome data strongly support the notion that resynchronization is the principle mechanism of benefit from CRT.