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Purpose: Optimization of cardiac resynchronization therapy (CRT) remains controversial as recently several large trials have shown no overall benefit and it is time consuming. We hypothesized that patients who remained dyssynchronous after CRT implant would be most likely to benefit from echo Doppler guided optimization.Methods:3D echocardiography (3DE) was performed before and within 3 days after CRT implant. 3 months after implant all patients underwent echo Doppler guided optimization of AV delays and VV delays. 3DE was performed before and immediately after optimization. 3D Systolic dyssynchrony index (SDI), left ventricular volumes and ejection fraction (EF) were calculated.Results:Adequate datasets from 41 patients were analyzed. The relative change in EF due to optimization was 6.6%. When the cohort was stratified by SDI post CRT, 30 patients had an SDI <10. In these patients, optimization led to a 5% relative increase in EF. In 11 patients with a post CRT SDI of >10, optimization led to a 10.8% relative increase in EF. Alternatively, if response was defined by a relative decrease in end-systolic volume of >10% at 3 months pre-optimization, then 8 out of 41 patients would be classified as non-responders. Optimization resulted in a mean relative increase in EF of 3.9% in these 8 patients, whereas the mean relative increase in EF was 7% in the other 33 patients.Conclusions: Echo-Doppler guided optimization of CRT resulted in an increase in EF across the whole cohort. However, these data suggest that 3D dyssynchrony after CRT implant can identify a cohort of patients who may derive greater benefit from CRT optimization.