Three dimensional echocardiography is an accurate and reproducible method to quantify LV dyssynchrony. It is Simetryn unclear if an elaborate echocardiographic approach to AV delay and VV interval optimization of CRT systems, including doppler echocardiography and three-dimensional echocardiography, leads to an improved acute outcome after CRT initiation. In the present study we therefore evaluated the feasibility of three-dimensional echocardiography to optimize the interventricular interval of biventricular pacemakers. In the present study we tested a new protocol of combined AV delay and VV interval optimization of CRT-systems including standard Doppler-echocardiography for AV delay, and 3D echocardiography for VV interval optimization. This elaborate protocol led to a significant improvement of LV function immediately after implantation of a CRT device compared to empiric device programming. The examined cohort existed of typical candidates for cardiac resynchronization therapy. All were highly symptomatic and on recommended optimal pharmacological therapy. Moreover, all patients showed QRS prolongation of more than 120 ms, and had a mean ejection fraction of 23%. After the first step of optimization the ejection fraction rose from 23% to 30% and could be increased even further by VV interval optimization. End-systolic volume was Veratramine reduced significantly already after AV delay optimization, with a moderate further reduction after VV interval optimization. The SDI, as a marker of interventricular dyssynchrony, fell sharply after each optimization step, whereas the aortic VTI, a surrogate marker of stroke volume, was only affected by AV delay optimization. In most patients the VV interval had to be programmed differently from the standard setting, only 28% of patients achieved the lowest possible SDI with the standard setting of simultaneous activation of left and right ventricle. These results strongly support an individualized optimization of CRT-systems, specifically tailored to the patients. CRT is used in patients with several etiologies of severely symptomatic heart failure, and one can imagine that a one fits all approach may not necessarily generate the best outcome. This has also been shown in a small cohort with Doppler optimization of AV delay and VV interval. Favorable hemodynamic response was more pronounced in the group of patients randomized to the optimization protocol. This is the first study to use 3DE for VV interval optimization. The only modest further improvement of LV-EF after VV interval optimization in addition to AV optimization was lower than anticipated.