Loss of biventricular (BiV) pacing occurs during ventricular sensed events such as frequent ventricular ectopy, nonsustained ventricular tachycardia, and intrinsic atrioventricular nodal conduction, such as in atrial fibrillation. Ventricular sense response (VSR) pacing, a novel cardiac resynchronization therapy pacing strategy, maintains BiV pacing during these sensed ventricular events. Patients who underwent echocardiographic optimization after BiV pacemaker implantation were enrolled, and aortic velocity-time integrals (VTIs) were recorded and compared during intrinsic conduction without pacing, optimized BiV pacing, and intrinsic conduction with VSR pacing alone. Thirty-two patients were enrolled (mean age 68 +/- 11 years, 78% men), with a mean baseline QRS duration of 164 +/- 24 ms and a mean left ventricular ejection fraction of 23 +/- 10%. The mean aortic VTI during intrinsic conduction with VSR pacing was 16.5 +/- 3.6 cm, compared with 15.3 +/- 3.4 cm during intrinsic conduction without pacing (p <0.001). The mean aortic VTI with optimized BiV pacing was 17.3 +/- 3.6 cm, significantly better (p <0.001) compared with intrinsic conduction without pacing. Improvements in aortic VTI were higher with optimized BiV pacing compared with VSR pacing alone (p = 0.02). In the subgroup of patients with left bundle branch block-type activation, the hemodynamic improvements realized with VSR pacing were similar to optimized BiV pacing. Mean aortic VTI improvements with VSR were similar in patients with ischemic and nonischemic cardiomyopathy. In conclusion, a cardiac resynchronization therapy algorithm that maintains BiV pacing during a ventricular sensed event appears to have an aortic VTI response that is significantly better compared with intrinsic conduction without pacing.