C ardiac resynchronization therapy (CRT) with biventricular pacing has emerged as a new approach for treating patients with heart failure and significant ventricular conduction delay and/or dyssynchrony. 1-3 CRT improves left ventricular systolic and diastolic function 4 and clinical status 5 and reduces functional mitral regurgitation (MR). 6 Whether CRT significantly affects exercise-induced changes in MR has never been investigated. This study examined the effects of CRT on MR and assessed the determinants of exercise-induced changes in MR under biventricular pacing.• • • This prospective study included 27 consecutive patients with heart failure who were clinically helped by biventricular pacing. Before CRT implantation, all were in New York Heart Association class III and had left ventricular ejection fractions Յ35%, functional MR, were in sinus rhythm, had QRS duration Ն140 ms, and had interventricular delay (the time interval between aortic and pulmonary valve opening) Ն50 ms. All patients underwent quantitative exercise Doppler echocardiography with and without active CRT. The causes of heart failure were idiopathic dilated cardiomyopathy in 9 patients and ischemic heart disease in 18. The protocol was approved by the human ethical committee of our university hospital, and all patients gave informed consent.A symptom-limited graded bicycle exercise test was performed in a semisupine position on a tilting exercise table. After an initial workload of 25 W maintained for 2 minutes, the workload was increased every 2 minutes by 25 W. Blood pressure and 12-lead electrocardiograms were recorded every 2 minutes. Two-dimensional and Doppler echocardiographic recordings were available throughout the test.Baseline and exercise echocardiographic studies were performed 45 Ϯ 16 days after implantation of the CRT system using the phased-array Acuson Sequoia (Siemens AG, Munich, Germany) or VIVID 7 (GE Healthcare, Little Chalfont, United Kingdom) imaging device. In 17 patients, after data acquisition during active CRT (CRT on), pacing was interrupted during 30 minutes before data acquisition during intrinsic conduction (CRT off). In the other 10 patients, data were first acquired with CRT off. All echocardiographic and Doppler recordings were obtained in digital format and stored on optical discs for off-line analysis. For each measurement, Ն3 cardiac cycles were averaged. The quantitation of MR was performed by the quantitative Doppler method using mitral and aortic stroke volumes and the proximal isovelocity surface area method, as previously described. 7,8 The results of these 2 methods were averaged, allowing the calculation of regurgitant volume and the effective regurgitant orifice (ERO). Left ventricular end-diastolic and end-systolic volumes and ejection fractions were measured by the bi-apical Simpson disk method. The left ventricular dP/dt was estimated from the steepest increasing segment of the continuous-