Early and late effects of cardiac resynchronization therapy on exercise-induced mitral regurgitation: relationship with left ventricular dyssynchrony, remodelling and cardiopulmonary performance

Aims Exercise-induced mitral regurgitation (MR) bears a poor prognosis in patients with congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) is associated with improved clinical outcome but its effects on exercise-induced MR remain undetermined. We investigated serial changes in functional MR in relation to left ventricular (LV) remodelling and cardiopulmonary performance after CRT. Methods and results Twenty-eight patients with CHF (LV ejection fraction 25 ± 7%), broad QRS complex (171 ± 27 ms), and at least mild MR [effective regurgitant orifice (ERO) 0.25 ± 0.12 cm2] were studied with quantitative exercise echocardiography and cardiopulmonary exercise testing prior, within 1 week, and 3 months after CRT. Early after CRT, a decrease in LV dyssynchrony (from 54 ± 21 to 19 ± 7 ms, P < 0.001) and in MR at rest (ERO from 0.25 ± 0.12 to 0.20 ± 0.10 cm2, P = 0.047) was observed. However, no change in exercise-induced increase in MR was observed (ERO from 0.34 ± 0.12 to 0.31 ± 0.16 cm2, NS). Three months after CRT, a decrease in the mitral valve tenting area (from 3.3 ± 1.2 to 2.0 ± 0.6 cm2, P < 0.001) and an increase in LV sphericity index (from 1.5 ± 0.3 to 1.8 ± 0.5, P < 0.001) were paralleled by an attenuation of exercise-induced MR (ERO 0.19 ± 0.06 cm2, P = 0.001 vs. prior CRT). This was associated with an increase in LV ejection fraction (from 25 ± 7 to 35 ± 9%, P < 0.001), peak oxygen uptake (from 11.7 ± 2.4 to 13.7 ± 3.8 mL/kg/min, P = 0.001), and a decrease in Nt-pro-BNP (from 2777 ± 1681 to 1963 ± 1361 pg/mL, P = 0.067). Conclusion CRT is associated with acute decrease in resting MR but does not immediately attenuate exercise-induced MR. In contrast, only late, CRT-induced reversed LV remodelling and reduced mitral apparatus deformation are associated with a reduction in both resting and exercise-induced MR and with an improvement in cardiopulmonary performance.