Changes in functional mitral regurgitation after cardiac resynchronization therapy.

Functional mitral regurgitation (MR) is a common finding in patients with global left ventricular (LV) dilatation and dysfunction. In these patients, the mitral leaflets are structurally normal and leaflet coaptation failure results from an imbalance between valve closing forces and valve tethering forces. Impaired LV contractility, global LV dyssynchrony, and reduced mitral annulus systolic contraction lead to a significant reduction in valve closing forces. In turn, valve tethering forces are increased due to mitral annulus dilatation, LV remodelling, and papillary muscle displacement. Furthermore, MR per se induces additional adverse ventricular remodelling through volume overload, and plays an important role in the progression of the cardiomyopathy. The presence of significant functional MR also has important prognostic implications, and is associated with a relatively high morbidity and mortality. Surgery is the preferred therapeutic option, but several recent studies demonstrated that cardiac resynchronization therapy (CRT) might also be able to reduce functional MR. –10 Reduction of MR following CRT was shown to be related to various issues. First, the reduction in LV dyssynchrony and the improvement in LV contraction immediately after CRT can significantly increase valve closing forces. Secondly, LV reverse remodelling and changes in mitral apparatus geometry can further reduce MR by reducing mitral leaflet tethering; this effect is observed at midand long-term (≥6 months) follow-up after CRT. Liang et al. have described for the first time the differential effects of CRT on the two components of functional MR: earlyand late-systolic MR. Understanding the mechanisms underlying these dynamic changes permits a more sophisticated interpretation of the effect of CRT on the different components of functional MR. In most patients, functional MR shows a unique biphasic pattern, with earlyand late-systolic peaks of regurgitant flow and a midsystolic decrease. These dynamic variations mainly result from the changes in mitral annulus dimension and transmitral pressure during systole (Figure 1). Mitral annulus area, and the tethering effect on the subvalvular apparatus related to LV remodelling, decrease to a minimum during LV contraction in midsystole and partially improve mitral valve competence. However, both these components increase at end-systole (during left atrial filling and LV isovolumetric relaxation), resulting in the late-systolic peak of regurgitant flow. The ventricular–atrial pressure gradient, which represents the closing forces, shows a slow rise during systole due to LV dysfunction, allowing the tethering forces to prevail at the beginning of the systole and resulting in the earlysystolic peak of regurgitant flow. However, the transmitral pressure gradient reaches its peak at mid-systole, leading to a more effective leaflet coaptation in this phase of the cardiac cycle. In the study by Liang et al., a significant effect of CRT was observed on both components, but with a predominant improvement in the early-systolic MR. Therefore, the main effect of CRT at short-term follow-up seems to be the improvement in LV contraction and transmitral pressure, which can reach its systolic peak relatively earlier and therefore reduces the early component of MR. In addition, significant LV reverse remodelling was observed and might explain the reduction in the tethering forces and the consequent improvement also in the late-systolic component of MR. However, since the echocardiographic follow-up was performed at 3 months after CRT onset, clear differentiation between the effects of CRT on the different components of functional MR is not possible. Ideally, an acute follow-up study (within 48 h after CRT onset) and a late follow-up study (6 months after CRT) would have been performed to understand further the pathophysiology underlying MR improvement and the precise time course of the changes in the two components of functional MR after CRT. An acute echocardiographic evaluation performed within 48 h after the implantation would explore whether the increase in LV contraction alone (increase in LV systolic pressure rise, dP/dt) would lead to a significant decrease in functional MR, with a