Mechanistic Features Associated With Improvement in Mitral Regurgitation After Cardiac Resynchronization Therapy and Their Relation to Long-Term Patient Outcome

Abstract

Background-Mechanisms of mitral regurgitation (MR) reduction with cardiac resynchronization therapy (CRT) are complex, and their association with long-term outcome is unclear. We sought to elucidate mechanistic features of reduction in MR with CRT, which impact long-term patient survival. Methods and Results-A prospective longitudinal study of 277 patients with heart failure with QRS width ≥120 ms and ejection fraction ≤35% for CRT was performed. Quantitative echocardiography, including dyssynchrony analysis, was performed at baseline. MR was quantified by color Doppler before and 6 months after CRT. Predefined end points of death, transplant, or left ventricular assist device were tracked during 4 years. There were 114 (48%) patients with CRT with significant MR (≥moderate) at baseline; of whom 48 (42%) patients had MR improvement, and 24 (19%) patients had MR worsening after CRT. The 66 events (47 deaths, 10 transplantations, and 9 left ventricular assist devices) were strongly associated with significant MR after CRT (hazard ratio, 3.58; 95% confidence interval, 2.18-5.87; P<0.0001). Three echocardiographic features were independently associated with amelioration of significant MR after CRT by multivariable analysis: anteroseptal to posterior wall radial strain dyssynchrony >200 ms, lack of severe left ventricular dilatation (end-systolic dimension index <29 mm/m 2 ), and lack of echocardiographic scar at papillary muscle insertion sites (all P<0.05) and, when combined, were additively associated with long-term survival (P=0.0001). Conclusions-Significant MR after CRT was strongly associated with less favorable long-term survival. Echocardiographic mechanistic features were identified that were associated with improvement in MR after CRT and favorable long-term survival. to body surface area. 8 Assessment for myocardial scar focused on the papillary muscle insertion sites using a wall motion score index where akinesis or dyskinesis and a reduction in end-diastolic wall thickness ≤0.6 cm were consistent with scar as suggested by the American Society of Echocardiography and European Association of Echocardiography. 8,9 Specifically, the wall motion score index at the level of the papillary muscle attachment site was determined from the corresponding 8 LV segments as previously reported. 10,11 Figure 1. Study patient flowchart. A flowchart of consecutive patients referred for cardiac resynchronization therapy (CRT) who were included in this study. The prevalence of significant mitral regurgitation (MR) before and after CRT is shown. Quantification of MR SeverityColor Doppler quantification of MR was based on the guidelines of the American Society of Echocardiography and European Society of Cardiology 11,12 using a multiparametric approach. A Nyquist limit of 40 to 60 cm/s and a color gain were used to optimize color Doppler jet visualization. Vena contracta width was measured as the narrowest portion of the MR color Doppler jet from zoomed optimized views. The ratio of the jet area to the left atrium area was m...

Longer Left Ventricular Electric Delay Reduces Mitral Regurgitation After Cardiac Resynchronization Therapy

“…Others have similarly identified immediate reductions in MR post CRT 5 and identified baseline mechanical dyssynchrony as a significant predictor of MR reduction. 3 In contrast, Madaric et al 24 identified 3-month LVRR as a more important predictor of MR reduction (rest and exercise) when compared with immediate reduction in mechanical dyssynchrony after CRT. To date, analyses of CRT and MR have been limited by the retrospective, post hoc evaluation of MR at varying time points after implant, 4,5 the absence of serial echocardiography at intermediate time points (eg, 3 months post implant), 3 or significant limitation in sample size (<100 patients).…”

“…3 In contrast, Madaric et al 24 identified 3-month LVRR as a more important predictor of MR reduction (rest and exercise) when compared with immediate reduction in mechanical dyssynchrony after CRT. To date, analyses of CRT and MR have been limited by the retrospective, post hoc evaluation of MR at varying time points after implant, 4,5 the absence of serial echocardiography at intermediate time points (eg, 3 months post implant), 3 or significant limitation in sample size (<100 patients). 3,24 Strengths of this study include its size and related power to detect significant mechanistic associations, the prospective availability of serial echocardiography with dyssynchrony assessment nested within a randomized controlled trial, and complementary multimodal analysis of MR reduction (linear and logistic models) accounting for regression to the mean with adjustment for baseline MR. We also uniquely assessed the impact of a clinically relevant intervention (ie, QLV-based pacing strategy) associated with both proposed mediators of MR reduction (ie, LVRR and mechanical resynchronization).…”

“…[3][4][5] The mechanisms of MR reduction after CRT have been variably attributed to acute improvements in LV contractility and papillary muscle resynchronization and subacute improvements in LV sphericity and tethering forces related to LVRR. 22 For example, in 63 patients undergoing CRT, Ypenburg et al 23 demonstrated immediate improvement in MR associated with acute reductions in mechanical dyssynchrony.…”

“…The VC width held primacy if jet area values were discordant as previously described. 3 Pulsed Doppler mitral inflow E-wave velocity and the tissue Doppler early diastolic velocity (E′) at the lateral and septal positions were obtained in the apical 4-chamber view to determine E/E′ as an estimation of LV filling pressure. LV volumes were determined in the apical 4-and 2-chamber views by the biplane method of discs.…”

“…2 Of these determinants, reduction in mitral regurgitation (MR) after CRT has emerged as a significant predictor of improved survival and has been linked to papillary muscle resynchronization and LV reverse remodeling (LVRR). [3][4][5] LV lead location at the time of CRT implant may influence these proposed mechanisms of MR reduction. For example, LV pacing at the site of the latest electric delay (ie, QLV) is associated with acute hemodynamic improvement and LVRR.…”