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“RFEF” and mitral regurgitation jet direction: surrogate markers for likelihood of left ventricle reverse remodeling in patients with moderate chronic ischemic mitral regurgitation

ABSTRACT: Purpose Surgical management of moderate chronic ischemic mitral regurgitation (CIMR) is controversial. We propose a simplified classification of moderate CIMR based on regurgitant fraction (RF), ejection fraction (EF), and jet direction (central/eccentric) to predict left ventricle (LV) remodeling and identify patient subsets which need mitral valve (MV) repair along with coronary artery bypass grafting (CABG). Methods In this prospective controlled study (n?=?210), patients with moderate CIMR were randomized. Group I (n?=?106) underwent off-pump CABG alone while group II (n?=?104) underwent CABG + MV repair. The product of regurgitation fraction and ejection fraction (“RFEF”) was taken as a surrogate for myocardial reserve. The cut-off defined was 0.12; patients with RFEF ??0.12 were categorized as the “bad” and those with RFEF >?0.12 as the “good” subset. The patients were further subdivided on the basis of their mitral regurgitation (MR) jet direction (central/eccentric). The percentage improvement in left ventricular end-systolic volume index (LVESVI) and MR grade were recorded 6 monthly. Results Analysis of the continuous variable “RFEF” in conjunction with jet direction was performed. At 12 months, the patient in good subset with central direction of jet showed improvement in LVESVI % in both groups (p?=?0.428), while the patients in bad subset with eccentric direction of jet showed significantly higher improvement in LVESVI %, group II as compared to group I (p?=?0.004). Conclusion This study thus identifies “RFEF” as a surrogate for reverse remodeling capacity. In association with MR jet direction, predicts the subset of moderate CIMR patients most likely to have maximum LVESVI and MR grade reduction.

SUBMITTER: Siddiqui S

PROVIDER: S-EPMC7525430 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Project description:BackgroundMild physiologic mitral regurgitation (MR) is common in normal individuals. Patients with primary MR due to mitral valve prolapse (MVP) may also exhibit less than moderate MR. We sought to determine whether MVP patients with less than moderate MR displayed early cardiac chamber remodeling or factors related to early remodeling and whether early remodeling predicted MR progression.MethodsConsecutive MVP patients with less than moderate MR by proximal isovelocity surface area-derived effective regurgitant orifice < 20 mm2 and regurgitant volume < 30 mL, were matched for age and sex with non-MVP patients (controls) having less than moderate MR. Patients with moderate or greater dysfunctional left- or right-sided valves and left ventricular ejection fraction < 50% were excluded. We evaluated left ventricle (LV) and left atrium (LA) remodeling parameters (LV end-diastolic and end-systolic indexed diameters, LA volume-index, and LV mass-index) as well as determinants of remodeling. The last available transthoracic echocardiography was reviewed to identify progression to moderate-severe MR or more.ResultsA total of 253 MVP patients with less than moderate MR were matched to 344 controls (P for age and sex, ≥.18) with less than moderate MR. Patients with MVP (mean effective regurgitant orifice and regurgitant volume, 12 ± 4 mm2 and 18 ± 6 mL, respectively) had more premature ventricular contractions (PVCs), larger LV and LA remodeling parameters, and more mild-to-moderate MR (all P < .0001). Multivariate linear regression models showed that larger LV remodeling parameters were independently associated with MVP and female sex but not MR severity (all P < .0001). The LA volume index was independently associated with MVP, age, and E/e' (all P < .0001). The LV mass index was associated with MVP, age, and hypertension (all P ≤ .002). Presence of PVCs was associated with LV end-systolic diameter ≥ 40 mm and indexed ≥ 22 mm2 (P = .005). Among 323 (54%) patients having subsequent transthoracic echocardiography, 17 patients (all MVP) progressed to moderate-severe MR or more at a median of 4.3 (interquartile range, 1.7-6.4) years. Isolated posterior leaflet prolapse was the single factor associated with MR progression (adjusted hazard ratio, 2.70; 95% CI, 0.99-7.34; P = .048) after adjustment for MR severity. At a median of 5.9 (interquartile range, 4.6-7.2) years of follow-up, female sex and MVP (vs controls) were protective factors for mortality.ConclusionsPatients with less than moderate MR due to MVP exhibit early LV and LA remodeling, which does not predict MR progression or mortality. Left ventricle remodeling is associated with MVP, female sex, and presence of PVCs. Early chamber remodeling associated with MVP may be the phenotypical expression of a genetically mediated process and is at least partially related to PVCs.

Project description:BackgroundIschemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain.MethodsWe randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank.ResultsAt 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year.ConclusionsIn patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Project description:Rationale: Ischemic mitral regurgitation (IMR) is frequently observed following myocardial infarction (MI) and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post-MI, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. Objective: We sought to elucidate MV remodeling post-MI at the tissue, cellular, and transcriptomic levels. Methods and Results: The mechanical behavior of ovine MV leaflets pre-MI and 8 weeks post-MI reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy MVs. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post-MI. Assessment of the MV interstitial cell (MVIC) nuclear aspect ratio, a metric of cellular deformation, revealed that MVICs were on average rounder following MI. RNA sequencing (RNA-seq) indicated that YAP-induced genes were elevated at 4 weeks post-MI and genes related to extracellular matrix organization were some of the most downregulated in sheep with IMR compared to sheep without IMR at 4 weeks post-MI. Additionally, RNA-seq revealed the possible recruitment of immune cells in this remodeling process due to the drastic elevation of CXCL9 and CLEC10A. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI.

Project description:BackgroundIn a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes.MethodsWe randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes.ResultsAt 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group.ConclusionsIn patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

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“RFEF” and mitral regurgitation jet direction: surrogate markers for likelihood of left ventricle reverse remodeling in patients with moderate chronic ischemic mitral regurgitation

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