Dataset Information

Endothelial Dysfunction in Patients with Severe Mitral Regurgitation.

ABSTRACT: Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. It has been reported that MVP patients-candidates for mitral valve repair (MVRep)-showed an alteration in the antioxidant defense systems as well as in the L-arginine metabolic pathway. In this study, we investigate if oxidative stress and endothelial dysfunction are an MVP consequence or driving factors. Forty-five patients undergoing MVRep were evaluated before and 6 months post surgery and compared to 29 controls. Oxidized (GSSG) and reduced (GSH) forms of glutathione, and L-arginine metabolic pathway were analyzed using liquid chromatography-tandem mass spectrometry methods while osteoprotegerin (OPG) through the ELISA kit and circulating endothelial microparticles (EMP) by flow cytometry. Six-month post surgery, in MVP patients, the GSSG/GSH ratio decreased while symmetric and asymmetric dimethylarginines levels remained comparable to the baseline. Conversely, OPG levels significantly increased when compared to their baseline. Finally, pre-MVRep EMP levels were significantly higher in patients than in controls and did not change post surgery. Overall, these results highlight that MVRep completely restores the increased oxidative stress levels, as evidenced in MVP patients. Conversely, no amelioration of endothelial dysfunction was evidenced after surgery. Thus, therapies aimed to restore a proper endothelial function before and after surgical repair could benefit MVP patients.

SUBMITTER: Porro B

PROVIDER: S-EPMC6616454 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Endothelial Dysfunction in Patients with Severe Mitral Regurgitation.

Porro Benedetta B Songia Paola P Myasoedova Veronika A VA Valerio Vincenza V Moschetta Donato D Gripari Paola P Fusini Laura L Cavallotti Laura L Canzano Paola P Turnu Linda L Alamanni Francesco F Camera Marina M Cavalca Viviana V Poggio Paolo P

Journal of clinical medicine 20190612 6

Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. It has been reported that MVP patients-candidates for mitral valve repair (MVRep)-showed an alteration in the antioxidant defense systems as well as in the L-arginine metabolic pathway. In this study, we investigate if oxidative stress and endothelial dysfunction are an MVP consequence or driving factors. Forty-five patients undergoing MVRep were evaluated before and 6 months post surgery and compared to 29 cont ...[more]

PMID: 31212807

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Project description:OBJECTIVES:The Cardiothoracic Surgical Trials Network recently reported no difference in the primary end point of left ventricular end-systolic volume index at 1 year postsurgery in patients randomized to repair (n = 126) or replacement (n = 125) for severe ischemic mitral regurgitation. However, patients undergoing repair experienced significantly more recurrent mitral regurgitation than patients undergoing replacement (32.6% vs 2.3%). We examined whether baseline echocardiographic and clinical characteristics could identify those who will develop moderate/severe recurrent mitral regurgitation or die. METHODS:Our analysis includes 116 patients who were randomized to and received mitral valve repair. Logistic regression was used to estimate a model-based probability of recurrence or death from baseline factors. Receiver operating characteristic curves were constructed from these estimated probabilities to determine classification cut-points maximizing accuracy of prediction based on sensitivity and specificity. RESULTS:Of the 116 patients, 6 received a replacement before leaving the operating room; all other patients had mild or less mitral regurgitation on intraoperative echocardiogram after repair. During the 2-year follow-up period, 76 patients developed moderate/severe mitral regurgitation or died (53 mitral regurgitation recurrences, 13 mitral regurgitation recurrences and death, and 10 deaths). The mechanism for recurrent mitral regurgitation was largely mitral valve leaflet tethering. Our model (including age, body mass index, sex, race, effective regurgitant orifice area, basal aneurysm/dyskinesis, New York Heart Association class, history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias) yielded an area under the receiver operating characteristic curve of 0.82. CONCLUSIONS:The model demonstrated good discrimination in identifying patients who will survive 2 years without recurrent mitral regurgitation after mitral valve repair. Although our results require validation, they offer a clinically relevant risk score for selection of surgical candidates for this procedure.

Project description:AimThe objective of this study was to investigate the prognostic importance of right ventricular dysfunction (RVD) and tricuspid regurgitation (TR) in patients with moderate-severe functional mitral regurgitation (FMR) receiving MitraClip procedure. RVD and TR grade are associated with cardiovascular mortality in the general population and other cardiovascular diseases. However, there are limited data from observational studies on the prognostic significance of RVD and TR in FMR receiving MitraClip procedure.Methods and resultsA systemic review and meta-analysis were performed using MEDLINE, Scopus, and Embase to assess the prognostic value of RVD and TR grade for mortality in patients with functional mitral regurgitation (FMR) receiving MitraClip procedure. Hazard ratios were extracted from multivariate models reporting on the association of RVD and TR with mortality and described as pooled estimates with 95% confidence intervals. A total of eight non-randomized studies met the inclusion criteria with seven studies having at least 12 months follow-up with a mean follow-up of 20.9 months. Among the aforementioned studies, a total of 1112 patients (71.5% being male) were eligible for being included in our meta-analysis with an overall mortality rate of 28.4% (n = 316). Of the enrolled patients, RVD was present in 46.1% and moderate-severe TR in 29.2%. RVD was significantly associated with mortality compared to normal RV function (HR, 1.79, 95% CI, 1.39-2.31, P < 0.001, I2 = 0). Patients with moderate-severe TR showed increased risk of mortality compared with those in the none-mild TR group (HR, 1.61. 95% CI, 1.11-2.33, P = 0.01, I2 = 14).ConclusionsThis meta-analysis demonstrates the prognostic importance of RVD and TR grade in predicting all-cause mortality in patients with significant FMR. RV function and TR parameters may therefore be useful in the risk stratification of patients with significant FMR undergoing MitraClip procedure.

Project description:Mitral annular disjunction (MAD) is routinely diagnosed by cardiac imaging, mostly by echocardiography, and shown to be a risk factor for ventricular arrhythmias. While MAD is associated with mitral valve (MV) prolapse (MVP), it is unknown which patients with MAD are at higher risk and which additional imaging features may help identify them. The value of cardiac computed tomography (CCT) for the diagnosis of MAD is unknown. Accordingly, we aimed to: (1) develop a standardized CCT approach to identify MAD in patients with MVP and severe mitral regurgitation (MR); (2) determine its prevalence and identify features that are associated with MAD in this population. We retrospectively studied 90 patients (age 63 ± 12 years) with MVP and severe MR, who had pre-operative CCT (256-slice scanner) of sufficient quality for analysis. The presence and degree of MAD was assessed by rotating the view plane around the MV center to visualize disjunction along the annulus. Additionally, detailed measurements of MV apparatus and left heart chambers were performed. Univariate logistic regression analysis was performed to determine which parameters were associated with MAD. MAD was identified in 18 patients (20%), and it was typically located adjacent to a prolapsed or flail mitral leaflet scallop. Of these patients, 75% had maximum MAD distance > 4.8 mm and 90% > 3.8 mm. Female gender was most strongly associated with MAD (p = 0.04). Additionally, smaller end-diastolic mitral annulus area (p = 0.045) and longer posterior leaflet (p = 0.03) were associated with greater MAD. No association was seen between MAD and left ventricular size and function, left atrial size, and papillary muscle geometry. CCT can be used to readily detect MAD, by taking advantage of the 3D nature of this modality. A significant portion of MVP patients referred for mitral valve repair have MAD. The presence of MAD is associated with female gender, smaller annulus size and greater posterior leaflet length.

Project description:AimsPatients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) accompanied by significant mitral regurgitation (MR) had poor outcome. Several vasodilator trials showed neutral results. We aimed to investigate the effect of early up-titration of hydralazine combined with conventional treatment in acute HF with severe systolic dysfunction and significant MR.Methods and resultsThe study was open-labelled, one-to-one ratio randomized designed. Consecutively hospitalized patients with decompensated HF symptoms, LVEF < 35%, and MR more than moderate severity were enrolled after exclusion. All participants with inadequate preload should have intake promotion with/without fluid supply. Patients receiving evidence-based medications (EBMs) as conventional treatment served as the control. Hydralazine + conventional treatment group received up-titration of hydralazine at Days 1-5 of the index admission combined with EBMs and throughout the course of follow-up. The endpoints included cardiovascular (CV) death and HF rehospitalization. Totally, 408 patients were enrolled (203 in conventional treatment and 205 in hydralazine + conventional treatment). The mean follow-up period was 3.5 years. The mean dose of hydralazine was 191 mg at index admission and 264 mg at study end in hydralazine + conventional treatment group. Both groups did not significantly differ in prescription rates and dosages of EBMs (all P > 0.05) at study end. Side effects did not differ between the two groups. Finally, 51% (104 out of 203 cases) reached endpoints in conventional group and 34.6% (71 out of 205 cases) in hydralazine + conventional treatment group, which had a significant reduction in CV events (hazard ratio 0.613, 95% confidence interval 0.427-0.877, P < 0.001). In-hospital death during the index admission was significantly higher in conventional group (5.4% vs. 0.5%, respectively; P = 0.001).ConclusionsWhen administered without inadequate preload, combining early up-titration of hydralazine with EBMs improves outcome in patients with severe systolic dysfunction and significant MR, and it is safe and well tolerated.

Project description:BackgroundIschemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited.MethodsWe randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank.ResultsAt 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months.ConclusionsWe observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).

Dataset Information

Endothelial Dysfunction in Patients with Severe Mitral Regurgitation.

Publications

Endothelial Dysfunction in Patients with Severe Mitral Regurgitation.

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