ABSTRACT: Regulatory Mechanisms of Atrial Remodeling of Mitral Regurgitation Pigs This study enrolled 6 pigs (age: 18 months) and divided into three groups: mitral regurgitation pigs (MR) (n = 2; 2 males sacrificed 12 months after surgery), MR pigs treated with valsartan (MRV) (n = 2; 2 males age-matched to MR sacrificed 12 months after surgery), and normal control pigs (NC) (n = 2; 2 males age-matched to MR pigs). Valsartan (3.43 mg/kg/day), a type I angiotensin II receptor blocker, was administered from one week before surgery and then daily after surgery in the MRV group. We sought to systemically elucidate critical differences in the alteration of RNA expression pattern between the atrial myocardium of pigs with and without MR, and between the atrial myocardium of MR pigs with and without valsartan using high-density oligonucleotide microarrays and functional network enrichment analysis.
Project description:Regulatory Mechanisms of Atrial Remodeling of Human Mitral Regurgitation Overall design: This study enrolled 10 human subjects and divided into two groups: mitral regurgitation patients (MR) (n = 7; 7 females), and normal control subjects (NC) (n= 3).We sought to systemically elucidate critical differences in the alteration of RNA expression pattern between the atrial myocardium of MR patients and normal subjects using high-density oligonucleotide microarrays and functional network enrichment analysis.
Project description:SIRT1 (silent information regulator 1) is a histone deacetylase. It can sense the energy level in cells and delay cell senescence, leading to resistance to external stress and improving metabolism. Mitral regurgitation (MR) is a common disease in cardiac surgery. However, there are no previous studies on SIRT1 and left atrial fibrosis caused by MR. In this study, we aimed to explore the regulatory effect of SIRT1 on left atrial fibrosis induced by MR. We used Guizhou miniature pigs to establish an MR model and a sham operation model after anaesthesia induction and respiratory intubation, and these model animals were followed for 30 months after the surgery. The differential distribution and expression of SIRT1 and collagen I in the left atrium was determined by immunofluorescence and Western blotting. Furthermore, we treated NIH3T3 fibroblasts (CFs) with resveratrol and Angiotensin II (Ang II) to analyse the specific mechanism involved in the development of myocardial fibrosis. The results showed that the MR model was successfully constructed. There were 8 pigs in the MR group and 6 pigs in the control group. In both the animal experiments and the cell experiments, the expression of collagen I in the MR group was increased significantly compared to that in the control group, while the expression of SIRT1 was decreased.
Project description:The porcine mitral regurgitation (MR) model is a common cardiovascular animal model. Standardized manufacturing processes can improve the uniformity and success rate of the model, and systematic research can evaluate its potential use. In this study, 17 pigs were divided into an experimental group (n=11) and a control group (n=6). We used a homemade retractor to cut the mitral chordae via the left atrial appendage to establish a model of MR; the control group underwent a sham surgery. The model animals were followed for 30 months after the surgery. Enlargement and fibrosis of the left atrium were significant in the experimental group compared with those in the control group, and left atrial systolic function decreased significantly. In addition, model animals showed preserved left ventricular systolic function. There were no differences in left atrial potential or left ventricular myocardial fibrosis between the two groups. Atrial fibrillation susceptibility in the experimental group was higher than that in the control group. Our method enables the simple and effective production of a MR model with severe reflux that can be used for pathophysiological studies of MR, as well as for the development of preclinical surgical instruments and their evaluation. This model could also be used to study atrial fibrillation and myocardial fibrosis but is not suitable for studies of heart failure.
Project description:The role of left ventricular (LV) longitudinal contraction in ischemic mitral regurgitation (MR) remains unclear. We hypothesized that reduced longitudinal contraction disrupts normal mitral valve plane displacement during systole and leads to mitral valve tethering, thereby inducing ischemic MR. Twenty-three Yorkshire pigs underwent induction of different-sized posterior myocardial infarction (MI) using a percutaneous approach. The incidence of MR and its association with LV longitudinal strain were examined using speckle-tracking echocardiography at 1 mo post-MI to determine their relationship. A total of 17 pigs survived MI and completed the study. Pigs developed no more than mild MR after proximal left circumflex artery (LCx) occlusion (LCx group; n = 7). Addition of a first diagonal branch (D1) occlusion to LCx-MI (LCx + D1 group; n = 7) resulted in moderate to severe MR development 1 mo post-MI. LCx + D1 animals had lower longitudinal strain compared with the LCx group, whereas circumferential strain and LV rotation did not differ significantly. Posterolateral annular displacement toward the apex was significantly reduced in LCx + D1 animals, whereas the septal annular displacement was similar, suggesting an asymmetric mitral annular plane excursion in the LCx + D1 group. To exclude the contribution of papillary muscle infarction in MR development in our model, three pigs underwent obtuse marginal branch + D1 occlusion. None of these pigs developed significant MR after 1 mo. In conclusion, reduced longitudinal contraction contributes to the development of ischemic MR in a large posterior MI. NEW & NOTEWORTHY In this study, using our unique swine models of different-sized myocardial infarction, we showed, for the first time, that reduced longitudinal contraction contributes to the development of ischemic mitral regurgitation in a large posterior myocardial infarction. Our study adds new insights into the mechanisms of ischemic mitral regurgitation pathophysiology.
Project description:Percutaneous edge-to-edge mitral valve repair (PMVR) is widely used for selected, high-risk patients with severe mitral valve regurgitation (MR). This report describes a case of 81-year-old woman presenting with severe and highly symptomatic mitral valve regurgitation (MR) caused by a flail of the posterior mitral valve leaflet (PML). PMVR turned out to be challenging in this patient because of a stenosis and tortuosity of both iliac veins as well as sclerosis of the interatrial septum, precluding the vascular and left atrial access by standard methods, respectively. We managed to achieve atrial access by venous percutaneous transluminal angioplasty (PTA) and balloon dilatation of the interatrial septum. Subsequently, we could advance the MitraClip® system to the left atrium, and deployment of the clip in the central segment of the mitral valve leaflets (A2/P2) resulted in a significant reduction of MR.
Project description:The diagnostic role of echocardiographic and hemodynamic assessment in acute mitral regurgitation (AMR) remains unclear. The central question of this study was to determine if echocardiographic and hemodynamic parameters can predict early clinical events in AMR. AMR was induced by percutaneously severing the mitral valve chordae tendineae in 39 Yorkshire pigs. Immediately after AMR induction, echocardiographic and hemodynamic exams were performed, and compared between those who died and those who survived within 30-days of the procedure. Echocardiographic indices of MR severity as well as the left atrial pressure showed significant differences between survivors and non-survivors in univariate analysis. Multi-variate logistic regression analysis revealed that echocardiography-derived regurgitant fraction and vena contracta as well as mean left atrial pressure could be used to segment the cohort into survivors and non-survivors. Our study demonstrated, for the first time, that echocardiographic and hemodynamic assessment of AMR provides predictive information on early clinical events in a clinically relevant animal model of AMR.
Project description:The incidence of mitral regurgitation (MR) is approximately 1.7% in the developed world, and this increases to more than 10% in patients aged over 75 years. Functional (or secondary) mitral regurgitation (FMR) is defined as poor leaflet coaptation and tethering secondary to either ischemic or non-ischemic left ventricular (LV) dysfunction and dilatation. FMR is more common than degenerative (or primary) MR and is associated with significantly worse outcomes in patients with heart failure, post myocardial infarction and following coronary artery bypass graft surgery. Patients with severe degenerative MR have excellent outcomes with surgical repair, however the benefits of surgery in FMR are less clear. Although annuloplasty is associated with a lower operative mortality compared to replacement, the recurrence rate of mitral regurgitation is high in patients with FMR and neither surgical repair or replacement have been shown to reduce hospitalisation or death in FMR. Furthermore, nearly half of patients are deemed too high risk for surgery and therefore most patients are managed conservatively and there remains an unmet clinical need. Transcatheter mitral valve interventions are an emerging alternative for those at high surgical risk. This mini review focuses on indirect mitral annuloplasty: anatomical considerations, patient selection, current devices, implantation techniques and the associated clinical outcome data.
Project description:The timing of mitral valve surgery in asymptomatic patients with primary mitral regurgitation (MR) is controversial. We hypothesized that the forward left ventricular (LV) ejection fraction (LVEF; ie, LV outflow tract stroke volume divided by LV end-diastolic volume) is superior to the total LVEF to predict outcomes in MR. The objective of this study was to examine the association between echocardiographic parameters of MR severity and LV function and outcomes in patients with MR.The clinical and Doppler-echocardiographic data of 278 patients with ?mild MR and no class I indication of mitral valve surgery at baseline were retrospectively analyzed. The primary study end point was the composite of mitral valve surgery or death. During a mean follow-up of 5.4±3.2 years, there were 147 (53%) events: 96 (35%) MV surgeries and 66 (24%) deaths. Total LVEF and global longitudinal strain were not associated with the occurrence of events, whereas forward LVEF (P<0.0001) and LV end-systolic diameter (P=0.0003) were. After adjustment for age, sex, MR severity, Charlson probability, coronary artery disease, and atrial fibrillation, forward LVEF remained independently associated with the occurrence of events (adjusted hazard ratio: 1.09, [95% confidence interval]: 1.02-1.17 per 5% decrease; P=0.01), whereas LV end-systolic diameter was not (P=0.48).The results of this study suggest that the forward LVEF may be superior to the total LVEF and LV end-systolic diameter to predict outcomes in patients with primary MR. This simple and easily measurable parameter may be useful to improve risk stratification and select the best timing for intervention in patients with primary MR.
Project description:The extent of mitral annular (MA) remodeling and dysfunction is correlated with the severity of mitral regurgitation (MR) as well as left atrial (LA) and left ventricular (LV) dilation. MA dysfunction may be a useful prognostic factor for operative timing and MR recurrence after successful mitral valve (MV) repair. The aim of this study was to evaluate additive prognostic factors of MA non-planarity using real-time 3D transesophageal echocardiography (RT3D-TEE) analysis in patients with chronic severe MR and preserved LV systolic function.Forty-seven patients with chronic severe MR and preserved LV systolic function scheduled for MV repair were prospectively enrolled. Echocardiographic studies were performed before surgery and postoperatively within 2 weeks and at least 6 months after surgery. RT3D-TEE was performed before the operation and immediately post-operative.Mean age was 55.4 ± 15.1 years and 24 were male. Annulus height/body surface area (BSA) obtained via RT3D-TEE was correlated with the degree of postoperative LA remodeling. Patients were divided into two groups by average baseline annulus height/BSA. Patients with normal annular height had a smaller postoperative LV end-diastolic dimension, LV end-systolic dimension and LA volume index than patients with decreased annular height. Preoperative annulus height/BSA values strongly predicted postoperative LA remodeling.MA height may be a useful prognostic factor for determining the timing of surgery in patients with chronic primary MR. Annulus height/BSA assessed via RT3D-TEE may provide additional information predictive of postoperative LA remodeling after successful MV repair.
Project description:We first describe the implantation of a MitraClip (Abbott Vascular, Abbott Park, IL, USA) between 2 previously implanted MitraClips to treat recurrent mitral regurgitation (MR). An 82-year-old male patient presented with dyspnea New York Heart Association NYHA class III due to recurrent severe MR 18 months after primarily successful implantation of 2 MitraClips. The initial procedure was performed to treat severe MR due to prolapse and flail of the anterior leaflet and resulted in mild MR after implantation of 2 MitraClips. Concomitant diseases were persistent atrial fibrillation, moderate tricuspid valve regurgitation, and chronic kidney disease stage 3. Thus, the patient was not considered a suitable candidate for surgical treatment. Using fluoroscopic guidance, 2D- and 3D-transesophageal echocardiographies, we succeeded in placing a third clip between the previously implanted clips and reduced the severe MR to mild MR without increase in the mean gradient. No periprocedural complications were observed. Six months after the procedure the patient presented with mild MR and NYHA class I. <Learning objective: Implantation of MitraClips offers the possibility of percutaneous mitral valve repair. It is feasible, safe, and effective to implant a 3rd MitraClip between 2 previously implanted MitraClips to treat recurrent mitral regurgitation between the clips.>.