Project description:Ischaemic mitral regurgitation (IMR), a frequent complication following myocardial infarction (MI), leads to higher mortality and poor clinical prognosis if untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post MI, and this remodelling increases both the severity of IMR and the occurrence of MV repair failures. However, the mechanisms of extracellular matrix maintenance and modulation by MV interstitial cells (MVICs) and their impact on MV leaflet tissue integrity and repair failure remain largely unknown. Herein, we sought to elucidate the multiscale behaviour of IMR-induced MV remodelling using an established ovine model. Leaflet tissue at eight weeks post MI exhibited significant permanent plastic radial deformation, eliminating mechanical anisotropy, accompanied by altered leaflet composition. Interestingly, no changes in effective collagen fibre modulus were observed, with MVICs slightly rounder, at eight weeks post MI. RNA sequencing indicated that YAP-induced genes were elevated at four weeks post MI, indicating elevated mechanotransduction. Genes related to extracellular matrix organization were downregulated at four weeks post MI when IMR occurred. Transcriptomic changes returned to baseline by eight weeks post MI. This multiscale study suggests that IMR induces plastic deformation of the MV with no functional damage to the collagen fibres, providing crucial information for computational simulations of the MV in IMR.
Project description:AimRandomized controlled trials comparing the use of the MitraClip device in addition to guideline directed medical therapy (GDMT) to GDMT alone in patients with secondary mitral regurgitation (MR) have shown conflicting results. However, if these differences could be due to the underlying MR aetiology is still unknown. Therefore, we aimed to evaluate if the effects of percutaneous edge-to-edge repair with MitraClip implantation could differ in patients with ischaemic (I-MR) and non-ischaemic mitral regurgitation (NI-MR).Methods and resultsPubMed, Embase, BioMed Central, and the Cochrane Central Register of Controlled Trials were searched for all studies including patients with secondary MR treated with the MitraClip device. Data were pooled using a random-effects model. Primary endpoint was the composite of all-cause death and heart failure-related hospitalization. Secondary endpoints were the single components of the primary endpoint, New York Heart Association functional Classes III and IV, and mitral valve re-intervention. Seven studies enrolling 2501 patients were included. Patients with I-MR compared with patients with NI-MR had a similar risk of the primary endpoint (odds ratio: 1.17; 95% confidence interval: 0.93 to 1.46; I2 : 0%). The risk of all-cause death was increased in patients with I-MR (odds ratio: 1.31; 95% confidence interval: 1.07 to 1.62; I2 : 0%), while no differences were observed between the two groups in terms of the other secondary endpoints.ConclusionsThe risk of mortality after MitraClip implantation is lower in patients with NI-MR than in those with I-MR. No absolute differences in the risk of heart failure related hospitalization were observed between groups.
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:ObjectivesThe current guidelines still do not include specific recommendations on the use of subvalvular repair (SV-r) for treatment of ischemic mitral regurgitation (IMR). Therefore, the objective of our study was to evaluate the clinical impact of mitral regurgitation (MR) recurrence and ventricular remodeling on long-term outcomes after SV-r combined with restrictive annuloplasty (RA-r).MethodsWe performed a subanalysis of the papillary muscle approximation trial, studying 96 patients with severe IMR and coronary artery disease undergoing restrictive annuloplasty alongside subvalvular repair (SV-r + RA-r group) or restrictive annuloplasty alone (RA-r group). We analyzed treatment failure differences, the influence of residual MR, left ventricular remodeling, and clinical outcomes. The primary endpoint was treatment failure (composite of death; reoperation; or recurrence of moderate, moderate-to-severe, or severe MR) within 5 years of follow-up after the procedure.ResultsA total of 45 patients showed failure of the treatment within 5 years, of which 16 patients underwent SV-r + RA-r (35.6%) and 29 underwent RA-r (64.4%, p = 0.006). Patients with significant residual MR presented with a higher rate of all-cause mortality at 5 years compared with trivial MR (HR 9.09, 95% CI 2.08-33.33, p = 0.003). MR progression occurred earlier in the RA-r group, as 20 patients in the RA-r group vs. 6 in SV-r + RA-r group had a significant MR 2 years after surgery (p = 0.002).ConclusionsRA-r remains a surgical mitral repair technique with an increased risk of failure and mortality at 5 years compared with SV-r. The rates of recurrent MR are higher, and recurrence occurs earlier, with RA-r alone compared to SV-r. The addition of the subvalvular repair increases the durability of the repair, thus extending all of the benefits of preventing MR recurrence.
Project description:Dr. O.P. Yadava, Editor-in-Chief, IJTC, and Dr. J.L. Pomar, Former President, EACTS, discuss issues related to secondary mitral regurgitation (MR). Though it is considered a ventricular disease, mitral valve leaflets are not entirely normal. Alignment of subvalvular apparatus plays a more dominant role than annular dilatation. Early repair is preferred.
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:ObjectivesThis study aimed to elucidate the mid-term outcomes and risk factors for recurrent mitral regurgitation after mitral valve (MV) surgery for atrial functional mitral regurgitation (AFMR).Methods and resultsWe retrospectively analyzed data of 50 consecutive patients (median age 74 years; 29 men) who underwent mitral valve surgery for AFMR between January 2001 and January 2019. Mean atrial fibrillation duration was 12 years. During the follow-up period of 4.6 ± 4.4 years, 5 cardiac-related deaths were identified. Five- and 10-year freedom from cardiac-related death rate for all patients was 88.4% and 78.6%. In total, 42 patients underwent MV repair with mitral annuloplasty and 8 underwent MV replacement. Five- and 10-year freedom from cardiac-related death rate in patients who underwent MV repair was 93.1% and 82.7%, which was better than MV replacement (log rank p = 0.04). During the follow-up period, MR recurrence rate was 16.8% at 5 and 10 years for the patients who underwent MV repair. Univariate analysis showed that partial band annuloplasty and preoperative elevated left ventricular end-systolic volume index were risk factors for recurrent MR after MV repair. Multivariate analysis identified partial band annuloplasty as the independent predictor for recurrent MR during long-term follow-up after MV repair for AFMR.ConclusionPatients who underwent MV repair for AFMR could have an acceptable mid-term outcome. However, MVR might not improve the mid-term outcome in patients with AFMR. The use of partial bands for mitral annuloplasty would not be recommended in terms of recurrent MR mid-term.
Project description:BackgroundLeft ventricular pseudoaneurysm (LVPA) is an infrequent but highly lethal complication of myocardial infarction. Early surgical repair with a resection of pseudoaneurysm is often performed, given that medical therapy alone is associated with a high risk of mortality. This report describes a case of a giant LVPA on the lateral wall post-infarction and mitral valve regurgitation that was successfully treated by surgical transatrial closure and mitral valve replacement.Case summaryA 77-year-old man with chronic kidney disease and a history of percutaneous coronary interventions for acute myocardial infarction was referred to the cardiac surgeons because of a spontaneous finding of an abnormal mass adjacent to the heart on imaging studies, which was missed on a chest radiograph obtained 3 months earlier. Cardiac studies revealed LVPA and severe mitral regurgitation with poor ejection fraction. Early repair of LVPA and concurrent mitral valve surgery were recommended. Transatrial patch closure and mitral valve replacement were performed using an interatrial approach via median sternotomy. Although the patient's post-operative course was complicated by congestive heart failure and irreversible renal failure, he was discharged with good functional status after 1 month of intermittent renal replacement therapy with haemodialysis.DiscussionTransatrial repair of LVPA and concurrent mitral valve replacement can be a treatment of choice for reducing surgical trauma to the left ventricle and protecting the sealing structure from rupture.
Project description:This review outlines the first trial experience with transcatheter therapy for mitral regurgitation (MR), developed from the EVEREST II MitraClip trial in a trial population comprised predominantly of patients with degenerative mitral regurgitation (DMR). Subsequent experience with MitraClip and several other devices has been mostly in functional MR patients. At the same time, there has been ongoing experience with MitraClip in DMR, and a variety of other devices have been developed for catheter-based treatment of MR. Annuloplasty devices have been indicated for DMR, and the potential for transcatheter annuloplasty to be used, in conjunction with other catheter techniques, such as chordal replacement, as it is in standard mitral repair, is developing. Transcatheter mitral valve replacement will clearly have some role for MR of both functional and degenerative etiologies, when repair is not feasible or fails. This review will discuss the evidence base and future development of these mitral repair and replacement approaches for DMR.