Ischemic Mitral Valve Regurgitation Research Articles

Echocardiographic and clinical outcomes following beating heart NeoChord DS1000 mitral valve repair: a single centre case series.

The NeoChord DS1000 system implants artificial neochords transapically, through a left mini-thoracotomy to treat degenerative mitral valve regurgitation (MR). Performed without cardiopulmonary bypass, neochord implantation and length adjustment is guided by transesophageal echocardiography. We describe imaging and clinical outcomes for a single center case series using this innovative device platform. In this prospective series, all study patients had degenerative MR and were considered for conventional mitral valve surgery. Moderate to high-risk candidates were screened for NeoChord DS1000 eligibility based on echocardiographic criteria. Study criteria included isolated posterior leaflet prolapse, leaflet-to-annulus index greater than 1.2, and coaptation length index greater than 5 mm. Patients with bileaflet prolapse, mitral annular calcification, and ischemic MR were excluded from our early experience. Ten patients underwent the procedure, including 6 males and 4 females, with a mean age of 76 ± 9.5 years. All patients had severe chronic MR and normal left ventricular function. One patient required conversion to an open procedure for failure to deploy neochords with the device transapically. The median number of NeoChord sets was 3 (IQR 2.3-3.8). Immediate post-procedure (POD#0) degree of MR on echocardiography ranged from mild or less, and on postoperative day 1 (POD#1) from moderate or less. Average length of coaptation was 0.85 ± 0.21 cm and average depth of coaptation was 0.72 ± 0.15 cm. At 1-month follow-up echocardiography, MR was graded from trivial to moderate and left ventricular inner diameter dimensions decreased from an average of 5.4 ± 0.4 cm to 4.6 ± 0.3 cm. None of the patients who had successful NeoChord implantation required blood products. There was 1 perioperative stroke with no residual deficits. There were no device-related complications or serious adverse events. The median length of hospital stay was 3 (IQR 2.3-10) days. 30-day and 6-weeks postoperative mortality and readmission rates were 0%. We report the first Canadian case series using the NeoChord DS1000 system for off-pump, transapical, beating heart mitral valve repair, through a left mini-thoracotomy. The early surgical outcomes suggest this approach is feasible, safe, and effective in reducing MR. This novel procedure has the advantage of offering a minimally invasive, off-pump option for select patients with high surgical risk.

Concomitant Mitral Valve Surgery Versus No Intervention in Patients with Moderate Ischemic Mitral Regurgitation Undergoing Coronary Artery Bypass Grafting: A Propensity Score Analysis

Objectives Ischemic mitral valve regurgitation (IMR) in patients undergoing coronary artery bypass grafting (CABG) is associated with worse long-term outcomes. This study aimed to assess the impact of mitral valve repair with CABG in patients with moderate IMR.Materials This observational study enrolled 3,215 consecutive patients from the Juntendo CABG registry with moderate IMR and multivessel coronary artery disease who underwent CABG between 2002 and 2017.Methods The CABG alone and CABG with mitral valve surgery (MVs) groups were compared. The propensity score was calculated for each patient. Long-term all-cause death, cardiac death, and major adverse cardiac and cerebrovascular events (MACCEs) were compared.Results Our database had 101 patients who underwent CABG with moderate IMR. Propensity score matching selected 40 pairs for final analysis. MVs was associated with increased risks of postoperative atrial fibrillation, blood transfusion, and longer hospitalization. Long-term outcomes, including all-cause mortality, cardiac mortality, and the incidence of MACCEs were similar.Conclusion Surgical treatment of moderate IMR combined with CABG was related to increased risk of several non-fatal short-term complications when compared to CABG alone, with similar long-term outcomes. Further studies are needed to determine the effects of MVs in patients with moderate IMR and severe coronary artery disease.

Coronary artery bypass on survival in patients with moderate ischemic mitral regurgitation: meta-analysis.

The objective of the study was to systematically evaluate the effect of coronary artery bypass grafting (CABG) or CABG combined with mitral valve surgery (cMVS) on post-operative survival in patients with moderate ischemic mitral valve regurgitation. Databases including PubMed, Web of Science, COCHRANE LIBRARY, WanFang Data, and CNKI Data were searched from inception to January 2020. According to the inclusion criterion, relevant articles were screened. After that we extracted data, assessed quality, and performed meta-analysis using RevMan 5.2. A total of 4 randomized controlled trial and 14 retrospective study involving 4476 patients were included in the study. The CABG group was 2278 and the cMVS group was 1698. The results of meta-analysis showed that compared with CABG group, there were no statistically significant differences in the recent mortality (odds ratio [OR] = 0.88, p = 0.62), 1-year survival (OR = 1.03, p = 0.82), 1-year survival (OR = 1.07, p = 0.62), and long-term survival (OR = 0.95, p = 0.61) of the cMVS group. Current evidence indicates that patients in the cMVS group did not benefit from CABG group in survival after surgery.

Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients.

Background: Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Nevertheless, little is known about how MV tissue responds to ischemic heart changes in humans.Methods: MVs were obtained by the Cardiothoracic Surgical Trials Network from 17 patients with ischemic mitral regurgitation (IMR). Echo-doppler imaging assessed MV function at time of resection. Cryosections of MVs were analyzed using a multi-faceted histology and immunofluorescence examination of cell populations. MVs were further analyzed using unbiased label-free proteomics. Echo-Doppler imaging, histo-cytometry measures and proteomic analysis were then integrated.Results: MVs from patients with greater MR exhibited proteomic changes associated with proteolysis-, inflammatory- and oxidative stress-related processes compared to MVs with less MR. Cryosections of MVs from patients with IMR displayed activated valvular interstitial cells (aVICs) and double positive CD31+ αSMA+ cells, a hallmark of EndMT. Univariable and multivariable association with echocardiography measures revealed a positive correlation of MR severity with both cellular and geometric changes (e.g., aVICs, EndMT, leaflet thickness, leaflet tenting). Finally, proteomic changes associated with EndMT showed gene-ontology enrichment in vesicle-, inflammatory- and oxidative stress-related processes. This discovery approach indicated new candidate proteins associated with EndMT regulation in IMR.Conclusion: We describe an atypical cellular composition and distinctive proteome of human MVs from patients with IMR, which highlighted new candidate proteins implicated in EndMT-related processes, associated with maladaptive MV fibrotic remodeling.

Changes in the In-vivo Functional State of the Mitral Valve in MitraClip Repair

Objective: In this study, our focus is on the MitraClip procedure (Abbott Inc.), which is a minimally invasive surgical repair procedure to correct ischemic mitral valve regurgitation (IMR). While initial short-term outcomes have been encouraging, the long-term efficacy of this procedure, as well as patient-specific guidelines for optimization, remain unknown. The overall objective will be to develop a rapid and accurate simulation pipeline to predict and quantitatively assess the efficacy and longevity of the MitraClip procedure for individual patients using only pre-surgical and related population-based data. Methods: Clinical, real-time three-dimensional echocardiography (rt-3DE) images of patients’ mitral valves (MV) were segmented by a neural network (NN)-based approach to produce high-fidelity spline representations, which were integrated using isogeometric analysis into our custom finite element solver. This solver incorporated previous plasticity material models of the MV, in addition to measured changes in MV boundary conditions. We then simulated leaflet strains before and after the procedure and at three- and six-month follow up intervals, ultimately using only pre-surgical images. Results: Results to date to investigate the response of the MV to the MitraClip demonstrated an increase of radial strain and a decrease of circumferential strain in the posterior leaflets of the MV (Figure). Furthermore, stress concentrations were observed in both the circumferential and radial directions. Conclusions: The MitraClip clearly induced major alterations in MV leaflet strain and stress behaviors. This work confirms that such minimally invasive procedures dramatically alter the MV functional behaviors. This may lead to the underlying reasons long-term MV remodeling occurs in response to the observed stress concentrations, possibly leading to limited repair durability.

STUDY OF CORRELATION BETWEEN SEVERITY OF ISCHEMIC MITRAL VALVE REGURGITATION BY ECHO DOPPLER AND ECG CHANGES IN ACUTE MYOCARDIAL INFARCTION

Background: Myocardial infarction (MI) accompanies with different mechanical complications including ischemic mitral regurgitation (IMR) which is correlated with increased risk of mortality and heart failure. IMR existence and its severity had significant prognostic effect on patients’ mortality following acute myocardial infarction (AMI). Echocardiography is the choice imaging modality for the diagnosis and assessment of IMR and establishing its etiology. IMR usually results from papillary muscle displacement, ventricular dilation and remodeling with reduced closing forces. Objective: Assessment of the correlation between echocardiographic severity of ischemic mitral valve regurgitation following acute myocardial infarction and its electrocardiographic location. Patients and methods: This was a prospective study that included 100 patients admitted to CCU OF Beni-Suief General Hospital in the period from October 2019 to May 2020 . Those patients were divided on two equal groups: Group I: patients with STEMI and no, trivial or mild MR and Group II: patients with STEMI and moderate or severe MR. Results: Mean age of group I involved in the study was 55.44 ± 7.23 years and 70% of them were males. Mean age of group II was 58.38 ± 7.8 and 56% were males. 70 % of the group II had inferolateral STEMI compared to group I who had more anterior STEMI. Group II were more smokers with hyperlipidemia. Group II was with higher previous stable and unstable angina, with less streptokinase treatment, with higher abnormal chest radiogrgh and higher killip class. Group II had significantly lower EF and higher LVEDD, LVESD, LA diameter, RV diameter, MV A velocity, tricuspid valve excursion TAPSI and pulmonary artery pressure and more diastolic dysfunction. Mechanism of IMR in case group was mono leaflet tethering in 43 cases, both leaflet tethering in 7 cases and ring dilation in 30 cases. MR jet direction was medial commissure posterior in 31 (62%), lateral commissure anterior in 12 (24%), and both commissures central in 7 (14%) cases. Conclusion: Mitral regurgitation is common after acute myocardial infarction, especially in cases with inferior mitral regurgitation. The echocardiographic findings are indicative of left ventricular remodeling and abnormality of mitral valve apparatus.

Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation

BackgroundWhether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain. ObjectivesThe goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery. MethodsPatients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years. ResultsPatients’ mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04). ConclusionsAfter IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart’s Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040)

Conventional cardiac surgery in patients with end-stage coronary artery disease: yesterday and today.

Surgical therapy of combined coronary artery disease (CAD) and heart failure, also referred to as end-stage CAD, has evolved throughout the years and patients are currently being offered traditional coronary artery bypass grafting (CABG), with or without surgical ventricle restoration (SVR), interventions for ischemic mitral valve regurgitation, heart transplantation or implantation of mechanical cardiovascular support systems. Among surgical methods, operative myocardial revascularization (with or without ventricle restoration) is still playing an important role, aiming at restoration of proper myocardial perfusion, especially if heart muscle viability is present. Facing the donor shortage, CABG may constitute a valuable alternative to transplantation in selected patients. In individuals considered not suitable for surgical revascularization, implantation of mechanical circulatory support (MCS) not only appears as a salvage procedure, but also allows for reevaluation of future therapy directions. This article aims at providing an overview of evolving and current surgical practices in patients with end-stage CAD.

Comparison of Clinical Outcomes Following Mitral Valve Repair and Replacement in Ischemic Mitral Valve Regurgitation

Objective: To compare clinical outcomes following mitral valve repair (MVP) to those after mitral valve replacement (MVR) in patients with ischemic mitral valve regurgitation. Materials and Methods: The authors retrospectively analyzed data of patients with ischemic mitral valve regurgitation that underwent MVR or repair concomitant with coronary artery bypass graft at Khon Kaen University’s Srinagarind Hospital and Queen Sirikit Heart Center between January 2006 and December 2016. Results: Postoperative results, including duration of ventilator support, incidence of post-operative bleeding, arrhythmia, sepsis, stroke, ICU length of stay, and hospital length of stay, in the two groups were similar, as were early and late postoperative mortality.No patients in the MVR group experienced post-operative valve failure compared to 8% of patients in the MVP group, who had residual moderate to severe mitral valve regurgitation and required reoperation. Conclusion: There was no significant difference in terms of survival or postoperative outcomes between the two groups. However, the MVR group had better long-term survival and lower rate of reoperation. Keywords: Ischemic mitral valve regurgitation, Mitral valve replacement, Mitral valve repair, Coronary artery bypass graft

Transfer of a minimally invasive mitral valve repair program from a high-volume center to a very low volume center: how many cases are necessary to maintain acceptable results?

To investigate whether minimally invasive mitral valve repair (MIMVR) can be transferred from a high-volume center into a very small volume center and to clarify how many cases are necessary for maintenance of this program, early outcomes of MIMVR in Asahikawa Medical University were compared with those results in patients operated by a single surgeon in Duesseldorf University Hospital. Sixty-five patients who underwent MIMVR in Asahikawa Medical University (group A) between May 2014 and July 2018 and 134 patients who underwent MIMVR in Duesseldorf University Hospital (group D) between September 2009 and January 2014 by a surgeon who started MIMVS later in Asahikawa were retrospectively analyzed. In group D, there were more patients with ischemic mitral valve regurgitation and with annular calcification than in group A. Survival rate at 6months and 1year was 98.5% and 98.5% in group A and 92.9% and 91.3% in group D, respectively. EuroSCORE II was significantly higher in patients dead within 30days and within the first year. The present study demonstrated that MIMVR programs can be transferred with acceptable early results into very low volume centers, if the team is developed by surgeons who are well trained and experienced in MIMVR. Moreover, the present study suggested that case number for maintenance of acceptable results may be obviously less than the previous recognition that this kind of specialized surgery could be maintained with at least 50 cases annually. However, meticulous preparations for surgery are essential for satisfactory surgical outcomes.

Abstract 17086: External Support of the Cardiac Base in the Treatment of Functional Mitral Regurgitation & Heart Failure

Introduction: Ventricular dysfunction in the presence of normal mitral leaflets is characteristic of functional mitral regurgitation (MR). Surgical treatment with mitral valve repair or replacement, address mitral valve annulus and leaflets, not the ventricular muscle. We describe early and mid-term clinical experience with extra-cardiac treatment of FMR with a novel device that is implanted on a beating heart. Hypothesis: External and adjustable support of the cardiac base can effectively reduce functional MR & HF. Methods: The BACE (Basal Annuloplasty of the Cardia Externally) device is a broad belt/band of silicone that is implanted at the base of the heart, by means of slim polyester belt loops sutured on atrial and ventricular sides of the Atrio-Ventricular groove. Forty one patients (mean age 60.24 years) with functional and ischemic MR were evaluated at 10 multi-national centers between December, 2008 and June, 2018. All patients had moderately severe or severe MR (Mean MR grade 3.3) on trans-thoracic and/or trans-esophageal echocardiography, and impaired LV function (Mean EF 38.5%). Risk assessment by Logistic Euroscore showed a mean of 16.5%. Implantation of the BACE device, was performed, according to sizing performed along the base of the heart, overlapping atrial and ventricular surfaces of the atrio-ventricular groove circumferentially. Mean number of coronary grafts was 2.5. Five patients had stand-alone procedures without CABG. Procedures were performed on a beating heart with the majority of them performed off-pump. Intra-operative trans-esophageal echocardiography allowed customized inflation of specific chambers to selectively deform the annulus and sub-annular myocardium. Results: Three patients required peri-operative adjustment of the BACE device. There were no deaths related to the BACE device or device failures. The degree of MR improved from a mean of 3.4 to 0.88. This >2 class improvement in MR was sustained over the 12 month follow up period in all patients. LVEDD decreased from 5.9±0.6 to 5.5±0.6 cm. Conclusions: Ischemic and functional mitral valve regurgitation can be treated by epicardial implantation and dynamic adjustment of the BACE device. Ventricular stabilization may impact HF progression.

Chronic ischemic mitral valve regurgitation and surgical perspectives.

Chronic ischemic mitral valve regurgitation is a result of disturbed left ventricular geometry secondary to myocardial ischemia in the absence of intrinsic mitral valve pathology. It is a common complication after myocardial infarction, and patients who have ischemic mitral regurgitation (IMR) have a worse prognosis compared to patients who have ischemic heart disease alone, and this is directly related to the severity of IMR. Medical therapy has limited efficacy, and surgical options including various repair techniques and valve replacement had been tried with variable success. Still there is intense debate among surgeons whether to interfere with moderate degree IMR at the time of coronary artery revascularization.

New Device for the Treatment of Functional Ischemic Mitral Regurgitation: Proof of Concept in an In Vitro Model.

Optimal surgical treatment of functional ischemic mitral regurgitation (FIMR) is still controversy. Due to the underlying pathophysiology, stand-alone ring annuloplasty is assumed with a high recurrence rate of mitral regurgitation, thus additional subvalvular repair techniques might improve the results. This in vitro study introduces a new device for subvalvular mitral valve repair. We developed a new device for subvalvular mitral valve repair, consisting of two frames for papillary muscle (PM) attachment, which are connected with two holding bars serving for fixation of the device on an annuloplasty ring. In the first experimental run, porcine mitral valves including the chordae tendineae and PMs were fixated on a holding device, consisting of a holding ring simulating mitral annulus dilation and height-adjustable frames for PM attachment simulating leaflet tethering. In vitro regurgitant volume was determined in a pulse duplicator. Afterward, the frames for PM attachment were replaced by our newly developed device and the measurements were repeated. In the model simulating FIMR, the regurgitant volume was 44.3 ± 12.38 mL/stroke. After subvalvular reconstruction with our new device, the regurgitant volume was significantly reduced to 33.1 ± 11.68 mL/stroke (p = 0.009). In this specific in vitro model, our new device for subvalvular mitral valve reconstruction led to a significant reduction of the regurgitant volume, thus representing a promising technique to potentially improve the results of mitral reconstruction in ischemic functional mitral valve regurgitation. Additional studies are required to further investigate and improve our device.

Correlation between echocardiographic severity of ischemic mitral valve regurgitation following acute myocardial infarction and its electrocardiographic location

Introduction: Ischemic mitral regurgitation (IMR) is common after acute myocardial infarction (AMI) which is associated with long-term cardiovascular mortality. Size, transmurality and location of the myocardial infarction (MI) has role on the development of IMR. In this study we evaluated the severity of IMR after different types of MI. Methods: One-hundred patients with the first AMI were recruited and according to echocardiographic findings were categorized to have moderate to severe IMR (case group, n=50) or trivial or no IMR (control group, n=50). Demographic and echocardiographic findings and MI location were compared between groups. Results: Case group compared to control group had significantly higher Killip class, more cases with left ventricular ejection fraction (LVEF) <30% and inferolateral STEMI. They had significantly higher left ventricular (LV) and right ventricular (RV) diastolic dysfunction. Mechanism of IMR was mono leaflet tethering in 88%, both leaflets tethering in 12% and ring dilatation in 62%. MR jet origin-direction was medial commisure-posterior in 66%, lateral commisure-anterior in 11 22% and both commisure-central direction in 12%. Conclusion: IMR is common after AMI, especially in cases with inferior MI. The echocardiographic findings are indicative of left ventricular remodeling and abnormality of mitral valve apparatus.

The value of adding sub-valvular procedures for chronic ischemic mitral regurgitation surgery: a meta-analysis.

The most performed repair technique for the treatment of chronic ischemic mitral regurgitation in patients referred for bypass grafting remains restricted annuloplasty. However, it is associated with a high rate of failure, especially if severe tenting exists. To understand if adjunctive sub-valvular mitral procedures may provide better repair performance. A systematic literature review identified six studies of which five fulfilled the criteria for meta-analysis. Outcomes for a total of 404 patients (214 had adjunctive sub-valvular procedures and 190 restricted annuloplasty) were meta-analyzed using random effects modeling. Heterogeneity and subgroup sensitivity analysis were assessed. Primary endpoints were: late recurrence of moderate mitral regurgitation, left ventricle remodeling and coaptation depth at follow-up. Secondary endpoints were: early mortality, mid-term survival and operative outcomes. Sub-valvular procedure technique was associated with a significantly lower late recurrence of mitral regurgitation (Odds ratio (OR) 0.34, 95% Confidence Interval (CI) [0.18, 0.65], p=0.0009), smaller left ventricle end-systolic diameter (Weighted Mean Difference (WMD) -4.06, 95% CI [-6.10, -2.03], p=0.0001) and reduced coaptation depth (WMD -2.36, 95% CI [-5.01, -0.71], p=0.009). These findings were consistent, even in studies that included patients at high risk for repair failure (coaptation depth >10 mm and tenting area >2.5 cm2). A low degree of heterogeneity was observed. There was no difference in terms of early mortality and mid-term survival; sub-valvular technique was associated with prolonged cardiopulmonary and cross-clamp time. Adding sub-valvular procedures when repairing ischemic chronic mitral valve regurgitation may be associated with better durability, even in the case of the presence of predictors for late failure. Surgical sub-valvular adjunctive procedures have to be considered in the case of the presence of echocardiographic predictors for late failure.

Short-Term and Long-Term Survival After Revascularization with or without Mitral Valve Surgery of Patients with Ischemic Mitral Valve Regurgitation: A Meta-Analysis.

BackgroundThere is no consensus on whether mitral valve repair or replacement (MVRR) must be performed to treat ischemic mitral regurgitation (MVR) after myocardial infarction. Our objective in this study was to investigate the efficacy of coronary artery bypass grafting (CABG) combined with or without MVRR for the ischemic MVR.Material/MethodsAn article search was performed in OvidSP, PubMed, Cochrane Library, and Embase. In these articles, researchers compared the efficacy of CABG with or without MVRR in treating patients with ischemic MVR after acute coronary syndrome (ACS). We performed a meta-analysis to compare the differences in the short-term and long-term survival rates of patients treated with CABG only and those treated with both CABG and MVRR. Secondary outcomes were compared with the preoperative and postoperative degree of MVR, left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class.ResultsOut of the 1183 studies, we selected only 5 articles. A total of 3120 patients were enrolled; the CABG and MVRR group included 575 patients, while the CABG only group included 2545 patients. Long-term survival was higher in the CABG only group (hazard ratio [HR], 1.34; 95% confidence interval [CI] 1.15–1.58, P=0.003). Hospital mortality was similar in both the groups (odds ratio [OR], 2.54; 95% CI, 0.65–9.95; P=0.18). No differences were found in the degree of residual MVR, the mean of LVESV, LVEF, or NYHA class.ConclusionsIn patients with ischemic MVR, the short-term survival rate was similar in both groups. Moreover, there was no significant improvement in the long-term survival rates of patients treated with both CAG and MVRR.

Abstract 14749: Extra-cardiac Mitral Valve Repair - Experience With the Adjustable BACE Device

Introduction: Functional mitral regurgitation (MR) is primarily due to abnormalities of the ventricular muscle in the presence of normal mitral leaflets. Present surgical treatment, repair or replacement, address the mitral valve annulus and leaflets, not the ventricular muscle. We describe our early and mid-term clinical experience with extra-cardiac treatment of MR with a novel, device that is implanted on a beating heart and can be adjusted remotely. Hypothesis: Evaluation of efficacy and outcomes Methods: Between Dec, 2008 and June, 2015, thirty one patients (mean age 59 years) with functional and ischemic MR were evaluated at 9 multi-national centers. All patients had severe MR (Mean MR grade 3.1) on trans-thoracic and/or trans-esophageal echocardiography, and impaired LV function (Mean EF 33.6%). Risk assessment by Logistic Euroscore was16.58%. Patients underwent implantation of a custom made BACE (Basal Annuloplasty of the Cardia Externally) device, along with CABG (mean 2.5 grafts per patient). The device was placed at the base of the heart, overlapping the atrial and ventricular surfaces of the atrio-ventricular groove circumferentially. All procedures were performed on a beating heart with the majority of them performed off-pump. Intra-operative trans-esophageal echocardiography allowed customized inflation of specific chambers to selectively deform the annulus and sub-annular myocardium. Two patients required delayed peri-operative adjustment of the BACE device. Results: The degree of MR improved from a mean of 3.1 to 0.9. This &gt;2 class improvement in MR was sustained over the 12 month follow up period in all patients. Moderately severe TR in 3 patients went down to trivial. There was one peri-operative death associated with balloon related leg ischemia. One device was explanted early at re-exploration for bleeding. There were no device related complications. Conclusions: Ischemic functional mitral valve regurgitation can be treated by epicardial implantation and dynamic adjustment of the BACE device. This technique has significant implications in the treatment of ischemic functional MR without entering the heart, with the added ability to remotely adjust the device.

Abstract 32: Mitral Valve Interstitial Cells With the Serotonin Transporter (SERT)-LL Polymorphism are More Efficiently Activated by Serotonin

Prolapse of the Mitral Valve (MV) leaflet is a hallmark of several cardiac disorders such as Myxomatous MV Disease (MMVD) or ischemic MV regurgitation (MR), and is only treated surgically. Elevated levels of serotonin (5HT) have been associated with valvulopathies. Ongoing studies in our laboratory suggest that 5HT signaling plays an important role in the progression of MMVD. In addition, a 44 base polymorphism in the promoter region of the 5HT transporter (SERT) gene, designated as short (S) or long (L) allele, has been reported with Mendelian distribution, with LL resulting in increased 5HT reuptake compared to SS. We hypothesized that patients with MMVD have enhanced 5HT signaling due to a high frequency of SERT-LL. DNA was extracted from 152 MMVD surgical patients, genomic fragment analysis performed to determine allelic frequencies, and a chi-square statistical test completed. We show that surgical patients with MMVD have a higher than expected frequency of SERT-LL (34% (52 of 152) vs. 25%). Notably, the frequency of SERT-LL is particularly enhanced (51% (21 of 41) vs. 25%) (p=0.009) in MMVD patients under 60 years old. Based on these findings, we tested whether MV interstitial cells (MVICs) expressing SERT-LL have increased susceptibility to 5HT-mediated activation. We demonstrate that SERT-LL MVICs respond to 5HT with a 4-fold increase in smooth muscle actin (SMA) mRNA expression, a marker of VIC activation, compared to a less than 1-fold increase in SERT-LS and SERT-SS cells. The SMA response is abrogated by specific pharmacological inhibitors of the 5HT receptors 5HTR2A and 5HTR2B, and SERT, as well as siRNA knockdown. Studies of 5HTR expression in cells of each genotype are in progress. Due to the enhanced frequency of the SERT-LL genotype among MMVD patients, particularly within the younger subset, and increased susceptibility of SERT-LL MVICs to 5HT, we postulate that the SERT-LL genotype may contribute to an increased risk of rapid disease progression by increasing the efficiency of 5HT signaling and uptake in MVICs resulting in extracellular matrix production leading to prolapse and impaired valve function. The SERT-genotype may constitute a novel means of identifying patients who may benefit from pharmacotherapy that alter 5HT-related mechanisms.

Mitral valve repair for ischemic mitral regurgitation.

Mitral valve repair for ischemic mitral valve regurgitation remains controversial. In moderate mitral regurgitation (MR), controversy exists whether revascularization alone will be adequate to restore native valve geometry or whether intervention on the valve (repair) should be performed concomitantly. When MR is severe, the need for valve intervention is not disputed. Rather, the controversy is whether repair versus replacement should be undertaken. In contrast to degenerative or myxomatous disease that directly affects leaflet integrity and morphology, ischemic FMR results from a distortion and dilation of native ventricular geometry that normally supports normal leaflet coaptation. To address this, the first and most crucial step in successful valve repair is placement of an undersized, complete remodeling annuloplasty ring to restore the annulus to its native geometry. The following article outlines the steps for repair of ischemic mitral regurgitation.

Reciprocal interactions between mitral valve endothelial and interstitial cells reduce endothelial-to-mesenchymal transition and myofibroblastic activation

Thickening of mitral leaflets, endothelial-to-mesenchymal transition (EndMT), and activated myofibroblast-like interstitial cells have been observed in ischemic mitral valve regurgitation. We set out to determine if interactions between mitral valve endothelial cells (VECs) and interstitial cells (VICs) might affect these alterations. We used in vitro co-culture in Transwell™ inserts to test the hypothesis that VICs secrete factors that inhibit EndMT and conversely, that VECs secrete factors that mitigate the activation of VICs to a myofibroblast-like, activated phenotype. Primary cultures and clonal populations of ovine mitral VICs and VECs were used. Western blot, quantitative reverse transcriptase PCR (qPCR) and functional assays were used to assess changes in cell phenotype and behavior. VICs or conditioned media from VICs inhibited transforming growth factor β (TGFβ)-induced EndMT in VECs, as indicated by reduced expression of EndMT markers α-smooth muscle actin (α-SMA), Slug, Snai1 and MMP-2 and maintained the ability of VECs to mediate leukocyte adhesion, an important endothelial function. VECs or conditioned media from VECs reversed the spontaneous cell culture-induced change in VICs to an activated phenotype, as indicated by reduced expression of α-SMA and type I collagen, increased expression chondromodulin-1 (Chm1), and reduced contractile activity. These results demonstrate that mitral VECs and VICs secrete soluble factors that can reduce VIC activation and inhibit TGFβ-driven EndMT, respectively. These findings suggest that the endothelium of the mitral valve is critical for the maintenance of a quiescent VIC phenotype and that, in turn, VICs prevent EndMT. We speculate that the disturbance of the ongoing reciprocal interactions between VECs and VICs in vivo may contribute to the thickened and fibrotic leaflets observed in ischemic mitral regurgitation, and in other types of valve disease.