Abstract
Aims
Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of ...the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder.
Methods and results
We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors.
Conclusion
We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-β signalling molecules and spectrin β. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.
Structured Graphical Abstract
Structured Graphical Abstract
This study meta-analysed 4884 mitral valve prolapse (MVP) cases versus 434 649 controls, and discovered 16 genetic loci associated to MVP. Downstream analyses implicated candidate genes involved in TGF-beta signalling, cardiomyopathy and the cytoskeleton. The results from the meta-analysis were used to calculate a polygenic risk score (PRS) to aid prediction of MVP. Adding the PRS to a model with age, sex and clinical risk factors improved MVP risk prediction. Abbreviations, MVP, mitral valve prolapse, p, p-value, PRS, polygenic risk score, RF, risk factors.
The objective of this study was to develop a mathematical model for mitral annular dilatation simulation and determine its effects on the individualized mitral valve (MV) coaptation reserve index ...(CRI).
A retrospective analysis of intraoperative transesophageal 3-dimensionalechocardiographic MV datasets was performed. A mathematical model was created to assess the mitral CRI for each leaflet segment (A1-P1, A2-P2, A3-P3). Mitral CRI was defined as the ratio between the coaptation reserve (measured coaptation length along the closure line) and an individualized correction factor. Indexing was chosen to correct for MV sphericity and area of largest valve opening. Mathematical models were created to simulate progressive mitral annular dilatation and to predict the effect on the individual mitral CRI.
At a single-center academic hospital.
Twenty-five patients with normally functioning MVs undergoing cardiac surgery.
None.
Direct measurement of leaflet coaptation along the closure line showed the lowest amount of coaptation (reserve) near the commissures (A1-P1 0.21 ± 0.05 cm and A3-P3 0.22 ± 0.06 cm), and the highest amount of coaptation (reserve) at region A2 to P2 0.25 ± 0.06 cm. After indexing, the A2-to-P2 region was the area with the lowest CRI in the majority of patients, and also the area with the least resistance to mitral regurgitation (MR) occurrence after simulation of progressive annular dilation.
Quantification and indexing of mitral coaptation reserve along the closure line are feasible. Indexing and mathematical simulation of progressive annular dilatation consistently showed that indexed coaptation reserve was lowest in the A2-to-P2 region. These results may explain why this area is prone to lose coaptation and is often affected in MR.
Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over ...2-dimensional echocardiography in predicting recurrence at 6 months.
Intraoperative transesophageal 2-dimensional echocardiography and 3-dimensional echocardiography were performed in 50 patients undergoing undersized annuloplasty for ischemic mitral regurgitation. Two-dimensional echocardiography annular diameter and tethering parameters were measured in the apical 2- and 4-chamber views. A customized protocol was used to assess 3-dimensional annular geometry and regional leaflet tethering. Recurrence (grade ≥2) was assessed with 2-dimensional transthoracic echocardiography at 6 months.
Preoperative 2- and 3-dimensional annular geometry were similar in all patients with ischemic mitral regurgitation. Preoperative 2- and 3-dimensional leaflet tethering were significantly higher in patients with recurrence (n = 13) when compared with patients without recurrence (n = 37). Multivariate logistic regression revealed preoperative 2-dimensional echocardiography posterior tethering angle as an independent predictor of recurrence with an optimal cutoff value of 32.0° (area under the curve, 0.81; 95% confidence interval, 0.68-0.95; P = .002) and preoperative 3-dimensional echocardiography P3 tethering angle as an independent predictor of recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84-1.00; P < .001). The predictive value of the 3-dimensional geometric multivariate model can be augmented by adding basal aneurysm/dyskinesis (area under the curve, 0.94; 95% confidence interval, 0.87-1.00; P < .001).
Preoperative 3-dimensional echocardiography P3 tethering angle is a stronger predictor of ischemic mitral regurgitation recurrence after annuloplasty than preoperative 2-dimensional echocardiography posterior tethering angle, which is highly influenced by viewing plane. In patients with a preoperative P3 tethering angle of 29.9° or larger (especially when combined with basal aneurysm/dyskinesis), chordal-sparing valve replacement should be strongly considered.
Chronic ischaemic mitral regurgitation (CIMR) remains one of the most complex and unresolved aspects in the management of ischaemic heart disease. This review provides an overview of the present ...knowledge about the different aspects of CIMR with an emphasis on mechanisms, current surgical treatment results and new mechanism-based surgical approaches. CIMR occurs in approximately 20–25% of patients followed up after myocardial infarction (MI) and in 50% of those with post-infarct congestive heart failure (CHF). The presence of CIMR adversely affects prognosis, increasing mortality and the risk of CHF in a graded fashion according to CIMR severity. The primary mechanism of CIMR is ischaemia-induced left ventricular (LV) remodelling with papillary muscle displacement and apical tenting of the mitral valve leaflets. CIMR is often clinically silent, and colour-Doppler echocardiography remains the most reliable diagnostic tool. The most commonly performed surgical procedure for CIMR (restrictive annuloplasty combined with coronary artery bypass grafting (CABG)) can provide good results in selected patients with minimal LV dilatation and minimal tenting. However, in general the persistence and recurrence rate (at least MR grade 3+) for restrictive annuloplasty remains high (up to 30% at 6 months postoperatively), and after a 10-year follow-up there does not appear to be a survival benefit of a combined procedure compared to CABG alone (10-year survival rate for both is approximately 50%). Patients at risk of annuloplasty failure based on preoperative echocardiographic and clinical parameters may benefit from mitral valve replacement with preservation of the subvalvular apparatus or from new alternative procedures targeting the subvalvular apparatus including the LV. These new procedures include second-order chordal cutting, papillary muscle repositioning by a variety of techniques and ventricular approaches using external ventricular restraint devices or the Coapsys device. In addition, percutaneous transvenous repair techniques are being developed. Although promising, at this point these new procedures still lack investigation in large patient cohorts with long-term follow-up. They will, however, be the subject of much anticipated and necessary ongoing and future research.
Abstract
Background
Transcatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the ...anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms.
Methods
A group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI).
Results
Six animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI.
Conclusions
Systolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms.
Libman-Sacks endocarditis of the mitral valve was first described by Libman and Sacks in 1924. Currently, the sterile verrucous vegetative lesions seen in Libman-Sacks endocarditis are regarded as a ...cardiac manifestation of both systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). Although typically mild and asymptomatic, complications of Libman-Sacks endocarditis may include superimposed bacterial endocarditis, thromboembolic events, and severe valvular regurgitation and/or stenosis requiring surgery. In this study we report two cases of mitral valve repair and two cases of mitral valve replacement for mitral regurgitation (MR) caused by Libman-Sacks endocarditis. In addition, we provide a systematic review of the English literature on mitral valve surgery for MR caused by Libman-Sacks endocarditis. This report shows that mitral valve repair is feasible and effective in young patients with relatively stable SLE and/or APS and only localized mitral valve abnormalities caused by Libman-Sacks endocarditis. Both clinical and echocardiographic follow-up after repair show excellent mid- and long-term results.
Anomalous coronary arteries may course in close proximity to the mitral annulus, which increases the risk of iatrogenic occlusion due to annular suture placement. We report a mitral valve repair in a ...55‐year‐old male with severe mitral regurgitation and an anomalous retro‐aortic left coronary artery, originating from the right coronary sinus, coursing in close proximity to the anterior mitral annulus. To minimize iatrogenic occlusion risk an open annuloplasty ring was used with good long‐term results. doi: 10.1111/jocs.12374 (J Card Surg 2014;29:782–784)
Abstract
Aims
Fourteen Dutch heart centres collected patient-relevant outcomes to support quality improvements in a value-based healthcare initiative that began in 2012. This study aimed to evaluate ...the current state of outcome-based quality improvement within six of these Dutch heart centres.
Methods and results
Interviews and questionnaires among physicians and healthcare professionals in the heart centres were combined in a mixed-methods approach. The analysis indicates that the predominant focus of the heart centres is on the actual monitoring of outcomes. A systematic approach for the identification of improvement potential and the selection and implementation of improvement initiatives is lacking. The organizational context for outcome-based quality improvement is similar in the six heart centres.
Conclusion
Although these heart centres in the Netherlands measure health outcomes for the majority of cardiac diseases, the actual use of these outcomes to improve quality of care remains limited. The main barriers are limitations regarding (i) data infrastructure, (ii) a systematic approach for the identification of improvement potential and the selection and implementation of improvement initiatives, (iii) governance in which roles and responsibilities of physicians regarding outcome improvement are formalized, and (iv) implementation of outcomes within hospital strategy, policy documents, and the planning and control cycle.
OBJECTIVES
Papillary muscle rupture (PMR) is a rare, but serious mechanical complication of myocardial infarction (MI). Although mitral valve replacement is usually the preferred treatment for this ...condition, mitral valve repair may offer an improved outcome. In this study, we sought to determine the outcome of mitral valve repair for post-MI PMR and to provide a systematic review of the literature on this topic.
METHODS
Between January 1990 and December 2010, 9 consecutive patients (mean age 63.5 ± 14.2 years) underwent mitral valve repair for partial post-MI PMR. Clinical data, echocardiographic data, catheterization data and surgical reports were reviewed. Follow-up was obtained in December of 2012 and it was complete; the mean follow-up was 8.7 ± 6.1 (range 0.2-18.8 years).
RESULTS
Intraoperative and in-hospital mortality were 0%. Intraoperative repair failure rate was 11.1% (n = 1). Freedom from Grade 3+ or 4+ mitral regurgitation and from reoperation at 1, 5, 10 and 15 years was 87.5 ± 11.7%. Estimated 1-, 5-, 10- and 15-year survival rates were 100, 83.3 ± 15.2, 66.7 ± 19.2 and 44.4 ± 22.2%, respectively. There were 3 late deaths, and 2 were cardiac-related. All late survivors were in New York Heart Association Class I or II. No predictors of long-term survival could be identified.
CONCLUSIONS
Mitral valve repair for partial or incomplete post-MI PMR is reliable and provides good short- and long-term results, provided established repair techniques are used and adjacent tissue is not friable. PMR type and adjacent tissue quality ultimately determine the feasibility and durability of repair.
High ischemic mitral regurgitation (IMR) recurrence rates continue to plague IMR repair with undersized ring annuloplasty. We have previously shown that pre-repair three-dimensional echocardiography ...(3DE) analysis is highly predictive of IMR recurrence. The objective of this study was to determine the quantitative change in 3DE annular and leaflet tethering parameters immediately after repair and to determine if intraoperative post-repair 3DE parameters would be able to predict IMR recurrence 6 months after repair.
Intraoperative pre- and post-repair transesophageal real-time 3DE was performed in 35 patients undergoing undersized ring annuloplasty for IMR. An advanced modeling algorhythm was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with transthoracic echocardiography 6 months after repair.
Annuloplasty significantly reduced septolateral diameter, commissural width, annular area, and tethering volume and significantly increased all segmental tethering angles (except A2). Intraoperative post-repair annular geometry and leaflet tethering did not differ significantly between patients with recurrent IMR (n = 9) and patients with non-recurrent IMR (n = 26). No intraoperative post-repair predictors of IMR recurrence could be identified.
Undersized ring annuloplasty changes mitral geometry acutely, exacerbates leaflet tethering, and generally fixes IMR acutely, but it does not always fix the delicate underlying chronic problem of continued left ventricular dilatation and remodeling. This may explain why pre-repair 3D valve geometry (which reflects chronic left ventricular remodeling) is highly predictive of recurrent IMR, whereas immediate post-repair 3D valve geometry (which does not completely reflect chronic left ventricular remodeling anymore) is not.
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