Degenerative mitral regurgitation (MR) represents a rather common pathology, affecting 1–2% of the general population. In patients requiring surgery for this disease, mitral valve repair is the standard of care. Whenever feasible it is preferable to prosthetic replacement, as it provides better preservation of left ventricular (LV) function, higher survival, lower rates of thromboembolism and endocarditis, excellent late durability and no need for anticoagulation.1–2 Building on these important achievements, progress in treating degenerative MR is expected in several areas in the near future. New diagnostic tools, better knowledge of the natural history of the disease, refinements to surgical techniques and the development of transcatheter methods of MR correction will certainly have an important clinical impact in the management of degenerative MR, and will be briefly discussed in this article.
Timing of Correction of Mitral Regurgitation
According to the current guidelines, mitral repair is indicated in patients with severe MR who are symptomatic and in those showing initial signs of LV dysfunction (end-systolic diameter >40mm, ejection fraction <60%). Surgical treatment is encouraged in asymptomatic patients with preserved LV function, when atrial fibrillation occurs or when systolic pulmonary artery pressure is >50mmHg at rest or >60mmHg during exercise. In addition, mitral repair is reasonable for asymptomatic patients with preserved LV function, in whom the likelihood of successful repair without residual MR is >90%.3 In spite of these recommendations, decision-making regarding the optimal time for surgery in the individual patient may remain difficult. Therefore, while some asymptomatic patients may be candidates for early repair, a more conservative approach (watchful waiting) remains a reasonable option for others.4
Early Repair
The purpose of an early repair policy in patients with severe MR is to neutralise the disease before the occurrence of structural and functional changes in the LV and left atrial (LA) chambers that are predictors of poor post-operative outcome.5 Quantification of MR is crucial since severe MR per se, independent of LV function, seems to be a predictor of adverse prognosis.6 In asymptomatic patients with preserved LV function, an effective regurgitant orifice (ERO) >0.4cm2 has been identified as a determinant of adverse outcome.7
However, it is important to emphasise that the ERO calculation may be affected by the proximal isovelocity surface area shape, multisite valve lesions, eccentricity of the regurgitant jet and intrabeat changes.8 More refined methods of quantification of MR are therefore necessary. In the meantime, to avoid potential clinical mismanagement focused on MR severity alone, severity of MR can be better evaluated using a multiparametric approach that includes ERO, vena contracta, regurgitant flow volume or fraction, LA extension jet and reverse pulmonary vein flow.
When an early mitral repair policy is adopted in asymptomatic patients with severe myxomatous degeneration of the mitral apparatus and small LV dimensions, the possibility of systolic anterior motion (SAM) of the mitral leaflets must always be considered. This complication occurs when the coaptation point of the anterior and posterior leaflets is too close to the LV septum, which creates LV outflow tract obstruction and residual MR. SAM is typically caused by either a large posterior leaflet that pushes the coaptation point towards the septum, or a too small annuloplasty ring; the latter is particularly responsible in patients without an enlarged LV chamber. In our own experience with mitral repair for degenerative mitral valve disease, systolic anterior motion has been demonstrated in 9.8% of patients, which is in accordance with other studies reported in the literature.9–10 In most cases, conservative management with intravascular volume expansion, discontinuation of inotropic drugs, increasing afterload and β-blocker administration is sufficient to resolve the SAM.
Occasionally, SAM persists after such conservative management and in these cases re-repair or replacement of the mitral valve should be promptly considered. In asymptomatic young patients submitted for mitral repair, the need for chronic β-blocker therapy because of persistent SAM eliminates the possibility of enjoying a normal life without medication and has to be considered a suboptimal result. Moreover, if mitral replacement becomes necessary at such an early stage of the mitral disease, a clear therapeutic failure has to be recognised. The incidence of SAM can be reduced by using large-diameter rings or a sliding plasty technique, which involves extensive leaflet resection and reconstruction. Recently, new rings have been specifically designed to deal with this problem. By moving the coaptation point away from the septum, they could reduce the need for complex sliding plasty and, hopefully, lead to increased rates of repair.11
Watchful Waiting
This strategy consists of close surveillance of asymptomatic patients with severe MR in order to safely postpone surgery,4 and is certainly reasonable in the presence of valve lesions that are not optimally repairable. The major challenge of this approach is the need to detect LV and LA changes at a very early stage. In particular, since LV deterioration may insidiously take place even in the presence of a normal resting ejection fraction, exercise Doppler echocardiography can be used to assess contractile reserve and identify latent LV dysfunction.12 Once contractile reserve has been lost, surgery should be performed as soon as possible to prevent irreversible post-operative contractile dysfunction and adverse cardiac events.13
A watchful waiting policy is also indicated for those patients who are not good surgical candidates because of advanced age or relevant co-morbidities; the proportion of such patients is progressively increasing due to the ageing of the population. According to the Euro Heart Survey on valve disease,14 mitral valve surgery is often denied to many of these patients because of the perceived higher operative risk and lower benefit expectation from correction of MR.15–17 However, in the last decade a growing percentage of these patients have been submitted to valve repair rather than replacement, with a significant decrease of surgical risk.18–19 Indeed, in patients 75 years of age or older, mitral repair is associated with lower post-operative mortality, decreased incidence of stroke and shorter intensive care unit and hospital stay compared with mitral replacement.19 Since long-term survival benefit is difficult to demonstrate in the elderly, relief of symptoms and improvement of quality of life are the main objectives of surgery in this subgroup of patients.20,21
Evolution of Diagnostic Tools
Pre-operative anatomical and functional study of the regurgitant MV is essential for deciding the timing and suitability of surgical repair. 2D transoesophageal echocardiography (TEE) is commonly used to assess the severity and mechanisms of degenerative mitral regurgitation. The main limitations of this technique include the high degree of expertise required and the reduction in diagnostic accuracy in the setting of complex disease such as bileaflet prolapse, commissural disease, multiple regurgitant mechanisms and extensive valve disease, for which repair is more difficult.
Some of the above shortcomings of 2D TEE might be overcome by 3D imaging, which offers visualisation of the mitral valve that is highly realistic, relatively easy to understand and similar to the surgeon’s view of the valve. 3D TEE has been demonstrated to be superior to 2D imaging in the description of all forms of mitral valve pathology and particularly helpful in complex valve disease with the involvement of several scallops and commissural segments, with high negative predictive value.22–25 A new tool is emerging that is also able to depict very accurately the mitral anatomy: realtime echocardiography, which offers the advantages of 3D imaging plus an easy and simple transthoracic acquisition. However, a potential limitation of this technique is poorer image definition compared with 3D TEE. Further technical improvements and larger studies will likely enhance the clinical applicability of this echocardiographic tool in the near future.
Refinement of Surgical Techniques
The principles of mitral valve repair have evolved and moved beyond the first generation of techniques and devices. Nowadays, approximately 90% of degenerative lesions can be repaired successfully in expert centres by use of contemporary techniques. Previous surgical methods associated with suboptimal results such as chordal shortening and the non-use of an annuloplasty ring have been recognised,26 with beneficial effects on the evolution of mitral valve reconstructive surgery. Moreover, new technical solutions have been added to the fundamental methods of repair first described by Carpentier, including the use of artificial chordae made of expanded polytetrafluoroethylene27 and the edge-to-edge technique.28 These innovations have significantly improved the results of mitral repair in complex anatomical settings such as anterior leaflet prolapse and commissural lesions.29,30 New rings have also been designed to increase the effectiveness of mitral valve repair, and it is hoped that these advances will translate into more predictable and durable outcomes.
Many efforts have been focused on less invasive means of performing mitral valve repair, including limited sternotomies and videoscopic minithoracotomies using 2D video assistance. A robotic surgical system (da Vinci) has also been used by a limited number of dedicated surgeons to perform truly endoscopic mitral repair through thoracic ports with 3D visualisation. The introduction of this robotic technology into cardiac surgery has been characterised by early enthusiasm, followed by early failures and then improved results with the increasing experience accumulated in highly specialised centres.
Chitwood and colleagues, in a series of more than 300 cases, have demonstrated that complex mitral repair can be performed through robotic surgical telemanipulation, with results that are equivalent to those achieved with open repairs.31 Despite the increasing complexity of the lesions treated, bypass and cross-clamp times are still falling as the learning curve continues. Continued follow-up will be important for establishing the long-term efficacy of robotic mitral valve operations. However, future developments of the robotic system are coming and will include significant refinements to instrumentation. Port sizes for the camera and working arms will become minuscule, 3D visualisation and videoscope manipulation will improve and tactile feedback will be provided to the operating surgeon.
With these and other technical refinements, progress in conventional and minimally invasive mitral valve reconstructive surgery will continue, providing the individual patient with the surgical option considered to be the most appropriate for his specific condition.
Percutaneous Approaches to Mitral Valve Repair
Percutaneous mitral valve repair (PMVR) is emerging as a possible alternative to surgical reconstruction in selected patients. Although a variety of devices are in early clinical use or undergoing pre-clinical investigation, transcatheter mitral repair is still regarded with some scepticism. Several reasons may explain such an attitude. First, to date the percutaneous methods can only reproduce edge-to-edge repair and annuloplasty – at present not even in combination – which restricts the applicability of these procedures to a minority of patients with haemodynamically relevant MR. Second, PMVR remains a complex procedure with results that are still not comparable to those obtained with surgery. Finally, unlike transcatheter aortic valve implantation (TAVI), which is commonly used as a life-saving procedure for patients with a lethal disease that is not otherwise treatable, PMVR is mainly offered as an alternative to patients who can be optimally treated surgically. Transcatheter methods of mitral valve repair include coronary sinus approaches, annular approaches and edge-to-edge repair.
Coronary Sinus Approaches
Reduction/remodelling of the mitral annulus with devices implanted in the coronary sinus has been reserved almost exclusively for patients with functional MR.32–34 However, this procedure, if proved to be effective, could also be applied to patients with degenerative MR to specifically address the problem of annular dilatation. The aim of these percutaneous approaches is to push against the posterior portion of the mitral annulus and improve coaptation of the posterior and anterior mitral valve leaflets. Although success in animals has been obtained, human trials have presented more difficulties. The clinical experience accumulated so far reveals a low rate of responders and limited reduction of MR. Anatomical considerations may account for these problems, because often the coronary sinus does not lie directly adjacent to the posterior mitral valve annulus. In addition, in 64% of patients the circumflex coronary artery may travel between the coronary sinus and the mitral annulus, making it vulnerable to compression, which limits the feasibility of the coronary sinus approach for some patients. Finally, the occurrence of adverse events (death, myocardial infarction, tamponade) has not been negligible in the clinical series, making precise patient selection criteria necessary for each device. Particularly in elderly patients, the wall of the coronary sinus may be quite thin, thereby increasing the possibility of perforation during manipulation of the device. The largest series in this category has been treated with the Monarc coronary sinus annuloplasty device (Edwards Lifesciences, Orange, CA), consisting of two self-expanding stents connected by a spring containing biodegradable material in the interstices. Due to biodegradation of the embedded material, the spring shortens in the first few weeks after implantation, constraining the coronary sinus and the adjoining mitral annulus and thereby improving MR. Results in terms of efficacy in reducing MR are currently under evaluation, and follow-up data are not yet available.
Annular Approaches
The aim of these approaches is to realise a percutaneous mitral valve annuloplasty by using different methods that act directly on the mitral valve annulus. Some of them provide shrinking of the mitral annulus by using magnets (MiCardia Corp, Irvine, CA) or heating (Quantum Corp, Irvine, CA).35 Others allow annular cinching by positioning stitches on the posterior annulus directly from the left ventricle (Mitralign Inc, Tewksbury, MA) or by approaching the posterior annulus from the atrial septum and tethering a device from the proximity of P2 towards the atrial septum (Ample Medical’s PS3 system, Foster City, CA).36 Further investigation is required with these approaches.
Percutaneous Edge-to-edge Repair
The edge-to-edge surgical concept for mitral valve repair has been modified for a percutaneous approach. The largest clinical experience has been accumulated with the MitraClip (Evalve Inc, Redwood City, CA), reproducing the surgical double-orifice repair. The MitraClip system includes a steerable guide catheter, a clip delivery catheter and an implantable clip. Utilising both fluoroscopic and transoesophageal echocardiographic guidance, after trans-septal puncture the clip is positioned at the site of the regurgitant jet and the leaflets are grasped to create a double-orifice mitral valve. A second clip can be placed if the first clip appears to be inadequate in decreasing the magnitude of MR. A feasibility trial was completed in the US, and a phase II randomised trial is ongoing.37–40 The interim results of these studies – the Endovascular Valve Edge to edge Repair Study (EVEREST) clinical trials – have been reported.38,41 The vast majority of the patients were affected by degenerative MR and only a small number of them had functional MR. According to an analysis based on 92 patients enrolled in the EVEREST trials, clips were successfully implanted in 89% of the cases without major intra-procedural complications. Partial clip detachment from one leaflet was observed in eight patients with no embolisation of the device. Acute procedural success, defined as successful clip placement with reduction in MR severity to ≤2+, was achieved in 68 patients. Major adverse events within 30 days occurred in five patients and included one death, one stroke, one non-elective cardiac surgery and two bleedings requiring transfusion. The median length of hospital stay was two days. Seventeen patients required surgery after clip implantation, with 12 patients undergoing valve repair using standard surgical techniques as late as 18 months after the interventional procedure. In the group of patients in whom a procedural success was achieved, freedom from death, re-operation or MR >2+ was 67% at three years.
This isolated percutaneous edge-to-edge repair may be effective in patients with MR and no annular dilatation. However, these cases represent only a minority of the current surgical candidates, since more than 90% of patients with surgical MR have important annular dilatation. In those cases an edge-to-edge procedure without annuloplasty is unlikely to provide durable results, and a coronary sinus annuloplasty should be added. Nevertheless, for the time being the validity of the coronary sinus approach remains questionable and greater clinical experience is needed to determine whether a combination of leaflet repair and annuloplasty will be possible in the future. There is no doubt that, if this is the case, the adoption rate of percutaneous correction of degenerative MR will expand significantly. Patients who are currently denied surgery because of age or heavy co-morbidities could take advantage from transcatheter mitral repair. Similarly, a safe and effective catheter-based method might lead to correction of degenerative MR at a very early stage of the disease, before the occurrence of ventricular and atrial changes. However, for the time being only a small proportion of the current surgical candidates can benefit from percutaneous techniques, which are therefore not expected to reduce the volume of surgical procedures in the years to come.