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Functional mitral regurgitation revisited

ESC Congress Report

  • Functional Mitral regurgitation (MR) is the most common etiology for mitral regurgitation in the adult population.
  • The common pathophysiological mechanism is involved myocardial remodeling.
  • The mitral valve is living tissue and also remodels and enlarges in parallel to ventricular remodeling.
  • Assessing severity is essential, although current methods have problems.
  • MV repair remains the treatment of choice for selected patients, although MR recurrence is a real issue.
  • Current percutaneous techniques offer an acceptable solution for patients not recommended for surgery by the current guidelines. 
Myocardial Disease

View the Slides from this session in ESC Congress 365

Julien Magne (Limoges, FR) gave the introductory presentation, describing the scope of the problem. Functional MR is habitually defined as regurgitation with an intact valve, and sometimes described as “secondary” Mitral regurgitation (MR). Julien Magne focused on the different etiologies of secondary MR.  Together, functional MR comprises 80% of all MR etiologies, with 2/3 of these having a post-MI background, and classified as “ischemic MR”. The caveat is that statistics vary greatly, depending on the modality of examination. The etiology has implication on MR mechanism, such as ischemic MR resulting from infero-posterior myocardial infarction (MI), which involves asymmetric tethering of the mitral leaflet, resulting in a posteriorly- directed eccentric regurgitant jet, while dilated cardiomyopathy (CMP) and MR resulting from apical MI and dilated cardiomyopathy create symmetric tethering and a central MR jet. MR post MI has a dismal prognosis, doubling mortality. The more severe the MR, the worse the prognosis. Functional MR is a dynamic lesion, and up to 30% of patients have exercise-induced increase in MR grade, conferring a worse prognosis. This may be due to an imbalance between tethering and closing forces, or possibly to exercise-induced dyssynchrony. Finally, as “MR begets MR” and remodeling is an ongoing process, repairing the valve (as opposed to changing it) entails the risk of recurrent MR in 32% of operated patients, while not having advantage over MV replacement in terms of prognosis. This last assertion was disputed by Dr de Bonis from the audience, and later by Prof. Ottavio Alfieri, claiming that the CTSN investigators who produced this statistic potentially included in the repair group patients that where unsuitable for repair according to current practice as stated in the guidelines.

Thierry Le Tourneau (Nantes, FR) presented novel insights into the biology of the mitral valve in functional MR. As the degree of valvular malcoaptation is the result of a balance between closing and tethering forces playing a “tug of war” with the mitral leaflets (as described almost a decade ago by Robert Levine’s group), there is emerging evidence that the leaflet themselves remodel and enlarge (more than 35%) to balance these forces, in parallel with ventricular remodeling.  When this mechanism fails, MR ensues, as demonstrated by Chaput et al. Indeed, excised valves from transplant recipients demonstrated that there is interstitial-cell proliferation and an abundance of collagen and glycosamino-glycans (GAG’s) when compared with autopsy controls. Also, there is a phenotypic shift, with a proliferation of myofibroblasts (fibroblasts expressing alpha smooth-muscle actin) resulting from epithelial to mesenchymal transformation (EMT). In animal models, there is evidence of increased collagen and elastin turnover. Although isolated annular dilatation should not cause significant regurgitation, in functional MR the mitral annulus also remodels, with flattening and loss of its saddle-like shape. As demonstrated by Topilsky et al, significant loss of this saddle shape early in diastole portended worse MR, and is related to the typical functional MR flow, maximal in early and late systole.

Victoria Delgado (Leiden, NL) presented the imaging aspect of functional MR and its relation to prognosis. She stressed the need to quantify MR, define LV and MV geometry, and determine dyssynchrony. Valve Diseases Guidelines have defined a lower cutoff value for severe regurgitation in functional MR (20 cmsq, compared with 40 cmsq in organic MR). This was determined according to a worse prognosis in these lower severity values. A significant caveat is that proximal isovelocity shape, used to calculate the regurgitant volume, is generally hemi-elliptical in functional MR, causing significant underestimation of MR severity using this method. A potential solution may be the use of 3D echo-based quantification, which has demonstrated considerable agreement with MRI-derived values. Measuring tethering and global remodeling is extremely important. In this aspect, cardiac CT and MRI have a definite role in assessing LV and MV anatomy. Finally, viability and synchronicity should be addressed, as improvement in MR following resynchronization therapy portends a better prognosis.

Ottavio Alfieri (Brescia, IT) addressed the surgical aspects, in the era of emerging percutaneous solutions. As questions arise related to an undersized ring as a solution for functional MR, Prof Afieri reminded us that repair entails a lower operative risk and long-term mortality, albeit at the price of more recurrent MR (up to 30%-50% at 3 years). In his opinion, achieving reverse remodeling will prevent this, and thus patients have to be selectively referred for his procedure, adhering to the anatomical criteria in the guidelines (smaller and less spherical ventricles and tenting areas, shorter duration of CHF, favorable coaptation distance and leaflet-annular angles, and small inter-papillary distances). Thus performed, it is still the first surgical line of treatment. When replacement is performed, care should be applied to preserve the sub-valvular apparatus, in order to maximize post-op systolic function. Finally, Prof. Alfieri reviewed the different percutaneous options available or in the horizon, focusing on Mitra-Clip. He emphasized the correct choice of patients for these procedures, as in the real-world patients are sicker, have low ejection-fractions and sever CHF, and thus are not suitable for MV operations according to current guidelines It is a well-tolerated procedure, and in these sick patients provides a meaningful clinical benefit. In concluding he described several novel methods for percutaneous annuloplasty (which may be complementary to MitraClip) and MV implantation.
This session emphasized once more the complexity and the multi-factorial character of this vexing condition, that still causes significant morbidity and mortality. The current clinical controversies, centered on the choice of patients for corrective procedures and the choice of the specific procedure, are really a call for more extensive and collaborative research in this common condition. Finding methods to tackle ventricular remodeling, the real culprit, early in the course of the disease, may potentially improve the prognosis of these patients and potentially avoid the need for invasive interventions.




Functional mitral regurgitation revisited

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.