Review
Basic Mechanisms of Mitral Regurgitation

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Abstract

Any structural or functional impairment of the mitral valve (MV) apparatus that exhausts MV tissue redundancy available for leaflet coaptation will result in mitral regurgitation (MR). The mechanism responsible for MV malcoaptation and MR can be dysfunction or structural change of the left ventricle, the papillary muscles, the chordae tendineae, the mitral annulus, and the MV leaflets. The rationale for MV treatment depends on the MR mechanism and therefore it is essential to identify and understand normal and abnormal MV and MV apparatus function.

Résumé

Toute détérioration structurelle ou fonctionnelle de l’appareil valvulaire mitral (VM) qui épuise l’excès tissulaire de la VM disponible pour la coaptation des feuillets entraînera la régurgitation mitrale (RM). Le mécanisme responsable de la mauvaise coaptation de la VM et de la RM peut être la dysfonction ou la modification structurelle du ventricule gauche, des muscles papillaires, des cordages tendineux, de l’anneau mitral et des feuillets de la VM. La justification du traitement de la VM repose sur le mécanisme de RM. Il est donc essentiel de cerner et de comprendre le fonctionnement normal et anormal de la VM et de l’appareil VM.

Section snippets

MV Apparatus

The MV has anterior and posterior leaflets and variable commissural scallops. The leaflet bases circumferentially insert into the MA, and the ventricular leaflet bodies and edges are connected to the PMs and LV wall via chordae (Fig. 1B and C). The leaflet cross-sectional structure is trilaminar and each layer's extracellular matrix (ECM) has unique characteristics and biomechanical properties important to the normal function of the MV. On the atrial side, the atrialis layer is rich in

MR Mechanism

MR develops if the MV leaflets do not sufficiently cover the MA orifice throughout LV systole, and is commonly classified as primary MR—indicating leaflet pathology—or secondary MR in the setting of LV myocardial pathology. MR can also be functionally classified based on MV leaflet pliability and motion (Carpentier classification).42, 43 To facilitate medical communication, MV leaflet malcoaptation and MR jet origin are commonly indicated by anterior (A) or posterior (P) leaflet and lateral

Chordal rupture and PM rupture

Elongation or rupture of marginal chordae due to degenerative tissue abnormalities, iatrogen, or endocarditis almost always lead to significant MR due to leaflet edge eversion (called flail leaflet; Fig. 3A).51 Secondary chordae rarely rupture, and because of their leaflet body insertion, are not critical to maintain coaptation. To the contrary, cutting secondary chordae is a strategy to potentially treat secondary MR when chordal tethering restricts coaptation (see section Secondary MR and

Secondary MR and Treatment Strategies

Functional or ischemic MR is the result of systolic leaflet restriction and tethering to displaced PMs in the setting of a distorted, remodelled LV (Fig. 3B). LV remodelling can be global, with LV dilatation and increased sphericity,5, 82, 83, 84, 85 or localized, affecting mainly the PM-bearing LV walls.86 LV remodelling that leads to outward apical/posterior/posterolateral PM displacement (Fig. 3B)86, 87, 88, 89, 90, 91 will increase the systolic PM heads-MA distance,92, 93, 94, 95 which

Hypertrophic Cardiomyopathy and Treatment Strategies

Hypertrophic cardiomyopathy (HCM) is morphologically characterized by significant LV hypertrophy in the absence of chronically increased afterload or infiltrative diseases (eg, cardiac amyloidosis) (Fig. 3C, double arrow).129 In HCM, total PM muscle mass is doubled and the number of heads increased.130 The PMs are anteriorly displaced (Fig. 3C, arrow) and the heads closer to each other,131, 132 which increases MV leaflet slack and positions the leaflets closer toward the LVOT. Larger and

Rheumatic Heart Disease and Treatment Strategies

Rheumatic heart disease can develop when T- and B-cell-guided autoimmune response triggered by an untreated streptococcus pharyngitis mistargets heart tissue (molecular mimicry).148 Streptococcal carbohydrate-directed antibodies recognize cardiac myosin and also target heart valve endothelium via the protein laminin. This prompts a local inflammatory response and exposure of collagen with development of autoantibodies against exposed collagen. Endothelial expression of vascular cell adhesion

Future Directions

Cardiovascular imaging advancements in MR quantification and LV function and structure assessment will be critical to refine the optimal time point of therapeutic MV intervention, which will no doubt further develop toward less invasive and transcatheter MV repair options. Ongoing genetic studies will lead to improved understanding of the mechanisms underlying and promoting primary MV disease. Such knowledge could allow identification of patients at risk without yet established MV disease and

Summary

Normal anatomy and function of the LV, PMs, chordae, MA, and leaflets ensure effective leaflet coaptation and prevent leaflet tethering, prolapse, and LVOT obstruction. Any temporal and spatial impairment of leaflet coaptation that exhausts leaflet redundancy might result in MR. Apical-annular leaflet tethering with restricted leaflet motion is characteristic for functional and/or ischemic MR; excessive leaflet and chordal motion and extensibility are characteristic for MVP (posterior leaflet),

Funding Sources

This work was supported in part by grant 07CVD04 of the Leducq Foundation, Paris, France, for the Leducq Transatlantic MITRAL Network, and by National Institutes of Health grants K24 HL67434, R01 HL72265, and HL109506.

Disclosures

The authors have no conflicts of interest to disclose.

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