ReviewBasic Mechanisms of Mitral Regurgitation
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.
References (151)
- et al.
Anatomy of the mitral valve apparatus: role of 2D and 3D echocardiography
Cardiol Clin
(2013) - et al.
Anatomy of mitral insufficiency
Prog Cardiovasc Dis
(1962) - et al.
Burden of valvular heart diseases: a population-based study
Lancet
(2006) - et al.
Comparison of mitral valve dimensions in adults with valvular aortic stenosis, pure aortic regurgitation and hypertrophic cardiomyopathy
Am J Cardiol
(1993) - et al.
Functional anatomy of the normal mitral valve
J Thorac Surg
(1956) - et al.
Analysis of shape and motion of the mitral annulus in subjects with and without cardiomyopathy by echocardiographic 3-dimensional reconstruction
J Am Soc Echocardiogr
(2000) - et al.
Annular dilatation increases stress in the mitral valve and delays coaptation: a finite element computer model
Cardiovasc Surg
(1997) - et al.
A saddle-shaped annulus reduces systolic strain on the central region of the mitral valve anterior leaflet
J Thorac Cardiovasc Surg
(2007) - et al.
Saddle shape of the mitral annulus reduces systolic strains on the P2 segment of the posterior mitral leaflet
Ann Thorac Surg
(2009) - et al.
Saddle-shaped mitral valve annuloplasty rings improve leaflet coaptation geometry
J Thorac Cardiovasc Surg
(2011)
A structural basis for the size-related mechanical properties of mitral valve chordae tendineae
J Biomech
Mitral valve basal chordae: comparative anatomy and terminology
Ann Thorac Surg
Development of the papillary muscles of the mitral valve: morphogenetic background of parachute-like asymmetric mitral valves and other mitral valve anomalies
J Thorac Cardiovasc Surg
Cardiac valve surgery–the “French correction”
J Thorac Cardiovasc Surg
Reconstructive surgery of mitral valve incompetence: ten-year appraisal
J Thorac Cardiovasc Surg
Evidence of atrial functional mitral regurgitation due to atrial fibrillation: reversal with arrhythmia control
J Am Coll Cardiol
Atrial functional mitral regurgitation: the left atrium gets its due respect
J Am Coll Cardiol
Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we use emergently revascularize Occluded Coronaries in cardiogenic shocK?
J Am Coll Cardiol
Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort
J Am Coll Cardiol
Reconsideration of echocardiographic standards for mitral valve prolapse: lack of association between leaflet displacement isolated to the apical four chamber view and independent echocardiographic evidence of abnormality
J Am Coll Cardiol
Papillary muscle traction in mitral valve prolapse: quantitation by two-dimensional echocardiography
J Am Coll Cardiol
Progression of mitral regurgitation: a prospective Doppler echocardiographic study
J Am Coll Cardiol
Correlation between clinical and histologic patterns of degenerative mitral valve insufficiency: a histomorphometric study of 130 excised segments
Cardiovasc Pathol
A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4
Am J Hum Genet
Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1
Am J Hum Genet
Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28
Am J Hum Genet
Mitral regurgitation
Lancet
Chronic mitral regurgitation and aortic regurgitation: have indications for surgery changed?
J Am Coll Cardiol
Early surgery versus conventional treatment for asymptomatic severe mitral regurgitation: a propensity analysis
J Am Coll Cardiol
Echocardiographic predictors of left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve after mitral valve reconstruction for myxomatous valve disease
J Am Coll Cardiol
Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure
J Am Coll Cardiol
On the mechanism of functional mitral regurgitation
Am J Cardiol
Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation
J Am Coll Cardiol
Pathogenesis of acute ischemic mitral regurgitation in three dimensions
J Thorac Cardiovasc Surg
Large animal model of ischemic mitral regurgitation
Ann Thorac Surg
The mitral complex. Interaction of the anatomy, physiology, and pathology of the mitral annulus, mitral valve leaflets, chordae tendineae, and papillary muscles
Am Heart J
Cross-sectional echocardiographic spectrum of papillary muscle dysfunction
Am Heart J
Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering
J Am Coll Cardiol
Mitral valve stiffening in end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation
J Thorac Cardiovasc Surg
Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study
J Am Coll Cardiol
Carpentier’s Reconstructive Valve Surgery. From Valve Analysis to Valve Reconstruction
Ischemic mitral regurgitation on the threshold of a solution: from paradoxes to unifying concepts
Circulation
Insights from three-dimensional echocardiography into the mechanism of functional mitral regurgitation: direct in vivo demonstration of altered leaflet tethering geometry
Circulation
Mitral leaflet adaptation to ventricular remodeling: prospective changes in a model of ischemic mitral regurgitation
Circulation
Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering
Circulation
In vivo measurement of mitral leaflet surface area and subvalvular geometry in patients with asymmetrical septal hypertrophy: insights into the mechanism of outflow tract obstruction
Circulation
Mitral leaflet adaptation to ventricular remodeling: occurrence and adequacy in patients with functional mitral regurgitation
Circulation
Studies of the mitral valve. I. Anatomic features of the normal mitral valve and associated structures
Circulation
The Mitral Valve-A Pluridisciplinary Approach
Three-dimensional echocardiographic reconstruction of the mitral valve, with implications for the diagnosis of mitral valve prolapse
Circulation
Cited by (48)
Mechanistic Insights into Tricuspid Regurgitation Secondary to Pulmonary Arterial Hypertension
2022, American Journal of CardiologyCitation Excerpt :Compensating for the acquired pressure overload, the normally crescent-shaped right ventricle elongates and becomes more spherical, as evidenced by a smaller sphericity index and greater right/left ventricular ratio. Akin to mechanical changes described in secondary mitral regurgitation,13 this may conceivably lead to dyssynchrony, reduced leaflet closing forces, and ultimately, impaired coaptation with resultant significant TR. Chronic TR, in turn, contributes to right ventricular volume overload, which can exacerbate ventricular remodeling and tricuspid annular changes and ultimately worsen ventricular dysfunction and compromise cardiac output.2,4,5
General Anesthesia Leads to Underestimation of Regurgitation Severity in Patients With Secondary Mitral Regurgitation Undergoing Transcatheter Mitral Valve Repair
2022, Journal of Cardiothoracic and Vascular AnesthesiaCitation Excerpt :Interestingly, this study showed practically no correlation between the decrease in MR severity and the change in vital parameters, suggesting that the decrease in MR under GA is a result of more cumulative factors and not only a direct result of drop in heart rate or blood pressure. The decrease of MR under GA in the authors’ study population was derived mainly by a decrease in patients with secondary MR, as they did not notice any statistically significant decrease in patients with primary MR. Mechanisms of MR differ significantly between primary and secondary MR. Whereas primary MR represents a mechanical problem leading to a coaptation defect between both mitral valve leaflets, secondary MR is caused by altered dimensions and geometry of the left ventricle.19 Therefore, secondary MR may be more susceptible to changes of hemodynamic or loading conditions on the left ventricle.
Clinical and echocardiographic outcomes of transcatheter mitral valve repair in atrial functional mitral regurgitation
2021, International Journal of CardiologyCitation Excerpt :Mitral regurgitation (MR) has been traditionally classified as primary or secondary depending on the etiology of the valvular disease [1].
Influence of Prolapse Volume in Mitral Valve Prolapse
2021, American Journal of CardiologyPredictors of Outcomes Following Transcatheter Edge-to-Edge Mitral Valve Repair
2020, JACC: Cardiovascular InterventionsCitation Excerpt :A flail gap ≥10 mm indicated a similar trend (HR: 3.1; 95% CI: 0.9 to 11.5; p = 0.077). The posterior leaflet is crescentic in shape, with a short radial length and a long circumferential base attached to the posterior mitral annulus (37). Restricted leaflet motion may emanate from apical tethering (i.e., in secondary MR), as well as leaflet fibrosis, thickening, and commissural fusion (i.e., advanced rheumatic disease) (28).
Comprehensive and Integrative Experimentation Setup for Large Animals’ Hybrid Valvular Heart Surgery
2019, Journal of Surgical ResearchCitation Excerpt :Understanding the different etiologies and the pathophysiology for both native MV diseases and bioprosthesis dysfunction is crucial for the heart specialists who are intending to repair and/or replace the MV, taking into consideration the more complicated structure of the MV apparatus compared to the aortic valve.7,41 Moreover, the interaction either between MV annulus and chordae or the LVOT and the LV wall is as vital for the structural preservation to increase the success of the surgical and the transcatheter approaches.42,43 Preclinical and experimental studies, like ours, are in the center of rapidly evolving trials to establish a competent minimally invasive approach for the MV.
See page 977 for disclosure information.