Mechanics of Healthy and Functionally Diseased Mitral Valves: A Critical Review

In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching. Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61+/-6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4+/-1.3 cm(2) (17+/-10%) from 14.3+/-1.9 to 16.7+/-1.9 cm(2) (P=0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18+/-0.14 versus 0.42+/-0.14 mm; P<0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31(+)) coexpressing alpha-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41+/-19% versus 9+/-5%; P=0.02), indicating endothelial-mesenchymal transdifferentiation. alpha-Smooth muscle actin-positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial alpha-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells. Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation.

Mitral valve prolapse has been diagnosed by two-dimensional echocardiographic criteria with surprising frequency in the general population, even when preselected normal subjects are examined. In most of these individuals, however, prolapse appears in the apical four-chamber view and is absent in roughly orthogonal long-axis views. Previous studies of in vitro models with nonplanar rings have shown that systolic mitral annular nonplanarity can potentially produce this discrepancy. However, to prove directly that apparent leaflet displacement in a two-dimensional view does not constitute true displacement above the three-dimensional annulus requires reconstruction of the entire mitral valve, including leaflets and annulus. Such reconstruction would also be necessary to explore the complex geometry of the valve and to derive volumetric measures of superior leaflet displacement. A technique was therefore developed and validated in vitro for three-dimensional reconstruction of the entire mitral valve. In this technique, simultaneous real-time acquisition of images and their spatial locations permits reconstruction of a localized structure by minimizing the effects of patient motion and respiration. By applying this method to 15 normal subjects, a coherent mitral valve surface could be reconstructed from intersecting scans. The results confirm mitral annular nonplanarity in systole, with a maximum deviation of 1.4 +/- 0.3 cm from planarity. They directly show that leaflets can appear to ascend above the mitral annulus in the apical four-chamber view, as they did in at least one view in all subjects, without actual leaflet displacement above the entire mitral valve in three dimensions, thereby challenging the diagnosis of prolapse by isolated four-chamber view displacement in otherwise normal individuals. This technique allows us to address a uniquely three-dimensional problem with high resolution and provide new information previously unavailable from the two-dimensional images. This new appreciation should enhance our ability to ask appropriate clinical questions relating mitral valve shape and leaflet displacement to clinical and pathologic consequences.

Leaflet curvature is known to reduce mechanical stress. There are 2 major components that contribute to this curvature. Leaflet billowing introduces the most obvious form of leaflet curvature. The saddle shape of the mitral annulus imparts a more subtle form of leaflet curvature. This study explores the relative contributions of leaflet billowing and annular shape on leaflet curvature and stress distribution. Both numerical simulation and experimental data were used. The simulation consisted of an array of numerically generated mitral annular phantoms encompassing flat to markedly saddle-shaped annular heights. Highest peak leaflet stresses occurred for the flat annulus. As saddle height increased, peak stresses decreased. The minimum peak leaflet stress occurred at an annular height to commissural width ratio of 15% to 25%. The second phase involved data acquisition for the annulus from 3 humans by 3D echocardiography, 3 sheep by sonomicrometry array localization, 2 sheep by 3D echocardiography, and 2 baboons by 3D echocardiography. All 3 species imaged had annuli of a similar shape, with an annular height to commissural width ratio of 10% to 15%. The saddle shape of the mitral annulus confers a mechanical advantage to the leaflets by adding curvature. This may be valuable when leaflet curvature becomes reduced due to diminished leaflet billowing caused by annular dilatation. The fact that the saddle shape is conserved across mammalian species provides indirect evidence of the advantages it confers. This analysis of mitral annular contour may prove applicable in developing the next generation of mitral annular prostheses.