Mitral Leaflet Remodeling in Dilated Cardiomyopathy

Background— Normal mammalian mitral leaflets have regional heterogeneity of biochemical composition, collagen fiber orientation, and geometric deformation. How leaflet shape and regional geometry are affected in dilated cardiomyopathy is unknown. Methods and Results— Nine sheep had 8 radio-opaque markers affixed to the mitral annulus (MA), 4 markers sewn on the central meridian of the anterior mitral leaflet (AML) forming 4 distinct segments S1 to S4 and 2 on the posterior leaflet (PML) forming 2 distinct segments S5 and S6. Biplane videofluoroscopy and echocardiography were performed before and after rapid pacing (180 to 230 bpm for 15±6 days) sufficient to develop tachycardia-induced cardiomyopathy (TIC) and functional mitral regurgitation (FMR). Leaflet tethering was defined as change of displacement of AML and PML edge markers from the MA plane from baseline values while leaflet length was obtained by summing the segments between respective leaflet markers. With TIC, total AML and PML length increased significantly (2.11±0.16 versus 2.43±0.23 cm and 1.14±0.27 versus 1.33±0.25 cm before and after pacing for AML and PML, respectively; P<0.05 for both), but only segments near the edge of each leaflet (S4 lengthened by 23±17% and S5 by 24±18%; P<0.05 for both) had significant regional remodeling. AML shape did not change and no leaflet tethering was observed. Conclusion— TIC was not associated with leaflet tethering or shape change, but both anterior and posterior leaflets lengthened because of significant remodeling localized near the leaflet edge. Leaflet remodeling accompanies mitral regurgitation in cardiomyopathy and casts doubt on FMR being purely “functional” in etiology.

[1]  B. Griffin,et al.  Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study. , 2005, Journal of the American College of Cardiology.

[2]  A. McCulloch,et al.  Nonhomogeneous Deformation in the Anterior Leaflet of the Mitral Valve , 2004, Annals of Biomedical Engineering.

[3]  M R de Leval,et al.  Innervation of human atrioventricular and arterial valves. , 1996, Circulation.

[4]  P. McCarthy,et al.  Mitral valve stiffening in end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation. , 2005, The Journal of thoracic and cardiovascular surgery.

[5]  A. DeAnda,et al.  Experimental evaluation of different chordal preservation methods during mitral valve replacement. , 1994, The Annals of thoracic surgery.

[6]  W. S. Ring,et al.  Differential collagen distribution in the mitral valve and its influence on biomechanical behaviour. , 1993, The Journal of heart valve disease.

[7]  P. Andersen,et al.  The hemodynamic and prognostic significance of echo-Doppler-proven mitral regurgitation in patients with dilated cardiomyopathy. , 1993, Cardiology.

[8]  M. S. Sacks,et al.  Surface Strains in the Anterior Leaflet of the Functioning Mitral Valve , 2002, Annals of Biomedical Engineering.

[9]  K S Kunzelman,et al.  Annular dilatation increases stress in the mitral valve and delays coaptation: a finite element computer model. , 1997, Cardiovascular surgery.

[10]  P. Dagum,et al.  Pathogenesis of Mitral Regurgitation in Tachycardia-Induced Cardiomyopathy , 2001, Circulation.

[11]  R. Brock THE SURGICAL AND PATHOLOGICAL ANATOMY OF THE MITRAL VALVE , 1952, British heart journal.

[12]  K. J. Grande-Allen,et al.  Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading. , 2004, Glycobiology.

[13]  Ajit P Yoganathan,et al.  In vitro dynamic strain behavior of the mitral valve posterior leaflet. , 2005, Journal of biomechanical engineering.

[14]  David Liang,et al.  Geometric Distortions of the Mitral Valvular-Ventricular Complex in Chronic Ischemic Mitral Regurgitation , 2003, Circulation.

[15]  A. Yoganathan,et al.  Structural characterization of the chordae tendineae in native porcine mitral valves. , 2005, The Annals of thoracic surgery.

[16]  S. Bolling Mitral Valve Reconstruction in the Patient with Heart Failure , 2001, Heart Failure Reviews.

[17]  Y. Hirabayashi,et al.  Assignment of a UDP-glucose:ceramide glucosyltransferase gene (UGCG) to human chromosome band 9q31 by in situ hybridization. , 1997, Cytogenetics and cell genetics.

[18]  A. Schwarzkopf,et al.  A comparison of two analytical systems for 3-D reconstruction from biplane videoradiograms , 1988, Proceedings. Computers in Cardiology 1988.

[19]  Richard P. Cochran,et al.  Collagen Synthesis Is Upregulated in Mitral Valves Subjected to Altered Stress , 1996, ASAIO journal.

[20]  A. Riegger,et al.  The renin-angiotensin-aldosterone system, antidiuretic hormone and sympathetic nerve activity in an experimental model of congestive heart failure in the dog. , 1982, Clinical science.

[21]  J. Gorman,et al.  Papillary muscle discoordination rather than increased annular area facilitates mitral regurgitation after acute posterior myocardial infarction. , 1997, Circulation.

[22]  N. Reichek,et al.  Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects. , 1987, Circulation.

[23]  M. Kotler,et al.  Dilated cardiomyopathy with mitral regurgitation: decreased survival despite a low frequency of left ventricular thrombus. , 1991, American heart journal.

[24]  D. C. Miller,et al.  Increases in mitral leaflet radii of curvature with chronic ischemic mitral regurgitation. , 2004, Journal of Heart Valve Disease.

[25]  J B Seward,et al.  Determinants of the Degree of Functional Mitral Regurgitation in Patients With Systolic Left Ventricular Dysfunction: A Quantitative Clinical Study , 2000, Circulation.