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 S 1 to S 4 and 2 on the posterior leaflet (PML) forming 2 distinct segments S 5 and S 6 . 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 (S 4 lengthened by 23±17% and S 5 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.