title: Mitral leaflet adaptation to ventricular remodeling: prospective changes in a model of ischemic mitral regurgitation.
abstract: BACKGROUND
  Ischemic mitral regurgitation is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about how chronic tethering affects leaflet area, in part because it cannot be measured repeatedly in situ. Recently, a new method for 3D echocardiographic measurement of mitral leaflet area was developed and validated in vivo against sheep valves, later excised. Clinical studies (n=80) showed that mitral leaflet area increased by >30% in patients with inferior myocardial infarction and dilated cardiomyopathy versus normal; greater adaptation independently predicted less mitral regurgitation. This study explored whether mitral valve area changes over time within the same heart with ischemic mitral regurgitation.
  
  
  RESULTS
  Twelve sheep were studied at baseline and 3 months after inferior myocardial infarction by 3D echocardiography; 6 were untreated and 6 were treated initially with an epicardial patch to limit left ventricular dilation and mitral regurgitation. Untreated sheep developed left ventricular dilation at 3 months, with global dysfunction (mean+/-SD ejection fraction, 24+/-10% versus 44+/-10% with patching, P=0.02) and moderate mitral regurgitation (vena contracta, 5.0+/-1.0 versus 0.8+/-1.0 mm, P<0.0002). In untreated sheep, total diastolic leaflet area increased from 13.1+/-1.3 to 18.1+/-2.5 cm(2) (P=0.0001). In patched sheep, leaflet area at 3 months was not significantly different from baseline sheep values (13.0+/-1.1 versus baseline, 12.1+/-1.8 cm(2), P=0.31).
  
  
  CONCLUSIONS
  Mitral valve area, independent of systolic stretch, increases over time as the left ventricular remodels after inferior myocardial infarction. This increase, however, fails to compensate adequately for tethering to prevent mitral regurgitation. Understanding the mechanism of valve adaptation can potentially suggest new biological and surgical therapeutic targets.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Chaput
authors.forename: Mark D
authors.initials: MD
authors.lastname: Handschumacher
authors.forename: J Luis
authors.initials: JL
authors.lastname: Guerrero
authors.forename: Godtfred
authors.initials: G
authors.lastname: Holmvang
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Dal-Bianco
authors.forename: Suzanne
authors.initials: S
authors.lastname: Sullivan
authors.forename: Gus J
authors.initials: GJ
authors.lastname: Vlahakes
authors.forename: Judy
authors.initials: J
authors.lastname: Hung
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics; D008943:Mitral Valve / Q000473:pathology*; D008944:Mitral Valve Insufficiency / Q000473:pathology* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications*; D012756:Sheep; D020257:Ventricular Remodeling