title: A novel approach for reducing ischemic mitral regurgitation by injection of a polymer to reverse remodel and reposition displaced papillary muscles.
abstract: BACKGROUND
  Ischemic mitral regurgitation (MR) relates to displacement of the papillary muscles from ischemic ventricular distortion. We tested the hypothesis that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) polymer, a biologically inert biomaterial that has been specially formulated to produce an encapsulated, stable, resilient gel once injected into the myocardium. The purpose is to materially support the infarcted myocardium while at the same time repositioning the papillary muscles that become apically tethered in MR.
  
  
  RESULTS
  Nine sheep underwent ligation of circumflex branches to produce acute ischemic MR. PVA polymer was then injected by echo guidance into the myocardium underlying the infarcted papillary muscle. Hemodynamic data, left ventricular ejection fraction, elastance, tau (relaxation constant), left ventricular stiffness coefficient, and 2-dimensional and 3-dimensional echocardiograms were obtained post-MR and post-PVA injection. One animal died after coronary ligation and 2 did not develop MR. In the remaining 6, moderate MR developed. With PVA injection, the MR decreased significantly from moderate to trace-mild (vena contracta: 5+/-0.4 mm versus 2+/-0.7 mm, post-MR versus post-PVA injection; P<0.0001). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (27+/-4 to 24+/-4 mm, post-MR versus post-PVA, P<0.001). Importantly, PVA injection was not associated with significant decreases in left ventricular ejection fraction (43+/-6% versus 37+/-4%, post-MR versus post-PVA, P=nonsignificant), elastance (3.5+/-1.4 versus 2.9+/-1.3; post-MR versus post-PVA injection, P=nonsignificant). Measures of left ventricular diastolic function, tau (100+/-51 ms to 84+/-37 ms, post-MR versus post-PVA; P=nonsignificant), and left ventricular stiffness coefficient (0.18+/-0.12 versus 0.14+/-0.08, post-MR versus post-PVA; P=nonsignificant) did not increase post-PVA.
  
  
  CONCLUSIONS
  PVA polymer injection resulted in acute reverse remodeling of the ventricle with papillary muscle repositioning to decrease MR. This was not associated with an adverse effect on left ventricular systolic and diastolic function. This new approach to alter pathological anatomy after infarction may offer an alternative strategy for relieving ischemic MR by correcting the position of the affected papillary muscle, thus relieving apical tethering.
authors.affiliation: Massachusetts General Hospital, Cardiac Ultrasound Laboratory, Blake 256, 55 Fruit Street, Boston, MA 02114, USA. jhung@partners.org
authors.forename: Judy
authors.initials: J
authors.lastname: Hung
authors.forename: Jorge
authors.initials: J
authors.lastname: Solis
authors.forename: J Luis
authors.initials: JL
authors.lastname: Guerrero
authors.forename: Gavin J C
authors.initials: GJ
authors.lastname: Braithwaite
authors.forename: Orhun K
authors.initials: OK
authors.lastname: Muratoglu
authors.forename: Miguel
authors.initials: M
authors.lastname: Chaput
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernandez-Friera
authors.forename: Mark D
authors.initials: MD
authors.lastname: Handschumacher
authors.forename: Van J
authors.initials: VJ
authors.lastname: Wedeen
authors.forename: Stuart
authors.initials: S
authors.lastname: Houser
authors.forename: Gus J
authors.initials: GJ
authors.lastname: Vlahakes
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
mesh_terms: D000818:Animals; D038524:Diffusion Magnetic Resonance Imaging; D019560:Echocardiography, Three-Dimensional; D005782:Gels; D006439:Hemodynamics; D007267:Injections; D008944:Mitral Valve Insufficiency / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications*; D009206:Myocardium; D010210:Papillary Muscles / Q000187:drug effects*; D011142:Polyvinyl Alcohol / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012756:Sheep; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D005782:Gels; D011142:Polyvinyl Alcohol