Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation.

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Citation: Journal of the American Heart Association. 7(21):e009777, 2018 Nov 06.PMID: 30571381Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Mitral Valve Annuloplasty/mt [Methods] | *Mitral Valve Insufficiency/su [Surgery] | *Mitral Valve/pa [Pathology] | *Mitral Valve/pp [Physiopathology] | *Postoperative Complications/pa [Pathology] | *Postoperative Complications/pp [Physiopathology] | Animals | Biomechanical Phenomena | Cardiovascular Physiological Phenomena | Mitral Valve Insufficiency/et [Etiology] | SwineYear: 2018ISSN:
  • 2047-9980
Name of journal: Journal of the American Heart AssociationAbstract: Background Undersized ring annuloplasty is a commonly used surgical repair for ischemic mitral regurgitation, in which annular downsizing corrects regurgitation, but alters valve geometry and elevates tissue stresses. In this study, we investigated if unphysiological leaflet kinematics after annuloplasty might cause pathogenic biological remodeling of the mitral valve leaflets, and if preserving physiologic leaflet kinematics with a better technique can moderate such adverse remodeling. Methods and Results Twenty-nine swine were induced with ischemic mitral regurgitation, and survivors were assigned to groups: 7 underwent annuloplasty, 12 underwent annuloplasty with papillary-muscle approximation, 6 underwent papillary-muscle approximation, and 3 were sham controls. Pre-and post-surgery leaflet kinematics were measured, and valve tissue was explanted after 3 months to assess biological changes. Anterior leaflet excursion was unchanged across groups, but persistent tethering was observed with annuloplasty. Posterior leaflet was vertically immobile after annuloplasty, better mobile with the combined approach, and substantially ( P=0.0028) mobile after papillary-muscle approximation. Procollagen-1 was higher in leaflets from annuloplasty compared with the other groups. Heat shock protein-47 and lysyl oxidase were higher in groups receiving annuloplasty compared with sham. alpha- SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor-beta expression. Conclusions This is the first study to demonstrate that surgical valve repairs that impose unphysiological leaflet mechanics have a deleterious, pathological impact on valve biology. Surgeons may need to consider restoring physiologic leaflet stresses as well as valve competence, while also exploring pharmacological methods to inhibit the abnormal signaling cascades.All authors: Corporan D, Guyton RA, Kalra K, Padala M, Sarin EL, Shi W, Sielicka A, Sulejmani F, Sun W, Thourani VHFiscal year: FY2019Digital Object Identifier: Date added to catalog: 2019-01-08
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Journal Article MedStar Authors Catalog Article 30571381 Available 30571381

Background Undersized ring annuloplasty is a commonly used surgical repair for ischemic mitral regurgitation, in which annular downsizing corrects regurgitation, but alters valve geometry and elevates tissue stresses. In this study, we investigated if unphysiological leaflet kinematics after annuloplasty might cause pathogenic biological remodeling of the mitral valve leaflets, and if preserving physiologic leaflet kinematics with a better technique can moderate such adverse remodeling. Methods and Results Twenty-nine swine were induced with ischemic mitral regurgitation, and survivors were assigned to groups: 7 underwent annuloplasty, 12 underwent annuloplasty with papillary-muscle approximation, 6 underwent papillary-muscle approximation, and 3 were sham controls. Pre-and post-surgery leaflet kinematics were measured, and valve tissue was explanted after 3 months to assess biological changes. Anterior leaflet excursion was unchanged across groups, but persistent tethering was observed with annuloplasty. Posterior leaflet was vertically immobile after annuloplasty, better mobile with the combined approach, and substantially ( P=0.0028) mobile after papillary-muscle approximation. Procollagen-1 was higher in leaflets from annuloplasty compared with the other groups. Heat shock protein-47 and lysyl oxidase were higher in groups receiving annuloplasty compared with sham. alpha- SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor-beta expression. Conclusions This is the first study to demonstrate that surgical valve repairs that impose unphysiological leaflet mechanics have a deleterious, pathological impact on valve biology. Surgeons may need to consider restoring physiologic leaflet stresses as well as valve competence, while also exploring pharmacological methods to inhibit the abnormal signaling cascades.

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