Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation
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 annulop...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-11-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.118.009777 |
| _version_ | 1819178053307203584 |
|---|---|
| author | Alicja Sielicka Eric L. Sarin Weiwei Shi Fatiesa Sulejmani Daniella Corporan Kanika Kalra Vinod H. Thourani Wei Sun Robert A. Guyton Muralidhar Padala |
| author_facet | Alicja Sielicka Eric L. Sarin Weiwei Shi Fatiesa Sulejmani Daniella Corporan Kanika Kalra Vinod H. Thourani Wei Sun Robert A. Guyton Muralidhar Padala |
| author_sort | Alicja Sielicka |
| collection | DOAJ |
| description | 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. α‐SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor‐β 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. |
| first_indexed | 2024-12-22T21:36:26Z |
| format | Article |
| id | doaj.art-fda09a4870f74602bbbb7199466510c0 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T21:36:26Z |
| publishDate | 2018-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-fda09a4870f74602bbbb7199466510c02022-12-21T18:11:44ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-11-0172110.1161/JAHA.118.009777Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral RegurgitationAlicja Sielicka0Eric L. Sarin1Weiwei Shi2Fatiesa Sulejmani3Daniella Corporan4Kanika Kalra5Vinod H. Thourani6Wei Sun7Robert A. Guyton8Muralidhar Padala9Structural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAWallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAWallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GAStructural Heart Research & Innovation Laboratory Carlyle Fraser Heart Center Emory University Hospital Midtown Atlanta GABackground 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. α‐SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor‐β 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.https://www.ahajournals.org/doi/10.1161/JAHA.118.009777animal model surgerymitral valve regurgitationmitral valve repair, mitral annuloplasty, subannular repair, mitral valve fibrosis, heart valve repair durability, mitral valve |
| spellingShingle | Alicja Sielicka Eric L. Sarin Weiwei Shi Fatiesa Sulejmani Daniella Corporan Kanika Kalra Vinod H. Thourani Wei Sun Robert A. Guyton Muralidhar Padala Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease animal model surgery mitral valve regurgitation mitral valve repair, mitral annuloplasty, subannular repair, mitral valve fibrosis, heart valve repair durability, mitral valve |
| title | Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation |
| title_full | Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation |
| title_fullStr | Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation |
| title_full_unstemmed | Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation |
| title_short | Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation |
| title_sort | pathological remodeling of mitral valve leaflets from unphysiologic leaflet mechanics after undersized mitral annuloplasty to repair ischemic mitral regurgitation |
| topic | animal model surgery mitral valve regurgitation mitral valve repair, mitral annuloplasty, subannular repair, mitral valve fibrosis, heart valve repair durability, mitral valve |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.118.009777 |
| work_keys_str_mv | AT alicjasielicka pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT ericlsarin pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT weiweishi pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT fatiesasulejmani pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT daniellacorporan pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT kanikakalra pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT vinodhthourani pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT weisun pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT robertaguyton pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation AT muralidharpadala pathologicalremodelingofmitralvalveleafletsfromunphysiologicleafletmechanicsafterundersizedmitralannuloplastytorepairischemicmitralregurgitation |