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Author Notes:

Correspondence to: Muralidhar Padala, PhD, Structural Heart Research and Innovation Laboratory in the Cardiothoracic Research Laboratories, Carlyle Fraser Heart Center, Division of Cardiothoracic Surgery, Emory University School of Medicine, 380B Northyards Blvd, Atlanta, GA 30313. E-mail: spadala@emory.edu

Dr Thourani reports consulting or other relationships with Abbott Vascular, Edwards Lifesciences, W. L. Gore, Boston Scientific, and JenaValve.

Dr Sarin reports relationships with Medtronic, and W.L. Gore.

The remaining authors have no disclosures to report.


Research Funding:

This work was partially supported by grant awards to Dr Padala from the American Heart Association (14SDG20380081), the National Heart Lung and Blood Institute (1R01HL135145‐01A1, 1R01HL133667‐01A1, 1R01HL140325‐01A1), and the Carlyle Fraser Heart Center at Emory University Hospital Midtown.

Dr Sielicka was supported by a post‐doctoral fellowship grant from the American Heart Association (17POST33680072).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cardiac & Cardiovascular Systems
  • Cardiovascular System & Cardiology
  • animal model surgery
  • mitral valve regurgitation
  • mitral valve repair
  • mitral annuloplasty, subannular repair, mitral, valve fibrosis, heart valve repair durability, mitral valve

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


Journal Title:

Journal of the American Heart Association


Volume 7, Number 21


, Pages e009777-e009777

Type of Work:

Article | Final Publisher PDF


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.

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© 2018 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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