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Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease
Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue, causing an increased pressure gradient in the left ventricular outflow tract (LVOT). While surgical resection of the membrane has shown some success in eliminating the obstruct...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166095/ https://www.ncbi.nlm.nih.gov/pubmed/30320123 http://dx.doi.org/10.3389/fcvm.2018.00122 |
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author | Massé, Danielle D. Shar, Jason A. Brown, Kathleen N. Keswani, Sundeep G. Grande-Allen, K. Jane Sucosky, Philippe |
author_facet | Massé, Danielle D. Shar, Jason A. Brown, Kathleen N. Keswani, Sundeep G. Grande-Allen, K. Jane Sucosky, Philippe |
author_sort | Massé, Danielle D. |
collection | PubMed |
description | Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue, causing an increased pressure gradient in the left ventricular outflow tract (LVOT). While surgical resection of the membrane has shown some success in eliminating the obstruction, it poses significant risks associated with anesthesia, sternotomy, and heart bypass, and it remains associated with a high rate of recurrence. Although a genetic etiology had been initially proposed, the association between DSS and left ventricle (LV) geometrical abnormalities has provided more support to a hemodynamic etiology by which congenital or post-surgical LVOT geometric derangements could generate abnormal shear forces on the septal wall, triggering in turn a fibrotic response. Validating this hypothetical etiology and understanding the mechanobiological processes by which altered shear forces induce fibrosis in the LVOT are major knowledge gaps. This perspective paper describes the current state of knowledge of DSS, articulates the research needs to yield mechanistic insights into a significant pathologic process that is poorly understood, and proposes several strategies aimed at elucidating the potential mechanobiological synergies responsible for DSS pathogenesis. The proposed roadmap has the potential to improve DSS management by identifying early targets for prevention of the fibrotic lesion, and may also prove beneficial in other fibrotic cardiovascular diseases associated with altered flow. |
format | Online Article Text |
id | pubmed-6166095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61660952018-10-12 Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease Massé, Danielle D. Shar, Jason A. Brown, Kathleen N. Keswani, Sundeep G. Grande-Allen, K. Jane Sucosky, Philippe Front Cardiovasc Med Cardiovascular Medicine Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue, causing an increased pressure gradient in the left ventricular outflow tract (LVOT). While surgical resection of the membrane has shown some success in eliminating the obstruction, it poses significant risks associated with anesthesia, sternotomy, and heart bypass, and it remains associated with a high rate of recurrence. Although a genetic etiology had been initially proposed, the association between DSS and left ventricle (LV) geometrical abnormalities has provided more support to a hemodynamic etiology by which congenital or post-surgical LVOT geometric derangements could generate abnormal shear forces on the septal wall, triggering in turn a fibrotic response. Validating this hypothetical etiology and understanding the mechanobiological processes by which altered shear forces induce fibrosis in the LVOT are major knowledge gaps. This perspective paper describes the current state of knowledge of DSS, articulates the research needs to yield mechanistic insights into a significant pathologic process that is poorly understood, and proposes several strategies aimed at elucidating the potential mechanobiological synergies responsible for DSS pathogenesis. The proposed roadmap has the potential to improve DSS management by identifying early targets for prevention of the fibrotic lesion, and may also prove beneficial in other fibrotic cardiovascular diseases associated with altered flow. Frontiers Media S.A. 2018-09-13 /pmc/articles/PMC6166095/ /pubmed/30320123 http://dx.doi.org/10.3389/fcvm.2018.00122 Text en Copyright © 2018 Massé, Shar, Brown, Keswani, Grande-Allen and Sucosky. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Massé, Danielle D. Shar, Jason A. Brown, Kathleen N. Keswani, Sundeep G. Grande-Allen, K. Jane Sucosky, Philippe Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease |
title | Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease |
title_full | Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease |
title_fullStr | Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease |
title_full_unstemmed | Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease |
title_short | Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease |
title_sort | discrete subaortic stenosis: perspective roadmap to a complex disease |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166095/ https://www.ncbi.nlm.nih.gov/pubmed/30320123 http://dx.doi.org/10.3389/fcvm.2018.00122 |
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