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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...

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Autores principales: Massé, Danielle D., Shar, Jason A., Brown, Kathleen N., Keswani, Sundeep G., Grande-Allen, K. Jane, Sucosky, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
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.
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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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