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Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease

BACKGROUND: Ischemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our gene...

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Autores principales: Nelson, Michael D., Mehta, Puja K., Wei, Janet, Sharif, Behzad, Thomson, Louise E. J., Berman, Daniel, Li, Debiao, Merz, C. Noel Bairey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439128/
https://www.ncbi.nlm.nih.gov/pubmed/28528579
http://dx.doi.org/10.1186/s13256-017-1307-2
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author Nelson, Michael D.
Mehta, Puja K.
Wei, Janet
Sharif, Behzad
Thomson, Louise E. J.
Berman, Daniel
Li, Debiao
Merz, C. Noel Bairey
author_facet Nelson, Michael D.
Mehta, Puja K.
Wei, Janet
Sharif, Behzad
Thomson, Louise E. J.
Berman, Daniel
Li, Debiao
Merz, C. Noel Bairey
author_sort Nelson, Michael D.
collection PubMed
description BACKGROUND: Ischemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our general understanding, however, optimal treatment of this cohort remains elusive. METHODS: To address this knowledge gap, we performed an open-label treatment trial to assess whether phosphodiesterase type 5 inhibition improves coronary microvascular perfusion and diastolic function in women with signs and symptoms of ischemia but no evidence of obstructive coronary artery disease. Left ventricular morphology and function, along with myocardial perfusion reserve index, were assessed by contrast-enhanced cardiac magnetic resonance imaging. RESULTS: A total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment. Her symptoms resolved after cessation of the study medication. In contrast to our hypothesis, phosphodiesterase type 5 inhibition reduced the rate of circumferential strain in diastole in all four women who completed the trial (that is, diastolic dysfunction). This impairment could not be explained by changes in heart rate, contractility, blood pressure, or preload, and was not associated with a change in myocardial perfusion reserve index. Frequency of angina also tended to increase with treatment, with the greatest increase occurring in the patient with the greatest impairment in diastolic strain. CONCLUSIONS: Taken together, these data question the efficacy of phosphodiesterase type 5 inhibition to treat women with ischemic heart disease, and highlight the need for further investigation.
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spelling pubmed-54391282017-05-23 Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease Nelson, Michael D. Mehta, Puja K. Wei, Janet Sharif, Behzad Thomson, Louise E. J. Berman, Daniel Li, Debiao Merz, C. Noel Bairey J Med Case Rep Research Article BACKGROUND: Ischemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our general understanding, however, optimal treatment of this cohort remains elusive. METHODS: To address this knowledge gap, we performed an open-label treatment trial to assess whether phosphodiesterase type 5 inhibition improves coronary microvascular perfusion and diastolic function in women with signs and symptoms of ischemia but no evidence of obstructive coronary artery disease. Left ventricular morphology and function, along with myocardial perfusion reserve index, were assessed by contrast-enhanced cardiac magnetic resonance imaging. RESULTS: A total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment. Her symptoms resolved after cessation of the study medication. In contrast to our hypothesis, phosphodiesterase type 5 inhibition reduced the rate of circumferential strain in diastole in all four women who completed the trial (that is, diastolic dysfunction). This impairment could not be explained by changes in heart rate, contractility, blood pressure, or preload, and was not associated with a change in myocardial perfusion reserve index. Frequency of angina also tended to increase with treatment, with the greatest increase occurring in the patient with the greatest impairment in diastolic strain. CONCLUSIONS: Taken together, these data question the efficacy of phosphodiesterase type 5 inhibition to treat women with ischemic heart disease, and highlight the need for further investigation. BioMed Central 2017-05-22 /pmc/articles/PMC5439128/ /pubmed/28528579 http://dx.doi.org/10.1186/s13256-017-1307-2 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Nelson, Michael D.
Mehta, Puja K.
Wei, Janet
Sharif, Behzad
Thomson, Louise E. J.
Berman, Daniel
Li, Debiao
Merz, C. Noel Bairey
Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
title Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
title_full Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
title_fullStr Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
title_full_unstemmed Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
title_short Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
title_sort phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439128/
https://www.ncbi.nlm.nih.gov/pubmed/28528579
http://dx.doi.org/10.1186/s13256-017-1307-2
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