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

Abstract 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...

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Main Authors: Michael D. Nelson, Puja K. Mehta, Janet Wei, Behzad Sharif, Louise E. J. Thomson, Daniel Berman, Debiao Li, C. Noel Bairey Merz
Format: Article
Language:English
Published: BMC 2017-05-01
Series:Journal of Medical Case Reports
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13256-017-1307-2
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author Michael D. Nelson
Puja K. Mehta
Janet Wei
Behzad Sharif
Louise E. J. Thomson
Daniel Berman
Debiao Li
C. Noel Bairey Merz
author_facet Michael D. Nelson
Puja K. Mehta
Janet Wei
Behzad Sharif
Louise E. J. Thomson
Daniel Berman
Debiao Li
C. Noel Bairey Merz
author_sort Michael D. Nelson
collection DOAJ
description Abstract 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 Results A total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment.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 doaj.art-37f3248bb31a4949a507755347b736d72022-12-21T18:52:23ZengBMCJournal of Medical Case Reports1752-19472017-05-011111410.1186/s13256-017-1307-2Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery diseaseMichael D. Nelson0Puja K. Mehta1Janet Wei2Behzad Sharif3Louise E. J. Thomson4Daniel Berman5Debiao Li6C. Noel Bairey Merz7Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart InstituteBarbra Streisand Women’s Heart Center, Cedars-Sinai Heart InstituteBarbra Streisand Women’s Heart Center, Cedars-Sinai Heart InstituteBiomedical Imaging Research Institute, Cedars-Sinai Medical CenterS. Mark Taper Foundation Imaging Center, Cedars-Sinai Medical CenterS. Mark Taper Foundation Imaging Center, Cedars-Sinai Medical CenterBiomedical Imaging Research Institute, Cedars-Sinai Medical CenterBarbra Streisand Women’s Heart Center, Cedars-Sinai Heart InstituteAbstract 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.http://link.springer.com/article/10.1186/s13256-017-1307-2Women’s ischemic syndromeCoronary microvascular dysfunctionDiastolic dysfunctionMyocardial perfusion reserve indexPhosphodiesterase type 5 inhibition
spellingShingle Michael D. Nelson
Puja K. Mehta
Janet Wei
Behzad Sharif
Louise E. J. Thomson
Daniel Berman
Debiao Li
C. Noel Bairey Merz
Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease
Journal of Medical Case Reports
Women’s ischemic syndrome
Coronary microvascular dysfunction
Diastolic dysfunction
Myocardial perfusion reserve index
Phosphodiesterase type 5 inhibition
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 Women’s ischemic syndrome
Coronary microvascular dysfunction
Diastolic dysfunction
Myocardial perfusion reserve index
Phosphodiesterase type 5 inhibition
url http://link.springer.com/article/10.1186/s13256-017-1307-2
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