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

Michael D Nelson,Debiao Li,C Noel Bairey Merz,Louise E J Thomson,Daniel Berman,Puja K Mehta,Behzad Sharif,Janet Wei

doi:10.1186/s13256-017-1307-2

Abstract

BackgroundIschemia, 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.MethodsTo 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magnetic resonance imaging.ResultsA total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment.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.ConclusionsTaken 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.

Highlights

Ischemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events
Sex-specific research initiatives, including the Women’s Ischemia Syndrome Evaluation (WISE) study sponsored by the National Heart, Lung, and Blood Institute (NHLBI), have established coronary microvascular dysfunction (CMD) and diastolic dysfunction as important etiologic features of this disease [2, 3]
We sought to determine whether PDE5 inhibition improves CMD-related perfusion and diastolic function in women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD)

Summary

Introduction

In the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. In the absence of obstructive coronary artery disease (CAD), is prevalent in women, and associated with increased risk for major cardiovascular events, including myocardial infarction, stroke, heart failure, and sudden cardiac death [1]. Sex-specific research initiatives, including the Women’s Ischemia Syndrome Evaluation (WISE) study sponsored by the National Heart, Lung, and Blood Institute (NHLBI), have established coronary microvascular dysfunction (CMD) and diastolic dysfunction as important etiologic features of this disease [2, 3]. Despite these advancements, effective treatment remains elusive [4]. We sought to determine whether PDE5 inhibition improves CMD-related perfusion and diastolic function in women with signs and symptoms of ischemia but no obstructive CAD

Methods

Results

Conclusion