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Coronary Microvascular DysfunctionNCT03876223

Women's Ischemia Syndrome Evaluation (WISE) Pre-HFpEF

An observational study of Coronary Microvascular Dysfunction and Heart Failure With Preserved Ejection Fraction (HFpEF), run by Cedars-Sinai Medical Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to examine small vessel disease (a condition in which the small arteries in the heart become narrowed). The investigators want to know how the small vessel disease contributes to pre-HFpEF (a condition with inadequate heart muscle function in the setting of preserved muscle pumping) and to… Read more about this study

Who is it for?
Ages 18 years and older
How many people
180 participants
Where
2 sitesUnited States
Study dates
24 Jul 2019to 28 Feb 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Men and women undergoing invasive coronary angiography for suspected ischemia with no obstructive CAD, defined as ≥ 50% luminal diameter stenosis in ≥ 1 epicardial coronary artery.

Who may be able to join

  • 180 symptomatic men and women undergoing invasive coronary angiography for suspected ischemia with no obstructive CAD, defined as ≥50% luminal diameter stenosis in ≥1 epicardial coronary artery.
  • Preserved left ventricular ejection fraction (EF) ≥45%
  • Be > 18 years old
  • Be able to meet the requirement for a cardiac MRI, which means no metal devices in your chest, no claustrophobia and no angioedema
  • Be competent to give informed consent

Who cannot join

  • Subjects with severe or chronic kidney disease (CKD) with GFR<405 or acute kidney injury
  • Subjects with allergy to animal dander will be excluded since imaging will be done in BIRI (BIRI scanners are also used to image animals).
  • Subjects who have had four or more prior previous gadolinium contrast scans
  • Allergy/ hypersensitivity to adenosine, gadolinium, aminophylline or regadenoson
  • Second- or third-degree A-V block
  • Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker)
  • Subjects with mild to severe asthma

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

BSWHC Research contact

310-423-9666

BSWHC.Research@cshs.org

Fatima Bataz contact

3102487888

fatima.bataz@cshs.org

United States2 sites, 2 recruiting

  • University of Florida

    Gainesville, Florida, 32610

    Eileen Handberg, PhD

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    C. Noel Bairey Merz, MD, 3102486960, noel.baireymerz@cshs.org

    Recruiting

Other trials in United States

About this study

Official title: Women's Ischemia Syndrome Evaluation (WISE) Mechanisms of Coronary Microvascular Dysfunction Leading to Pre-Heart Failure With Preserved Ejection Fraction (HFpEF)

The purpose of this study is to examine small vessel disease (a condition in which the small arteries in the heart become narrowed). The investigators want to know how the small vessel disease contributes to pre-HFpEF (a condition with inadequate heart muscle function in the setting of preserved muscle pumping) and to better identify potential treatment for prevention of HFpEF. The main procedures of this study include up to 2 clinic visits (initial visit and a second clinical visit only if participants are unable to complete all research procedures at the initial visit); a 6-week phone interview visit, 4 quarterly follow-up phone interview visits in year 1; year 1 follow up cardiac MRI based on availability and ongoing annual follow-up phone interview visits to track progress. If participants choose to take part in this study, participants direct participation will end after 1 year, participants will then have the option of participating in ongoing annual check-in calls. Participants will be asked to undergo a physical exam and provide a completed medical history; complete a Cardiovascular (or Cardiac) Magnetic Resonance Imaging (CMRI) with contrast agent; complete questionnaires to describe heart symptoms and overall quality of life status; undergo blood draws to provide blood samples for research testing, and allow the study team to have access to medical records.

Read the detailed description

Coronary microvascular dysfunction (CMD) due to changes in the function and structure of coronary microcirculation in the absence of obstructive coronary artery disease (CAD) is poorly understood. Ischemia with no obstructive CAD (INOCA) and myocardial infarction with no obstructive CAD (MINOCA) are increasingly observed in women and men.

Once established, the investigators will be well positioned to aggressively target identified mechanistic targets in a specific well-characterized at-risk population, with the primary goal of preventing progression to HFpEF.

To address this novel hypothesis, the investigators propose the following Specific Aims:

Aim 1: Test the hypothesis that CMD-related ischemia contributes to myocellular damage and impaired ventricular relaxation. CMD will be measured directly, using our established intracoronary pharmacological vasoactive protocol, in subjects with signs/symptoms of ischemia but no obstructive CAD. In our labs (>420 patients), ~60% of those tested have evidence for CMD. All subjects will perform provocative stress testing with isometric handgrip - chosen for its unique ability to increase myocardial afterload and myocardial oxygen demand - while myocardial ischemia will be assessed directly through invasive simultaneous arterial and coronary sinus/great cardiac vein oxygen tension and lactate measurements, and continuous ECG's recordings. Left ventricular function will be directly assessed using Millar-catheter LV pressure-volume loops (perfected in our lab over the past 24 months). Stress-induced myocellular damage will be directly measured by coronary sinus/great cardiac vein hs-cTnI.

Aim 2: Test the hypothesis that CMD-related ischemic myocellular damage contributes to LV diastolic dysfunction progression. Subjects from Aim 1 will also undergo comprehensive cardiac magnetic resonance imaging (CMRI) at enrollment and 1-2 years later. The investigators will evaluate CMRI LV perfusion, myocardial scar, diffuse fibrosis, LV remodeling, and diastolic function. The investigatorswill leverage the strengths and resources of our world-renowned proteomics core to establish evidence of chronic myocellular damage using prospectively repeated ambulatory hs-cTnI determinations.

Keywords
Coronary Microvascular Dysfunction (CMD), Coronary Vascular Dysfunction (CVD), Coronary angiography, Magnetic resonance imaging (MRI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CMR imaging

    Change from Baseline at 1 year follow up will be assessed.

    Measured: Baseline, Annual follow up

  2. Rest-stress Millar pressure-volume measurement

    LV diastolic function will be measured using LV end-diastolic pressure, minimal rate of LV pressure change (dP/dtmin).

    Measured: Baseline

Secondary outcomes (4)

  1. Questionnaire

    Symptom History Questionnaire. Change from Baseline at each visit will be measure. There is no scale ranges for this questionnaire. This questionnaire results in raw data that is not calculated into a score or scale.

    Measured: Baseline, 6 week, quarterly(year 1) and annual follow up

  2. Questionnaire WISE Symptoms History

    Detailed information on chest pain symptoms will include the WISE female angina questionnaire.

    Change from Baseline at each visit will be measure. There is no scale ranges for this questionnaire. This questionnaire results in raw data that is not calculated into a score or scale.

    Measured: Baseline, quarterly(year 1) and annual follow up

  3. SEATTLE ANGINA QUESTIONNAIRE

    The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life.

    Each scale is transformed to a score of 0 to 100. A higher score means better control of chest pain, chest tightness, angina, or shortness of breath.

    Change from Baseline at each visits will be measure.

    Measured: Baseline, 6 week and annual follow up

  4. Duke Activity Status Inventory (DASI)

    It is a self-administered questionnaire that measures a patient's functional capacity.

    Change from Baseline at each visit will be measure. Maximum response is a total of 16.7 while minimum is 0.

    Measured: Baseline, 6 week and annual follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2019
  2. Study start24 Jul 2019
  3. Primary completion28 Feb 2027 (estimated)
  4. Study completion28 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
180 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03876223
Sponsor's protocol ID
54999
Status last verified
Aug 2026
First submitted
22 Feb 2019
Last updated
26 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Has Silemek AC, Wertheimer JC, Wei J, Xie Y, Gonzales M, Li D, Dumitrascu O, Kremen S, Tan ZS, Nelson MD, Bairey Merz CN, Sati P, Gao W. The "Brain's Traffic Map" Reveals Neural Pathways Linked to Coronary Microvascular Dysfunction in Women. Brain Behav. 2026 Jun;16(6):e71559. doi: 10.1002/brb3.71559.

    PubMed 42348298

  • Takahashi T, Wei J, Iribarren AC, Gulati M, Cook-Wiens G, Nelson MD, Sharif B, Handberg EM, Anderson RD, Petersen J, Berman DS, Pepine CJ, Merz CNB. Rationale and design of the women's ischemia syndrome evaluation mechanisms of coronary microvascular dysfunction leading to preheart failure with preserved ejection fraction (WISE Pre-HFPEF). Am Heart J. 2025 Jun;284:47-56. doi: 10.1016/j.ahj.2025.02.017. Epub 2025 Feb 24.

    PubMed 40010584

Questions about this trial

What is this clinical trial studying?

An observational study of Coronary Microvascular Dysfunction and Heart Failure With Preserved Ejection Fraction (HFpEF), run by Cedars-Sinai Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact BSWHC Research (310-423-9666, BSWHC.Research@cshs.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CMR imaging (time frame: Baseline, Annual follow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03876223, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

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