Microvascular Coronary DysfunctionNCT02582021
WISE CVD - Continuation (WISE HFpEF)
An observational study of Microvascular Coronary Dysfunction and Cardiovascular Disease, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
The Women's Ischemia Study Evaluation (WISE), a cohort study of over 1000 women, has made many contributions to the understanding of cardiovascular disease. A milestone acknowledged in the 2011 AHA Herrick Lecture is the role of Coronary Microvascular Dysfunction (CMD) in women with symptoms/signs of ischemia without… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Microvascular Coronary Dysfunction, Cardiovascular Disease
- What is being tested?
- Coronary Angiography, Coronary Reactivity Testing and Cardiac Magnetic Resonance Imaging
- Type of treatment
- Surgery or procedure
- How many people
- 220 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Feb 2030
- 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: A group of symptomatic women undergoing coronary angiography (n=120) for suspected ischemia and no obstructive CAD, defined as ≥50% luminal diameter stenosis in ≥1 epicardial artery, will be recruited. A group of women and men hospitalized for HFpEF, defined by the ESC criteria (n=100) who have not yet undergone coronary angiography will also be recruited for the study.
Who may be able to join
- For the new cohort n=120 women undergoing coronary angiography:
- Symptomatic angina or anginal equivalent
- Age ≥ 18
- Participant is willing to give written informed consent
- For the cohort n=100 women and men hospitalized for HFpEF (defined by ESC guidelines):
- Age ≥ 18
Show all 11Show fewer
- Signs and symptoms of heart failure
- Preserved ejection fraction, left ventricular ejection fraction (LVEF) ≥45% prior to study entry.
- Structural evidence of cardiovascular abnormalities: elevated brain naturetic peptide, evidence of abnormal filling or relaxation, left ventricular hypertrophy, or an increased left atrial size
- Evidence of elevated filling pressures: LVEDP or PCWP at rest > 15 mmHg and/or with exercise ≥25 mmHg, exercise E/e' >13, elevated BNP, or use of diuretic
- Participant is willing to give written informed consent
Who cannot join
- For the new cohort n=120 women undergoing invasive coronary angiography:
- Obstructive CAD ≥ 50% luminal diameter stenosis in ≥ 1 epicardial coronary artery
- STEMI within 3-7 days post MI, or Acute coronary syndrome/NSTEMI with with symptoms or signs of acute myocardial ischemia within the last 12 to 24 hours prior to the research procedure, as outlined in ACC/AHA guidelines.
- Primary valvular heart disease clearly indicating the need for valve repair or replacement
- Patients with concurrent cardiogenic shock or requiring inotropic or intra-aortic balloon support or LVEF<45%
- Prior or planned percutaneous coronary intervention or coronary artery bypass grafting for obstructive coronary atherosclerosis
Show all 28Show fewer
- Non-cardiac illness with a life expectancy < four years
- Unable to give informed consent
- Chest pain which has an alternative non-ischemic etiology, i.e. pericarditis, pulmonary embolism, pleurisy, pneumonia, esophageal spasm, etc.
- Contraindications to CMRI, such as internal cardiac defibrillator, untreatable claustrophobia or known angioedema
- Contraindications to adenosine or regadenoson including severe COPD and asthma
- End stage renal or liver disease
- Women with intermediate coronary stenoses (>20% but <50% luminal diameter stenosis assessed visually at the time of angiography) will undergo clinically indicated fractional flow reserve (FFR) based on the judgment of the operator; those determined to have flow-obstructing stenosis will be excluded.
- Documented allergy to gadolinium
- For the new cohort n=100 women and men hospitalized for HFpEF:
- Current LVEF <45%
- STEMI within 3-7 days post MI, or Acute coronary syndrome/NSTEMI with with symptoms or signs of acute myocardial ischemia within the last 12 to 24 hours prior to the research procedure, as outlined in ACC/AHA guidelines.
- Acute coronary syndrome (defined by ACC/AHA guidelines, including MI) within 3 months of entry. Patients who have had an MI or other event within the 6 months prior to entry unless an echo measurement performed after the event confirms a LVEF ≥45%.
- Primary valvular heart disease (moderate regurgitation or>mild stenosis), primary cardiomyopathies (hypertrophic, infiltrative or restrictive), constrictive pericarditis, high-output heart failure, and right ventricular myopathies)
- Patients with concurrent cardiogenic shock or requiring inotropic or intra-aortic balloon support or current acute decompensated HF requiring therapy including due to trauma, infection.
- Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dl, or body mass index (BMI) > 40 kg/m2.
- Systolic blood pressure (SBP) ≥ 180 mmHg at entry, or SBP >150 mmHg and <180 mmHg at entry unless the patient is receiving 3 or more antihypertensive drugs.
- Prior or planned percutaneous coronary intervention or coronary artery bypass grafting for obstructive coronary atherosclerosis
- Non-cardiac illness with a life expectancy < four years
- Unable to give informed consent
- Contraindications to CMRI, such as internal cardiac defibrillator, untreatable claustrophobia or known angioedema
- Contraindications to adenosine or regadenoson including severe COPD and asthma.
- Obstructive stenoses (≥50% luminal diameter stenosis assessed visually at the time of research CTA) will be excluded from further analyses. Subjects with obstructive or borderline obstructive coronary CTA stenoses will be referred to their clinicians for further clinical care and clinical decision making. End stage renal or liver disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cedars-Sinai Women's Heart Center
Los Angeles, California, 90048
BSWHC Research, 310-423-9666, bswhc.research@cshs.org
Fatima Bataz, 3102487888, fatima.bataz@cshs.org
About this study
Official title: Women's Ischemia Syndrome Evaluation (WISE) - Coronary Microvascular Dysfunction (CMD) and Heart Failure With Preserved Ejection Fraction (HFpEF)
The Women's Ischemia Study Evaluation (WISE), a cohort study of over 1000 women, has made many contributions to the understanding of cardiovascular disease. A milestone acknowledged in the 2011 AHA Herrick Lecture is the role of Coronary Microvascular Dysfunction (CMD) in women with symptoms/signs of ischemia without obstructive coronary artery disease (CAD). While in 1996, CMD was considered "an imaging artifact", in 2013, it is a widely accepted as a pathophysiologic process requiring systematic cohesive scientific pursuit. CMD is prevalent, associated with adverse clinical outcomes, poor quality of life and healthcare costs rivaling obstructive CAD. There are 2-3 million US women with CMD, and 100,000 new cases projected annually placing CMD prevalence, morbidity and costs higher than all female reproductive cancers combined.
Among women with ischemia, preserved ejection fraction and no obstructive CAD, it has been observed that there are relatively more new onset heart failure (HF) hospitalizations than nonfatal myocardial infarction (MI). It has been hypothesized that CMD contributes to left ventricular (LV) diastolic dysfunction and subsequent heart failure with preserved ejection fraction (HFpEF). Preliminary data further suggests that left ventricular diastolic dysfunction is linked to CMD via a mechanism of augmentation and/or perpetuation by cardiomyocyte fat accumulation. HFpEF is prevalent in women and older men, but poorly understood. Mechanistic understanding is critical to HFpEF intervention and guideline development.
Read more
The study hypotheses are as follows:
- Risk factor conditions (hypertension, dyslipidemia, dysglycemia, loss of estrogen) promote an inflammatory and pro-oxidative state making the microvasculature vulnerable;
- Vulnerable coronary microvasculature becomes dysregulated (sympathetic nervous system activation, endothelial dysfunction, changes in vascular smooth muscle activation, spasm) causing repeated episodes of transient ischemia;
- Repeated ischemia-reperfusion episodes facilitate preconditioning with preservation of cardiomyocyte contractile and microvascular function against ischemic injury;
- Ischemia-reperfusion and preconditioning lead to cardiomyocyte fat accumulation and relaxation impairment resulting in diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF).
Read the detailed description
The current application will study new cohorts of women and men with the following specific aims:
Specific Aim 1: LV diastolic dysfunction is linked to CMD. Sub-Aim 1: LV diastolic dysfunction and CMD are linked via the mechanism of cardiomyocyte fat accumulation.
Specific Aim 2: Comprehensive noninvasive Cardiac Magnetic Resonance Imaging (CMRI) that includes LV diastolic function is linked with invasive measures of LV diastolic function and can optimize diagnosis of CMD.
Sub-Aim 2: Coronary Magnetic Resonance Angiography (CMRA) can exclude obstructive CAD in CMD.
Specific Aim 3: Add completely de-identified data sharing to prepare for future large precision medicine research and to advance precision medicine initiative.
Exploratory Aim: Blood proteomic and metabolomics biomarkers of extracellular matrix remodeling and fibrosis combined with ischemia measures will predict HFpEF.
In this prospective, cohort design study, investigators intend to enroll 220 new subjects including 120 symptomatic women undergoing invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease (CAD) defined as ≥50% luminal diameter stenosis in ≥1 epicardial coronary artery and 100 women and men hospitalized for Heart Failure with preserved Ejection Fraction (HFpEF) defined by the European Society of Cardiology (ESC) criteria who have not yet undergone coronary angiography.
New and existing samples and longer term follow-up will be analyzed in an exploratory fashion looking for potential HFpEF biomarkers for pilot data purposes.
After baseline evaluation, the n=120 cohort will undergo noninvasive high resolution, comprehensive CMRI imaging, invasive angiography, coronary reactivity testing and rest-stress Millar pressure-volume measurement. Handgrip, mild leg exercise, and brief Valsalva Maneuver will be conducted during CMRI and Millar pressure-volume assessment to characterize cardiac response to stress. Lastly, these patients will also undergo MR Coronary Angiography, for validation purposes against gold-standard angiography.
The cohort of 100 women and men with HFpEF admitted to the hospital who have not yet undergone coronary angiography will also undergo CMRI (with stress), including MR coronary angiography (CMRA) and noninvasive computed coronary tomographic angiography (CCTA)(CSMC only).
This will provide understanding of a non-cath-lab based population regarding links between CMD, diastolic function and HFpEF, and will result in data to test the hypothesis that coronary MRA can exclude obstructive CAD and diagnose CMD without ionizing radiation. Proteomic and metabolomics biomarker assays in the (n=567) subjects with no obstructive CAD (Exploratory Aim) will be performed.
- Being tested
- Coronary Angiography, Coronary Reactivity Testing, Cardiac Magnetic Resonance Imaging, Cardiac Magnetic Resonance Angiography, Computed Coronary Tomographic Angiography
- Keywords
- Microvascular Coronary Dysfunction (MCD), Magnetic resonance imaging (MRI), Coronary angiography, Coronary Vascular Dysfunction (CVD)
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coronary AngiographyProcedure or surgery
A coronary angiogram is a procedure that uses x-ray imaging to see the heart's blood vessels; it is a part of Heart (cardiac) catheterization procedure. During a coronary angiogram, a type of dye that's visible by an x-ray machine is injected into the blood vessels of the heart. The x-ray machine rapidly takes a series of images (angiograms).
The Coronary Reactivity test (CRT), heart pressure (Millar) evaluation, and Millar stress testing are performed during the coronary angiography.
Coronary Reactivity TestingProcedure or surgery
Also called CRT
An angiography procedure specifically designed to examine the blood vessels in the heart and how they respond to different medications.
Cardiac Magnetic Resonance ImagingProcedure or surgery
Also called CMRI
Noninvasive high resolution imaging test; Optimized magnetic resonance imaging technique for use in the cardiovascular system - use of ECG gating and rapid imaging sequences.
Handgrip, mild leg exercise, and brief Valsalva Maneuver will be conducted to characterize cardiac response to stress. The CMRA is performed as part of the CMRI.
Cardiac Magnetic Resonance AngiographyProcedure or surgery
Also called CMRA
Test for validation purposes against gold-standard Angiography. CMRA is a part of the CMRI test. The residual contrast (gadolinium) circulating in the blood stream (following the CMRI prior images) is sufficient for CMRA evaluation.
Computed Coronary Tomographic AngiographyProcedure or surgery
Also called CCTA
Noninvasive, imaging method that uses a computed tomography (CT) scanner to look at the structures and blood vessels of the heart.
Rest-Stress Millar TestingProcedure or surgery
Handgrip, mild leg exercise, and brief Valsalva Maneuver will be conducted to characterize cardiac response to stress. They are designed to test how your heart muscle is functioning.
Rest-stress Millar testing is performed during the coronary angiography and Cardiac Magnetic Resonance Imaging.
Aortic vasorelaxation testsProcedure or surgery
Also called Aortic pulse wave velocity-Pulse wave analysis
Non-invasive clinical test. Repeat blood pressure and heart rate per minute will be read for three times; Your pulse wave velocity, pulse wave analysis and central pressure measurements will be recorded.
| Study group | Role | What they receive |
|---|---|---|
| Women | Women undergoing clinically-ordered coronary angiography for signs and symptoms of ischemia who have no obstructive coronary artery disease (CAD) Receives: Procedure: Coronary Angiography; Procedure: Coronary Reactivity Testing; Procedure: Cardiac Magnetic Resonance Imaging; Procedure: Cardiac Magnetic Resonance Angiography; Procedure: Rest-Stress Millar Testing; Procedure: Aortic vasorelaxation tests | |
| Women or men | Women and men hospitalized for signs and symptoms of ischemia and evidence of Heart Failure with preserved ejection fraction (HFpEF) who have not undergone a clinically-ordered coronary angiography Receives: Procedure: Cardiac Magnetic Resonance Imaging; Procedure: Cardiac Magnetic Resonance Angiography; Procedure: Computed Coronary Tomographic Angiography; Procedure: Rest-Stress Millar Testing; Procedure: Aortic vasorelaxation tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiovascular (CV) events
Measured: up to 30 years
Secondary outcomes (4)
Persistent Chest Pain Symptoms: SAQ
Detailed information on chest pain symptoms will include the traditional angina questionnaire. Two SAQ scales measure chest pain: Anginal Stability is a measure of whether a patient's symptoms are changing over time and Anginal Frequency is a measure of how often a patient is having symptoms now.
Measured: up to 30 years
Persistent Chest Pain Symptoms: WISE female angina Questionnaire
Detailed information on chest pain symptoms will include the WISE female angina questionnaire.
Measured: Up to 30 years
Quality of Life Outcomes: SAQ
Quality of life and functional capacity will be collected using the standard instruments of Seattle Angina Questionnaire (SAQ). SAQ scale Quality of Life is a measure of the overall impact of a patient's condition on a patient's interpersonal relationships and state of mind.
Measured: up to 30 years
Quality of Life Outcomes: DASI
Quality of life and functional capacity will be collected using the standard instruments of Duke Activity Status Index for Cardiovascular Diseases (DASI). It is a self-administered questionnaire that measures a patient's functional capacity.
Measured: up to 30 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2015 (estimated)
- Study startOct 2015
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Microvascular Coronary DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Noel Bairey Merz, Cedars-Sinai Medical Center
- Investigators
- C. Noel Bairey Merz, MD, FACC, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02582021
- Sponsor's protocol ID
- Pro00037321
- Status last verified
- Aug 2026
- First submitted
- 5 Oct 2015
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Nelson MD, Gomez-Arnold JM, Wei J, Lauzon M, Zamani SK, Maughan J, Obrutu O, Shufelt C, Handberg E, Pepine C, Bairey Merz CN. Contributors to high left ventricular ejection fraction in women with ischemia and no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) Study. Am Heart J. 2024 Dec;278:41-47. doi: 10.1016/j.ahj.2024.08.021. Epub 2024 Sep 2.
PubMed 39233211Ya'Qoub L, Elgendy IY, Pepine CJ. Non-obstructive Plaque and Treatment of INOCA: More to Be Learned. Curr Atheroscler Rep. 2022 Sep;24(9):681-687. doi: 10.1007/s11883-022-01044-4. Epub 2022 Jul 4.
PubMed 35781776Quesada O, Hermel M, Suppogu N, Aldiwani H, Shufelt C, Mehta PK, Cook-Wiens G, Maughan J, Berman DS, Thomson LEJ, Handberg EM, Pepine CJ, Bairey Merz CN, Wei J. Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1-Year Follow-Up: Results From WISE-CVD. J Am Heart Assoc. 2020 Jul 7;9(13):e016305. doi: 10.1161/JAHA.119.016305. Epub 2020 Jun 24.
PubMed 32578481Joung S, Wei J, Nelson MD, Aldiwani H, Shufelt C, Tamarappoo B, Berman D, Thomson LEJ, Bairey Merz CN. Progression of coronary microvascular dysfunction to heart failure with preserved ejection fraction: a case report. J Med Case Rep. 2019 May 6;13(1):134. doi: 10.1186/s13256-019-2074-z.
PubMed 31056078
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Women's Ischemia Syndrome Evaluation (WISE) - Coronary Microvascular Dysfunction (CMD) and Heart Failure With Preserved Ejection Fraction (HFpEF)
- ClinicalTrials.gov ID
- NCT02582021
- Acronym / sponsor ID
- Pro00037321
- Keywords
- Microvascular Coronary Dysfunction (MCD), Magnetic resonance imaging (MRI), Coronary angiography, Coronary Vascular Dysfunction (CVD)
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 21 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Women's Ischemia Study Evaluation (WISE), a cohort study of over 1000 women, has made many contributions to the understanding of cardiovascular disease. A milestone acknowledged in the 2011 AHA Herrick Lecture is the role of Coronary Microvascular Dysfunction (CMD) in women with symptoms/signs of ischemia without obstructive coronary artery disease (CAD). While in 1996, CMD was considered "an imaging artifact", in 2013, it is a widely accepted as a pathophysiologic process requiring systematic cohesive scientific pursuit. CMD is prevalent, associated with adverse clinical outcomes, poor quality of life and healthcare costs rivaling obstructive CAD. There are 2-3 million US women with CMD, and 100,000 new cases projected annually placing CMD prevalence, morbidity and costs higher than all female reproductive cancers combined.
Among women with ischemia, preserved ejection fraction and no obstructive CAD, it has been observed that there are relatively more new onset heart failure (HF) hospitalizations than nonfatal myocardial infarction (MI). It has been hypothesized that CMD contributes to left ventricular (LV) diastolic dysfunction and subsequent heart failure with preserved ejection fraction (HFpEF). Preliminary data further suggests that left ventricular diastolic dysfunction is linked to CMD via a mechanism of augmentation and/or perpetuation by cardiomyocyte fat accumulation. HFpEF is prevalent in women and older men, but poorly understood. Mechanistic understanding is critical to HFpEF intervention and guideline development.
The study hypotheses are as follows:
- Risk factor conditions (hypertension, dyslipidemia, dysglycemia, loss of estrogen) promote an inflammatory and pro-oxidative state making the microvasculature vulnerable;
- Vulnerable coronary microvasculature becomes dysregulated (sympathetic nervous system activation, endothelial dysfunction, changes in vascular smooth muscle activation, spasm) causing repeated episodes of transient ischemia;
- Repeated ischemia-reperfusion episodes facilitate preconditioning with preservation of cardiomyocyte contractile and microvascular function against ischemic injury;
- Ischemia-reperfusion and preconditioning lead to cardiomyocyte fat accumulation and relaxation impairment resulting in diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF).
Detailed description
The current application will study new cohorts of women and men with the following specific aims:
Specific Aim 1: LV diastolic dysfunction is linked to CMD. Sub-Aim 1: LV diastolic dysfunction and CMD are linked via the mechanism of cardiomyocyte fat accumulation.
Specific Aim 2: Comprehensive noninvasive Cardiac Magnetic Resonance Imaging (CMRI) that includes LV diastolic function is linked with invasive measures of LV diastolic function and can optimize diagnosis of CMD.
Sub-Aim 2: Coronary Magnetic Resonance Angiography (CMRA) can exclude obstructive CAD in CMD.
Specific Aim 3: Add completely de-identified data sharing to prepare for future large precision medicine research and to advance precision medicine initiative.
Exploratory Aim: Blood proteomic and metabolomics biomarkers of extracellular matrix remodeling and fibrosis combined with ischemia measures will predict HFpEF.
In this prospective, cohort design study, investigators intend to enroll 220 new subjects including 120 symptomatic women undergoing invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease (CAD) defined as ≥50% luminal diameter stenosis in ≥1 epicardial coronary artery and 100 women and men hospitalized for Heart Failure with preserved Ejection Fraction (HFpEF) defined by the European Society of Cardiology (ESC) criteria who have not yet undergone coronary angiography.
New and existing samples and longer term follow-up will be analyzed in an exploratory fashion looking for potential HFpEF biomarkers for pilot data purposes.
After baseline evaluation, the n=120 cohort will undergo noninvasive high resolution, comprehensive CMRI imaging, invasive angiography, coronary reactivity testing and rest-stress Millar pressure-volume measurement. Handgrip, mild leg exercise, and brief Valsalva Maneuver will be conducted during CMRI and Millar pressure-volume assessment to characterize cardiac response to stress. Lastly, these patients will also undergo MR Coronary Angiography, for validation purposes against gold-standard angiography.
The cohort of 100 women and men with HFpEF admitted to the hospital who have not yet undergone coronary angiography will also undergo CMRI (with stress), including MR coronary angiography (CMRA) and noninvasive computed coronary tomographic angiography (CCTA)(CSMC only).
This will provide understanding of a non-cath-lab based population regarding links between CMD, diastolic function and HFpEF, and will result in data to test the hypothesis that coronary MRA can exclude obstructive CAD and diagnose CMD without ionizing radiation. Proteomic and metabolomics biomarker assays in the (n=567) subjects with no obstructive CAD (Exploratory Aim) will be performed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women | – | Procedure: Coronary Angiography, Procedure: Coronary Reactivity Testing, Procedure: Cardiac Magnetic Resonance Imaging, Procedure: Cardiac Magnetic Resonance Angiography, Procedure: Rest-Stress Millar Testing, Procedure: Aortic vasorelaxation testsWomen undergoing clinically-ordered coronary angiography for signs and symptoms of ischemia who have no obstructive coronary artery disease (CAD) |
| Women or men | – | Procedure: Cardiac Magnetic Resonance Imaging, Procedure: Cardiac Magnetic Resonance Angiography, Procedure: Computed Coronary Tomographic Angiography, Procedure: Rest-Stress Millar Testing, Procedure: Aortic vasorelaxation testsWomen and men hospitalized for signs and symptoms of ischemia and evidence of Heart Failure with preserved ejection fraction (HFpEF) who have not undergone a clinically-ordered coronary angiography |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A group of symptomatic women undergoing coronary angiography (n=120) for suspected ischemia and no obstructive CAD, defined as ≥50% luminal diameter stenosis in ≥1 epicardial artery, will be recruited. A group of women and men hospitalized for HFpEF, defined by the ESC criteria (n=100) who have not yet undergone coronary angiography will also be recruited for the study.
Key inclusion criteria (11 listed)
- Symptomatic angina or anginal equivalent
- Age ≥ 18
- Participant is willing to give written informed consent
- Age ≥ 18
- Signs and symptoms of heart failure
Key exclusion criteria (28 listed)
- Obstructive CAD ≥ 50% luminal diameter stenosis in ≥ 1 epicardial coronary artery
- STEMI within 3-7 days post MI, or Acute coronary syndrome/NSTEMI with with symptoms or signs of acute myocardial ischemia within the last 12 to 24 hours prior to the research procedure, as outlined in ACC/AHA guidelines.
- Primary valvular heart disease clearly indicating the need for valve repair or replacement
- Patients with concurrent cardiogenic shock or requiring inotropic or intra-aortic balloon support or LVEF<45%
- Prior or planned percutaneous coronary intervention or coronary artery bypass grafting for obstructive coronary atherosclerosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coronary AngiographyA coronary angiogram is a procedure that uses x-ray imaging to see the heart's blood vessels; it is a part of Heart (cardiac) catheterization procedure. During a coronary angiogram, a type of dye that's visible by an x-ray machine is injected into the blood vessels of the heart. The x-ray machine rapidly takes a series of images (angiograms). The Coronary Reactivity test (CRT), heart pressure (Millar) evaluation, and Millar stress testing are performed during the coronary angiography. | Procedure or surgery | Women |
| Coronary Reactivity TestingAlso: CRTAn angiography procedure specifically designed to examine the blood vessels in the heart and how they respond to different medications. | Procedure or surgery | Women |
| Cardiac Magnetic Resonance ImagingAlso: CMRINoninvasive high resolution imaging test; Optimized magnetic resonance imaging technique for use in the cardiovascular system - use of ECG gating and rapid imaging sequences. Handgrip, mild leg exercise, and brief Valsalva Maneuver will be conducted to characterize cardiac response to stress. The CMRA is performed as part of the CMRI. | Procedure or surgery | Women, Women or men |
| Cardiac Magnetic Resonance AngiographyAlso: CMRATest for validation purposes against gold-standard Angiography. CMRA is a part of the CMRI test. The residual contrast (gadolinium) circulating in the blood stream (following the CMRI prior images) is sufficient for CMRA evaluation. | Procedure or surgery | Women, Women or men |
| Computed Coronary Tomographic AngiographyAlso: CCTANoninvasive, imaging method that uses a computed tomography (CT) scanner to look at the structures and blood vessels of the heart. | Procedure or surgery | Women or men |
| Rest-Stress Millar TestingHandgrip, mild leg exercise, and brief Valsalva Maneuver will be conducted to characterize cardiac response to stress. They are designed to test how your heart muscle is functioning. Rest-stress Millar testing is performed during the coronary angiography and Cardiac Magnetic Resonance Imaging. | Procedure or surgery | Women, Women or men |
| Aortic vasorelaxation testsAlso: Aortic pulse wave velocity-Pulse wave analysisNon-invasive clinical test. Repeat blood pressure and heart rate per minute will be read for three times; Your pulse wave velocity, pulse wave analysis and central pressure measurements will be recorded. | Procedure or surgery | Women, Women or men |
Primary outcome
Cardiovascular (CV) events
Time frame: up to 30 years
4 secondary outcomes
Persistent Chest Pain Symptoms: SAQ
Time frame: up to 30 years
Persistent Chest Pain Symptoms: WISE female angina Questionnaire
Time frame: Up to 30 years
Quality of Life Outcomes: SAQ
Time frame: up to 30 years
Quality of Life Outcomes: DASI
Time frame: up to 30 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Derived from this study: PubMed 39233211Nelson MD, Gomez-Arnold JM, Wei J, Lauzon M, Zamani SK, Maughan J, Obrutu O, Shufelt C, Handberg E, Pepine C, Bairey Merz CN. Contributors to high left ventricular ejection fraction in women with ischemia and no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) Study. Am Heart J. 2024 Dec;278:41-47. doi: 10.1016/j.ahj.2024.08.021. Epub 2024 Sep 2.
- Derived from this study: PubMed 35781776Ya'Qoub L, Elgendy IY, Pepine CJ. Non-obstructive Plaque and Treatment of INOCA: More to Be Learned. Curr Atheroscler Rep. 2022 Sep;24(9):681-687. doi: 10.1007/s11883-022-01044-4. Epub 2022 Jul 4.
- Derived from this study: PubMed 32578481Quesada O, Hermel M, Suppogu N, Aldiwani H, Shufelt C, Mehta PK, Cook-Wiens G, Maughan J, Berman DS, Thomson LEJ, Handberg EM, Pepine CJ, Bairey Merz CN, Wei J. Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1-Year Follow-Up: Results From WISE-CVD. J Am Heart Assoc. 2020 Jul 7;9(13):e016305. doi: 10.1161/JAHA.119.016305. Epub 2020 Jun 24.
- Derived from this study: PubMed 31056078Joung S, Wei J, Nelson MD, Aldiwani H, Shufelt C, Tamarappoo B, Berman D, Thomson LEJ, Bairey Merz CN. Progression of coronary microvascular dysfunction to heart failure with preserved ejection fraction: a case report. J Med Case Rep. 2019 May 6;13(1):134. doi: 10.1186/s13256-019-2074-z.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
C. Noel Bairey Merz, MD, FACC principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Microvascular Coronary Dysfunction and Cardiovascular Disease, run by Cedars-Sinai Medical Center at 1 site 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 11 inclusion and 28 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 21 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 1 site 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, MS (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?
Cardiovascular (CV) events (time frame: up to 30 years). 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 NCT02582021, which also lists 4 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 21 Aug 2026.