Cardiovascular DiseaseNCT00832702
Women's Ischemia Syndrome Evaluation (WISE) Coronary Vascular Dysfunction
An observational study of Cardiovascular Disease, run by Cedars-Sinai Medical Center at 2 sites in United States.
Trial summary
This research study is designed to investigate the approaches to noninvasive detection and assessment of coronary vascular dysfunction in women by comparing the testing results from the invasive standard care diagnostic procedure Angiogram and from the additional noninvasive diagnostic procedure CMR Imaging. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Cardiovascular Disease
- What is being tested?
- Cardiac MRI
- Type of treatment
- Surgery or procedure
- How many people
- 433 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Sep 2008to 31 Aug 2051
- 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 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Women undergoing clinically-ordered coronary angiography for suspected ischemia will be recruited. See the inclusion and exclusion criteria for details.
Who may be able to join
- Symptomatic angina or anginal equivalent;
- Aged 18 years or older;
- No obstructive CAD at coronary angiography (performed within the previous 24 months).
- Competent to give informed consent.
Who cannot join
- Obstructive CAD ≥ 50% luminal diameter stenosis in ≥ 1 epicardial coronary artery,
- Acute coronary syndrome (defined by the ACC/AHA criteria, Braunwald 2000),
- 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;
- Prior or planned percutaneous coronary intervention or CABG,
- Acute MI;
Show all 14Show fewer
- Prior non-cardiac illness with an estimated life expectancy < 4 years;
- Unable to give informed consent;
- Chest pain with a non-ischemic etiology (e.g.,pericarditis, pneumonia, esophageal spasm);
- Contraindications to CMRI (e.g., AICD, pacemaker, untreatable claustrophobia or known angio-edema).
- Contraindications to adenosine or Regadenoson (Lexiscan)
- Women with intermediate coronary stenoses (> 20% but < 50% luminal diameter stenosis assessed visually at the time of angiography) will undergo clinically indicated IVUS testing based on the judgment of the operator; those determined to have flow-obstructing stenosis will be excluded from the overall study.
- Participation in a research study that conflicts with the current WISE study.
- Women with coronary stenosis ≥ 50% in any epicardial coronary artery, assessed visually at the time of angiography, will not be included in the CRT subgroup.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32610-0277
Cedars-Sinai Barbra Streisand Women's Heart Center
Los Angeles, California, 90048
About this study
This research study is designed to investigate the approaches to noninvasive detection and assessment of coronary vascular dysfunction in women by comparing the testing results from the invasive standard care diagnostic procedure Angiogram and from the additional noninvasive diagnostic procedure CMR Imaging. The investigators want to specifically study 375 female patients who have signs or symptoms suggestive of heart disease but don't have obstructive coronary artery disease. Two study sites (Cedars-Sinai Medical Center and University of Florida) are recruiting participants.
The standard of care procedures include demographics, review of recent clinical symptoms, review of medications being taken, a physical exam, pre-angiogram blood collection, chest x-ray, ECG and heart angiogram. The research procedures for this study are the cold pressor testing, blood/urine collection, health questionnaire, the post-angiogram ECG and cardiac MRI.
Read more
Patients will be asked to undergo heart angiogram testing to test for abnormalities in their heart arteries. If the heart angiogram shows that the patients do not have blockages in major heart arteries, then the patients will have coronary flow reserve measurement test (as part of the heart angiogram) to determine whether the patients have abnormally functioning of the small heart arteries. This test will be performed by infusing the three drugs: adenosine, acetylcholine and nitroglycerin. The three drugs are naturally occurring substances and have been used for routine heart angiograms.
Cardiac Magnetic Resonance (CMR) imaging may help us more easily and non-invasively detect abnormalities in the inner layer of the heart muscle resulting from the abnormal function of the heart arteries. All the 375 participants will undergo baseline CMR imaging test and a subgroup of 200 participants will undergo a second CMR imaging test at their at least 1-year followup visit.
Patients will be followed up using phone questionnaires at 6 weeks, 6 months for 5 years, and than annually for 20 years thereafter. Other procedures in this study include obtaining informed consent, review of demographics, physical examination, ECG, blood and urine tests, clinical symptoms, medications, questionnaires, etc. The core laboratories include Blood, Lipoprotein, Chemistry Core Lab, Reproductive Hormone Core Lab, Inflammatory Marker Core Lab, Oxidative Stress Core Lab, and Angiographic Core Lab. Additionally, GCRC at Cedars Sinai will process, store and ship samples as needed/required.
Read the detailed description
See Brief Summary above.
- Conditions
- Cardiovascular Disease
- Being tested
- Cardiac MRI
- Keywords
- Cardiac, MRI, Coronary Vascular Dysfunction
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac MRIProcedure or surgery
CMRI provides unique clinical utilities including excellent soft tissue characterization and contrast, three-dimensionality, quantitation of blood flow, and overall superior temporal and spatial resolution to image vascular and myocardial abnormalities.
What is being measured
The primary outcome is the main question the study is designed to answer.
Abnormal cardiac magnetic resonance imaging (CMRI)
Subjects will be contacted at 6-week followup and then annually indefinitely.
Measured: 30 years
Secondary outcomes (3)
Resource utilization and costs
Annual costs will include cardiovascular hospitalizations, coronary revascularizations and angiography, outpatient testing, and visits to generalists, specialists, nurse practitioners/ physician's assistants, or community clinics.
Measured: 30 years
Persistent Chest Pain Symptoms
Detailed information on chest pain symptoms will include the traditional angina questionnaire and the WISE female angina questionnaire
Measured: 30 years
Quality of Life Outcomes
Quality of life and functional capacity will be collected using the standard instruments of SAQ and DASI
Measured: 30 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2009 (estimated)
- Study start17 Sep 2008
- Primary completion15 Sep 2015
- Study completion31 Aug 2051 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- 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
- Other
- Time perspective
- Prospective
- Enrolment
- 433 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), University of Florida, University of Pittsburgh
- Responsible party
- Principal investigator, Noel Bairey Merz, Cedars-Sinai Medical Center
- Investigators
- C. Noel Bairey Merz, MD, FACC, Principal investigator, Cedars-Sinai Medical CenterCarl J Pepine, MD, MACC, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832702
- Sponsor's protocol ID
- IRB# 14906
- Other IDs
- 5R01HL090957
- Status last verified
- Aug 2026
- First submitted
- 28 Jan 2009
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Landes S, Aldiwani H, Thomson L, Wei J, Al-Badri A, Mehta PK, Pedram M, Motwani M, Cook-Weins G, Sopko G, Pepine CJ, Merz CNB, Dey D. Pericardial fat volume is related to endothelial-mediated coronary blood flow in women with suspected coronary microvascular dysfunction. A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study. Am Heart J Plus. 2024 Mar 7;40:100379. doi: 10.1016/j.ahjo.2024.100379. eCollection 2024 Apr.
PubMed 38586431Jalnapurkar S, Landes S, Wei J, Mehta PK, Shufelt C, Minissian M, Pepine CJ, Handberg E, Cook-Wiens G, Sopko G, Bairey Merz CN. Coronary endothelial dysfunction appears to be a manifestation of a systemic process: A report from the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study. PLoS One. 2021 Sep 27;16(9):e0257184. doi: 10.1371/journal.pone.0257184. eCollection 2021.
PubMed 34570768AlBadri A, Wei J, Quesada O, Mehta PK, Xiao Y, Ko YA, Anderson RD, Petersen J, Azarbal B, Samuels B, Henry TD, Cook-Wiens G, Handberg EM, Van Eyk J, Pepine CJ, Bairey Merz CN. Coronary Vascular Function and Cardiomyocyte Injury: A Report From the WISE-CVD. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):3015-3021. doi: 10.1161/ATVBAHA.120.314260. Epub 2020 Oct 8.
PubMed 33028098Wei J, Bakir M, Darounian N, Li Q, Landes S, Mehta PK, Shufelt CL, Handberg EM, Kelsey SF, Sopko G, Pepine CJ, Petersen JW, Berman DS, Thomson LEJ, Bairey Merz CN. Myocardial Scar Is Prevalent and Associated With Subclinical Myocardial Dysfunction in Women With Suspected Ischemia But No Obstructive Coronary Artery Disease: From the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Study. Circulation. 2018 Feb 20;137(8):874-876. doi: 10.1161/CIRCULATIONAHA.117.031999. No abstract available.
PubMed 29459474Thomson LE, Wei J, Agarwal M, Haft-Baradaran A, Shufelt C, Mehta PK, Gill EB, Johnson BD, Kenkre T, Handberg EM, Li D, Sharif B, Berman DS, Petersen JW, Pepine CJ, Bairey Merz CN. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. A National Heart, Lung, and Blood Institute-sponsored study from the Women's Ischemia Syndrome Evaluation. Circ Cardiovasc Imaging. 2015 Apr;8(4):10.1161/CIRCIMAGING.114.002481 e002481. doi: 10.1161/CIRCIMAGING.114.002481.
PubMed 25801710Wei J, Mehta PK, Johnson BD, Samuels B, Kar S, Anderson RD, Azarbal B, Petersen J, Sharaf B, Handberg E, Shufelt C, Kothawade K, Sopko G, Lerman A, Shaw L, Kelsey SF, Pepine CJ, Merz CN. Safety of coronary reactivity testing in women with no obstructive coronary artery disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study. JACC Cardiovasc Interv. 2012 Jun;5(6):646-53. doi: 10.1016/j.jcin.2012.01.023.
PubMed 22721660
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Women's Ischemia Syndrome Evaluation (WISE) Coronary Vascular Dysfunction
- ClinicalTrials.gov ID
- NCT00832702
- Acronym / sponsor ID
- IRB# 14906
- Conditions
- Cardiovascular Disease
- Keywords
- Cardiac, MRI, Coronary Vascular Dysfunction
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 433 participants (estimated)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), University of Florida, University of Pittsburgh
- Study start
- 17 Sep 2008 (actual)
- Primary completion
- 15 Sep 2015 (actual)
- Study completion
- 31 Aug 2051 (estimated)
- First posted
- 30 Jan 2009 (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.
This research study is designed to investigate the approaches to noninvasive detection and assessment of coronary vascular dysfunction in women by comparing the testing results from the invasive standard care diagnostic procedure Angiogram and from the additional noninvasive diagnostic procedure CMR Imaging. The investigators want to specifically study 375 female patients who have signs or symptoms suggestive of heart disease but don't have obstructive coronary artery disease. Two study sites (Cedars-Sinai Medical Center and University of Florida) are recruiting participants.
The standard of care procedures include demographics, review of recent clinical symptoms, review of medications being taken, a physical exam, pre-angiogram blood collection, chest x-ray, ECG and heart angiogram. The research procedures for this study are the cold pressor testing, blood/urine collection, health questionnaire, the post-angiogram ECG and cardiac MRI.
Patients will be asked to undergo heart angiogram testing to test for abnormalities in their heart arteries. If the heart angiogram shows that the patients do not have blockages in major heart arteries, then the patients will have coronary flow reserve measurement test (as part of the heart angiogram) to determine whether the patients have abnormally functioning of the small heart arteries. This test will be performed by infusing the three drugs: adenosine, acetylcholine and nitroglycerin. The three drugs are naturally occurring substances and have been used for routine heart angiograms.
Cardiac Magnetic Resonance (CMR) imaging may help us more easily and non-invasively detect abnormalities in the inner layer of the heart muscle resulting from the abnormal function of the heart arteries. All the 375 participants will undergo baseline CMR imaging test and a subgroup of 200 participants will undergo a second CMR imaging test at their at least 1-year followup visit.
Patients will be followed up using phone questionnaires at 6 weeks, 6 months for 5 years, and than annually for 20 years thereafter. Other procedures in this study include obtaining informed consent, review of demographics, physical examination, ECG, blood and urine tests, clinical symptoms, medications, questionnaires, etc. The core laboratories include Blood, Lipoprotein, Chemistry Core Lab, Reproductive Hormone Core Lab, Inflammatory Marker Core Lab, Oxidative Stress Core Lab, and Angiographic Core Lab. Additionally, GCRC at Cedars Sinai will process, store and ship samples as needed/required.
Detailed description
See Brief Summary above.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Women undergoing clinically-ordered coronary angiography for suspected ischemia will be recruited. See the inclusion and exclusion criteria for details.
Key inclusion criteria (4 listed)
- Symptomatic angina or anginal equivalent;
- Aged 18 years or older;
- No obstructive CAD at coronary angiography (performed within the previous 24 months).
- Competent to give informed consent.
Key exclusion criteria (14 listed)
- Obstructive CAD ≥ 50% luminal diameter stenosis in ≥ 1 epicardial coronary artery,
- Acute coronary syndrome (defined by the ACC/AHA criteria, Braunwald 2000),
- 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;
- Prior or planned percutaneous coronary intervention or CABG,
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 |
|---|---|---|
| Cardiac MRICMRI provides unique clinical utilities including excellent soft tissue characterization and contrast, three-dimensionality, quantitation of blood flow, and overall superior temporal and spatial resolution to image vascular and myocardial abnormalities. | Procedure or surgery | – |
Primary outcome
Abnormal cardiac magnetic resonance imaging (CMRI)
Time frame: 30 years
Subjects will be contacted at 6-week followup and then annually indefinitely.
3 secondary outcomes
Resource utilization and costs
Time frame: 30 years
Persistent Chest Pain Symptoms
Time frame: 30 years
Quality of Life Outcomes
Time frame: 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 27 Aug 2026.
- Derived from this study: PubMed 38586431Landes S, Aldiwani H, Thomson L, Wei J, Al-Badri A, Mehta PK, Pedram M, Motwani M, Cook-Weins G, Sopko G, Pepine CJ, Merz CNB, Dey D. Pericardial fat volume is related to endothelial-mediated coronary blood flow in women with suspected coronary microvascular dysfunction. A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study. Am Heart J Plus. 2024 Mar 7;40:100379. doi: 10.1016/j.ahjo.2024.100379. eCollection 2024 Apr.
- Derived from this study: PubMed 34570768Jalnapurkar S, Landes S, Wei J, Mehta PK, Shufelt C, Minissian M, Pepine CJ, Handberg E, Cook-Wiens G, Sopko G, Bairey Merz CN. Coronary endothelial dysfunction appears to be a manifestation of a systemic process: A report from the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study. PLoS One. 2021 Sep 27;16(9):e0257184. doi: 10.1371/journal.pone.0257184. eCollection 2021.
- Derived from this study: PubMed 33028098AlBadri A, Wei J, Quesada O, Mehta PK, Xiao Y, Ko YA, Anderson RD, Petersen J, Azarbal B, Samuels B, Henry TD, Cook-Wiens G, Handberg EM, Van Eyk J, Pepine CJ, Bairey Merz CN. Coronary Vascular Function and Cardiomyocyte Injury: A Report From the WISE-CVD. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):3015-3021. doi: 10.1161/ATVBAHA.120.314260. Epub 2020 Oct 8.
- Derived from this study: PubMed 29459474Wei J, Bakir M, Darounian N, Li Q, Landes S, Mehta PK, Shufelt CL, Handberg EM, Kelsey SF, Sopko G, Pepine CJ, Petersen JW, Berman DS, Thomson LEJ, Bairey Merz CN. Myocardial Scar Is Prevalent and Associated With Subclinical Myocardial Dysfunction in Women With Suspected Ischemia But No Obstructive Coronary Artery Disease: From the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Study. Circulation. 2018 Feb 20;137(8):874-876. doi: 10.1161/CIRCULATIONAHA.117.031999. No abstract available.
- Derived from this study: PubMed 25801710Thomson LE, Wei J, Agarwal M, Haft-Baradaran A, Shufelt C, Mehta PK, Gill EB, Johnson BD, Kenkre T, Handberg EM, Li D, Sharif B, Berman DS, Petersen JW, Pepine CJ, Bairey Merz CN. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. A National Heart, Lung, and Blood Institute-sponsored study from the Women's Ischemia Syndrome Evaluation. Circ Cardiovasc Imaging. 2015 Apr;8(4):10.1161/CIRCIMAGING.114.002481 e002481. doi: 10.1161/CIRCIMAGING.114.002481.
- Derived from this study: PubMed 22721660Wei J, Mehta PK, Johnson BD, Samuels B, Kar S, Anderson RD, Azarbal B, Petersen J, Sharaf B, Handberg E, Shufelt C, Kothawade K, Sopko G, Lerman A, Shaw L, Kelsey SF, Pepine CJ, Merz CN. Safety of coronary reactivity testing in women with no obstructive coronary artery disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study. JACC Cardiovasc Interv. 2012 Jun;5(6):646-53. doi: 10.1016/j.jcin.2012.01.023.
- 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. This study is not recruiting at the moment.
C. Noel Bairey Merz, MD, FACC principal investigator
Cedars-Sinai Medical Center
Carl J Pepine, MD, MACC principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Disease, 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 4 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 27 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Abnormal cardiac magnetic resonance imaging (CMRI) (time frame: 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 NCT00832702, which also lists 6 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 27 Aug 2026.