NCT02582021 · Cedars-Sinai Medical Center
WISE CVD - Continuation (WISE HFpEF)
What this study is about
The Women's Ischemia Study Evaluation (WISE), a group of participants 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).
View original scientific description
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: 1. Risk factor conditions (hypertension, dyslipidemia, dysglycemia, loss of estrogen) promote an inflammatory and pro-oxidative state making the microvasculature vulnerable; 2. Vulnerable coronary microvasculature becomes dysregulated (sympathetic nervous system activation, endothelial dysfunction, changes in vascular smooth muscle activation, spasm) causing repeated episodes of transient ischemia; 3. Repeated ischemia-reperfusion episodes facilitate preconditioning with preservation of cardiomyocyte contractile and microvascular function against ischemic injury; 4. Ischemia-reperfusion and preconditioning lead to cardiomyocyte fat accumulation and relaxation impairment resulting in diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF).
Interventions
PROCEDURE
Coronary Angiography
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.
PROCEDURE
Coronary Reactivity Testing
An angiography procedure specifically designed to examine the blood vessels in the heart and how they respond to different medications.
PROCEDURE
Cardiac Magnetic Resonance Imaging
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.
PROCEDURE
Cardiac Magnetic Resonance Angiography
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.
PROCEDURE
Computed Coronary Tomographic Angiography
Noninvasive, imaging method that uses a computed tomography (CT) scanner to look at the structures and blood vessels of the heart.
PROCEDURE
Rest-Stress Millar Testing
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.
PROCEDURE
Aortic vasorelaxation tests
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.
Primary outcome measures
Cardiovascular (CV) events
Time frame: up to 30 years
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- For the new cohort n=120 women undergoing coronary angiography:
- Symptomatic angina or anginal equivalent
- Participant is willing to give written informed consent For the cohort n=100 women and men hospitalized for HFpEF (defined by ESC guidelines):
- 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
Exclusion criteria
- 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
- 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
Where
- Los Angeles, California
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
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Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 24, 2025 · Source of record for eligibility and locations