WISE CVD - Continuation (WISE HFpEF)
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorCedars-Sinai Medical Center
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Symptomatic angina or anginal equivalent
Age ≥ 18
Participant is willing to give written informed consent
Age ≥ 18
Disqualifiers
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%
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Coronary Angiography
Procedure/SurgeryA 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 Testing
Procedure/SurgeryAn angiography procedure specifically designed to examine the blood vessels in the heart and how they respond to different medications.
Cardiac Magnetic Resonance Imaging
Procedure/SurgeryNoninvasive 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 Angiography
Procedure/SurgeryTest 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 Angiography
Procedure/SurgeryNoninvasive, imaging method that uses a computed tomography (CT) scanner to look at the structures and blood vessels of the heart.
Rest-Stress Millar Testing
Procedure/SurgeryHandgrip, 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 tests
Procedure/SurgeryNon-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.
Treatment groups
220 Participants
are divided into 2 treatment groupsGroup A: Women6 interventions
Group B: Women or men5 interventions
Trial outcomes
Primary outcomes
1
Cardiovascular (CV) events
Time frame
up to 30 yearsSecondary outcomes
1
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.
Time frame
up to 30 years2
Persistent Chest Pain Symptoms: WISE female angina Questionnaire
Detailed information on chest pain symptoms will include the WISE female angina questionnaire.
Time frame
Up to 30 years3
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.
Time frame
up to 30 years4
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.
Time frame
up to 30 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov