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

Coronary Microvascular Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03876223
• Other study ID #: 54999
• Status: Recruiting
• Start date: July 24, 2019
• Est. completion date: February 28, 2025

Study information

• Verified date: February 2024
• Source: Cedars-Sinai Medical Center
• Contact: Nicole Tovar
• Phone: 310-248-6960
• Email: nicole.tovar[@]cshs.org
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: February 28, 2025
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion:

1. 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.

2. Preserved left ventricular ejection fraction (EF) =45%

3. Be > 18 years old

4. Be able to meet the requirement for a cardiac MRI, which means no metal devices in your chest, no claustrophobia and no angioedema

5. Be competent to give informed consent

Exclusion:

1. Subjects with severe or chronic kidney disease (CKD) with GFR<405 or acute kidney injury

2. Subjects with allergy to animal dander will be excluded since imaging will be done in BIRI (BIRI scanners are also used to image animals).

3. Subjects who have had four or more prior previous gadolinium contrast scans

4. Allergy/ hypersensitivity to adenosine, gadolinium, aminophylline or regadenoson

5. Second- or third-degree A-V block

6. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker)

7. Subjects with mild to severe asthma

Related Conditions & MeSH terms

• Coronary Microvascular Dysfunction
• Heart Failure
• Heart Failure With Preserved Ejection Fraction (HFpEF)
• Ischemia

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center	University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CMR imaging	Change from Baseline at 1 year follow up will be assessed.	Baseline, Annual follow up
Primary	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).	Baseline
Secondary	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.	Baseline, 6 week, quarterly(year 1) and annual follow up
Secondary	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.	Baseline, quarterly(year 1) and annual follow up
Secondary	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.	Baseline, 6 week and annual follow up
Secondary	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.	Baseline, 6 week and annual follow up