Investigating heart function and blood markers in women with coronary dysfunction

Women's Ischemia Syndrome Evaluation (WISE) - Coronary Microvascular Dysfunction (CMD) and Heart Failure With Preserved Ejection Fraction (HFpEF)

This study is testing how heart function and certain blood markers are related in women with coronary issues and men, to help understand heart failure better.

Quick facts

• Study type: Observational
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cedars-Sinai Medical Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT02582021 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the relationship between left ventricular diastolic dysfunction and coronary microvascular dysfunction (CMD) in women and men. It will enroll 220 participants, including symptomatic women undergoing coronary angiography and individuals hospitalized for heart failure with preserved ejection fraction (HFpEF). The study will utilize advanced imaging techniques such as Cardiac Magnetic Resonance Imaging (CMRI) and Coronary Magnetic Resonance Angiography (CMRA) to assess heart function and exclude obstructive coronary artery disease. Additionally, it will analyze blood biomarkers to predict heart failure outcomes and contribute to future precision medicine research.

Who should consider this trial

Good fit: Ideal candidates include symptomatic women aged 18 and older undergoing coronary angiography and individuals hospitalized for HFpEF with preserved ejection fraction.

Not a fit: Patients with obstructive coronary artery disease or those under 18 years old may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnosis and treatment strategies for women suffering from coronary microvascular dysfunction and heart failure.

How similar studies have performed: Previous studies have established the significance of coronary microvascular dysfunction in women, indicating a promising avenue for further exploration.

Eligibility criteria

Inclusion Criteria:

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
* 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 this trial is running

Los Angeles, California

• Cedars-Sinai Women's Heart Center — Los Angeles, California, United States (Recruiting)

Study contacts

• Principal investigator: C. Noel Bairey Merz, MD, FACC — Cedars-Sinai Medical Center
• Study coordinator: BSWHC Research, MS

Conditions Microvascular Coronary Dysfunction; Cardiovascular Disease; Magnetic resonance imaging; Coronary angiography; Coronary Vascular Dysfunction