RECRUITING

WISE CVD - Continuation (WISE HFpEF)

Conditions

Microvascular Coronary Dysfunction Cardiovascular Disease Microvascular Coronary Dysfunction (MCD)Magnetic resonance imaging (MRI)Coronary angiography Coronary Vascular Dysfunction (CVD)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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).

Official Title

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

Quick Facts

Study Start:2015-11

Study Completion:2025-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02582021

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Symptomatic angina or anginal equivalent * Age ≥ 18 * Participant is willing to give written informed consent * 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	* 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 * 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

Inclusion Criteria

Exclusion Criteria

* Symptomatic angina or anginal equivalent
* Age ≥ 18
* Participant is willing to give written informed consent
* 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

* 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
* 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

Contacts and Locations

Study Contact

Nicole Tovar

CONTACT

310-248-6960

nicole.tovar@cshs.org

BS WHC, MS

CONTACT

310-426-9666

bswhc.research@cshs.org

Principal Investigator

C. Noel Bairey Merz, MD, FACC

PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Study Locations (Sites)

Cedars-Sinai Women's Heart Center

Los Angeles, California, 90048

United States

Collaborators and Investigators

Sponsor: Cedars-Sinai Medical Center

C. Noel Bairey Merz, MD, FACC, PRINCIPAL_INVESTIGATOR, Cedars-Sinai Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2015-11

Study Completion Date2025-02

Study Record Updates

Study Start Date2015-11

Study Completion Date2025-02

Terms related to this study

Keywords Provided by Researchers

Microvascular Coronary Dysfunction (MCD)
Magnetic resonance imaging (MRI)
Coronary angiography
Coronary Vascular Dysfunction (CVD)

Additional Relevant MeSH Terms

Microvascular Coronary Dysfunction
Cardiovascular Disease