Ignite Creation Date:
2024-05-06 @ 7:42 AM
Last Modification Date:
2024-10-26 @ 11:51 AM
Study NCT ID:
NCT02582021
Status:
RECRUITING
Last Update Posted:
2023-07-20
First Post:
2015-10-05
Brief Title:
WISE CVD - Continuation WISE HFpEF
Sponsor:
Cedars-Sinai Medical Center
Organization:
Cedars-Sinai Medical Center
Study Overview
Official Title:
Womens Ischemia Syndrome Evaluation WISE - Coronary Microvascular Dysfunction CMD and Heart Failure with Preserved Ejection Fraction HFpEF
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The Womens 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 symptomssigns 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 100000 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 andor 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
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 andor 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
Detailed Description:
The current application will study new cohorts of women and men with the following specific aims
Specific Aim 1 LV diastolic dysfunction is linked to CMD Sub-Aim 1 LV diastolic dysfunction and CMD are linked via the mechanism of cardiomyocyte fat accumulation
Specific Aim 2 Comprehensive noninvasive Cardiac Magnetic Resonance Imaging CMRI that includes LV diastolic function is linked with invasive measures of LV diastolic function and can optimize diagnosis of CMD
Sub-Aim 2 Coronary Magnetic Resonance Angiography CMRA can exclude obstructive CAD in CMD
Specific Aim 3 Add completely de-identified data sharing to prepare for future large precision medicine research and to advance precision medicine initiative
Exploratory Aim Blood proteomic and metabolomics biomarkers of extracellular matrix remodeling and fibrosis combined with ischemia measures will predict HFpEF
In this prospective cohort design study investigators intend to enroll 220 new subjects including 120 symptomatic women undergoing invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease CAD defined as 50 luminal diameter stenosis in 1 epicardial coronary artery and 100 women and men hospitalized for Heart Failure with preserved Ejection Fraction HFpEF defined by the European Society of Cardiology ESC criteria who have not yet undergone coronary angiography
New and existing samples and longer term follow-up will be analyzed in an exploratory fashion looking for potential HFpEF biomarkers for pilot data purposes
After baseline evaluation the n120 cohort will undergo noninvasive high resolution comprehensive CMRI imaging invasive angiography coronary reactivity testing and rest-stress Millar pressure-volume measurement Handgrip mild leg exercise and brief Valsalva Maneuver will be conducted during CMRI and Millar pressure-volume assessment to characterize cardiac response to stress Lastly these patients will also undergo MR Coronary Angiography for validation purposes against gold-standard angiography
The cohort of 100 women and men with HFpEF admitted to the hospital who have not yet undergone coronary angiography will also undergo CMRI with stress including MR coronary angiography CMRA and noninvasive computed coronary tomographic angiography CCTACSMC only
This will provide understanding of a non-cath-lab based population regarding links between CMD diastolic function and HFpEF and will result in data to test the hypothesis that coronary MRA can exclude obstructive CAD and diagnose CMD without ionizing radiation Proteomic and metabolomics biomarker assays in the n567 subjects with no obstructive CAD Exploratory Aim will be performed
Specific Aim 1 LV diastolic dysfunction is linked to CMD Sub-Aim 1 LV diastolic dysfunction and CMD are linked via the mechanism of cardiomyocyte fat accumulation
Specific Aim 2 Comprehensive noninvasive Cardiac Magnetic Resonance Imaging CMRI that includes LV diastolic function is linked with invasive measures of LV diastolic function and can optimize diagnosis of CMD
Sub-Aim 2 Coronary Magnetic Resonance Angiography CMRA can exclude obstructive CAD in CMD
Specific Aim 3 Add completely de-identified data sharing to prepare for future large precision medicine research and to advance precision medicine initiative
Exploratory Aim Blood proteomic and metabolomics biomarkers of extracellular matrix remodeling and fibrosis combined with ischemia measures will predict HFpEF
In this prospective cohort design study investigators intend to enroll 220 new subjects including 120 symptomatic women undergoing invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease CAD defined as 50 luminal diameter stenosis in 1 epicardial coronary artery and 100 women and men hospitalized for Heart Failure with preserved Ejection Fraction HFpEF defined by the European Society of Cardiology ESC criteria who have not yet undergone coronary angiography
New and existing samples and longer term follow-up will be analyzed in an exploratory fashion looking for potential HFpEF biomarkers for pilot data purposes
After baseline evaluation the n120 cohort will undergo noninvasive high resolution comprehensive CMRI imaging invasive angiography coronary reactivity testing and rest-stress Millar pressure-volume measurement Handgrip mild leg exercise and brief Valsalva Maneuver will be conducted during CMRI and Millar pressure-volume assessment to characterize cardiac response to stress Lastly these patients will also undergo MR Coronary Angiography for validation purposes against gold-standard angiography
The cohort of 100 women and men with HFpEF admitted to the hospital who have not yet undergone coronary angiography will also undergo CMRI with stress including MR coronary angiography CMRA and noninvasive computed coronary tomographic angiography CCTACSMC only
This will provide understanding of a non-cath-lab based population regarding links between CMD diastolic function and HFpEF and will result in data to test the hypothesis that coronary MRA can exclude obstructive CAD and diagnose CMD without ionizing radiation Proteomic and metabolomics biomarker assays in the n567 subjects with no obstructive CAD Exploratory Aim will be performed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None