Understanding the Mechanisms of Diastolic Dysfunction
| Status: | Withdrawn |
|---|---|
| Conditions: | Healthy Studies, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/10/2018 |
| Start Date: | June 1, 2018 |
| End Date: | August 2022 |
A New Framework for Understanding the Mechanism of Diastolic Dysfunction
Heart failure is a clinical syndrome marked by breathlessness, even at low levels of
exertion, general fatigue, and fluid retention and is estimated to affect 5.1 million people
in the United States. Heart failure with preserved ejection fraction (HFpEF) means that the
heart pumps enough blood to the body, but patients still have terrible symptoms. It is
estimated to account for about 50% of all heart failure cases. Experts agree that impaired
filling of the heart, perhaps due to "stiffness" of the heart muscle itself, critically
underlies HFpEF. There is currently no clinical technique for measuring heart muscle
(myocardial) stiffness; the very definition of "myocardial stiffness" remains poorly
established. Consequently, the ability to study the mechanisms that underlie HFpEF is
virtually non-existent, and limited treatment options will persist without significant
advances. The objective of this project is to use an Equilibrium-Material-Stability (EMS)
framework that couples patient-specific clinical MRI and heart pressure data in a
computational model of the heart to diagnose changes in myocardial stiffness. The central
hypothesis is that the new EMS framework for understanding the mechanisms of diastolic
dysfunction in HFpEF will be more sensitive and outperform currently available approaches.
exertion, general fatigue, and fluid retention and is estimated to affect 5.1 million people
in the United States. Heart failure with preserved ejection fraction (HFpEF) means that the
heart pumps enough blood to the body, but patients still have terrible symptoms. It is
estimated to account for about 50% of all heart failure cases. Experts agree that impaired
filling of the heart, perhaps due to "stiffness" of the heart muscle itself, critically
underlies HFpEF. There is currently no clinical technique for measuring heart muscle
(myocardial) stiffness; the very definition of "myocardial stiffness" remains poorly
established. Consequently, the ability to study the mechanisms that underlie HFpEF is
virtually non-existent, and limited treatment options will persist without significant
advances. The objective of this project is to use an Equilibrium-Material-Stability (EMS)
framework that couples patient-specific clinical MRI and heart pressure data in a
computational model of the heart to diagnose changes in myocardial stiffness. The central
hypothesis is that the new EMS framework for understanding the mechanisms of diastolic
dysfunction in HFpEF will be more sensitive and outperform currently available approaches.
The study has three aims. The first aim of the project is to refine MRI techniques using
"free-breathing" versus "breath-holding" measurements. Twenty-five normal volunteers will
undergo MRI to refine "free-breathing" cardiac imaging and enable construction of
patient-specific computer models of the heart. The second aim of the project is to validate
and test the myocardial stiffness evaluation framework derived through the first objective in
human subjects. Twenty-five normal volunteers will undergo MRI and the data from these images
will be compared to specially constructed 3D printed models of the heart, enabling refinement
of the EMS framework to separate structural stiffness from material stiffness. The third aim
of the project is to measure changes in myocardial stiffness in patients with HFpEF.
Thirty-three subjects with current diagnostic criteria for HFpEF will be evaluated at
baseline and at six months to evaluate myocardial stiffness and cardiac MRI biomarkers.
Specifically, this aim will establish the diagnostic sensitivity of the EMS framework with
comparison to cardiac MRI biomarkers of increased stiffness, thereby providing mechanistic
insight to one critical underlying cause of HFpEF.
"free-breathing" versus "breath-holding" measurements. Twenty-five normal volunteers will
undergo MRI to refine "free-breathing" cardiac imaging and enable construction of
patient-specific computer models of the heart. The second aim of the project is to validate
and test the myocardial stiffness evaluation framework derived through the first objective in
human subjects. Twenty-five normal volunteers will undergo MRI and the data from these images
will be compared to specially constructed 3D printed models of the heart, enabling refinement
of the EMS framework to separate structural stiffness from material stiffness. The third aim
of the project is to measure changes in myocardial stiffness in patients with HFpEF.
Thirty-three subjects with current diagnostic criteria for HFpEF will be evaluated at
baseline and at six months to evaluate myocardial stiffness and cardiac MRI biomarkers.
Specifically, this aim will establish the diagnostic sensitivity of the EMS framework with
comparison to cardiac MRI biomarkers of increased stiffness, thereby providing mechanistic
insight to one critical underlying cause of HFpEF.
Inclusion Criteria:
Healthy volunteers
1. Healthy adults
Patients with Heart Failure with Preserved Ejection Fraction
1. Patient scheduled for catheterization at UCLA Medical Center
2. Ejection fraction >/= 50%
3. Signs and symptoms of heart failure
4. Excluded other potential non-cardiac etiologies of heart failure
Exclusion Criteria:
Healthy volunteers
1. Known medical condition that impacts heart health
2. Contraindications to MRI (e.g., pacemaker/ICD, or claustrophobia)
Patients with Heart Failure with Preserved Ejection Fraction
Exclusion Criteria:
1. Contraindications to MRI (e.g., pacemaker/ICD, or claustrophobia)
2. Prior MI or history of PCI/CABG
3. Worse than mild valvular disease
4. Any indication for ICD implantation
5. Contraindication to MRI contrast agents or eGRF <30 ml/min/1.73m2 or MRI exams (e.g.,
pacemaker/ICD or claustrophobia).
6. Atrial fibrillation or unstable cardiac rhythm
We found this trial at
1
site
Los Angeles, California 90095
310-825-4321
Phone: 310-794-0376
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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