Understanding the Mechanisms of Diastolic Dysfunction

Healthy Clinical Trial

Official title:

A New Framework for Understanding the Mechanism of Diastolic Dysfunction

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03340233
• Other study ID #: IRB#17-000695
• Secondary ID: 1R01HL131823-01A
• Status: Withdrawn
• Phase: N/A
• Start date: June 1, 2018
• Est. completion date: August 2022

Study information

• Verified date: April 2019
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Diagnostic Test:
• MRI (cardiac) off-label use gadolinium contrast (IND exempt)
Clinical MRI
• MRI (cardiac)
MRI without contrast

Locations

Country	Name	City	State
United States	University of California Los Angeles	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The 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.	Assess the diagnostic sensitivity of MRI method by analyzing baseline and six month longitudinal characteristics in myocardial stiffness measured in patients with HFpEF	Five years