Development of Novel Physiological CMR Methods in Health and Disease
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 135
- Locations
- 1
- Primary Endpoint
- 4D CMR Flow
Study Overview
Brief Summary
Physiological cardiovascular stress test plays a crucial role in the assessment of patients with suspected heart disease. There are several methods of cardiac physiological stress tests and each of them offer varied insight into cardiac physiological adaptation: passive leg raise, intra-venous fluid challenge, pharmacological stressors and physical exercise stress test. Echocardiography, which is the mainstay for the non-invasive rest/stress assessment of the left ventricular (LV) haemodynamics has several limitations. Novel methods of CMR imaging allow to map intra-cardiac flow in three-dimension using novel flow acquisitions. These novel flow acquisitions are called four-dimensional flow CMR, where the fourth dimension is time. Additionally, traditional cine CMR imaging for functional assessment can now be done without breath-holds using advanced acceleration methods, allowing them to be used during exercise. A comprehensive understanding of functional-flow coupling at rest, during increased pre-load (fluid challenge) to the heart or during exercise, is lacking in the literature. There is an important need to validate these novel CMR methods for developing mechanistic insight into physiological cardiac adaptation to increased pre-load or to exercise in health and how it alters in heart disease.
Detailed Description
For this study, the investigators will perform comprehensive physiological CMR in healthy volunteers and patients with suspected or known heart disease (coronary artery disease and heart failure). A sub-set of patients will have follow-up scans after they receive treatment to investigate the therapeutic target role of these physiological CMR metrics.
Patients who have given informed consent for this research will receive one physiological stress test depending on the clinical context. There will be 5 clinical subgroups to which patients will be recruited to:
Group 1. Heart failure with preserved ejection fraction (HFpEF), Group 2. Heart failure with reserved ejection fraction (HFrEF), Group 3. Pulmonary hypertension (PH), Group 4. Acute myocardial infarction (AMI) and Group 5. Suspected but not treated coronary artery disease (sCAD).
Patients will be selected in each group by the clinical specialist/research team as per the published guidelines and local protocols - Group 1 and 2 (19), Group 3 (20), Group 4 (21) and Group 5 (22).
First 4 groups of patients will receive pre-load increasing stress test (either passive leg raise or equivalent 500mls intravenous fluid challenge depending on the tolerability). This will be done to investigate if increase in pre-load will help unravel subtle dysfunction which is not apparent at euvolemic state. AMI patients may also receive ischaemia testing stress CMR depending on the main clinically question needed to answer. Patients with sCAD will receive clinically relevant pharmacological stress test (dobutamine, adenosine or regadenoson, inhaled nitric oxide) to diagnose ischaemia.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy Volunteers age 20 to 80, recruited from Sheffield Teaching Hospitals staff members
- •Patients age 20 to 80 with suspected or known heart disease (group 1 to 5)
- •Capable of giving written informed consent
Exclusion Criteria
- •Inability to perform the study protocol secondary to severe heart failure requiring IV therapy
- •Patients recruited in the suspected CAD and acute myocardial infarction arms of the study and in need for detection of ischaemia should not have any past medical history of MI, ACS or cardiomyopathy
- •Patients with significant valvular heart disease will be excluded from any patient group
- •Patient with in atrial fibrillation will be excluded
- •Contraindication to MRI (as per standard MRI screening questionnaire issued to patients prior to clinical MRI procedures)
Arms & Interventions
Group 4
Patients with acute myocardial infarction
Intervention: intravenous fluid challenge (Other)
Group 5
Patients with suspected but not treated coronary artery disease
Intervention: intravenous fluid challenge (Other)
Group 6
Healthy Volunteers
Intervention: intravenous fluid challenge (Other)
Group 1
Heart failure patients with preserved ejection fraction
Intervention: intravenous fluid challenge (Other)
Group 2
Heart failure patients with reserved ejection fraction
Intervention: intravenous fluid challenge (Other)
Group 3
Patients with pulmonary hypertension
Intervention: intravenous fluid challenge (Other)
Outcomes
Primary Outcomes
4D CMR Flow
Time Frame: Through study completion, average 5 years
The primary outcome measures will include 4D flow CMR derived mitral inflow diastolic parameter: E/A ratio. This parameter will be quantified once both at rest and during physiological stress.
Secondary Outcomes
- Secondary 4D CMR Flow(Through study completion, average 5 years)
- Volumetric and functional parameters(Through study completion, average 5 years)