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Development of Novel Physiological CMR Methods in Health and Disease

Sponsor
Sheffield Teaching Hospitals NHS Foundation Trust (Other)
Overall Status
Recruiting
CT.gov ID
NCT03854071
Collaborator
(none)
150
Enrollment
1
Location
6
Arms
58.2
Anticipated Duration (Months)
2.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: intravenous fluid challenge
 N/A

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.

Healthy volunteers who have given informed consent will receive matched physiological stress test so that head-on comparison can be made with the relevant patient cohort. The CMR scan protocol will involve minimal breath-holds and will be patient-friendly. This is achieved by using accelerated, advanced cine and late gadolinium enhancement (LGE)-imaging techniques which require fewer breath-holds and shorter scan. All CMR stress studies will be supervised by an Advanced Life Support (ALS) certified doctor.

The CMR protocol for healthy volunteers will include the following components (45 minutes):

  1. Survey

  2. Baseline cine imaging for functional imaging (rest)

  3. Tissue characterisation with native T1-mapping (rest)

  4. 4D flow CMR (rest)

  5. Record blood pressure, heart rate and oxygen saturation

  6. Start of physiological stress (increase pre-load or pharmacological stressors)

  7. 4D flow CMR (stress, at low-moderate intensity exercise aiming for heart rate up to 110bpm only)

  8. Functional cines (stress, at low-moderate intensity exercise aiming for heart rate up to 110bpm only)

  9. Record blood pressure, heart rate and oxygen saturation

  10. First pass perfusion imaging (only if adenosine/regadenoson used for myocardial hyperaemia)

  11. Record blood pressure, heart rate and oxygen saturation

  12. Gadolinium contrast injection

  13. Early/Late gadolinium enhancement imaging in short-axis

  14. Post contrast T1-mapping End of study

For patient's receiving clinical CMR scans, the 'bolt-on' stress CMR protocol will include the following components (20-25minutes):

  1. 4D flow CMR (rest)

  2. Record blood pressure, heart rate and oxygen saturation

  3. Start of physiological stress (increase pre-load or pharmacological stressors)

  4. 4D flow CMR (stress, at low-moderate intensity exercise aiming for heart rate up to 110bpm only)

  5. Functional cines (stress, at low-moderate intensity exercise aiming for heart rate up to 110bpm only)

  6. Record blood pressure, heart rate and oxygen saturation

  7. First pass perfusion imaging (only if adenosine/regadenoson used for myocardial hyperaemia)

  8. Record blood pressure, heart rate and oxygen saturation

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Patients will be selected in each group by the clinical specialist/research team as per the published guidelines and local protocols - Group 1, Group 2, Group 3, Group 4 and Group 5.Patients will be selected in each group by the clinical specialist/research team as per the published guidelines and local protocols - Group 1, Group 2, Group 3, Group 4 and Group 5.
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Development of Novel Physiological CMR Methods in Health and Disease
Actual Study Start Date :
Jul 30, 2018
Anticipated Primary Completion Date :
Jun 4, 2022
Anticipated Study Completion Date :
Jun 5, 2023

Arms and Interventions

Arm Intervention/Treatment
Other: Group 1

Heart failure patients with preserved ejection fraction

Other: intravenous fluid challenge
Patients will undergo a receive a pre-load increasing stress test with intravenous fluids depending on tolerability
Other: Group 2

Heart failure patients with reserved ejection fraction

Other: intravenous fluid challenge
Patients will undergo a receive a pre-load increasing stress test with intravenous fluids depending on tolerability
Other: Group 3

Patients with pulmonary hypertension

Other: intravenous fluid challenge
Patients will undergo a receive a pre-load increasing stress test with intravenous fluids depending on tolerability
Other: Group 4

Patients with acute myocardial infarction

Other: intravenous fluid challenge
Patients will undergo a receive a pre-load increasing stress test with intravenous fluids depending on tolerability
Other: Group 5

Patients with suspected but not treated coronary artery disease

Other: intravenous fluid challenge
Patients will undergo a receive a pre-load increasing stress test with intravenous fluids depending on tolerability
Other: Group 6

Healthy Volunteers

Other: intravenous fluid challenge
Patients will undergo a receive a pre-load increasing stress test with intravenous fluids depending on tolerability

Outcome Measures

Primary Outcome Measures

  1. 4D CMR Flow [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 Outcome Measures

  1. Secondary 4D CMR Flow [Through study completion, average 5 years]

    Other 4D flow CMR derived outcome metrics will include mitral, tricuspid and pulmonary valve flow quantification - net forward flow (mls), E-velocity (cm/sec), E-velocity deceleration time (msec, both for mitral and tricuspid), A-velocity (cm/sec) and valvular regurgitation (mls).

  2. Volumetric and functional parameters [Through study completion, average 5 years]

    2) Right and left heart volumetric and functional parameters: end-diastolic and end-systolic volumes; ejection fraction

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years to 80 Years
Sexes Eligible for Study:
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Sheffield Teaching Hospitals NHS FT Sheffield England United Kingdom S10 2JF

Sponsors and Collaborators

  • Sheffield Teaching Hospitals NHS Foundation Trust

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT03854071
Other Study ID Numbers:
  • STH20184
First Posted:
Feb 26, 2019
Last Update Posted:
Jul 8, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Hypertension, Pulmonary
Coronary Artery Disease
Myocardial Infarction
Infarction

Study Results

No Results Posted as of Jul 8, 2021