Development of Novel Physiological CMR Methods in Health and Disease

March 16, 2026 updated by: Sheffield Teaching Hospitals NHS Foundation Trust
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

135

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
    • England
      • Sheffield, England, United Kingdom, S10 2JF
        • Recruiting
        • Sheffield Teaching Hospitals NHS FT
        • Contact:
          • Sam Walmsley

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through study completion, average 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary 4D CMR Flow
Time Frame: 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).
Through study completion, average 5 years
Volumetric and functional parameters
Time Frame: Through study completion, average 5 years
2) Right and left heart volumetric and functional parameters: end-diastolic and end-systolic volumes; ejection fraction
Through study completion, average 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2018

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

January 1, 2031

Study Registration Dates

First Submitted

February 19, 2019

First Submitted That Met QC Criteria

February 25, 2019

First Posted (Actual)

February 26, 2019

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH20184

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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