Development of Novel Physiological CMR Methods in Health and Disease

  • End date
    Jun 5, 2023
  • participants needed
  • sponsor
    Sheffield Teaching Hospitals NHS Foundation Trust
Updated on 15 July 2021
heart disease
exercise stress test


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.


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

Condition Coronary Artery Disease, Coronary heart disease, Heart failure, Heart disease, Pulmonary Hypertension, Myocardial Infarction, Ischemic Heart Disease, Cancer Prevention, Surviving Abuse, Joint Injuries, Abdominal Surgery, Mental Disability, Pelvic Adhesions, Low Testosterone, Dental Filling, Habit Reversal, Complicated Grief, Chronic Pelvic Pain, Gambling Problems, Myopic Macular Degeneration, Nerve Injury, Severe Premenstrual Symptom, Stasis Dermatitis, Pulmonary Arterial Hypertension, Heart Attack (Myocardial Infarction), Open Heart Surgery, Recurrent Pregnancy Loss, Effects of Chemotherapy, Renal Anemia, Functional Dyspepsia, Catheter Complications, Serial Evaluation of Ductal Epithelium, Chronic Renal Anemia, Cancer Treatment, Anemic Cancer, Spinocerebellar Disorders, Pseudobulbar Affect, Spine Athroplasty, Indikation: Diabetes - Typ II, Partial Medial Meniscectomy, Primary Insulin Hypersecretion, Testotoxikose, Infantile Fibrosarcoma, Late Infantile Neuronal Ceroid Lipfuscinsosis, Congestive Heart Failure, Cardiac Ischemia, Memory Problems, Myocardial Ischemia, Cardiac Disease, heart attack, myocardial infarction (mi), cardiac infarction, heart attacks, myocardial necrosis, cardiac failure, congestive heart disease
Treatment intravenous fluid challenge
Clinical Study IdentifierNCT03854071
SponsorSheffield Teaching Hospitals NHS Foundation Trust
Last Modified on15 July 2021


Yes No Not Sure

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)
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