Evaluating Myocardial Ischemia in Chest Pain Using Exercise CMR

Ischemic Heart Disease (IHD) is a condition of recurring chest pain or discomfort that occurs when a part of the heart is not receiving sufficient blood flow. It is a major public health concern internationally and in Singapore, the leading cause of death from cardiovascular disease. Cardiovascular magnetic resonance (CMR) has the ability to assess heart structures, scarring or lack of blood supply to the heart muscle with great accuracy and without any radiation involved. A CMR-compatible cycle ergometer can offer a safe and low cost stress equipment to assess heart function and motion abnormalities, and restrictions of the blood supply to the heart tissues due to partial or complete blockages of the blood vessels.

This study aims

1. to develop an exercise-CMR stress protocol by testing its feasibility and robustness in assessing changes in cardiac volumes and function due to physical exertion in healthy individuals and
2. to assess the accuracy of the multiparametric stress-CMR as a diagnostic tool for ischemic-causing coronary artery disease (CAD) with coronary fractional flow reserve (FFR) as a reference.
3. to measure the overall economic impact of ischaemic heart disease by estimating the direct and indirect medical costs for each participant. The current sample costs will be extrapolated to estimate the annual costs of treating and managing ischaemic heart disease in the local population.
4. to evaluate the effects of coronary microvascular dysfunction on coronary flow and regulation, physiological response and cardiac sympathetic signaling in patients with chest pain.

Suspected ischemic heart disease (IHD) or coronary artery disease (CAD) is commonly diagnosed by stress testing where patients undergo exercise tests in order to make their hearts work hard and beat fast to require more blood and oxygen. Pharmacological-induced stress is employed in the case where the patient is unable to exercise. Since plaque-narrowed arteries cannot supply enough oxygen-rich blood to meet the heart's needs, the stress test can show signs and symptoms of IHD. Some of the symptoms include abnormal changes in the heart rate or blood pressure, shortness of breath, chest pain, or abnormal changes in the heart's rhythm and electrical activity.

As part of the stress tests, images of the heart are taken while the patient is exercising and while the patient is at rest. The imaging stress tests will show how well the blood flows in and out of the heart. An example would be a stress echocardiogram where an ultrasound is performed on the chest to produce video images of the heart to. IHD is detected through development of new regional wall motion abnormalities or worsening of preexisting regional wall motions. The patient will be required to exercise on a treadmill before lying on the examination bed for the ultrasound scan. This however, would require the patient to move from the treadmill to the bed, which would result in some time delay.

Another diagnostic test commonly used to diagnose IHD would be a nuclear scan known as myocardial perfusion imaging where a radioactive isotope acting as a tracer is injected into the bloodstream. During exercise, the tracer is monitored while it flows through the heart and lungs to allow detection for any blood-flow problems. However, this test would involve ionizing radiation due to the radioactive isotopic tracer used.

A detailed test to view blood flow through the heart, would be through a cardiac catheterization or an angiogram where a thin and flexible tube known as a catheter is threaded through an artery, usually in the leg, to the heart arteries. An invisible dye is injected through the catheter and special x-rays will be taken while the dye flows through the coronary arteries, allowing the doctor to study the blood flow through the heart and blood vessels. Due to the nature of the catheterization with the insertion of the tube, it makes the procedure invasive and hence involving risks although they are rare.

Cardiovascular magnetic resonance (CMR) is able to accurately and non-radiatively assess the heart structure, any scarring or lack of blood supply to the heart muscle. A CMR-compatible cycle ergometer offers a one-stop diagnostic test that is non-radiative and non-invasive. Hence, our investigators aim to develop a protocol that does not require any invasive procedure by assessing its accuracy and develop reference ranges in healthy individuals.

Eligibility Criteria:
Inclusion Criteria:

Healthy Volunteers:

* 21 years and above
* Normal physical examination
* No known significant medical history
* Able to give informed consent

Patients:

* 21 years and above
* Stable angina or angina-equivalent
* Has at least one of the following risk factors:

  1. Smoking
  2. Diabetes (fasting glucose level \> 140 mg/dL)
  3. Hyperlipidemia (total cholesterol level \> 250 mg/dL)
  4. Abnormal ECG
  5. Hypertension

Exclusion Criteria:

Healthy Volunteers:

* Contraindications to CMR implantable devices, cerebral aneurysm clips, cochlear implants
* Claustrophobia
* Women who are pregnant
* Inability to comply with study protocol
* Not able to exercise

Patients:

* Unstable cardiac conditions that are deemed by primary investigator to be unsuitable for this study
* Prior coronary revascularization or percutaneous coronary intervention
* Pulmonary disease
* Anemia
* Asthma
* Hyperthermia
* Hyperthyroidism
* Sympathomimetic toxicity
* Polycythemia
* Severely uncontrolled hypertension despite being on at least 3 anti-hypertensive medications