Coronary artery disease (CAD) remained the leading cause of death in the United States and was responsible for 840,768 deaths in 2016. Cardiovascular disease is the number one cause of mortality worldwide, with 17.6 million deaths annually.[1] Cardiac stress testing is an important diagnostic tool for known or suspected coronary artery disease.[2] Eight million nuclear stress tests are performed annually in the United States.
While stress testing can be performed in a variety of ways, more commonly performed and widely available are exercise electrocardiography (EKG) and exercise or pharmacological stress testing along with imaging such as echocardiography or radionuclide myocardial perfusion imaging (rMPI). It can help establish the diagnosis, risk stratify, and guide therapy in patients with coronary artery disease.
An intravenous radioactive tracer is administered, and gamma photons are captured using single-photon emission computer tomography (SPECT) or positron emission tomography (PET).
Myocardial perfusion images are obtained during rest and after stress with either exercise or pharmacological agents, preferably vasodilators. Both the images are then compared to detect myocardial perfusion, viability, and global left ventricular systolic function, which generally signifies the presence and extent of coronary artery disease.
Radionuclide MPI provides essential information on myocardial perfusion at rest and exercise or pharmacological testing with the help of radioactive tracer.
Commonly used tracers for SPECT MPI is technetium-99m based (Tc99m and Tc99m tetrofosmin) or thallium-201.[3] Dual isotope in combination with thallium-201 and technetium-99m are sometimes used, while PET MPI uses rubidium-82 or N13-ammonia. Half-lives of PET tracers are short, hence pharmacological stress testing with vasodilators is preferred than exercise stress testing.[4] When the radioactive tracer is administered intravenously, it allows visual assessment of coronary blood flow and perfusion to the cardiac muscles.
In recent years, the number of modalities for evaluation of CAD has rapidly expanded. Non-invasive testing now includes perfusion echocardiography, computed tomography, and magnetic resonance imaging.
The clinician must determine the pre-test probability for CAD prior to selecting the diagnostic test. Patients with intermediate probability for CAD are most likely to benefit from additional cardiovascular testing.[5] Nuclear stress testing plays an important role in determining the management of these patients, especially when revascularization is being considered.
Pharmacologic stress testing with myocardial perfusion imaging is indicated when exercise stress testing cannot be performed due to an abnormal EKG or the patient's inability to exercise.
Scenarios in which a nuclear stress test may be used for evaluation include:
There are primarily two modalities of stress – exercise or pharmacological.
In patients who can exercise, it is the preferred form of stress to achieve cardiac workload. It can also measure several factors such as symptoms, hemodynamic response, physical activity, and prognosis of cardiac activity. The radioactive tracer is injected near the peak of physical activity, and it should be continued for at least a minute of exercise to allow the radioactive tracer to distribute. Depending on the SPECT radioactive tracer, images acquisition may begin immediately or can be delayed up to a few hours. Due to the short half-life of PET tracer, pharmacological stress is preferred in these patients.
In patients who are unable to exercise or achieve an adequate heart rate response, there are several pharmacological agents to achieve cardiac stress. Broadly speaking, there are two types, vasodilator or inotropic/chronotropic drugs.
Examples of vasodilators are adenosine, dipyridamole, and regadenoson. They primarily cause coronary vasodilation and increase coronary blood flow during stress, which is 3 to 5 times the resting blood flow. The flow through the normal coronary arteries increases up to fourfold during coronary vasodilation and radiotracer uptake.[6] The presence of flow-limiting stenosis in the coronary artery causes a relative reduction in blood flow during stress leading to reduced radiotracer uptake, reflecting as a perfusion defect.
Examples of inotropic/chronotropic agents are dobutamine with or without atropine.
The most commonly used radioisotope for SPECT imaging is 99m-technetium labeled perfusion agents such as 99m-Tc-sestamibi, 99m-Tc-tetrofosmin. Use of thallium-201 is becoming increasingly less common as Tc99 has higher energy, less attenuation, and less scatter of photons.
PET imaging utilizes Rubidium-82 and 13-N ammonia tracers. Rubidium-83 is widely used because it does not require on-site cyclotrons, unlike 13-N ammonia, but it requires a rapid delivery system because its half-life is 75 seconds. PET imaging is different from SPECT in the fact that it requires additional external radiation sources for image acquisition in addition to image acquisition after tracer administration. Both images are then used for attenuation correction. Rubidium-81 causes approximately 3 millisieverts radiation exposure, while N-13 ammonia causes 2 millisieverts radiation exposure.
Major complications usually do not occur with stress testing. Some of the side effects associated with pharmacological agents are described here.
Adenosine might cause wheezing, chest pain with possible ST-segment changes, hypotension. Symptoms rapidly resolve because of the short half-life, with rarely requiring aminophylline to reverse the effects. More common minor side effects are nausea, flushing, dyspnea, and headache.
Serious adverse events with dipyridamole, such as nonfatal myocardial infarction, cardiac death rate, sustained ventricular tachycardia, have been reported, albeit rare. And some minor side effects such as chest pain, headache, and dizziness may occur. Symptoms are completely reversible after the administration of aminophylline. Side effects of regadenoson and dobutamine are as mentioned above.
Patient education prior to the stress test is important. The most common side effects are headache and flushed feeling. Procedures can occur over a day or two.
Following instructions should be given prior to the procedure:
Coronary artery disease is becoming an increasing cause of morbidity and mortality worldwide. In 2020, it is estimated that deaths from CAD may increase to 11.1 million globally.[11] Healthy lifestyle choices such as exercise, dietary interventions, reducing weight, and smoking cessation can substantially reduce CAD.[12] Cardiac stress testing is an extraordinary diagnostic and prognostic tool for patients with suspected heart disease. It evaluates cardiac perfusion and function at rest and after stress, such as exercise or pharmacological. It also assesses functional and anatomic CAD. Multiple secondary interventions to prevent MI and the progression of CAD can be undertaken. An appropriate intervention targeted towards individual patients can reduce the global burden, morbidity, and improved quality of life in patients with CAD.[13]
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