Impression:
Mrs. Smith presents with two different types of chest discomfort. Retrosternal chest discomfort on exertion may be suggestive of ischemic heart disease, especially given the risk factors of positive family history, smoking, obesity, hypertension and sedentary lifestyle. The second type is less suggestive of cardiac origin, but sometimes it's difficult to differentiate between the two. Heartburn and cardiac manifestations may also coexist.

Plan:
Mrs. Smith is given a requisition for complete blood count, creatinine, electrolytes, liver function tests, creatine kinase (to confirm that there's no acute coronary syndrome and to get a baseline before potential lipid therapy), fasting lipids, glucose and a baseline ECG at rest. Lifestyle adjustments are addressed and a follow-up appointment is booked.

Atherosclerosis is responsible for almost all cases of coronary artery disease (CAD). The process begins in childhood with fatty streaks that progress into plaques in early adulthood. As they grow, they may manifest as angina pectoris or cause coronary events. Early detection of atherosclerosis allows the physician to begin interventions that slow the progression of CAD. Sometimes it's a difficult task, however, to determine whether a patient's chest discomfort is indeed due to coronary disease or caused by some other condition. An example of this situation would be a case where the biochemical markers and ECG are unchanged.

Also, keep in mind the possibility of atypical presentation, often seen in women and patients with significant risk factors for CAD but no symptoms, e.g. those with long-standing diabetes mellitus. In this article, we review resources available to the doctor that may aid in making the diagnosis and guide the necessary treatment.

On her follow-up appointment, Mrs. Smith denies any episodes of chest discomfort over the past 2 weeks, although she continued normally with her daily activities. She only gets mild heartburn after meals. Her BP now is 160/95 mm Hg, and the HR is 75 beats/min.

The blood work indicates mild glucose intolerance and slightly elevated lipids. The rest of her results are within normal limits. Baseline ECG, however, shows a left bundle branch block (LBBB).

Impression:
Mrs. Smith has multiple risk factors for CAD. Her initial presentation was suggestive of angina pectoris, but now she denies any symptoms on exertion.

Plan:
You recommend a low-fat and low-sugar diet and again encourage physical activity, weight loss and smoking cessation. Further testing to determine whether she has ischemic heart disease is considered as follows.

Treadmill or bicycle exercise tolerance test
Consider this test first, as it helps determine whether blood supply is decreased -- due perhaps to plaque -- during higher myocardial demand. The cardiac stress test is the most common method used to increase heart rate, but it requires the patient to be physically able to walk without any aids. The main ECG contraindications to the test are LBBB, abnormal baseline ECG including left ventricular hypertrophy, and a continuously paced rhythm, which can make the tracing difficult to interpret. A physician must be present during the study as this test carries a risk of death of 1/10,000.

According to the available literature, the mean sensitivity and specificity of exercise tolerance testing are about 68% and 77%, respectively, for detecting significant flow-limiting CAD.¹ More importantly, the study can also be used to monitor physical fitness. For every metabolic equivalent (MET) increase in activity, mortality from heart disease falls by 10%.

Though this is controversial, a starting systolic BP > 140 mm Hg and a maximum BP > 220 mm Hg at peak exercise is considered a hypertensive response, and is a marker for reduced survival. Diastolic BP should go down with activity. Again, the treadmill can provide complementary information on hypertension. In patients who participate in cardiac rehabilitation, repeat testing after a baseline study is often done at around 3-6 months to evaluate the success of rehabilitation.

Although exercise stress testing is the simplest screening tool for coronary disease, Mrs. Smith is not a good candidate because of the LBBB on her baseline ECG. So what are the alternatives?

Pharmacologic stress testing
This approach to accelerating the heart rate is reserved for patients who aren't able to exercise. The commonly used agent is dipyridamole; dobutamine is also an option. The other indications and contra-indications are similar to those of the exercise tolerance test; however, longer preparation time is required as the pharmacologic agent may interact with commonly used substances such as caffeine. Dipyridamole testing is also contraindicated in individuals with known bronchospastic disease. The sensitivity is between 80 and 90%. Ideally, all drugs that affect ischemia should be stopped for this test.

Stress echocardiography
Here's an option that can be combined with stress testing. Immediately after achieving target heart rate -- either with pharmacologic agents or because of actual exercise on the treadmill -- the patient's heart wall motion is assessed with an echocardiogram. The heart segments that aren't receiving adequate blood supply will appear abnormal. This assessment requires the presence of an experienced cardiologist who specializes in echo interpretation, as well as a skilled echocardiography technician. The results may be limited by the patient's body habitus. In general, exercise echo has a sensitivity of 85% and a specificity of 77% for detecting flow-limiting CAD.²

Patients with LBBB often show wall motion abnormalities on the echocardiogram (due to septal dyssynergy). So Mrs. Smith is again not the ideal candidate for this particular modality.

Exercise myocardial perfusion imaging
Myocardial perfusion imaging involves the visualization of a radiopharmaceutical that is distributed throughout the myocardium in proportion to coronary blood flow. Regional blood flow determines the amount of tracer activity within that specific area. The visualization depends on the physical properties and delivery of the radiolabelled tracer, as well as the extraction and retention by the myocyte. Retained tracer activity is consistent with myocyte viability.

Several radiolabelled myocardial perfusion agents are now available, and the most common include thallium-201, Tc99m-sestamibi and Tc99m-tetrofosmin. This form of cardiac diagnostic imaging demands time and preparation, complicated equipment and skilled personnel. Again, the results of the test may be altered by a patient's body habitus or artifacts (such as motion), or due to uptake in other tissues and organs. There's also modest radiation exposure.

Mrs. Smith is a good candidate for a myocardial perfusion study, and she's referred for the test. The results come back positive for reversible ischemia in the anterior wall. There's also a possibility of a small fixed defect in the inferior wall, but this could be a tissue attenuation artifact due to her body habitus.

Impression:
The study confirms that Mrs. Smith does have significant coronary disease and is symptomatic. It's not unusual to experience symptoms of angina after meals, during exposure to cold weather, in stressful situations and typically with exertion.

Plan:
She's appropriately started on a low-dose aspirin, lipid-lowering agent and BP-lowering medication. A nitroglycerin spray is also prescribed for occasional use. A cardiology consultation is requested.

Positron emission tomography (PET)
PET is a non-invasive diagnostic tool that offers physiologic information about myocardial blood flow (perfusion) and tissue metabolism (viability). Unlike standard radionuclide imaging techniques, PET allows the assessment of dynamic physiologic and biochemical processes in the heart.

Rubidium-82, a radioactive tracer that emits subatomic particles (called positrons) is injected into the patient's arm and carried through the blood stream to the heart muscle. A special PET camera detects the emitted positrons and constructs a picture of the heart. This type of imaging is most useful in determining the amount of viable myocardium in patients who've sustained an MI. While for a thallium test (i.e. myocardial perfusion imaging) sensitivity is about 79% and specificity is 73%, the PET scan has an estimated sensitivity of 91% and specificity of 82%. The PET scan, though, requires more expensive and complicated equipment and trained specialists.

Although a reasonable test to consider for Mrs. Smith given that she may already have a scar in the inferior wall, accessibility to this test modality is still very limited.

Computed tomography coronary angiography (CTA)
This is a new, non-invasive method of assessing coronary anatomy and diagnosing CAD. It's reserved for patients who present with atypical chest pain, where it's used to rule out CAD or abnormal coronary anatomy. A contrast agent is being injected intravenously and images of the heart and coronary arteries are obtained with a CT scanner. Cardiac CT may also be used to quantify coronary artery calcification. These tests are contraindicated in patients with significant renal disease or arrhythmias, and during pregnancy. Test interpretation may be limited because of motion artifacts, inadequate contrast opacification, foreign body or the patient's body habitus. Again, there's limited radiation exposure and sophisticated equipment and highly trained staff are needed for this study.

If Mrs. Smith had undergone an exercise tolerance test and if the results of the functional study were equivocal, this would be a good test to rule out or confirm ischemic heart disease. We already know, however, that she has multiple risk factors for CAD, that she is symptomatic and that she does have a positive functional study confirming reversible ischemia and possible myocardial scarring. Therefore, she's not a good candidate for CTA at this time.

Cardiac MRI
This method uses magnetic resonance to create cardiac images that may be used, among others, to assess cardiac function, ischemia, viability or inflammation. There's no radiation exposure, although the test is contraindicated in patients with significant renal dysfunction or previously implanted metallic objects. Availability of this modality is currently limited to a small number of hospitals, as it requires special equipment and assistance of trained specialists.

Mrs. Smith doesn't need this test, as adequate information is already available from previously ordered investigations.

Coronary angiography
This is a gold standard for ruling in or ruling out coronary artery disease. It's the standard of diagnosis and can even include treatment for eligible patients presenting with acute coronary syndrome. risk of dying from the procedure is 1/1,000. It's an invasive test requiring arterial access and exposing the patient to a moderate amount of radiation. Contraindications to an elective procedure may include: lack of consent or patient's cooperation, coagulopathy or bleeding problem, recent stroke, active infection, renal dysfunction, pregnancy, contrast medium allergy and advanced age. Complications occur in less than 1% of patients and may include MI, pericardial tamponade, bleeding, hematoma, nerve damage at the site of arterial access, stroke or embolization, kidney impairment and allergic reaction. The procedure is done by an interventional cardiologist in a catheterization laboratory, and it requires variable length of observation postprocedure. Depending on the angiogram result, it may be immediately followed by angioplasty and stenting.

The bottom line
Clearly, there are multiple options when it comes to cardiac imaging. The local expertise in your area is one of the factors that will determine what the appropriate workup and follow-up should be. Remember that it's insufficient in challenging patients to simply do cardiac testing. In many circumstances, early use of angiography -- even though it has a higher risk of complications -- may be needed to "clear the air." Non-invasive testing can give misleading results at times and can't explore the microcirculation that we still know very little about.