4. If your patient requires a pharmacologic stress test, what are your options besides adenosine?
While adenosine is the agent of choice, dipyridamole and dobutamine are other options. When any of these agents are used, it’s important to consider the side effects of each, and which drugs your patient will need to avoid prior to the stress test.
Adenosine is a mediator of coronary vasodilation. The drug dilates normal coronary arteries preferentially to stenotic vessels and causes redistribution of blood flow away from areas of the myocardium with compromised circulation.
Dipyridamole, a mediator of adenosine release, is sometimes used instead. Both drugs are given as a 4-minute infusion, with injection of the tracer late in the infusion.
The adverse effects of adenosine occur early in the infusion, and include dyspnea, bronchospasm, chest pain, nausea, and headache. Bradycardia can be marked, and brief periods of complete heart block and long sinus pauses may occur. Hypotension can likewise be profound. Many of these effects are extremely disturbing to the patient under-going the test, but they disappear within 30 seconds of stopping the infusion.
Dipyridamole has similar adverse effects, although heart block is not part of its adverse effect profile. In addition, the drug’s adverse effects occur later in the infusion than those associated with adenosine and last well after it is finished. However, dipyridamole’s side effects can be reversed with intravenous aminophylline without compromising the accuracy of the test.
Drugs to avoid that day. Methylxanthines antagonize adenosine and dipyridamole, and thus must be avoided on the day of the test. Caffeine and theophylline are among the substances to be avoided, although the degree to which they affect test results has been questioned recently.15
Severe COPD and asthma—especially in patients with uncontrolled wheezing—are relative contraindications to the use of adenosine and dipyridamole.
Interestingly, the cardiovascular effects (and EKG changes) associated with these drugs are not necessarily indicative of CAD. Thus, the entire EKG portion of a pharmacologic stress test is not useful in interpreting the finding. One small study suggests that, unlike exercise stress testing, adenosine stress testing may be safe in patients with severe aortic stenosis.16
Dobutamine is another alternative for pharmacologic stress testing, for patients who cannot take adenosine or are unable to stop theophylline or similar medications. An infusion of dobutamine with an escalating dose, sometimes including atropine, is used to accelerate the heart rate to 85% of the patient’s age-predicted maximum. The stress is primarily due to the chronotropic effect of the drug, but dobutamine has some coronary vasodilatory activity and may also induce some redistribution of coronary blood flow, similar to the effect of adenosine.
The positive and negative predictive values of pharmacologic stress testing are the same as for nuclear stress testing. Unlike exercise testing, however, functional capacity cannot be inferred from a pharmacologic stress test.
About 10% of patients undergoing pharmacologic stress testing will have a nondiagnostic test. The sensitivity of the test varies among studies, but it is approximately 84%, 95%, and 100% for single-, double-, and triplevessel disease, respectively. Patients with negative tests have an event rate of less than 1% per year.17
5. Is stress echocardiography comparable to stress testing?
Yes. Stress echocardiography, which involves echocardiographic studies taken before and after stress, can substitute for either exercise or pharmacologic stress testing (the stress can be achieved either with exercise or an infusion of dobutamine), and it has certain advantages: Stress echocardiography is cheaper than nuclear stress testing, and there is no radiation involved. In addition, stress echocardiography yields positive and negative predictive values similar to those seen with nuclear stress testing.2,3 The presence of ischemia is inferred from localized wall motion abnormalities.
The primary disadvantage of stress echocardiography is that it can be administered only by a cardiologist who has been specially trained in this procedure. In contrast, any community hospital nuclear medicine department has the capacity to perform nuclear imaging, and most radiologists are able to interpret the nuclide scans. In my experience, decisions about whether to order nuclear cardiac stress testing or stress echocardiography are influenced not only by the availability of these modalities, but also by the skill of the physicians who will interpret the tests.
6. Which exercise-induced EKG changes are related to ischemia?
The only changes that correlate with myocardial ischemia are ST depression and ST elevation. J-point depression is almost universally seen with exercise. For this reason, the ST level is measured 80 milliseconds after the J point.
ST depression—the most common abnormal finding—indicates subendocardial ischemia. ST changes are most commonly seen in the inferior and lateral leads, but do not correlate with the location of ischemia. ST depression can be downsloping, horizontal, or upsloping. The first 2 are the most significant patterns, and 1 mm of ST depression is the minimum significant level. Upsloping ST depression is less significant, and 1.5 mm of depression is the minimum significant change.1 The greater the degree of ST depression, the higher the likelihood that significant occlusion will be seen on coronary angiography. ST depression that develops in the recovery period is a rare occurrence but of equal significance to ST depression that occurs with exercise, and is probably due to ischemia caused by shunting of blood into skeletal muscle and away from the heart.1