Answer: The first issue we need to consider are the goals of testing. In this circumstance, the goals are presumably both diagnostic, to see whether myocardial ischemia is a cause of the patient's dyspnea on exertion, and prognostic, to stratify this patient’s risk of cardiac events. Given those dual goals, there are several issues that need to be addressed in the choice of testing. The first is whether the patient is able to exercise. In this case, given his complaint of dyspnea on exertion, it seems he is capable of some exertion. In this situation, I would strongly advise doing some sort of exercise stress test because it will provide information about exercise capacity and exercise-induced arrhythmias that would not be available from pharmacologic testing. An exercise stress test may also shed some light on whether or not this patient's complaint is purely a reflection of deconditioning. Too often, we see patients like this who were sent for pharmacologic testing rather than exercise testing.

Next, we need to address whether the patient has had previous revascularization. If the patient has had previous percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG), the standard of care is to use exercise imaging because of its ability to localize the area of ischemia and the important implications that might have for subsequent management of a patient with prior revascularization.

Lastly, we need to consider the patient's resting electrocardiogram (ECG). Certainly, we know that pre-existing abnormalities on the resting ECG may preclude adequate interpretation of the exercise ECG. Those abnormalities include pre-excitation, left bundle branch block or a paced rhythm, or at least 1 millimeter of resting ST-depression. In patients who have one of those pre-existing resting ECG abnormalities and therefore don't have an interpretable exercise ECG, exercise imaging is preferred.¹

Now, assuming that the patient does not have prior revascularization and has an interpretable resting ECG, an exercise ECG is a reasonable choice for a first test. That has been the position in the ACC/AHA guidelines since 1998, and I think it's a reasonable starting point. Certainly that doesn't assume that we’ll always get a definitive answer from this single test, since the results may put the patient in an intermediate risk category and necessitate subsequent imaging studies.

Some might argue that it makes sense to go straight to radionuclide imaging in this patient, given the possibility of needing to do additional testing. We recently had a middle-aged man like this with a complaint of dyspnea on exertion, and it turned out he had atrial fibrillation with exertion that was clearly the cause of his symptoms. He and his exercise ECG were fine until the moment he developed atrial fibrillation. So he certainly didn't require radionuclide imaging to establish that this was his problem.

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Answer: National guidelines from the ACC and AHA have pointed out for some time that the diagnostic yield of cardiac imaging is greatest in patients with an intermediate pretest probability of disease.² In these patients, a positive test greatly increases their likelihood of disease, and the negative test greatly decreases their likelihood of disease. So the rationale for doing stress testing in general is greatest in that category of patients.

The rationale for doing stress imaging in a low-risk patient is far weaker. Such patients often can be assessed with an exercise treadmill alone because if the test is negative, their probability of disease goes even lower and they don't really require additional testing. Although some have argued that they are more confident in the findings from stress imaging in such patients, if one looks carefully at the available literature, stress imaging adds relatively little to a patient with a low clinical risk who has a low-risk treadmill test.

One study showed that the additional information that came from imaging low-risk patients actually had no prognostic value whatsoever (Table).³ These patients had an excellent prognosis if they had a low clinical risk and a low risk treadmill regardless of what the images showed.

Finally, patients with a high probability of CAD present a substantially different issue because their diagnosis is generally not in doubt. Usually this is a man over the age of 50 or a woman older than that with typical angina. Such patients have a very high likelihood of disease, so the diagnosis for them is already established. The value of testing therefore is primarily prognostic. While there is still a substantial argument for starting with an exercise electrocardiogram, exercise perfusion imaging will add substantial additional prognostic information in many of those patients.

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Answer: Patients with reactive airway disease, such as a history or testing that suggests overt asthma or chronic obstructive pulmonary disease (COPD) with a substantial component of reversible bronchospasm, are a challenge with respect to stress testing. I believe that the first principle is again to exercise such a patient if at all possible. Often such patients are being tested because they have some symptoms during exercise and the clinician is concerned that those symptoms might not just reflect their lung function, but also their heart function.

However, some patients with reactive airway disease have a very limited exercise capacity. When pharmacologic testing is deemed to be required, the agent needs to be selected very carefully. We need to distinguish patients with definite asthma by either history or testing from those with COPD and modest reversible airway disease. The guiding principle is patient safety, so if there is a history of asthma or methacholine challenge testing that suggests asthma, I do not believe that adenosine or adenosine agonists are safe. Certainly, adenosine has known potential to create bronchospasm. The newer adenosine agonists have not yet been tested in large enough patient populations to establish whether they are safe in these particular patients. So in patients with overt asthma, dobutamine is the stress agent of choice.

In contrast, patients who have COPD and a modest component of bronchospasm can be tested safely with adenosine in certain selected circumstances. This was demonstrated in a study from the Mayo Clinic.⁴ We found that patients who have a forced expiratory volume during the first second (FEV₁) of at least 40% of predicted and a bronchodilator response < 31% can be safely tested with adenosine if they are pretreated with an albuterol inhaler (Figure).

We have been following that protocol in our laboratory ever since and we have not yet had a significant respiratory event or arrest. So certain patients with COPD can be safely studied with adenosine or an adenosine agonist. Obviously though, these patients must receive prior pulmonary function testing. In the absence of that testing and with a history that suggests bronchospasm, dobutamine would have to be the preferred agent.

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