Cardiac Stress Testing

by H. Lynn Magill, M.D. and Paul Hess, M.D.

Myocardial perfusion imaging may be performed using thallium-201 or technetium-99m labeled radiopharmaceuticals (sestamibi or tetrofosmin). Clinical experience is greatest with thallium, previously performed as 3-view planar studies and currently most often as tomographic (SPECT) imaging. Conventional stress-redistribution thallium imaging is optimally used for detection or evaluation of the coronary artery disease (CAD) in average sized to thin patients. Those patients with obesity, large breast, large barrel-shaped chest, or protuberant abdomen may benefit from a technetium agent. The higher photon energy of technetium (140 keV) is less attenuated by soft tissue than is the lower energy of thallium (83-87 keV), potentially decreasing false positive results.

The Cardiac Non-Invasive Stress Laboratory frequently serves as an intermediary between referring physicians evaluating patients with potential cardiac disease and subsequent cardiac diagnostic and/or interventional activities. The stress laboratory has grown in complexity to address a variety of clinical cardiac problems. At the risk of over simplifying a complex process, we present some basic concepts to guide physicians in the optimal use of stress techniques.

Appropriate patient selection is crucial to optimal clinical decisions and to resource utilization. The majority of patients referred to the stress laboratory require further evaluation of a "chest pain syndrome" to determine the presence/absence and the severity of potential functional myocardial ischemia related to obstructive CAD. In this broad patient population, the pretest probability of functionally significant obstructive CAD has an important impact on the diagnostic accuracy of the non-invasive stress test outcome. In those patients presenting with either high or low probability of functionally significant obstructive CAD on the basis of presenting clinical syndrome, non-invasive stress protocols may yield a significant percentage of falsely negative or falsely positive outcomes potentially confounding clinical decisions. Non-invasive stress protocols are most relevant in terms of incremental diagnostic value in those patients presenting with "chest pain syndrome" who fall into the category of "intermediate probability of functionally significant CAD" on the basis of their pretest clinical data. In addition to clarifying "chest pain syndromes", Nuclear Cardiology protocols may also be helpful to determine the presence/location/severity of reversible/irreversible ischemia, to determine rest and/or stress LV/RV systolic-diastolic dysfunction, or to determine viable/nonviable myocardium. These data may inform decisions regarding medical therapy or revascularization/surgical therapy, e.g., PTCA- Stents, CABG, Transplant, etc.

The preferred method of stress involves either bicycle or treadmill symptom-limited exercise testing to elicit symptoms and/or hemodynamic/electrocardiographic and/or nuclear imaging responses. If the patient is unable to perform adequate exercise, IV Adenosine infusion then becomes the preferred pharmacologic stress-in the presence of contradictions to IV Adenosine, IV Dobutamine infusion serves as an alternative pharmacologic stress. A variety of nuclear imaging techniques have expanded the capability of the cardiac stress laboratory.

The use of sestamibi or tetrofosmin provides opportunity to study left ventricular (LV) function in conjunction with myocardial perfusion imaging. Gated SPECT gives information about resting LV function, regional wall motion, and systolic wall thickening. A fixed perfusion defect demonstrating systolic wall thickening and wall motion is most likely an artifact, rather than scar or severe ischemia. First-pass radionuclide left ventriculography (RNA) can be performed on radiopharmaceutical injection for an exercise or pharmacologic stress perfusion study. A normal stress RNA with a good LV injection fraction will increase confidence in a normal interpretation and substantiate as a probable artifact a mild fixed or reversible perfusion defect. The technetium labeled agents may underestimate mild ischemia and the extent of ischemic myocardium (false negative) relative to thallium, but the clinical significance of this has not been established.

Stress-redistribution thallium imaging is a one day test, whereas sestamibi or tetrofosmin stress and rest studies are most accurate when performed on separate days (two day test). When these studies are performed on the same day (either stress-rest or rest-stress sequences), myocardial ischemia may be misdiagnosed as scar (particularly with the stress-rest sequence). An alternative single day dual isotope protocol, using thallium for the rest study and sestamibi or tetrofosmin for the stress study, preserves most of the benefits of imaging with a technetium labeled radiopharmaceutical. This protocol is less likely to provide diagnostic quality images in very large or morbidly obese patients, who will also be limited to planar imaging if their weight exceeds safety limits of the SPECT imaging table (300 pounds). It is unlikely that a planar study will be adequate in patients whose weight exceeds 350 pounds.

Although a number of protocols have been proposed to evaluate myocardial viability, the most widely used clinical methods are thallium stress or rest studies with reinjection and/or delayed (7-24 hour) imaging, dobutamine echo, and flourine-18 fluorodeoxyglucose (FDG) metabolic imaging with PET or more recently SPECT imaging (special modification of gamma camera required). FDG imaging, currently considered an imperfect clinical "gold standard", has the highest sensitivity for detection of viable myocardium, but like other available imaging techniques it does not always differentiate partial scar and does not definitively determine whether myocardial revascularization will benefit a patient.

Myocardial perfusion imaging depicts tissue flow/perfusion, whereas coronary arteriography shows the internal surface of and flow within the epicardial and larger subendocardial coronary arteries. Coronary arteriography may show a high grade stenosis, but if the vascular territory is well perfused by collateral vessels, perfusion imaging may be normal. The severity of a stenosis may be over or underestimated by arteriography, but the effect of that stenosis on regional myocardium is shown by perfusion imaging. False positive or false negative results may occur with either of these studies, resulting in divergent interpretations. False positive results may occur with myocardial perfusion imaging because of patient motion, variable attenuation by breast or diaphragm, or left bundle branch block (more likely to occur with exercise or dobutamine stress than with adenosine). A false negative result may occur when the level of stress is insufficient, e.g., a patient is unable or unwilling to perform adequate exercise or has taken medication or food that interferes with pharmacologic stress. Caffeine and other xanthine derivatives interfere with adenosine and should be avoided by patient for 24 hours prior to a study with pharmacologic vasodilatation. Beta blockers interfere with dobutamine and should be discontinued for a time period approximating 4 times the particular drug's biological half-life.

Cardiac stress testing, particularly with nuclear cardiology functional imaging studies, can serve as an invaluable technique in screening appropriate patients. In this era of managed care, these techniques may frequently be interposed between referral physicians confronted with problems patients and the invasive cardiac laboratory. We hope that this brief discussion may assist in patient selection for the Cardiac Stress Laboratory to optimize our patient care and enhance our practice of good medicine. We encourage communication between our referring physicians and the Cardiologists/Nuclear Radiologists.