Stress Testing Review

Cardiac stress testing is a means to diagnose coronary artery disease in the presence of anginal symptoms, and is important in evaluating patients with symptoms of chest pain. Stress testing can answer the question: "Are the patient's symptoms caused by occlusive coronary disease?" Significant prognostic information can be obtained as well, especially using the well-validated Duke Treadmill Score. On rare occasion, stress testing is used to evaluate valvular heart disease such as aortic stenosis or mitral stenosis, or to diagnose heart rhythm disorders, such as in 2:1 AV block or Wolff-Parkinson-White syndrome.

There are many ways to perform a stress test; however, the two main things to consider are how the heart will be stressed and the mechanism used to determine whether coronary stenosis is present. This is done by either ECG or different types of cardiac imaging. Keep in mind that coronary CT angiography is a quickly emerging means to diagnosis coronary disease, as well. Also, stress testing is very safe, with a 1 in 10,000 risk of a major complication.

How to Stress the Heart

Stress can be induced on the heart in one of two ways: exercise stress testing or drug-induced (pharmacological stress testing). Pharmacological stress testing can be done using either regadenoson (Lexiscan, Astellas) or dobutamine. The use of persantine and adenosine is much less common.

The best way to induce cardiac stress is exercise, as it is more natural and physiologic. When a patient is able to exercise to induce cardiac stress, this is indeed the preferred method. The goal is to achieve a specific target heart rate in order to induce an adequate level of stress to detect flow-limiting coronary stenosis. This has been determined to be 85% of the age-predicted maximum heart rate using the simple equation below:

Maximum Heart Rate = 220 - Age

When a patient is not able to exercise adequately to achieve 85% of the age-predicted maximum heart rate, or when beta-blockers or other AV blocking agents are inhibiting the heart rate increase needed, the sensitivity of the stress test to detect coronary stenosis will be reduced and pharmacologic stress testing should be considered.

The standard Bruce protocol on a treadmill is most commonly utilized to increase the heart rate with exercise and is summarized below. This uses 3-minute stages with progressive increases in speed and incline. 

  Time % grade MPH km/h Mets
Stage I 3 min 10% 1.7 2.7 5.0
Stage II 6 min 12% 2.5 4.0 7.0
Stage III 9 min 14% 3.4 5.4 10.0
Stage IV 12 min 16% 4.2 6.7 13.0
Stage V 15 min 18% 5.0 8.0 15.0
Stage VI 18 min 20% 5.5 8.8 18.0
Stage VII 21 min 22% 6.0 9.6 20.0

Note that exercise should be terminated if any of the following occur (ACC/AHA Guidelines2):

  1. severe hypertension (systolic blood pressure > 200/110 mmHg before test or > 250/115 mmHg during exercise);
  2. hypotension (decrease in SYSTOLIC blood pressure > 10 mmHg);
  3. exercise limiting chest pains;
  4. sustained ventricular tachycardia;
  5. new ST segment elevation in leads without diagnostic Q waves;
  6. central nervous system symptoms (ataxia, severe dizziness, near-syncope);
  7. signs of poor perfusion (cyanosis or pallor); and
  8. patient's desire to stop.

Regadenoson is easy to use, as it is administered as a single bolus, is short-acting (half-life: 2-3 minutes) and has a good side effect profile. Regadenoson is a coronary vasodilator that acts by stimulating adenosine receptors. Diseased coronary arteries do not respond as well to the effects of regadenoson, thus normal segments will receive disproportionate coronary flow after regadenoson injection, allowing nuclear imaging to detect stenosis (see below). There is no target heart rate necessary with regadenoson, as the stress induced is from the vasodilation and not increased oxygen demand. Side-effects include flushing, nausea/vomiting, chest pains and shortness of breath. Aminophylline or caffeine can be given to reverse the effects of regadenoson. Caffeine intake must be avoided 24 hours prior to using regadenoson.

Dobutamine acts by stimulating beta-receptors, specifically beta-1, to increase chronotropy (heart rate). This drug is given in a continuous infusion with doses starting at 5 mcg/kg/min and increased to 40 mcg/kg/min every 3 minutes (protocols vary) until 85% of the age-predicted maximum heart rate is achieved. Atropine is sometimes given to further increase the heart rate if the desired effect is not seen with dobutamine. Side effects are somewhat minimal with dobutamine but may include palpitations, headache, hypertension or hypotension.

How to Image the Heart

Imaging the heart helps determine whether inducing stress using the above methods caused detectable myocardial ischemia, which would then indicate a significant coronary stenosis. The means to image the heart include electrocardiography (ECG stress testing), echocardiography, nuclear imaging and magnetic resonance imaging (MRI). 

ECG stress testing is performed in all cases. Once target heart rate is achieved, myocardial ischemia can be detected by examining the ST segment. An abnormal response is present if there is > 1 mm of horizontal or downsloping ST segment depression at least 80 ms after the J point (0.08 seconds or two small boxes) in both lead V5 and V6. ST depression in the inferior leads II, III and aVF is less sensitive and not examined by some interpreters. Note that the same criteria are used regardless of the means of stress (exercise, regadenoson or dobutamine); however, the diagnostic accuracy is greater when exercise is used, and frequently ST segment changes from dobutamine are ignored as they can occur in normal individuals. Also note that due to a low sensitivity/specificity, a plain dobutamine ECG or plain regadenoson ECG is never performed and an additional imaging modality is always used in combination (echocardiography or nuclear).

Stress echocardiography can detect regional wall motion abnormalities during stress that were not present at rest, indicating a significant coronary stenosis. The images must be acquired at or above 85% of the age-predicted maximum heart rate when dobutamine is used as a means to stress, or simply within 1 minute of exercise termination when exercise is used. Note that regadenoson echocardiography is not validated and is not routinely performed.

Nuclear stress testing requires the injection of a tracer, commonly technicium 99M (Myoview or Cardiolyte), which is then taken up by healthy, viable myocardial cells. A camera (detector) is used afterwards to image the heart and compare segments. A coronary stenosis is detected when a myocardial segment takes up the nuclear tracer at rest, but not during cardiac stress. This is called a "reversible defect." Scarred myocardium from prior infarct will not take up tracer at all and is referred to as a "fixed defect."

Stress MRI is only performed with the infusion of adenosine and is a newer means of detecting ischemia. This is a good method when myocardial viability is also in question (from hibernating myocardium).

Special Situations

Aortic valve stenosis, when severe, is considered a relative contraindication to stress testing. The fixed valve orifice area does not increase adequately when the muscles demand more cardiac output, thus vasodilation in the muscles causes hypotension, which results in syncope or cardiac arrest. In some patients with possibly asymptomatic severe aortic stenosis, treadmill ECG testing can be done to assess functional capacity. 

A left bundle branch block (LBBB) is a contraindication to exercise stress testing to detect myocardial ischemia. Recall that ischemia cannot be diagnosed on ECG when a LBBB is present. Interestingly, there is alteration of coronary flow due to the abnormal septal motion that occurs from a LBBB, thus when heart rates are elevated and diastole shortens (recall the coronary arteries fill in diastole), there will be deceased coronary perfusion. This can create a "false positive" nuclear stress test showing reversibility in the septum, and similarly the abnormal septal motion can make stress echocardiography difficult, as well. Using regadenoson with nuclear imaging is the preferred means of obtaining cardiac stress when a LBBB is present since it does not cause the heart rate to increase to a large degree.

References:

Fletcher GF, et al. Circulation. 2001;104:1694-1740.

Gibbons RJ, et al.Circulation. 2002;106:1883-1892.