There are many cardiac stress testing procedures available to physicians. This online brochure has been prepared by the staff of the Nuclear Cardiology/Cardiac Stress Laboratory to help referring physicians choose the most appropriate procedure for their patients.

Division of Cardiology
College of Physicians & Surgeons of Columbia University
630 West 168th Street
New York, NY 10032
Phone: 212-305-5996
Fax: 212-305-9049

Treadmill Testing

Stress Testing: Treadmill and Pharmacologic

Indications For Exercise Testing – AHA/ ACC Guidelines

Class I

1. Patients undergoing initial evaluation with suspected or known CAD. Specific exceptions are noted in Class IIb.
2. Previously evaluated patients, with suspected or known CAD that have had significant change in clinical status.

Class IIb

1. Patients with the following ECG abnormalities
   
   Preexcitation (WPW) syndrome
   Electrically paced ventricular rhythm
   Greater than 1 mm resting ST depression
   Complete LBBB
   
   
2. Patients with a stable clinical course who undergo periodic monitoring to guide treatment.

Class III

1. Patients with severe comorbidity likely to limit life expectancy and/or candidacy for revascularization.

Gibbons et al JACC 1997

Approaches to Diagnosis of CAD

Baysian approach - Pretest probability.

Treadmill stress testing first.
Consider diagnostic accuracy.
Consider cost.

Stress imaging test first.
Consider diagnostic accuracy.
Consider cost

Chest Pain Syndromes-the dilemma

Very common: 16% of 2717 healthy subjects in the Framingham cohort complained of chest pain.

Outcome could be fatal if patient has ischemic pain, dissecting aortic aneurysm, or pulmonary embolism.

Incidence of potentially fatal causes is very low.

Large number of people must be evaluated in cost effective manner.

Gender differences in chest pain proven to be ischemic in origin

Characteristics of chest pain are different in women than men..

Acute MI: Neck and shoulder pain, nausea, vomiting, fatigue, dyspnea.

Chronic stable angina: Pain with emotional or mental stress or during sleep.

Probability of CAD in women

Major determinants:Typical angina, postmenopausal status without HRT, diabetes mellitus, peripheral vascular disease.

Intermediate determinants: HTN, smoking, low HDL.

Minor determinants: age > 65 yr, obesity, sedentary lifestyle, FH.

Risk:High- 2 or more major or one major and one or more intermediate or minor determinants (80%), moderate- one major or multiple
intermediate and minor (20-80%), low- no major and one or no intermediate or < 2 minor (<20%).

Douglas et al NEJM 1996

Other causes of chest pain

Chest pain with normal coronaries

Aortic dissection

Pulmonary causes

Esophageal disorders

Musculoskeletal pain

Panic disorder

Testing modalities

Treadmill ECG

Exercise perfusion

Exercise echo

Pharmacologic stress
Vasodilator with nuclear imaging
Dobutamine with nuclear
Dobutamine with echo

Clinical factors to consider in selecting a stress modality

Age

Symptoms

Risk profile

Body habitus

Functional capacity

Contraindications to Exercise Testing

Absolute

Acute MI or recent change in ECG

Active unstable angina

Serious arrhythmias

Acute pericarditis

Endocarditis

Severe AS

Decompensated CHF

Acute PE

Relative

Less serious noncardiac disorder

Significant arterial or pulmonary HTN

Tachy- or bradyarrhythmias

Moderate valvular disease or heart failure

Drug effect or electrolyte abnls

LM CA obstruction or equivalent

HoCM

Psychiatric disorders

Fletcher et al Circ 1990

Patient Preparation and Instruction for Stress Test

Instruct Patients: No food or smoking for 3 hours before test. Dress for exercise.

Take a history and perform brief PE before test to look for contraindications for testing or detect important clinical signs such as murmur,
gallop, bronchospasm, rales.

Consider withdrawal of medications that interfere with HR response. For dipyridamole or adenosine, no xanthines x 48 hours prior to testing.

Measurements Available from the ETT

Electrocardiographic

Maximum ST depression

Maximum ST elevation

ST depression slope (downsloping, horizontal, upsloping)

Number of leads showing ST changes

Duration of ST deviation during recovery

ST/HR indices

Exercise-induced ventricular arrhythmias

Time to onset of ST deviation

Hemodynamic

Maximum exercise HR

Maximum exercise systolic BP

Maximum exercise double product (HR x BP)

Total exercise duration

Exertional hypotension

Chronotropic incompetence

Symptomatic

Exercise induced angina

Exercise limiting symptoms

Time to onset of angina

Gibbons et al JACC 1997

Clinically Significant METs

1 Met = resting = 3.5 ml kg-1 min -1 oxygen uptake.

2 Mets = level walking at 2 mph

4 Mets = level walking at 4 mph

<5 Mets = poor prognosis; usual limit immediately after MI; peak cost of basic activities of daily living.

10 Mets = prognosis with medical therapy as good as CABG

13 Mets = excellent prognosis

18 Mets = elite endurance athletes

20 Mets = world class athletes

Fletcher et al Circ 1990

Predictive value of exercise stress testing in men vs women
Because of higher incidence of false positive tracings among women the specificity is reduced compared to men.

Barolsky et al Circ 1979

Summary

Consider all indictions and contraindications to stress testing

Prepare patient especially stopping medications that blunt HR response if clinical question is presence or absence of CAD.

Select the best mode of stress for your patient

Consider value of functional capacity

If pharmacological stress necessary imaging is necessary,

Consider gender differences

Pharmacologic Stress Testing

Pharmacological stress testing is used, as an alternative to exercise, in patients in whom exercise stress testing is impossible, contraindicated, or when exercise fails to achieve 85% of predicted maximal heart rate for age.

Definition:

Pharmacologic stress testing refers to the administration of the pharmacological agent and observation of symptoms, clinical findings, homodynamic variables, electrocardiography, and usually the performance of nuclear studies or echocardiography. Pharmacological agents in general clinical use include dobutamine (a beta-adrenergic agent used to simulate exercise and increase myocardial oxygen consumption) or the infusion of a coronary vasodilator (adenosine or dipyridamole).

Indications:

1. To assist in the diagnosis of chest pain or discomfort that is suspected to possibly be cardiac in origin in patients who are unable to perform treadmill stress testing.
2. To evaluate the extent of coronary disease in presence of recent myocardial infarction.
3. To detect significant coronary artery disease in the presence of risk factors such as coronary artery calcification on CT, hypercholesterolemia, diabetes mellitus, hypertension, cigarette smoking and/or family history of premature coronary disease in patients who are unable to perform treadmill stress testing.

Absolute Contraindications:

1. Acute myocardial infarction or suspicion of acute myocardial infarction (within 36 hr of onset of symptoms).
2. Unstable angina with resting ECG changes from prior baseline.
3. Known severe left main coronary artery disease.
4. Aortic stenosis greater than moderate severity.
5. Serious uncontrolled arrhythmia.
6. Uncontrolled CHF, severe orthopnea, dyspnea at rest.
7. Acute pericarditis or myocarditis
8. Acute pulmonary infarction or pulmonary embolism.
9. Mental incapacity such that patient is unable to cooperate with the study.

Relative contraindications include:

1. Mental incapacity (inability to understand the protocol or give informed consent) unless a healthcare proxy or other responsible individual is present and able to consent.

Contraindications to Dipyridamole or Adenosine:

1. History of active bronchospastic disease, asthma, or pulmonary disease requiring bronchodilators such as theophylline, beta-2 agonists or corticosteroids.
2. Ingestion of caffeine or drugs containing caffeine or methylxanthines (i.e., aminophylline) within 12 hours of the test.
3. Patients receiving dipyridamole within 48 hours.
4. A-V block in patients without a pacemaker. (PR >240 msec or second degree) (for adenosine).
5. Ingestion of caffeine or drugs containing caffeine or methylxanthines (i.e., aminophylline) within 12 hours of the test.
6. Baseline hypotension (systolic blood pressure < 90 mmHg).
7. Aortic stenosis
8. Severe pulmonary hypertension

Contraindications to dobutamine:

1. History of ventricular tachycardia within 48 hours
2. Use of beta-blocker medication within 12 hours

Major complications

Potential serious complications of pharmacologic stress testing include myocardial infarction, death, serious and life threatening arrhythmias, hypotension, and acute bronchospasm requiring endotracheal intubations.

Choice of Pharmacologic agent:

In general adenosine is the agent of choice because it provides the best sensitivity and has a very short half-live abbreviating systemic symptoms from the vasodilation. In patients with bronchospasm, those having taken theophylline, caffeine etc, those with baseline low BP dobutamine is the agent of choice. In patients receiving oral dipyridamole or intravenous dipyridamole within 48 hours, or AV block, dipyridamole is the agent of choice.

Adenosine

Adenosine is a potent coronary vasodilator and is our preferred agent for pharmacological stress testing because it has a very reproducible response. It has a half-life of approximately 9-10 seconds. Symptoms and side effects abate within 1 to 2 minutes after termination of the infusion. Adenosine is continuously infused at a rate of 140 mcg/kg/min (total dose: 0.56 or 0.84 mg/kg) for 6 minutes via a syringe pump. Radiopharmaceutical is administered at either 2 or 3 minutes of adenosine infusion.

Dipyridamole

Dipyridamole (Persantine) is a coronary vasodilator. It works by increasing the adenosine levels locally at the receptor sites. It has a longer half-life than adenosine. Symptoms associated with dipyridamole are malaise, headache, nausea, breathlessness, chest discomfort, and flushing. Symptoms can be reversed promptly by the administration of aminophylline. The incidence of myocardial infarction is 0.1% and the incidence of death is 0.05% (based on a study of 3900 patients).

Dipyridamole is infused at a rate of 0.14 mg/kg/min for 4 minutes. Dipyridamole can be infused continuously via a syringe pump or by hand giving aliquots every 30 seconds. The maximum permissible dose is 60 mg.Radiopharmaceutical is administered 3 minutes after completion of the dipyridamole infusion.

Reversal of dipyridamole effect with aminophylline:

Most adverse effects can be attenuated reversed with intravenous aminophylline (50 to 125 mg) given by slow bolus and which may be repeated every 3 to 5 minutes up to a total dose of 6 mg/kg. If the patient develops a severe side effect, which requires termination of the infusion or administration of aminophylline, the radioisotope can be injected early. If at all possible, administration of aminophylline should be delayed at least 2 minutes after the injection of the radioisotope.

Elective Administration of Aminophylline

It is reasonable to reverse the symptoms with aminophylline even if they are no serious side effects. For these cases, it is best to administer the aminophylline 5 to 10 minutes after the administration of the radioisotope.

Effects of Caffeine:

Ingestion of food or drink containing caffeine, or use of drugs containing either caffeine or other methylxanthines (such as aminophylline or theophylline preparations) mitigates the effect of dipyridamole for coronary vasodilation,which may cause a false negative test. Therefore a patient with known caffeine ingestion within 12 hours should not have a dipyridamole test performed. Note that many "clear" sodas contain significant caffeine.

Dobutamine

Dobutamine pharmacologic stress testing is used if a patient has a contraindication to adenosine and dipyridamole, usually asthma. Symptoms associated with dobutamine are shortness of breath, chest discomfort, palpitations, and rapid heart beat. The standard concentration is 1mg/ml, which is obtained by diluting 50mg (4ml of standard vial concentration of 12.5mg/ml) to 50ml with normal saline. The syringe pump is used in dose mode and the dobutamine is infused starting at either 5 or 10mcg/kg/min, increasing by 5 or 10mcg/kg/min every 3 minutes to a maximum dosage of 40mcg/kg/min.

If satisfactory heart rate response is not obtained with dobutamine alone, further increase in HR may be achieved either by addition of leg exercise or administration of intravenous atropine (0.2 to 2 mg)

Radiopharmaceutical is administered 1 minutes prior to completion of the dobutamine infusion. Dobutamine infusion may need to be terminated prematurely if the patient develops ventricular tachycardia, severe hypotension or hypertension or any other medical emergency. Metoprolol (2.5 – 5 mg slow bolus, i.v. repeated up to 15mg) can be used to antagonize dobutamine effect. Dobutamine infusion is continued until the patient experiences symptoms that preclude continuing such as worsening chest pain, or until at least 85% of predicted maximum heart rate for age has been achieved or until the dose of 40mcg/kg/min has been achieved.

Myocardial Perfusion Imaging and Ventricular Function

The following table is taken from an ACCF/ASNC Appropriateness Criteria document appearing in JACC in 2005 (Oct 1, pp 1587-605). The document was prepared by a panel of experts who combined evidence-based information and clinical experience. We believe it is a fair presentation of all of the indications for ordering stress perfusion imaging that will yield useful information for patient management in a cost-effective manner. The only change we made was to replace resting perfusion scanning for ED chest pain patients with stress perfusion imaging for level III ED chest pain patients. Indications for test ordering were scored on a scale of 1-9 with scores 1-3 in inappropriate category, 4-6 in the uncertain category, and 7-9 as appropriate. Only the latter are presented here. For more information please go to the article referenced above.

Table 11. Appropriate Indications (Median Rating of 7 to 9)

Detection of CAD: Symptomatic- Evaluation of Chest Pain Syndrome

Intermediate pre-test probability of CAD

ECG interpretable AND able to exercise

Intermediate pre-test probability of CAD

ECG uninterpretable OR unable to exercise

High pre-test probability of CAD

ECG interpretable AND able to exercise

High pre-test probability of CAD

ECG uninterpretable OR unable to exercise

Detection of CAD: Symptomatic- Acute Chest Pain (ED Level III cps) Intermediate pre-test probability of CAD

ECG: no ST elevation AND initial cardiac enzymes negative

Detection of CAD: Symptomatic- New-Onset/Diagnosed Heart Failure With Chest Pain Syndrome

Intermediate pre-test probability of CAD

Detection of CAD: Asymptomatic- New-Onset or Diagnosed Heart Failure or LV Systolic Dysfunction Without Chest Pain Syndrome

Moderate CHD risk (Framingham)

No prior CAD evaluation AND no planned cardiac catheterization

Detection of CAD: Asymptomatic (Without Chest Pain Syndrome)- New-Onset Atrial Fibrillation

High CHD Risk (Framingham)

Part of the evaluation

Detection of CAD: Asymptomatic (Without Chest Pain Syndrome)-Ventricular Tachycardia

Moderate to high CHD risk (Framingham)

Risk Assessment: General and Specific Patient Populations- Asymptomatic

Moderate to high CHD risk (Framingham)

High-risk occupation (e.g., airline pilot)

Risk Assessment With Prior Test Results: Asymptomatic OR Stable Symptoms? Normal Prior SPECT MPI Study

Normal initial RNI study

High CHD risk (Framingham)

Repeat SPECT MPI study after 2 years or greater

Risk Assessment With Prior Test Results: Asymptomatic OR Stable Symptoms? Abnormal Catheterization or Prior SPECT MPI Study

Known CAD on catheterization OR prior SPECT MPI study in patients who have not had revascularization procedure

Greater than or equal to 2 years to evaluate worsening disease

Risk Assessment With Prior Test Results: Worsening Symptoms? Abnormal Catheterization OR Prior SPECT MPI Study

Known CAD on catheterization OR prior SPECT MPI study

Risk Assessment With Prior Test Results: Asymptomatic? Prior Coronary Calcium Agatston Score

Agatston score greater than or equal to 400

Risk Assessment With Prior Test Results: UA/NSTEMI, STEMI, or Chest Pain Syndrome-Coronary Angiogram

Stenosis of unclear significance

Risk Assessment With Prior Test Results?Duke Treadmill Score

Intermediate Duke treadmill score

Intermediate CHD risk (Framingham)

Risk Assessment: Preoperative Evaluation for Non-Cardiac Surgery-Intermediate-Risk Surgery

Intermediate perioperative risk predictor OR

Poor exercise tolerance (less than 4 METS)

Risk Assessment: Preoperative Evaluation for Non-Cardiac Surgery? High-Risk Surgery

Minor perioperative risk predictor AND

Poor exercise tolerance (less than 4 METS)

Risk Assessment: Following Acute Coronary Syndrome?STEMI-Hemodynamically Stable

Thrombolytic therapy administered

Not planning to undergo catheterization

Risk Assessment: Following Acute Coronary Syndrome?UA/NSTEMI?No Recurrent Ischemia OR No Signs of HF

Not planning to undergo early catheterization

Risk Assessment: Post-Revascularization (PCI or CABG)? Symptomatic

Evaluation of chest pain syndrome

Risk Assessment: Post-Revascularization (PCI or CABG)? Asymptomatic

Asymptomatic prior to previous revascularization

Greater than or equal to 5 years after CABG

Symptomatic prior to previous revascularization

Greater than or equal to 5 years after CABG

Assessment of Viability/Ischemia: Ischemic Cardiomyopathy (Includes SPECT Imaging for Wall Motion and Ventricular Function)

Known CAD on catheterization

Patient eligible for revascularization

Evaluation of Left Ventricular Function

Non-diagnostic echocardiogram

Evaluation of Ventricular Function: Use of Potentially Cardiotoxic Therapy (e.g., Doxorubicin)

Baseline and serial measurements

Positron Emission Tomography (PET)

Patient Preparation

To prepare for this exam:

If your patient's appointment is before 12 noon, please advise patient not to eat or drink after midnight the night before the exam.
The patient may have some water if they need it.

If your patient's appointment is for 12 noon or after, please advise patient to have a light breakfast before 8 am.
Please advise the patient not eat or drink after that.  The patient may have water if they need it.

Please advise patient not to eat or drink anything with caffeine, including coffee, tea, soda, or chocolate after midnight the night before the exam.
Advise patient not eat or drink anything that says "decaffeinated" or "caffeine free".

Please advise patient to wear comfortable clothing.

Please advise patient to bring a list of all the medications they take, with the times and doses.

Advise patient to try to avoid strenuous activities, such as jogging or running, before the appointment.

Furthermore, if the patient takes any medications, advise your patient before the appointment about whether they should take them before the exam.

Safety in the Nuclear Cardiology Laboratory

Our commitment to the safety of our patients serves as a cornerstone of our mission to deliver the highest quality of healthcare possible.

Before the Test

All patients, prior to stress testing, are screened for contraindications to such testing. Absolute contraindications to stress testing include:

1. Acute myocardial infarction or suspicion of acute myocardial infarction.
2. Unstable angina with resting ECG changes from prior baseline.
3. Known severe left main coronary artery disease.
4. Serious uncontrolled arrhythmia.
5. Uncontrolled CHF, severe orthopnea, dyspnea at rest.
6. Acute pericarditis or myocarditis
7. Acute pulmonary infarction or pulmonary embolism.
8. Any acute, serious non-cardiac disorder such as uncontrolled asthma, severe pain, fever.
9. Mental incapacity such that patient is unable to be cooperative with the study.

All female patients between age 12 and 55 years presenting for nuclear imaging are asked if they are, or might be, pregnant or breast feeding. In the case of the patient not being sure regarding her status, pregnancy testing is available on the site.

Stress testing is performed in our laboratory using either treadmill exercise testing or pharmacologic stress testing with intravenous adenosine, dipyridamole, or dobutamine. Each stressor has method-specific absolute and relative contraindications, and the choice of stressor is dependent on the presence of such contraindications. In addition to the general contraindications above, all patients are screened for such method-specific contraindications. For example, patients with critical aortic stenosis will not undergo stress testing of any kind; patients with atrioventricular block or on oral dipyridamole will not receive adenosine; patients with obstructive pulmonary disease will not receive dipyridamole; and patients with a history of ventricular tachycardia will not receive dobutamine.

All patients or their health care proxies are instructed about stress testing, have an opportunity to ask questions about the procedure, and sign informed consent, all prior to the test.

During the Test

All stress tests are supervised by a Columbia University Medical Center attending cardiologist, and performed by a staff member including cardiologists, cardiology fellows, and registered nurses, who are all certified in Advanced Cardiac Life Support. An external cardiac defibrillator, tested on a daily basis, is always present in case of emergency. All nuclear image acquisition and dose calibration is performed by licensed nuclear technologists.

While we strive to perform the test as safely as possible, side effects from cardiac stress testing are not uncommon, and serious complications occur on rare occasion. All patients are carefully monitored for these effects.

Exercise Stress Testing
Exercise is the preferred stressor for patients who are able to safely walk on the treadmill. Safety of exercise stress testing has been extensively studied. In a report of over 500,000 patients, myocardial infarction occurred in 0.04%, serious arrhythmia in 0.05%, and death in 0.005%. Data from our laboratory are similar.

Adenosine Stress Testing
Adenosine stress testing is our preferred method of pharmacologic stress, due to its reproducible vasodilatory response and short half-life which typically results in side effects abating within two minutes of completing the infusion. A majority of patients who receive adenosine will note some minor side effects during the six minute infusion. Common side effects include flushing and chest pain, each of which was reported in about one third of patients in a large series, as well as headache and dyspnea, which occur in about one fifth of patients. Chest pain, when it occurs, is a nonspecific finding and need not reflect underlying coronary artery disease. In some patients, we augment adenosine administration with low level exercise, which can decrease the occurrence of symptoms.

Serious complications from adenosine stress testing are rare. AV block occurs in less than 8% of cases, but in over 95% of these cases the block is benign and does not require stopping administration of adenosine. The risk of complete heart block is less than 1%. The risk of fatal or nonfatal myocardial infarction from adenosine is less than 0.1%. Our laboratory has been involved in clinical research studies to develop even safer adenosine receptor agonists.

Dipyridamole Stress Testing
Minor side effects occur in about half of patients receiving dipyridamole. Common side effects from dipyridamole include chest pain, headache, and dizziness. Side effects from dipyridamole may last longer than those from adenosine, necessitating the administration of aminophylline to reverse its effects. Because of its longer duration of action, dipyridamole is the stressor of choice for PET perfusion imaging. This risk of fatal or nonfatal myocardial infarction from dipyridamole stress testing in one large study was approximately 0.1%, and the risk of death was 0.05%.

Dobutamine Stress Testing
Dobutamine pharmacologic stress testing is used if a patient has a contraindication to adenosine and dipyridamole, such as asthma. Three quarters of patients receiving dobutamine develop symptoms, including up to half of patients who develop palpitations. Other symptoms associated with dobutamine include chest pain, flushing, headache, and dyspnea. The more serious side effects include hypertension, hypotension, myocardial ischemia, and arrhythmias. In one large study, major cardiac complications (sustained ventricular tachycardia, ventricular fibrillation, or myocardial infarction) occurred in 0.25% of patients undergoing dobutamine stress testing.

Radiation Safety and Dosimetry
All patients in the nuclear cardiology laboratory receive radiopharmaceuticals. The attributable risk of cancer, while extremely low, is not zero, and the consensus of current scientific opinion is that this risk is directly proportional to the radiation dose to the patient. Our laboratory strives to minimize the dose received by patients, in accordance with the ALARA (as low as reasonably achievable) principle. We have an active research program dedicated to optimizing strategies to minimize the risks from radiation to nuclear cardiology patients. Several different stress testing protocols are in use, depending on the clinical scenario, and the radiation dose to the patient varies depending on the protocol, ranging from about 6 to 22 milli-Sieverts (mSv). By way of comparison, the typical annual background radiation dose to an individual in the United States is about 3 mSv, so a nuclear cardiology study results in a dose equal to 2 to 7 years of background radiation.

The more clinical information that is available to the nuclear laboratory, the better we are able to optimize the patient's protocol to minimize the small risk from radiation to your patient. For example, patients with low pretest probability of disease, such as many preoperative patients, may have "stress only" imaging performed, obviating the need for a second set of rest images and its attendant radiation dose.

After the Test

Patients are electrocardiographically and hemodynamically monitored after stress testing for at least four minutes, until the effects of the stressor have resolved. Patients typically have no restrictions on activity after the stress test. Female patients who are nursing are given specific instructions about resumption of breastfeeding, depending on the radiopharmaceuticals used. Patients who expect prolonged close contact with pregnant women or newborns should ask for specific directives; these too depend on the radiopharmaceuticals used.

Selected References

Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: results from Adenoscan Multicenter Trial Registry. J Am Coll Cardiol 1994;23:384-390.

Einstein AJ, Moser KW, Thompson RC, Cerqueira MD, Henzlova MJ. Effect of proposed new ICRP guidelines on effective dose for SPECT and PET myocardial perfusion imaging studies. J Nucl Cardiol 2006; 13: S15-S16.

Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters WL Jr. ACC/AHA 2002 guideline update for exercise testing: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). Available at: www.acc.org/clinical/guidelines/exercise/dirIndex.htm. Accessed October 20, 2006.

Hays JT, Mahmarian JJ, Cochran AJ, Verani MS. Dobutamine thallium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or vasodilator pharmacologic stress testing. J Am Coll Cardiol. 1993;21:1583-90.

Henzlova MJ, Cerqueira MD, Mahmarian JJ, Yao S-S. Stress protocols and tracers. In: EG DePuey (ed.) Imaging Guidelines for Nuclear Cardiology Procedures. Available at: http://www.asnc.org/imageuploads/Imaging%20Guidelines%20Stress%20Protocols.pdf. Accessed October 20, 2006.

Mathias W Jr, Arruda A, Santos FC, Arruda AL, Mattos E, Osorio A, Campos O, Gil M, Andrade JL, Carvalho AC. Safety of dobutamine-atropine stress echocardiography: A prospective experience of 4,033 consecutive studies. J Am Soc Echocardiogr 1999; 12:785-91.

Mertes H, Sawada SG, Ryan T, Segar DS, Kovacs R, Foltz J, Feigenbaum H. Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients. Circulation 1993; 88:15-9.

Ranhosky A, Kempthorne-Rawson J. The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Intravenous Dipyridamole Thallium Imaging Study Group. Circulation 1990; 81:1205-9.

Stuart RJ, Ellestad MH. National survey of exercise testing. Chest 1980; 77:94-7.