Dennis P. Breen, MD

Evidence summary

Limiting further evaluation of men with a first UTI to those at increased risk (TABLE) may reduce unnecessary radiological, endoscopic, or urodynamic investigation.

Approximately 20% of all UTIs occur in men,^1-3 and the lifetime prevalence is about 14%.³ The incidence in elderly men is high, often attributable to a bladder outflow obstruction.⁴ (For this review, the definition of UTI is limited to bacterial infections of the kidney, ureter, or bladder, and does not include urethritis, epididymitis, prostatitis, or orchitis.)

TABLE
Conditions that increase risk of urinary tract infection in men^3,7,9,10

Get a urine culture

A urine culture is recommended to reliably diagnose an infection and guide treatment.⁵

• A cohort of 66 men (mean age, 66±13 years) presenting to a VA urology clinic for procedures, dysuria, or bacteriuria had urine samples taken while voiding, as well as directly from the bladder, either via suprapubic aspiration or urethral catheterization. Using bladder cultures as a gold standard, midstream urine culture had a specificity and sensitivity of >97% at a threshold of 1000 CFU/mL.⁶

The usual organisms are colonic bacteria: Escherichia coli (75%), enterococci (20%), and, less commonly, Klebsiella and Proteus.⁴

No need for routine imaging

Consider a workup for men who have no response to antibiotic therapy or have persistent hematuria.

There is little evidence to support routine imaging in low-risk men with a first UTI, whether with or without fever:

• A very small prospective study of 29 heterosexual, circumcised men 16 to 45 years old (those who were sexually active had a steady partner) who were hospitalized with a first febrile UTI failed to find any significant structural or functional urinary tract abnormalities.⁴
• Another small prospective study of 85 men, 18 to 86 years of age, with febrile UTI, concluded that routine imaging of the upper urinary tract was unnecessary, and that, if indicated, further workup should focus on the lower urinary tract.⁷ Abnormalities in this group were suggested by a history of voiding problems, hematuria, or recurrent infection. One limitation of this study was the incomplete urodynamic and endoscopic evaluation of the lower urinary tract.
• Another study enrolled 114 men, 18 to 85 years of age, with proven UTIs, who underwent ultrasonography and plain radiography, as well as an IVP.⁸ (Only 100 had complete data at enrollment.) All men had urinary flow rates measured. The combination of a plain abdominal film and ultrasonography detected more abnormalities than an IVP. (The primary role of the plain film was in detecting urinary calculi.)

Final “clinical” diagnoses were reported, but the study did not report a comparison of clinical and radiological findings. Almost half of the abnormalities were lower tract obstructions (bladder outlet obstruction, underactive detrusor, and chronic retention). There was no comment on the importance or treatment of any abnormalities found.

Recommendations from others

PRODIGY (from the British National Health Service) recommends:

• Men under 45 years with a first UTI who respond well to antibiotic treatment are not likely to have a urologic abnormality.⁹
• Older men who do not respond well to antibiotics or who have recurrent UTIs are likely to have abnormalities and may benefit from further investigation.⁹

Neither the American Academy of Urology, the US Preventive Services Task Force, nor the Agency for Healthcare Research and Quality has published guidelines for evaluation of adult men with a first UTI.

Evidence summary

Limiting further evaluation of men with a first UTI to those at increased risk (TABLE) may reduce unnecessary radiological, endoscopic, or urodynamic investigation.

Approximately 20% of all UTIs occur in men,^1-3 and the lifetime prevalence is about 14%.³ The incidence in elderly men is high, often attributable to a bladder outflow obstruction.⁴ (For this review, the definition of UTI is limited to bacterial infections of the kidney, ureter, or bladder, and does not include urethritis, epididymitis, prostatitis, or orchitis.)

TABLE
Conditions that increase risk of urinary tract infection in men^3,7,9,10

Get a urine culture

A urine culture is recommended to reliably diagnose an infection and guide treatment.⁵

• A cohort of 66 men (mean age, 66±13 years) presenting to a VA urology clinic for procedures, dysuria, or bacteriuria had urine samples taken while voiding, as well as directly from the bladder, either via suprapubic aspiration or urethral catheterization. Using bladder cultures as a gold standard, midstream urine culture had a specificity and sensitivity of >97% at a threshold of 1000 CFU/mL.⁶

The usual organisms are colonic bacteria: Escherichia coli (75%), enterococci (20%), and, less commonly, Klebsiella and Proteus.⁴

No need for routine imaging

Consider a workup for men who have no response to antibiotic therapy or have persistent hematuria.

There is little evidence to support routine imaging in low-risk men with a first UTI, whether with or without fever:

• A very small prospective study of 29 heterosexual, circumcised men 16 to 45 years old (those who were sexually active had a steady partner) who were hospitalized with a first febrile UTI failed to find any significant structural or functional urinary tract abnormalities.⁴
• Another small prospective study of 85 men, 18 to 86 years of age, with febrile UTI, concluded that routine imaging of the upper urinary tract was unnecessary, and that, if indicated, further workup should focus on the lower urinary tract.⁷ Abnormalities in this group were suggested by a history of voiding problems, hematuria, or recurrent infection. One limitation of this study was the incomplete urodynamic and endoscopic evaluation of the lower urinary tract.
• Another study enrolled 114 men, 18 to 85 years of age, with proven UTIs, who underwent ultrasonography and plain radiography, as well as an IVP.⁸ (Only 100 had complete data at enrollment.) All men had urinary flow rates measured. The combination of a plain abdominal film and ultrasonography detected more abnormalities than an IVP. (The primary role of the plain film was in detecting urinary calculi.)

Final “clinical” diagnoses were reported, but the study did not report a comparison of clinical and radiological findings. Almost half of the abnormalities were lower tract obstructions (bladder outlet obstruction, underactive detrusor, and chronic retention). There was no comment on the importance or treatment of any abnormalities found.

Recommendations from others

PRODIGY (from the British National Health Service) recommends:

• Men under 45 years with a first UTI who respond well to antibiotic treatment are not likely to have a urologic abnormality.⁹
• Older men who do not respond well to antibiotics or who have recurrent UTIs are likely to have abnormalities and may benefit from further investigation.⁹

Neither the American Academy of Urology, the US Preventive Services Task Force, nor the Agency for Healthcare Research and Quality has published guidelines for evaluation of adult men with a first UTI.

Evidence summary

Limiting further evaluation of men with a first UTI to those at increased risk (TABLE) may reduce unnecessary radiological, endoscopic, or urodynamic investigation.

Approximately 20% of all UTIs occur in men,^1-3 and the lifetime prevalence is about 14%.³ The incidence in elderly men is high, often attributable to a bladder outflow obstruction.⁴ (For this review, the definition of UTI is limited to bacterial infections of the kidney, ureter, or bladder, and does not include urethritis, epididymitis, prostatitis, or orchitis.)

TABLE
Conditions that increase risk of urinary tract infection in men^3,7,9,10

Get a urine culture

A urine culture is recommended to reliably diagnose an infection and guide treatment.⁵

• A cohort of 66 men (mean age, 66±13 years) presenting to a VA urology clinic for procedures, dysuria, or bacteriuria had urine samples taken while voiding, as well as directly from the bladder, either via suprapubic aspiration or urethral catheterization. Using bladder cultures as a gold standard, midstream urine culture had a specificity and sensitivity of >97% at a threshold of 1000 CFU/mL.⁶

The usual organisms are colonic bacteria: Escherichia coli (75%), enterococci (20%), and, less commonly, Klebsiella and Proteus.⁴

No need for routine imaging

Consider a workup for men who have no response to antibiotic therapy or have persistent hematuria.

There is little evidence to support routine imaging in low-risk men with a first UTI, whether with or without fever:

• A very small prospective study of 29 heterosexual, circumcised men 16 to 45 years old (those who were sexually active had a steady partner) who were hospitalized with a first febrile UTI failed to find any significant structural or functional urinary tract abnormalities.⁴
• Another small prospective study of 85 men, 18 to 86 years of age, with febrile UTI, concluded that routine imaging of the upper urinary tract was unnecessary, and that, if indicated, further workup should focus on the lower urinary tract.⁷ Abnormalities in this group were suggested by a history of voiding problems, hematuria, or recurrent infection. One limitation of this study was the incomplete urodynamic and endoscopic evaluation of the lower urinary tract.
• Another study enrolled 114 men, 18 to 85 years of age, with proven UTIs, who underwent ultrasonography and plain radiography, as well as an IVP.⁸ (Only 100 had complete data at enrollment.) All men had urinary flow rates measured. The combination of a plain abdominal film and ultrasonography detected more abnormalities than an IVP. (The primary role of the plain film was in detecting urinary calculi.)

Final “clinical” diagnoses were reported, but the study did not report a comparison of clinical and radiological findings. Almost half of the abnormalities were lower tract obstructions (bladder outlet obstruction, underactive detrusor, and chronic retention). There was no comment on the importance or treatment of any abnormalities found.

Recommendations from others

PRODIGY (from the British National Health Service) recommends:

• Men under 45 years with a first UTI who respond well to antibiotic treatment are not likely to have a urologic abnormality.⁹
• Older men who do not respond well to antibiotics or who have recurrent UTIs are likely to have abnormalities and may benefit from further investigation.⁹

Neither the American Academy of Urology, the US Preventive Services Task Force, nor the Agency for Healthcare Research and Quality has published guidelines for evaluation of adult men with a first UTI.

Are you a wise “consumer” of stress tests? That is: Do you consider your patient’s CAD probability score before ordering an exercise treadmill test or pharmacologic stress myocardial imaging (PSMI)? Are you as well-versed as you’d like to be on the predictive value of things like the Duke Treadmill Score?

If your answer is No to either question, this review may help guide your use of stress tests, based on evidence.

What is the pretest probability of CAD?

The decision to order an exercise stress test or a PSMI should be based on history, physical examination, and pretest probability for CAD. You can estimate the pretest probability for CAD in a chest pain patient based on the patient’s age, sex, and pain characteristics.¹

Determine whether symptoms are typical, atypical, or nonanginal, based on whether the chest pain is substernal, brought on by exertion, or relieved by rest or nitroglycerin.²

To recap:

• Typical angina requires all 3 pain characteristics
• Atypical angina, only 2
• Nonanginal chest pain, 1.²

Use this information (along with the patient’s age) to determine whether he has a high, intermediate, low, or very low likelihood of CAD (TABLE 1). From the low, to the intermediate, to the high pretest probability levels, the positive predictive value increases progressively (21%, 62%, and 92%) and the negative predictive value decreases progressively (94%, 72%, and 28%).³ (These values are based on a review of symptomatic patients who had angiography following stress testing.)

TABLE 1
How to determine pretest probability of coronary artery disease

Your patients’ score dictates whether testing is required, and if so what kind.

Very low pretest probability patients should not have an exercise test, since they have a high risk of false-positive results. Evaluate and treat them for noncardiac causes of chest pain and begin primary prevention of CAD.

Low pretest probability patients should undergo exercise treadmill testing alone since negative results carry a high negative predictive value in both men and women, but positive test results may be false and can be evaluated by more studies.³

Intermediate pretest probability patients, including those with complete right bundle branch block or less than 1 mm ST depression at rest should have an exercise treadmill test without imaging modality.^3-5 However, intermediate pretest probability patients with baseline ECG abnormalities such as electronically paced ventricular rhythm or left bundle-branch block will require myocardial perfusion imaging.⁵

High pretest probability patients should have coronary angiography as an initial strategy for diagnosis of CAD.³

History, exam, and ECG determine test suitability

Can your patient take an exercise stress test, or will he need a pharmacologic stress test instead? (See “A guide to sensitivity, specificity, and likelihood ratios for stress tests.”) Can he pedal a bicycle, walk, or exercise for 6 minutes? On physical examination, take note of his gait, mobility, and limb strength.

What medications is the patient taking? Digoxin may cause false ST changes, beta-blockers may prevent attaining maximum heart rate, and antihypertensive agents and vasodilators may alter the blood pressure response, producing a false negative result. Nitrates attenuate angina and the associated ST depression of ischemia.⁶ In addition, metabolic abnormalities and cocaine or alcohol use may affect heart rate, metabolic oxygen demand and the ability to perform the exercise treadmill testing.

On examination, document murmurs, rhythm abnormalities, vascular bruits, and abnormal pulses. Limit laboratory studies to recent cardiac damage screening if indicated. Screen with a resting ECG for arrhythmias, conduction abnormalities or preexisting cardiac damage. ST-segment (≥1 mm) and T-wave changes such as inversions secondary to strain or old injury or conduction abnormalities such as bundle branch blocks and prolonged QT interval may obscure exercise treadmill testing findings. Consider spirometry for patients with asthma or chronic lung disease.

The decisive factors

Absolute contraindications to exercise treadmill testing include recent MI; significant aortic stenosis,⁷ and weight exceeding equipment capacity. Relative contraindications to exercise treadmill testing (which can be superseded if the benefits of exercise outweigh the risks) include: hypertension (systolic >200 mm Hg/diastolic >110 mm Hg),⁵ left main coronary stenosis and stenotic valvular disease. (For more on “Contraindications to exercise testing,” see TABLE 2.)

The role of imaging: Important, yes—routine, no

An important element of stress testing is, of course, the imaging method(s) that will be used. The options include myocardial perfusion imaging with thallium Tl 201 or technetium Tc 99m, and echocardiography.

Indications for myocardial perfusion imaging with exercise treadmill testing are a high pretest probability for CAD, an abnormal baseline ECG such as left bundle branch block, previous myocardial damage or coronary revascularization, or a previous equivocal or unexpected exercise ECG result. In women with an intermediate pretest probability for CAD, the sensitivity and specificity of an exercise treadmill testing is less than in men, which suggests that nuclear imaging would improve this test.⁸ There is, however, insufficient data to justify initial routine stress imaging tests in women.¹

TABLE 2
Contraindications to exercise testing

Of the 2 agents used for myocardial perfusion imaging, technetium Tc 99m has more favorable imaging characteristics.⁹ It has a shorter half-life (6 hours) than thallium Tl 201 (73 hours), and larger doses of technetium Tc99m may be used, permitting the assessment of ventricular function.¹⁰

Echocardiography may also be done with either exercise treadmill testing or PSMI to evaluate relative myocardial perfusion. While radionuclide technique assesses relative myocardial perfusion, echocardiography also evaluates global and regional function. Indications for echocardiography are similar to myocardial perfusion imaging but also include the need for prognostic information after MI, and to assess physiologic significance of a lesion or to determine the success of an intervention.

Time for the test: Selecting the protocol

While the Bruce exercise treadmill testing protocol is the most commonly used (82% of tests)¹¹ in healthy adults, it may not be appropriate for women or the elderly as most protocols were developed for the evaluation of men.¹² A ramp method with gradual increase in grade each minute is preferred by some clinicians when patients are unable to perform a standard Bruce protocol. Another option, the Modified Bruce protocol, which is more gradual than the standard Bruce protocol; it has two 3-minute warm-up stages.¹²

The 3 PSMI protocols include adenosine, dipyridamole, and dobutamine. Each has a different administration routine,⁹ though ECG, blood pressure and pulse are taken every minute for all 3.

• Adenosine is infused with a pump over 6 minutes and technetium Tc99m is injected 3 minutes into the infusion.
• Dipyridamole is infused over 4 minutes and technetium Tc99m is injected 2 to no more than 5 minutes after the infusion. Theophylline is injected, after dipyridamole if necessary, no earlier than 1 minute after technetium Tc99m is administered to avoid interference with the uptake.
• Dobutamine is titrated with a dose increase every 3 minutes. Tc99m is injected after the first minute at the highest concentration. (Typically dobutamine is used with echocardiography.⁶)

Ideal endpoints and the realities that may creep in

The ideal endpoint in an exercise treadmill testing is 100% of the age-predicted maximum heart rate (220–age). Eighty-five percent of maximum heart rate is the minimum for an acceptable test.

Absolute contraindications

Absolute indicators for stopping an exercise treadmill test are either a 10 mm Hg systolic drop in blood pressure from standing baseline, moderate to severe angina symptoms, feelings of syncope, skin color changes suggestive of hypoxia or hypotension, ischemic ST changes, or the patient’s desire to stop.

Relative contraindications

Relative indicators to stop include fatigue, shortness of breath, leg pain, increased arrhythmias—particularly PVCs that increase with the exercise level—and blood pressure ≥250 systolic or 115 diastolic.⁶

Ideally, PSMI evaluations are terminated according to the prescribed length of infusions. They will also be terminated if a patient develops wheezing, severe or increasing chest pain or hypotension, neurological symptoms, ST-segment elevation abnormalities, or arrhythmias. To reverse the side effects of adenosine or dipyridamole, aminophylline IV will be administered (1–2 mg/kg slowly, up to 250 mg).

Heart of the matter: What a report should cover

Assuming you have ordered the stress test (and not done it yourself), a complete report should include

• ST changes
• symptoms during testing
• reason for ending the test
• estimation of exercise capacity
• blood pressure response
• the presence and frequency of arrhythmias or ectopy.

Abnormal. ST segment change is the most important ECG finding in a positive test; it’s defined as >1 mm horizontal or down sloping depression or elevation, at least 60 to 80 milliseconds after the end of the QRS complex and should prompt further workup to confirm CAD.⁵ An abnormal ECG during a PSMI test indicates an elevated risk of multivessel CAD and should prompt further evaluation regardless of normal myocardial perfusion imaging.¹³

Equivocal. Reports that come back as equivocal will have ECG changes nondiagnostic of ischemia such as alterations in P- or T-wave morphology and nondiagnostic changes in AV conduction, particularly if changes revert to baseline during the rest period. Unifocal PACs or PVCs (<5/min) are not specific indicators for CAD and the development of bundle branch blocks are nondiagnostic findings. Equivocal results need additional testing such as myocardial perfusion imaging or angiography to document ischemia if the pretest probability is high.

Incomplete or failure. If your patient’s test involves equipment failure or if he (or the operator) was unable to complete the test, you should get a report to that effect. Depending on the nature of the failure, you may need to repeat the test, consider PSMI, or make a cardiology referral.

Duke Treadmill Score

A helpful calculation following treadmill testing

If your patient had a positive or negative exercise treadmill test, consider calculating his Duke Treadmill Score (DTS), which is predictive of 5-year survival and significant severe CAD for patients who are younger than 75 years.^4,14

DTS helps you to exclude low-risk patients from further invasive testing and ensure high-risk patients receive further evaluation and appropriate treatment. DTS appears to be more useful in women with an intermediate pretest score but not with a low pretest score.¹⁵

The DTS score typically ranges from –25 to +15.⁵ Patients at low risk will have a score of > +5), moderate risk will have scores ranging from –10 to +4, and those at high risk will have a score of ≤–11.⁴

A modified DTS is used for patients older than 65 years who may have a limited exercise capacity, controlled asymptomatic congestive heart failure, or be on digoxin, which may affect their ability to perform a maximal exercise treadmill test.⁵ The values for the Elderly Alternative Treadmill Score are as follows: low risk (< –2); moderate risk (–2 to 2); and high risk (>2). (See “The calculations behind the scores.”)

Bottom line

DTS scores, Elderly Alternative Treadmill Scores, and pre–stress test CAD probability scores are all extremely useful. Integrating them into your practice can ensure that patients get the prompt care they may need, while sparing them unnecessary tests along the way.

FIGURE
Template for dictating noninvasive cardiac tests

Correspondence
Dennis P. Breen, MD, Eau Claire Family Medicine Clinic, 617 Clairemont Avenue, Eau Claire, WI 54701. [email protected]

Are you a wise “consumer” of stress tests? That is: Do you consider your patient’s CAD probability score before ordering an exercise treadmill test or pharmacologic stress myocardial imaging (PSMI)? Are you as well-versed as you’d like to be on the predictive value of things like the Duke Treadmill Score?

If your answer is No to either question, this review may help guide your use of stress tests, based on evidence.

What is the pretest probability of CAD?

The decision to order an exercise stress test or a PSMI should be based on history, physical examination, and pretest probability for CAD. You can estimate the pretest probability for CAD in a chest pain patient based on the patient’s age, sex, and pain characteristics.¹

Determine whether symptoms are typical, atypical, or nonanginal, based on whether the chest pain is substernal, brought on by exertion, or relieved by rest or nitroglycerin.²

To recap:

• Typical angina requires all 3 pain characteristics
• Atypical angina, only 2
• Nonanginal chest pain, 1.²

Use this information (along with the patient’s age) to determine whether he has a high, intermediate, low, or very low likelihood of CAD (TABLE 1). From the low, to the intermediate, to the high pretest probability levels, the positive predictive value increases progressively (21%, 62%, and 92%) and the negative predictive value decreases progressively (94%, 72%, and 28%).³ (These values are based on a review of symptomatic patients who had angiography following stress testing.)

TABLE 1
How to determine pretest probability of coronary artery disease

Your patients’ score dictates whether testing is required, and if so what kind.

Very low pretest probability patients should not have an exercise test, since they have a high risk of false-positive results. Evaluate and treat them for noncardiac causes of chest pain and begin primary prevention of CAD.

Low pretest probability patients should undergo exercise treadmill testing alone since negative results carry a high negative predictive value in both men and women, but positive test results may be false and can be evaluated by more studies.³

Intermediate pretest probability patients, including those with complete right bundle branch block or less than 1 mm ST depression at rest should have an exercise treadmill test without imaging modality.^3-5 However, intermediate pretest probability patients with baseline ECG abnormalities such as electronically paced ventricular rhythm or left bundle-branch block will require myocardial perfusion imaging.⁵

High pretest probability patients should have coronary angiography as an initial strategy for diagnosis of CAD.³

History, exam, and ECG determine test suitability

Can your patient take an exercise stress test, or will he need a pharmacologic stress test instead? (See “A guide to sensitivity, specificity, and likelihood ratios for stress tests.”) Can he pedal a bicycle, walk, or exercise for 6 minutes? On physical examination, take note of his gait, mobility, and limb strength.

What medications is the patient taking? Digoxin may cause false ST changes, beta-blockers may prevent attaining maximum heart rate, and antihypertensive agents and vasodilators may alter the blood pressure response, producing a false negative result. Nitrates attenuate angina and the associated ST depression of ischemia.⁶ In addition, metabolic abnormalities and cocaine or alcohol use may affect heart rate, metabolic oxygen demand and the ability to perform the exercise treadmill testing.

On examination, document murmurs, rhythm abnormalities, vascular bruits, and abnormal pulses. Limit laboratory studies to recent cardiac damage screening if indicated. Screen with a resting ECG for arrhythmias, conduction abnormalities or preexisting cardiac damage. ST-segment (≥1 mm) and T-wave changes such as inversions secondary to strain or old injury or conduction abnormalities such as bundle branch blocks and prolonged QT interval may obscure exercise treadmill testing findings. Consider spirometry for patients with asthma or chronic lung disease.

The decisive factors

Absolute contraindications to exercise treadmill testing include recent MI; significant aortic stenosis,⁷ and weight exceeding equipment capacity. Relative contraindications to exercise treadmill testing (which can be superseded if the benefits of exercise outweigh the risks) include: hypertension (systolic >200 mm Hg/diastolic >110 mm Hg),⁵ left main coronary stenosis and stenotic valvular disease. (For more on “Contraindications to exercise testing,” see TABLE 2.)

The role of imaging: Important, yes—routine, no

An important element of stress testing is, of course, the imaging method(s) that will be used. The options include myocardial perfusion imaging with thallium Tl 201 or technetium Tc 99m, and echocardiography.

Indications for myocardial perfusion imaging with exercise treadmill testing are a high pretest probability for CAD, an abnormal baseline ECG such as left bundle branch block, previous myocardial damage or coronary revascularization, or a previous equivocal or unexpected exercise ECG result. In women with an intermediate pretest probability for CAD, the sensitivity and specificity of an exercise treadmill testing is less than in men, which suggests that nuclear imaging would improve this test.⁸ There is, however, insufficient data to justify initial routine stress imaging tests in women.¹

TABLE 2
Contraindications to exercise testing

Of the 2 agents used for myocardial perfusion imaging, technetium Tc 99m has more favorable imaging characteristics.⁹ It has a shorter half-life (6 hours) than thallium Tl 201 (73 hours), and larger doses of technetium Tc99m may be used, permitting the assessment of ventricular function.¹⁰

Echocardiography may also be done with either exercise treadmill testing or PSMI to evaluate relative myocardial perfusion. While radionuclide technique assesses relative myocardial perfusion, echocardiography also evaluates global and regional function. Indications for echocardiography are similar to myocardial perfusion imaging but also include the need for prognostic information after MI, and to assess physiologic significance of a lesion or to determine the success of an intervention.

Time for the test: Selecting the protocol

While the Bruce exercise treadmill testing protocol is the most commonly used (82% of tests)¹¹ in healthy adults, it may not be appropriate for women or the elderly as most protocols were developed for the evaluation of men.¹² A ramp method with gradual increase in grade each minute is preferred by some clinicians when patients are unable to perform a standard Bruce protocol. Another option, the Modified Bruce protocol, which is more gradual than the standard Bruce protocol; it has two 3-minute warm-up stages.¹²

The 3 PSMI protocols include adenosine, dipyridamole, and dobutamine. Each has a different administration routine,⁹ though ECG, blood pressure and pulse are taken every minute for all 3.

• Adenosine is infused with a pump over 6 minutes and technetium Tc99m is injected 3 minutes into the infusion.
• Dipyridamole is infused over 4 minutes and technetium Tc99m is injected 2 to no more than 5 minutes after the infusion. Theophylline is injected, after dipyridamole if necessary, no earlier than 1 minute after technetium Tc99m is administered to avoid interference with the uptake.
• Dobutamine is titrated with a dose increase every 3 minutes. Tc99m is injected after the first minute at the highest concentration. (Typically dobutamine is used with echocardiography.⁶)

Ideal endpoints and the realities that may creep in

The ideal endpoint in an exercise treadmill testing is 100% of the age-predicted maximum heart rate (220–age). Eighty-five percent of maximum heart rate is the minimum for an acceptable test.

Absolute contraindications

Absolute indicators for stopping an exercise treadmill test are either a 10 mm Hg systolic drop in blood pressure from standing baseline, moderate to severe angina symptoms, feelings of syncope, skin color changes suggestive of hypoxia or hypotension, ischemic ST changes, or the patient’s desire to stop.

Relative contraindications

Relative indicators to stop include fatigue, shortness of breath, leg pain, increased arrhythmias—particularly PVCs that increase with the exercise level—and blood pressure ≥250 systolic or 115 diastolic.⁶

Ideally, PSMI evaluations are terminated according to the prescribed length of infusions. They will also be terminated if a patient develops wheezing, severe or increasing chest pain or hypotension, neurological symptoms, ST-segment elevation abnormalities, or arrhythmias. To reverse the side effects of adenosine or dipyridamole, aminophylline IV will be administered (1–2 mg/kg slowly, up to 250 mg).

Heart of the matter: What a report should cover

Assuming you have ordered the stress test (and not done it yourself), a complete report should include

• ST changes
• symptoms during testing
• reason for ending the test
• estimation of exercise capacity
• blood pressure response
• the presence and frequency of arrhythmias or ectopy.

Abnormal. ST segment change is the most important ECG finding in a positive test; it’s defined as >1 mm horizontal or down sloping depression or elevation, at least 60 to 80 milliseconds after the end of the QRS complex and should prompt further workup to confirm CAD.⁵ An abnormal ECG during a PSMI test indicates an elevated risk of multivessel CAD and should prompt further evaluation regardless of normal myocardial perfusion imaging.¹³

Equivocal. Reports that come back as equivocal will have ECG changes nondiagnostic of ischemia such as alterations in P- or T-wave morphology and nondiagnostic changes in AV conduction, particularly if changes revert to baseline during the rest period. Unifocal PACs or PVCs (<5/min) are not specific indicators for CAD and the development of bundle branch blocks are nondiagnostic findings. Equivocal results need additional testing such as myocardial perfusion imaging or angiography to document ischemia if the pretest probability is high.

Incomplete or failure. If your patient’s test involves equipment failure or if he (or the operator) was unable to complete the test, you should get a report to that effect. Depending on the nature of the failure, you may need to repeat the test, consider PSMI, or make a cardiology referral.

Duke Treadmill Score

A helpful calculation following treadmill testing

If your patient had a positive or negative exercise treadmill test, consider calculating his Duke Treadmill Score (DTS), which is predictive of 5-year survival and significant severe CAD for patients who are younger than 75 years.^4,14

DTS helps you to exclude low-risk patients from further invasive testing and ensure high-risk patients receive further evaluation and appropriate treatment. DTS appears to be more useful in women with an intermediate pretest score but not with a low pretest score.¹⁵

The DTS score typically ranges from –25 to +15.⁵ Patients at low risk will have a score of > +5), moderate risk will have scores ranging from –10 to +4, and those at high risk will have a score of ≤–11.⁴

A modified DTS is used for patients older than 65 years who may have a limited exercise capacity, controlled asymptomatic congestive heart failure, or be on digoxin, which may affect their ability to perform a maximal exercise treadmill test.⁵ The values for the Elderly Alternative Treadmill Score are as follows: low risk (< –2); moderate risk (–2 to 2); and high risk (>2). (See “The calculations behind the scores.”)

Bottom line

DTS scores, Elderly Alternative Treadmill Scores, and pre–stress test CAD probability scores are all extremely useful. Integrating them into your practice can ensure that patients get the prompt care they may need, while sparing them unnecessary tests along the way.

FIGURE
Template for dictating noninvasive cardiac tests

Correspondence
Dennis P. Breen, MD, Eau Claire Family Medicine Clinic, 617 Clairemont Avenue, Eau Claire, WI 54701. [email protected]

Are you a wise “consumer” of stress tests? That is: Do you consider your patient’s CAD probability score before ordering an exercise treadmill test or pharmacologic stress myocardial imaging (PSMI)? Are you as well-versed as you’d like to be on the predictive value of things like the Duke Treadmill Score?

If your answer is No to either question, this review may help guide your use of stress tests, based on evidence.

What is the pretest probability of CAD?

The decision to order an exercise stress test or a PSMI should be based on history, physical examination, and pretest probability for CAD. You can estimate the pretest probability for CAD in a chest pain patient based on the patient’s age, sex, and pain characteristics.¹

Determine whether symptoms are typical, atypical, or nonanginal, based on whether the chest pain is substernal, brought on by exertion, or relieved by rest or nitroglycerin.²

To recap:

• Typical angina requires all 3 pain characteristics
• Atypical angina, only 2
• Nonanginal chest pain, 1.²

Use this information (along with the patient’s age) to determine whether he has a high, intermediate, low, or very low likelihood of CAD (TABLE 1). From the low, to the intermediate, to the high pretest probability levels, the positive predictive value increases progressively (21%, 62%, and 92%) and the negative predictive value decreases progressively (94%, 72%, and 28%).³ (These values are based on a review of symptomatic patients who had angiography following stress testing.)

TABLE 1
How to determine pretest probability of coronary artery disease

Your patients’ score dictates whether testing is required, and if so what kind.

Very low pretest probability patients should not have an exercise test, since they have a high risk of false-positive results. Evaluate and treat them for noncardiac causes of chest pain and begin primary prevention of CAD.

Low pretest probability patients should undergo exercise treadmill testing alone since negative results carry a high negative predictive value in both men and women, but positive test results may be false and can be evaluated by more studies.³

Intermediate pretest probability patients, including those with complete right bundle branch block or less than 1 mm ST depression at rest should have an exercise treadmill test without imaging modality.^3-5 However, intermediate pretest probability patients with baseline ECG abnormalities such as electronically paced ventricular rhythm or left bundle-branch block will require myocardial perfusion imaging.⁵

High pretest probability patients should have coronary angiography as an initial strategy for diagnosis of CAD.³

History, exam, and ECG determine test suitability

Can your patient take an exercise stress test, or will he need a pharmacologic stress test instead? (See “A guide to sensitivity, specificity, and likelihood ratios for stress tests.”) Can he pedal a bicycle, walk, or exercise for 6 minutes? On physical examination, take note of his gait, mobility, and limb strength.

What medications is the patient taking? Digoxin may cause false ST changes, beta-blockers may prevent attaining maximum heart rate, and antihypertensive agents and vasodilators may alter the blood pressure response, producing a false negative result. Nitrates attenuate angina and the associated ST depression of ischemia.⁶ In addition, metabolic abnormalities and cocaine or alcohol use may affect heart rate, metabolic oxygen demand and the ability to perform the exercise treadmill testing.

On examination, document murmurs, rhythm abnormalities, vascular bruits, and abnormal pulses. Limit laboratory studies to recent cardiac damage screening if indicated. Screen with a resting ECG for arrhythmias, conduction abnormalities or preexisting cardiac damage. ST-segment (≥1 mm) and T-wave changes such as inversions secondary to strain or old injury or conduction abnormalities such as bundle branch blocks and prolonged QT interval may obscure exercise treadmill testing findings. Consider spirometry for patients with asthma or chronic lung disease.

The decisive factors

Absolute contraindications to exercise treadmill testing include recent MI; significant aortic stenosis,⁷ and weight exceeding equipment capacity. Relative contraindications to exercise treadmill testing (which can be superseded if the benefits of exercise outweigh the risks) include: hypertension (systolic >200 mm Hg/diastolic >110 mm Hg),⁵ left main coronary stenosis and stenotic valvular disease. (For more on “Contraindications to exercise testing,” see TABLE 2.)

The role of imaging: Important, yes—routine, no

An important element of stress testing is, of course, the imaging method(s) that will be used. The options include myocardial perfusion imaging with thallium Tl 201 or technetium Tc 99m, and echocardiography.

Indications for myocardial perfusion imaging with exercise treadmill testing are a high pretest probability for CAD, an abnormal baseline ECG such as left bundle branch block, previous myocardial damage or coronary revascularization, or a previous equivocal or unexpected exercise ECG result. In women with an intermediate pretest probability for CAD, the sensitivity and specificity of an exercise treadmill testing is less than in men, which suggests that nuclear imaging would improve this test.⁸ There is, however, insufficient data to justify initial routine stress imaging tests in women.¹

TABLE 2
Contraindications to exercise testing

Of the 2 agents used for myocardial perfusion imaging, technetium Tc 99m has more favorable imaging characteristics.⁹ It has a shorter half-life (6 hours) than thallium Tl 201 (73 hours), and larger doses of technetium Tc99m may be used, permitting the assessment of ventricular function.¹⁰

Echocardiography may also be done with either exercise treadmill testing or PSMI to evaluate relative myocardial perfusion. While radionuclide technique assesses relative myocardial perfusion, echocardiography also evaluates global and regional function. Indications for echocardiography are similar to myocardial perfusion imaging but also include the need for prognostic information after MI, and to assess physiologic significance of a lesion or to determine the success of an intervention.

Time for the test: Selecting the protocol

While the Bruce exercise treadmill testing protocol is the most commonly used (82% of tests)¹¹ in healthy adults, it may not be appropriate for women or the elderly as most protocols were developed for the evaluation of men.¹² A ramp method with gradual increase in grade each minute is preferred by some clinicians when patients are unable to perform a standard Bruce protocol. Another option, the Modified Bruce protocol, which is more gradual than the standard Bruce protocol; it has two 3-minute warm-up stages.¹²

The 3 PSMI protocols include adenosine, dipyridamole, and dobutamine. Each has a different administration routine,⁹ though ECG, blood pressure and pulse are taken every minute for all 3.

• Adenosine is infused with a pump over 6 minutes and technetium Tc99m is injected 3 minutes into the infusion.
• Dipyridamole is infused over 4 minutes and technetium Tc99m is injected 2 to no more than 5 minutes after the infusion. Theophylline is injected, after dipyridamole if necessary, no earlier than 1 minute after technetium Tc99m is administered to avoid interference with the uptake.
• Dobutamine is titrated with a dose increase every 3 minutes. Tc99m is injected after the first minute at the highest concentration. (Typically dobutamine is used with echocardiography.⁶)

Ideal endpoints and the realities that may creep in

The ideal endpoint in an exercise treadmill testing is 100% of the age-predicted maximum heart rate (220–age). Eighty-five percent of maximum heart rate is the minimum for an acceptable test.

Absolute contraindications

Absolute indicators for stopping an exercise treadmill test are either a 10 mm Hg systolic drop in blood pressure from standing baseline, moderate to severe angina symptoms, feelings of syncope, skin color changes suggestive of hypoxia or hypotension, ischemic ST changes, or the patient’s desire to stop.

Relative contraindications

Relative indicators to stop include fatigue, shortness of breath, leg pain, increased arrhythmias—particularly PVCs that increase with the exercise level—and blood pressure ≥250 systolic or 115 diastolic.⁶

Ideally, PSMI evaluations are terminated according to the prescribed length of infusions. They will also be terminated if a patient develops wheezing, severe or increasing chest pain or hypotension, neurological symptoms, ST-segment elevation abnormalities, or arrhythmias. To reverse the side effects of adenosine or dipyridamole, aminophylline IV will be administered (1–2 mg/kg slowly, up to 250 mg).

Heart of the matter: What a report should cover

Assuming you have ordered the stress test (and not done it yourself), a complete report should include

• ST changes
• symptoms during testing
• reason for ending the test
• estimation of exercise capacity
• blood pressure response
• the presence and frequency of arrhythmias or ectopy.

Abnormal. ST segment change is the most important ECG finding in a positive test; it’s defined as >1 mm horizontal or down sloping depression or elevation, at least 60 to 80 milliseconds after the end of the QRS complex and should prompt further workup to confirm CAD.⁵ An abnormal ECG during a PSMI test indicates an elevated risk of multivessel CAD and should prompt further evaluation regardless of normal myocardial perfusion imaging.¹³

Equivocal. Reports that come back as equivocal will have ECG changes nondiagnostic of ischemia such as alterations in P- or T-wave morphology and nondiagnostic changes in AV conduction, particularly if changes revert to baseline during the rest period. Unifocal PACs or PVCs (<5/min) are not specific indicators for CAD and the development of bundle branch blocks are nondiagnostic findings. Equivocal results need additional testing such as myocardial perfusion imaging or angiography to document ischemia if the pretest probability is high.

Incomplete or failure. If your patient’s test involves equipment failure or if he (or the operator) was unable to complete the test, you should get a report to that effect. Depending on the nature of the failure, you may need to repeat the test, consider PSMI, or make a cardiology referral.

Duke Treadmill Score

A helpful calculation following treadmill testing

If your patient had a positive or negative exercise treadmill test, consider calculating his Duke Treadmill Score (DTS), which is predictive of 5-year survival and significant severe CAD for patients who are younger than 75 years.^4,14

DTS helps you to exclude low-risk patients from further invasive testing and ensure high-risk patients receive further evaluation and appropriate treatment. DTS appears to be more useful in women with an intermediate pretest score but not with a low pretest score.¹⁵

The DTS score typically ranges from –25 to +15.⁵ Patients at low risk will have a score of > +5), moderate risk will have scores ranging from –10 to +4, and those at high risk will have a score of ≤–11.⁴

A modified DTS is used for patients older than 65 years who may have a limited exercise capacity, controlled asymptomatic congestive heart failure, or be on digoxin, which may affect their ability to perform a maximal exercise treadmill test.⁵ The values for the Elderly Alternative Treadmill Score are as follows: low risk (< –2); moderate risk (–2 to 2); and high risk (>2). (See “The calculations behind the scores.”)

Bottom line

DTS scores, Elderly Alternative Treadmill Scores, and pre–stress test CAD probability scores are all extremely useful. Integrating them into your practice can ensure that patients get the prompt care they may need, while sparing them unnecessary tests along the way.

FIGURE
Template for dictating noninvasive cardiac tests

Correspondence
Dennis P. Breen, MD, Eau Claire Family Medicine Clinic, 617 Clairemont Avenue, Eau Claire, WI 54701. [email protected]