Pharmacologic Stress Testing Technique

In pharmacologic stress testing, the patient reclines while the pharmacologic agent is injected through an IV line. A nuclear tracer is injected through the IV. Blood pressure, heart rate, and ECG are monitored before, during, and after the test, and imaging is obtained at specified times.

Additional imaging may be considered. Software fusion of coronary computed tomography angiography (CCTA) and single photon emission computed tomography (SPECT) images allows for a comprehensive, noninvasive assessment of coronary artery disease (CAD). According to a study by Pazhenkottil et al, hybrid SPECT/CCTA images have a demonstrated synergistic prognostic value. The annual rate of death/myocardial infarction among patients who underwent hybrid imaging was 6%, 2.8%, and 1.3% for patients with matched, unmatched, and normal defect findings, respectively. ^[4] Stress imaging by MRI with strain encoding improves predictive accuracy of coronary events and stenoses at catheterization even further. In a 28-month follow up, MRI with strain encoding improved sensitivity from 84% to 96% (p< 0.001) with an insignificant drop in specificity (88% vs. 94%). ^[10] Various pharmacologic agents are used for cardiovascular stress testing and are usually used in combination with radionuclideisotopesthataretakenupby the myocardium during routine testing. The common ones are discussed below.

Dosing and practical considerations

The use of adenosine requires an infusion pump that delivers the dose (140 mcg/kg/min) over a 6-minute period. The patient should have an intravenous line with a 3-way stopcock or should have 2 intravenous lines. If one intravenous line is used, take care to inject the radiopharmaceutical slowly because a bolus or any forceful injection will cause an abrupt increase in the infusion rate of the adenosine running through the same line. This can lead to significant AV nodal block. ECG monitoring of the vital signs is necessary as with exercise stress testing.

Adenosine is infused at a rate of 140 mcg/kg/min for 6 minutes. At the 3-minute mark, the stress radiopharmaceutical is injected and the infusion is continued for 3 more minutes. Some have suggested that patients determined to be at high risk for complications (eg, questionable history of asthma, hypotension, recent ischemic event, severe bradycardia) should undergo an incremental 7-minute adenosine protocol. This protocol starts at 50 mcg/kg/min and increases to 75, 100, and 140 mcg/kg/min at 1-minute intervals followed by injection of the stress radiopharmaceutical at 1 minute after the highest tolerated dose.

The test continues for 3 minutes following injection of the radiopharmaceutical. Unlike dipyridamole, the effect of adenosine dissipates promptly with discontinuation of the infusion. Thus, the infusion must continue during stress imaging until the imaging is completed, whereas for dipyridamole, imaging may follow but in a limited time window. For a stress/rest protocol, adenosine does not require reversal, whereas dipyridamole requires theophylline administration to assure prompt reversal of its stress effects.

Early termination indications

Early termination indications include the following:

• Severe hypotension (SBP < 90 mm Hg)

• Symptomatic Mobitz-I second-degree heart block

• Mobitz-II or third-degree heart block

• Bronchospasm

• Severe chest pain associated with ECG changes (>2 mm ST depression or any ST elevation in a non–Q-wave lead): In most cases, discontinuation of the adenosine infusion is followed by a prompt (< 1 min) resolution or improvement of the adverse effect. In rare cases, aminophylline may be required.

Adenosine-walk protocol

For patients who are able, combined low-level treadmill exercise during adenosine infusion has been demonstrated in several reports to be associated with a significant decrease in the frequency of adverse effects (eg, flushing, nausea, headache). In addition, less-symptomatic hypotension and bradycardia occur. These studies have also uniformly reported improved image quality, as demonstrated by an increased target-to-background ratio.

An additional advantage is that simultaneous low-level exercise allows for immediate imaging, as would be performed with exercise stress testing. This is due to the peripheral vasodilation and splanchnic vasoconstriction induced by exercise.

Dosing and practical considerations

The standard dose of dipyridamole 0.56 mg/kg infused over 4 minutes.

Dipyridamole should be infused via an infusion pump over 4 minutes. However, some choose to infuse the dipyridamole by hand, which is also acceptable. The radiopharmaceutical is then injected 3-5 minutes following the completion of the dipyridamole infusion.

Perform a standard ECG and monitoring of the vital signs as with exercise stress testing until the hemodynamic effects of dipyridamole have resolved.

Dipyridamole-walk protocol

The protocol is similar to that of adenosine; however, the treadmill portion does not begin until 1 minute prior to the injection of the radiopharmaceutical (after completion of the infusion of dipyridamole) and should be continued for at least 2 minutes after the injection of the radiopharmaceutical.

Dosing and practical considerations

Dobutamine is infused in incremental doses starting at 5 mcg/kg/min for 3 minutes. Then, 10, 20, 30, and 40 mcg/kg/min are administered until the stress end point is reached. The end points are similar to those of exercise stress testing (eg, target heart rate, chest pain with ECG changes, hypotension).

Dobutamine must be infused using an infusion pump. The patient should have an intravenous line with a 3-way stopcock or should have 2 intravenous lines. If 1 intravenous line is used, take care to infuse the radiopharmaceutical slowly because a bolus or forceful injection will cause an abrupt increase in the infusion rate of the dobutamine running through the same line, which can lead to significant tachycardia, hypotension, and myocardial ischemia. Perform standard ECG and blood pressure monitoring as with exercise stress testing.

Dobutamine is infused at a rate of 5 mcg/kg/min for 3 minutes, followed by infusion of 10, 20, 30, and 40 mcg/kg/min each at 3 minutes until a target heart rate is achieved. If the target heart rate is not achieved, atropine can be administered (as much as 2 mg). Once the target heart rate is achieved, the radiopharmaceutical is injected and the dobutamine infusion is discontinued.

The indications for early termination of dobutamine stress testing are similar to those of exercise stress testing. ST elevation and ventricular tachycardia are more likely with dobutamine stress testing than any other type of stress testing.

Typically, adverse effects requiring early termination subside within 5-10 minutes of discontinuation of the infusion (the half-life of dobutamine is 2 min). The effect of dobutamine can be reversed with beta-blockers; typically, an intravenous agent with an ultrashort half-life, such as esmolol, is used. Because most patients who undergo dobutamine stress testing have bronchospastic lung disease, beta-blockers should be used with caution.

Hemodynamic effects

A dose-related increase in both heart rate and SBP occurs with dobutamine. However, diastolic pressure falls as the dose of dobutamine increases. These hemodynamic changes are similar to those of exercise stress.

Dosing and practical considerations

The recommended intravenous dose of regadenoson is 5 mL (0.4 mg regadenoson)

Administer regadenoson as a rapid (approximately 10 seconds) injection into a peripheral vein using a 22 gauge or larger catheter or needle. This should be followed by a 5 mL saline flush immediately after the injection of regadenoson. Administer the radionuclide myocardial perfusion imaging agent 10–20 seconds after the saline flush. The radionuclide may be injected directly into the same catheter as regadenoson.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not administer regadenoson if it contains particulate matter or is discolored.

Hemodynamic effects

A rapid increase in coronary blow flow of a short duration occurs when regadenoson is the agent of choice. Clinical studies showed that most patients manifested a decrease in blood pressure and an increase in heart rate within 45 minutes after administration of regadenoson.

Laboratory tests are used to determine myocardial ischemia or risk of infarction; electrolytes, drug levels; toxicities; levels of thyroid-stimulating hormone; and BNP level.

Clinical chemistry

Clinical chemistry studies include measurements of the following:

• Troponin-1

• Creatine kinase

• Myoglobin

• Brain-type natriuretic peptide

• Calcium

• Magnesium

• Potassium

• Bicarbonate

Elevations in cardiac enzyme (troponin, creatine kinase, myoglobin) levels may indicate ischemia and MI. The extent of myocardial damage usually can be correlated to the extent of elevation in the enzyme levels. Patients are at increased risk for arrhythmia in the peri-infarct period.

BNP has predictive value especially in post MI patients and in patients with heart failure. Although preliminary and not conclusive, emerging data support the notion that an elevated BNP level may provide prognostic information on the risk of SCD, independent of clinical information and LVEF.

Severe metabolic acidosis, hypokalemia, hyperkalemia, hypocalcemia, and hypomagnesemia are some of the conditions that can increase the risk for arrhythmia and sudden death.

Metabolic and endocrine tests

Obtain levels of thyroid-stimulating hormone. Hyperthyroidism can lead to tachycardia and tachyarrhythmias. Over a period of time, it also can lead to heart failure. Hypothyroidism can lead to QT prolongation.

Therapeutic-drug monitoring and toxicology

Therapeutic drug monitoring and toxicology includes obtaining the following:

• Drug levels (quinidine, procainamide, tricyclic antedepressants, digoxin)

• Amitriptyline level

• Desipramin level

• Doxepin level

• Imipramine level

• Nortriptyline level

• Serum toxicology screening

Drug (quinidine, procainamide, tricyclic antidepressants, digoxin) levels higher than the levels indicated in the therapeutic index may have a proarrhythmic effect. Subtherapeutic levels of these drugs in patients being treated for specific cardiac conditions also can lead to an increased risk for arrhythmia. Most of the antiarrhythmic medications also have a proarrhythmic effect.

Looking for drugs, such as cocaine, that can lead to vasospasm-induced ischemia is warranted if suspicion exists. Obtaining levels of drugs (antiarrhythmics) also may be warranted.

Urine Analysis

Obtain a urine toxicology screen to test for the types and approximate amounts for legal and illegal drugs that can affect heart function.