The Role of Pharmaceuticals in the Evaluation of Heart Disease

Inadequate flow to meet myocardial demands leads to myocardial ischemia. With exercise stress testing, we evoke ischemia by increasing demand for blood. Arteries dilate in response to the demand for oxygen. Areas where plaque has stiffened the coronaries will not dilate, causing transient (temporary) ischemia.

Using medications which alter blood flow is an effective and safe means to the same end. It is important that patients follow the prep guidelines the day of the exam with respect to food and beverage intake, and in many cases, caffeine or chocolate consumption.

Patients suffering from COPD, emphysema, reactive airway disease (asthma), or who are taking certain medications must be evaluated for active wheezing prior to administration of any vasodilator.

Pharmacologic agents are formulated to bind temporarily to specific receptors in the inner arterial lining for the purpose of affecting heart rate and/or blood pressure (dilatation). There are Alpha and Beta Receptor sites which, when stimulated, raise or lower heart rate and blood pressure.

Theophylline and caffeine are nonselective competitive blockers of adenosine receptors, and should be avoided 12-24 hours prior to administration of adenosine.

IV DOBUTAMINE

Dobutamine is an effective alternative to exercise for patients with severe asthma or bronchospastic disease. IV Dobutamine initiates an increase in oxygen demand, indirectly resulting in coronary vasodilation. Dobutamine is classified as a Synthetic Sympathomimetic amine, a synthetic catecholamine with sympathomimetic activity. Dobutamine stimulates Beta 1 and Beta 2 Adrenergic Receptors. It increases coronary blood flow by increasing cardiac contractility and heart rate with a mild increase in vasodilation.

Certain factors or conditions may interfere with a dobutamine stress test. These factors include, but are not limited to, the following: smoking or ingesting caffeine within three hours of the procedure, and beta-blocking medications may make it difficult to increase the heart rate.

Dobutamine is administered according to patient weight, starting with a low concentration and increasing with every three-minute stage. Dobutamine stress tests may be safely administered to the asthmatic patient and is routinely used with echocardiography in patients who are unable to exercise on a treadmill.

An advantage to Dobutamine is that it has a short half-life. One drawback to Dobutamine from a nuclear medicine tech's point of view is that the radiotracer may not be absorbed into myocardial tissue adequately, and persistent liver activity makes it difficult to obtain decent gated SPECT images.

• Good for use in the asthmatic patient

• Dose titrated at 5, 10, 20, 30, and 40 mcg/kg/min by infusion pump in 3 minute stages

• Monitor patient for changes in ECG, HR, BP

• Dobutamine accelerates heart rate, resulting in coronary vasodilation

• Radiotracer injected at peak HR*, or when symptomatic, continue infusion 1 more minute

• Recovery stage 5 minutes

• Esmolol (a beta blocker) is the antidote

* atropine may be used to bring HR to peak after stage 5 completed

IV DIPYRIDAMOLE (Persantine)

When Dipyridamole first came on the scene in the 1980's, an oral suspension was being used for nuclear perfusion testing. The intravenous version of the drug quickly gained widespread acceptance to evaluate myocardial perfusion in patients unable to walk on a treadmill.

• NOTE: Persantine can cause bronchospasm in the asthmatic patient and MUST NOT be used!

• NPO 4 hours, 2 hours if diabetic

• Caffeine, decaf avoided 24 hours

• Xanthine derivatives avoided 36-48 hours

Dipyridamole induces coronary vasodilation by elevating interstitial adenosine concentration by inhibition of adenosine uptake in vascular endothelium and on red blood cell membranes.

Dosage and Administration Protocol: Calculate patient weight in kg x .57 mg/kg= dose in mg, not to exceed 60 mg. Draw up in 60 cc syringe, then dilute to 40 cc with 0.9% normal saline. The patient is prepped with 10 electrodes and baseline and serial electrocardiograms are taken each minute. Administer dose at rate of 10 cc per minute over 4 minutes, wait until minute 7, then inject radiopharmaceutical intravenously. The tracer must circulate a minimum of one to two minutes prior to reversing the drug with Aminophylline.

OPTIONAL: Handgrip, hand weights and arm movement, bicycle ergometer, walk on flat treadmill 1 mph for 1 minute post DIP infusion and 1 minute following tracer injection.

Wait 45 to 60 minutes when imaging Tc99m tracers, within 10 minutes when using Thallium-201.

IV ADENOSINE (Adenoscan)

Adenoscan is a vasodilator which has a very short half-life. Adenoscan dose is calculated according to patient weight and is administered slowly over a 4 to 5 minute infusion using a pump.

Side effects most often include flushing, chest discomfort, and mild dyspnea. Rarely, stomach upset resulting in vomiting may occur. Because Adenoscan has an effective half-life of 30 seconds, side effects usually resolve quickly when infusion is terminated and generally do not interfere with test results.

Adenosine is a natural purine. In the heart, adenosine causes coronary vascular smooth muscle relaxation, inhibits norepinephrine released from sympathetic nerve endings, reduces AV node conduction velocity, and has inotropic and chronotropic effects. Coronary arteriole peripheral vasodilation leads to a small increase in heart rate and a fall in systolic blood pressure. Side effects include flushing, chest pain, headache, dyspnea, nausea and dizziness. Plasma half-life is very short, and the side effects, although common (80%), are short lived and well tolerated. Adverse effects include atrioventricular conduction block, sinus node dysfunction and bronchospasm. Adenosine should not be used in patients who have heart block without pacemaker protection, in those with sick sinus syndrome, or in those with asthma.

Aminophylline or nitroglycerine should be on hand for any serious reactions. Recovery begins when infusion is terminated and is typically 5 minutes.

• Not for use in the asthmatic patient due to exacerbation of bronchspasm.

• NPO 4 hrs – 2 hrs. if diabetic

• Caffeine and chocolate products avoided 24 hours prior to testing

• Dose: 140 mcg/kg/min by infusion pump over 4 minutes

• Half-life of less than 2 seconds

• Monitor patient for changes in ECG, HR, BP

• When half of adenosine infused, inject tracer into port over 5-10 sec., infuse remaining adenosine

 

IV LEXISCAN (Regadenoson)

is an A2A adenosine receptor agonist that is a coronary vasodilator. It produces maximal hyperemia quickly and maintains it for an optimal duration that is practical for radionuclide myocardial perfusion imaging.

Regadenoson has a 2-3 minute biological half-life, as compared with adenosine's 30 second half life. Regadenoson stress protocols using a single bolus have been developed, obviating the need for an intravenous line. Regadenoson stress tests are not affected by the presence of beta blockers, as regadenoson vasodilates but does not stimulate beta adrenergic receptors.

Regadenoson is a selective A2A-adenosine receptor agonist for potential use as a pharmacologic stress agent in myocardial perfusion imaging (MPI) studies. Regadenoson has been designed to be delivered as a rapid bolus with no dose adjustment required by weight, and to selectively stimulate the A2A-adenosine receptor, the receptor responsible for coronary vasodilation.

Contraindications to Regadenoson include

• Heart block, second or third degree (type of abnormal heart rhythm) or

• Sinus node dysfunction (type of abnormal heart rhythm)—Should not use in these conditions unless patients have a pacemaker that works.

• Breathing problems or lung disease (e.g., asthma or COPD) or

• Ischemia or

• Low blood pressure (hypotension)—Use with caution. May make these conditions worse

The nuclear technologist can administer the drug under the supervision of a physician in many clinics. A prefilled 5-cc syringe containing the Lexiscan is administered as a bolus (10 sec.), followed by a 5-cc saline flush. Immediately inject the radiotracer, followed by another 5-cc saline flush. The drug and the tracer should be completely injected and flushed by the 1.0 minute mark, so the Recovery phase may begin at that point.

Side effects most often reported are headache and stomach upset. Iv aminophylline may be given 2 minutes ofter raditracer, or just have the patient get a cup of coffee or cola after the stress test. Imaging may be commenced 45 minutes post stress.

Side effects to Pharmacologic Vasodilation

Dipyridamole and Adenosine can sometimes increase heart rate as a result of secondary response to vasodilation plus decrease in BP. Patients may exhibit a spike in heart rate during infusion, not the usual response to Dipyridamole, but it may be an effect of mild allergic reaction. In my own experience, unless the patient is also complaining of chest tightening or pain, we have continued infusion while closely monitoring the patient for adverse effects.

It is normal to experience 'flushing', an overall sensation of warmth, an the effect of vasodilation of all arteries and veins simultaneously. Other symptoms to watch for include chest pain, nausea and vomiting, dizziness, headache, shortness of breath, and a drop in blood pressure. Adenoscan has such a short half-life that reversal is not needed, except in extreme cases of acute shortness of breath or vomiting. Patients with emphysema may experience acute chest tightening within seconds of infusion, and administration of the stress agent must be immediately aborted.

To lessen the severity of the side-effects experienced with agents such as Dipyridamole and Adenosine, a "walking" medicine stress test can help the patient who is able to walk flat on a 1.0 mph belt speed. Getting the large leg and arm muscles involved, with walking, isometric leg and arm exercises, handgrip or stressball squeezing, may help the patient focus on something other than the appearance of side effects and helps burn off the medicine a little faster.

IV Aminophylline as an Antidote to Vasodilation

Aminophylline is a vasoconstrictor, having the same action on the vessels as caffeine, negating or reversing the effects of pharmacologic stress agents. Intravenous Aminophylline must be ready to administer should the patient experience unpleasant side effects from vasodilation, particularly from Dipyridamole, Regadenoson, and in cases of extreme reaction, Adenoscan.

An initial infusion of 50-75 mg Aminophylline is injected over the course of 30 seconds to 1 minute IV. A second dose may be repeated 2 minutes later. In some laboratories, Aminophylline is routinely administered after tracer uptake is complete (2 min post injection) as a prophyllactic against delayed unpleasant side-effects. The aminophylline should not be administered prior to radiopharmaceutical injection, since the vasoconstrictive effects would render the exam invalid. Severe angina is treated with sublingual nitroglycerin.

DOWNLOAD THESE RESOURCES:

1. Current Methods of Pharmacologic Stress Testing and the Potential Advantages of New Agents