Stress Protocols
  1. Treadmill exercise
    1. Medication
      1. Stop beta and calcium channel blockers 24 to 48 hours prior to exercise - Why?
      2. Long acting beta blocker should be d/c 4 days prior to test - Why?
      3. Long acting nitrates should be d/c 6 hours prior to test - Why?
      4. As a general rule - If medication cannot be discontinued then the patient should undergo a pharmacological stress test (I have seen exceptions)
    2. Test protocols
      1. Bruce protocol increases the speed and angle of the treadmill every 3 minutes
      2. Remember the formula (220 - pt age) x 0.85 = Maximum heart rate (85%) achieve prior to injecting the radiopharmaceutical
      3. Modified Bruce protocol starts the stress test at even a lower exercise level
      4. The table below identifies the properties of Modified Bruce and Bruce Protocols. Note how the modified protocol starts off with zero grade and does not "catches up" to Bruce protocol until its third stage

        5. Modified Bruce Time Total Time

        Speed (mph)

        		 % Grade
        1
        -
        3 / 0
        - / -
        1.7
        0
        2
        -
        3 / 0
        6 / -
        1.7
        5
        3
        1
        3 / 3
        9 / -
        1.7
        10
        4
        2
        3 / 3
        12 / 6
        2.5
        12
        5
        3
        3 / 3
        15 / 9
        3.4
        14
        6
        4
        3 / 3
        18 / 12
        4.2
        16
        7
        5
        3 / 3
        21 / 15
        5.0
        18
        -
        6
        - / 3
        - / 18
        6.0
        20

      5. Naughton protocol is done on patient that have had a recent MI. It is a lower level stress test where the patient exercise is more gradual and the patient only reaches 75% maximum heart rate
      6. Cold pressor - instead of stressing the patient on a treadmill the patient's hand is immersed in cold water - Have you ever kept your hand in ice cold water for a period of time?

      7. Stress testing and the dynamics behind it when partial occlusion and collateral circulation is applied
    3. At what point should the radiopharmaceutical be injected?
      1. At 85% stress level or greater
      2. Following the injection the patient should stress for 1 additional minute before completing the stress procedure
  2. Pharmacological stress
    1. If the patient cannot reach a maximum level of stress then certain drugs maybe administered so that the same type of hemodynamic effects are achieved with blood flowing into the coronary arteries
    2. Dipyridamole/adenosine/regadenoson administration increases myocardial blood flow 3 - 5 times that of a resting heart - this will be discussed in greater detail in a future lecture, but here are some points of interest
      1. Can we capture Myocardial Blood Flow (MBF) and Myocardial Fraction Reserve (MFR)
      2. Acquire during radiotracer uptake
      3. What does reduced MBF mean?
    3. Coronary steal occurs when blood flows to the area of least resistance, "stealing" blood from areas that has a partial occlusion
    4. Patients on beta/calcium blockers should undergo this method of stress, however, ischemic disease is usually underestimated
    5. Hypotension and asthmatic patients should not be considered for this procedure
  3. Pharmacological test causing vasodilation via dipyridamole (Persantine) infusion

    Contraindications

    1. Administered IV while the patient is in the supine position
    2. Dipyridamole/Persantine blocks the adenosine receptor sites resulting in build-up of adenosine in the blood stream that results in vasodilation
    3. Should not be done on patients on Xanthine medication
    4. T1/2 = 3 - 12 minutes (there is a tri-exponential biological decay factor)
    5. Some patients may have a severe reaction (chest pain leading to heart block), in which case aminophylline is administered to relieve the affect of dipyridamole
    6. Dose = 0.56 mg/kg administered IV drip over a four minutes time frame
    7. Determine the dose:
      1. What is the total dose of dipyridamole given to a 200 pound person?
      2. What is the dose per minute setting? 
    8. Discontinue the dipyridamole and inject the radiotracer three to four later
    9. Should a reaction occurs to dipyridamole aminophylline is given IV STAT. Dose is usually 100 mg
    10. If aminophylline is given prior to the radiopharmaceutical injection the imaging procedure is terminated. However, if aminophylline can be given after after the radiopharmaceutical injection the the patient can continue with the imagine procedure

      11. Timeline

    11. Timeline for the radiotracer administration is noted
    12. Low level stress is occasionally done by certain clinics
      1. Hand-grip exercise can be done while the pharmacological agent is being administered
      2. Modified Bruce protocol may also be considered
      3. Advantage to this approach
        1. Reduces side effects
        2. Improve myocardial extraction of the radiotracer
    13. Some clinics just automatically given aminophylline 1 - 2 minutes post radiopharmaceutical injection which may prevent adverse event from  occurring
    14. Side effects can be broken down into several categories
      1. Dizziness, headache, hypotension, and/or flushing
      2. Development of myocardial ischemia with angina pectoris and/or ST segment depression
      3. Nausea with an uneasy feeling in the stomach
      4. The chances of a serious events occur in approximately 2 in 10,000 patients
    15. Patient should always be monitored by the physician for at least 20 to 30 minutes post dose
  4. Oral dipyridamole maybe another method of stressing the patient, however, this is usually not done. Reason? When does the oral dose enter the blood stream to a significant level where vasodilation has occurs?
  5. Pharmacological test causing vasodilation via adenosine
    1. Patient should be NPO at least 4 hours prior to study
    2. Administered IV while the patient is in the supine position
    3. Adenosine overloads the adenosine receptor sites in the heart causing vasodilation
    4. T1/2 = 10 seconds
    5. If an adverse side effect occurs usually all you need to do is stop the IV drip, however, aminophylline
      6. can still be used (if necessary)
    6. Dose = 140 ugm/kg/min for 6 minutes
    7. Calculate the dose and compare
      1. What is the total dose of adenosine for a 200 pound person?
      2. What is the dose per minute on this person?
      3. Compare the difference between Adenosine and Persantine doses
    8. Usually the patient is given adenosine for 4 minutes and the infusion is stopped
      1. 99mTc-radiotracer is administered
      2. Adenosine infusion then continued for two additional minutes

      9. Timeline

    9. Timeline of adenosine administration is noted above
    10. Start imaging once there the target is clearly seen and the background no longer interferes
  6. Pharmacological test causing increased heart rate via dobutamine infusion

    7. Contraindications

    1. Dobutamine can be ordered, but is usually not the preferred method for pharmacological stressing
      1. Usually there is a contraindication for adenosine in which some clinics will use this alternative
      2. Most common reasons to cancel a adenosine/persantine stress test are:  patient has has consumed caffeine, fluid in the lungs, inhaler has xanthine derivative, or patient is a chronic asthmatic
    2. Procedure
      1. Patient is placed in the supine position and an IV dobutamine administration is prepared
      2. Dobutamine administration causes the heart rate to increase it its contractility. This is accomplished by stimulating the beta-1 receptors in the myocardium
      3. Infused starts at either 5 or 10 ug/kg/min for three minutes (usually starts at 10)
      4. Rate increases every three minutes by 10 ug/kg/min up to a maximum of 50 ug/kg/min (just like a treadmill test)
      5. At a point where the heart rate reaches 85% dobutamine is stopped and the radiopharmaceutical is injected
      6. Dobutamine administration may or may not continue for 2 more minutes pending if the heart rate stays at +85%
      7. My observations
        1. Usually by the third level of "stress" (30 ug/kg/min) the physician will administer atropine if the heart rate isn't responding quick enough
        2. This part is tricky, because a small amount will make the heart rate increase very quickly
        3. At times I have seen more than one dose of atropine administered (because the heart does not respond to the first dose)
        4. Once the dobutamine/atropine administration is completed it takes the heart a considerable amount of time to return to its "resting" state. Patient should be continually monitored until the heart rate goes below 100
    3. Antagonist to dobutamine are beta blockers (a lot of these drugs end with the letters "lol") [this does not mean laugh out loud]
  7. Pharmacological stressing with regadenoson (lexiscan)

    1. Contraindication

      2. Administration of Lexiscan takes less than a minute

    2. Procedure
      1. Place the patient in a supine position and establish an IV site for dose administration
      2. Lexiscan always comes in a 0.4 mg dose and is supplied in a pre calibrated syringe (mg/kg of body weight does not need to be calculated) 
      3. Dose administration should take less than 10 seconds
      4. Flush with saline ~ 5 seconds
      5. Wait 20 seconds and then give the radiotracer

      3.  

      Hemodynamic Response to Lexiscan and Aminophylline

    1. The hyperemic response following the injection of regadenoson is noted above1
      1. Takes approximately 30 seconds post pharmaceutical injection
      2. Peaks in about 2 minutes
      3. Then slowly declines
      4. It also response quickly to aminophylline if there becomes a need to inject it
    2. Adenosine receptors uses the A2A antagonist (but also goes to the other three "A" receptor sites)
      1. A1 - Decreases heart rate
      2. A2A - causes coronary artery vasodilation (specific to Lexiscan)
        1. Uses a small dose and stimulate a amount A2A receptor to create hemodynamics changes
        2. Adenoscan(card) requires a higher dose (140 mcg/kg/min) and is less specific, simulating all adenosine receptors
      3. A2B - causes bronchospasm
      4. A3 - Used to help the heart during cardiac ischemia and inhibits neutrophil degranulation
    3. The claim is that that there are fewer side effects with Lexiscan when compared to adenosine and persantine. The following table compares Lexiscan and Adenosine
      Comparing Lexiscan to Adenosine
      Adverse Reaction Lexiscan Adenosine
      Dyspnea
      Headache
      Flushing
      Chest  Discomfort
      Angina or ST Depression
      Dizziness  
      Chest pain
      Nausea
      Abdominal Discomfort
      Dyspepsia
      Feeling Hot

      1. What is your assessment regarding the use of lexiscan vs adenosine?
      2. Consider the graph on of comparison of lexiscan and adenosine: up arrow apply a negative value, each down arrow apply a positive value, and equal has no value
    4. Package insert
  8. Chart for contraindications of Adenosine, Dipyridamole, and Lexiscan2
    Contraindications Adenosine Dipyridamole Lexiscan
    2nd or 3rd Degree Heart Block X   X
    Sinus node dysfunction     X
    Bronchospasm/constriction (Lung Disease) X    
    Hypersensitive to Drug X X X
    Cardiovascular risk associated with stress agent X X X
    SA and AV nodal block X   X
    Hypotension X   X
    Hypertension X    
    Bronchoconstriction X X X
    Myasthenia gravis   X  
  9. Current literature search regarding the efficacy of lexiscan and adenosine3
    1. Brink, HL, et al. evaluated lexiscan and adenosine in two difference facilities where one clinic used regadenoson and the other used adenosine
    2. Study group
      1. A total of 489 patients were identified (235 adenosine and 254 regadenoson)
      2. Age range - 18 to 88 years
    3. Results
      1. Eighty percent that was administered regadenoson had some type of adverse reaction with 31.5% related to the adenosine group
      2. Reactions included
        1. Arrhythmia (30.6% to 16.1%)
        2. Dyspnea (66% to 17.7%)
        3. Headache (25.1% to 3.1%)
        4. Required aminophylline (19.2% to 0.8%)
    4. Conclusion
      1. Adenosine is better tolerated
      2. Adenosine cost was $25,00 less

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2/23

1 - Product Monograph, Lexiscan (regadenoson)

2 - Regadenoson Injection by DJ Cada, et al., Formulary Drug Review

3. Adenosine vs. Regadenoson in Cardiac Stress Testing by Brink HL, et al. (1/2016)