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Flashcards in Laboratory Evaluation of Coronary Artery Disease Deck (14):
1

Determinants of Myocardial Oxygen Demand at Rest & During Exercise

  • 4 clinically important determinants of myocardial oxygen demand
  • Myocardial oxygen demand vs. exercise

  • 4 clinically important determinants of myocardial oxygen demand
    • HR: most important
      • Increase HR --> increase myocardial oxygen demand --> increase coronary blood flow
    • LV systolic pressure
    • LV radius or volume (Laplace relationship)
      • Pressure loaded ventricle (ex. systemic arterial HTN or aortic valve stenosis) has a higher myocardial oxygen demand than a volume loaded ventricle (ex. MR)
    • Contractility
      • Increase contractility --> increase myocardial oxygen demand
  • Myocardial oxygen demand vs. exercise
    • Exercise --> increase HR --> increase MOD
    • Exercise --> increase systolic BP --> increase MOD
    • Exercise --> may or may not increase volume
    • Exercise --> increase circulating catecholamines + increase Treppe effect --> increae contractility --> increase MOD
    • ► max exercise --> increase coronary blood flow 2.5x

2

Autoregulation of Coronary Blood Flow

  • Myocardial oxygen demand vs. supply
  • How heart increases MOD normally
  • How heart increases MOD in CAD
    • MOD vs. MOS
    • Ischemic area
    • Ischemic threshold

  • Myocardial oxygen demand vs. supply
    • Increase MOD --> autoregulation of coronary blood flow --> increase MOS linearly
  • How heart increases MOD normally
    • Myocardial oxygen extraction in coronary circulation is nearly max at rest
    • Heart can't increase oxygen consumption by increasing oxygen extraction
    • ► increase in supply i.r.t. increase in demand is mediated through increased coronray blood flow
  • How heart increases MOD in CAD
    • In CAD, MOS increases linearly w.r.t. MOD until max vasodilation of R2 resistance vessels
      • At this point, autrogregulatory reserve of coronary circulation is expended
      • Can't further increase MOS
    • Ischemic area: difference b/n normal & CAD MOD vs. MOS curves where supply < demand
    • Ischemic threshold: point where curves digress
      • Measure of CAD severity
      • Mild CAD: ischemic threshold occurs at higher MOD
      • Severe CAD: ischemic threshold occurs at lower MOD

3

Lab Diagnosis of CAD & Severity Assessment

  • Predicted by...
  • Stress modalities
  • Monitored parameters: assessing response to stress

  • Predicted by...
    • Increasing blood flow above resting levels to max levels
  • Stress modalities
    • Exercise
      • Increase HR --> increase BP & contractility --> increase MOD
      • Not all pts are able to exercise to adequate levels to allow effective diagnosit cevaluation
    • Vasodilators
      • Adenosine: natrual mediator of coronary blood flow
      • Dypyridamole: slows metabolism of adenosine --> increases adenosine levels
      • Ragedenson: selective adenosine 2A receptor agonist
    • Inotropic agents
      • Dobutamine: increases HR, BP, & contractility --> increases MOD --> increases coronary blood flow
  • Monitored parameters: assessing response to stress
    • Ecercise ECG
    • Myocardial perfusion scintigraphy (perfusion scan)
      • Images blood flow int he myocardium using radioisotopes
      • Thallium or technetium based radiopharmaceuticals
    • LV function assessment (global & segmental wall motion)
      • Radionuclide ventriculography: exercise MUGA scans
      • Stress echo: exercise or dobutamine stress

4

Exercise ECG

  • Ischemic response indicating CAD
  • ST depression vs. mortality risk
  • ST depression magnitude
  • ST depression slope
  • Influence of chest pain on ST depression predictive power

  • Ischemic response indicating CAD
    • > 1 mm ST depression 80 ms after the J point
  • ST depression vs. mortality risk
    • ST depression during exercise --> increased mortality risk in pts w/ CAD
  • ST depression magnitude
    • Influences predictive power of exercise ECG
    • Marked ST depression --> increase risk of coronray events in follow=up, esp when it occurs early in exercise
    • Less powerful predictor of risk when occurs at higher levels of exercise
    • Greater magnitude --> greater post-test likelihood of disease
  • ST depression slope
    • Downsloping ST depression --> increased risk of coronary events compared to horizontal ST depression
  • Influence of chest pain on ST depression predictive power
    • ST depression + chest pain during exercise --> increased event rates

5

Implications of Peak HR During Exercise

  • HR vs. coronary blood flow
  • Peak HR during exercise vs. age
  • Peak HR during exercise stress test vs. pt outcome
  • Chronotropic incompetence

  • HR vs. coronary blood flow
    • Increase HR --> increase coronary blood flow linearly
  • Peak HR during exercise vs. age
    • Increase age --> decrease peak HR during exercise
  • Peak HR during exercise stress test vs. pt outcome
    • Higher peak HR (>160 bpm) during exercise --> better survival
    • Lower peak HR (<120 bpm) during exercise --> high mortality risk
  • Chronotropic incompetence
    • Inability to reach the expected target HR during exercise
    • Marker of increased risk of adverse cardiac events

6

Exercise Predictors of Mortality Risk

  • Strongest predictor
  • Another strong predictor

  • Strongest predictor
    • Abnormal functional capacity
    • Abnormal functional capacity --> slower HR recovery
  • Another strong predictor
    • HR recovery
    • Faster HR decreases in recovery --> better prognosis
    • Decrease HR < 12 bpm in 1st minute --> abnormal

7

Sensitivty & Specificity of Exercise Stress Testing

  • 4 variables related to sensitivity
  • 3 variables related to specificity

  • 4 variables related to sensitivity (68%)
    • Equivocal test results
    • Comparison w/ a "better" test (ex. scintigraphy)
    • Exclusion of pts on digitalis
    • Publication year
  • 3 variables related to specificity (77%)
    • Treatment of upsloping ST depression
    • Exclusion of subjects w/ prior MI or LBBB
    • Pre-exercise hyperventilation tracing

8

Pre-Test Likelihood of Disease: Baye's Theorem

  • Probablity that the result of a test is true or false is based on the pre-test estimation of probability of disease
  • Low pre-test probability --> unlikely to have disease even w/ positive test result
    • Post-test probability of disease w/ a positive test result = 85%
  • High pre-test probability --> likely to have disease even w/ negative test result
    • Post-test probability of disease w/ a negative test result = 20%
  • Intermediate pre-test probability --> greatest differentiation of presence or absence of disease b/n a positive & negative test result

9

Prevalence of CAD

  • Pre-test probability of CAD estimated from...
  • Effect of exercise tests on pts w/ typical angina pectoris
    • Pre-test probability of CAD
    • Post-test probability of CAD
      • Positive exercise test
      • Negative exercise test
    • Implication
  • Effect of exercise tests on pts w/ atypical chest pain
    • Pre-test probability of CAD
    • Post-test probability of CAD
      • Positive exercise test
      • Negative exercise test
    • Implication
  • Effect of exercise tests on pts w/ non-anginal chest pain (asymptomatic)
    • Pre-test probability of CAD
    • Post-test probability of CAD
      • Positive exercise test
      • Negative exercise test
    • Implication

  • Pre-test probability of CAD estimated from...
    • Age, gender, & symptoms of chest discomfort
  • Effect of exercise tests on pts w/ typical angina pectoris
    • Pre-test probability of CAD = 90%
    • Post-test probability of CAD
      • Positive exercise test = 97%
      • Negative exercise test = 77%
    • Exercise testing has potential value in evaluating pts w/ typical angina for stratifying risk, developing exercise prescriptions, & reassessing course of disease over time & in response to therapy
  • Effect of exercise tests on pts w/ atypical chest pain
    • Pre-test probability of CAD = 50%
    • Post-test probability of CAD
      • Positive exercise test = 78%
      • Negative exerciset test = 27%
    • Exercise testing has diagnostic value in identifying pts w/ atypical chest pain who have high vs. low likelihoods of having CAD
  • Effect of exercise tests on pts w/ non-anginal chest pain (asymptomatic)
    • Pre-test probability of CAD ≈ 5%
      • Depends on age, gender, & other risk factors
    • Post-test probability of CAD
      • Positive exercise test = 17%
      • Negative exercise test = 1%
    • An isolated positive exercise test has limited value in diagnosing CAD in asymptomatic pts, but it identifies pts w/ a greater liklihood of disease than pts w/ negative tests
      • Pts w/ a positive test can undergo further non-invasive diagnostic evaluation to differentiate false from treu positve results

10

Ischemic Cascade

  • ST depression
  • Regional heterogeneity of flow
  • Ischemia

  • ST depression
    • Chest pain is a late manifestation of ischemia
    • ST depression occurs earlier in the cascade than symptom development but is still a relatively late manifestation of ischemia
  • Regional heterogeneity of flow
    • Occurs earlier in exercise than ST depression or symptoms
    • This appears as a perfusion defect in myocardial perfusion scinitgraphy
    • Improves the sensitivity for detecting disease
  • Ischemia
    • Affects regional & global myocardial function earlier in the cascade than ST depression or symptoms
    • Assessed by perfusion scintigraphy, blood pool scanning (radionuclide ventriculography or MUGA scans), & echo

11

Planar Perfusion Scan Views

  • Planar 2D imaging
  • Sensitivity & specificity of qualitative planar thallium scintigraphy vs. exercise ECG

  • Planar 2D imaging
    • Initial camera technology for myocardial perfusion imaging
    • 3 images of the heart are obtained from different angles around the heart to allow visualization of the perfusion regions in the distribution fo each of the major epicardial coronary vessels
    • Replaced by tomographic (3D) imaging (SPECT: single photon emission computerized tomography)
  • Sensitivity & specificity of qualitative planar thallium scintigraphy vs. exercise ECG
    • Sensitivity for planar thallium > exercise ECG
    • Specificity for planar thallium > exercise ECG

12

SPECT Camera

  • SPECT imaging
  • Slices
  • Indication of prior MI
  • Indication of exercise-induced ischemia w/o infarction
  • Sensitivity & specificity of SPECT vs. planar imaging
  • Candidates

  • SPECT imaging
    • Allows visualization of the myocardium in 3D as tomographic slices that can be generated in each plane of the heart
    • Images are acquired by the camera rotating around the patient over 180o b/c the heart is in the anterior portion of the chest
    • Images are reconstructed to generate tomographic slices
  • Slices
    • Short axis slices: cut the LV like a loaf of bread from apex to base (donut shaped)
    • Vertical long axis slices (horse-shoe shaped)
    • Horizontal long axis slices (hore-shoe shaped)
  • Indication of prior MI
    • Perfusion abnormality present both at rest & after exercise
    • Severity of the defect indicates the severity of hte infarct & the amt of residual viable myocardium that might be present in the infarcted zone
  • Indication of exercise-induced ischemia w/o infarction
    • Perfusion abnormality present after exercise but not at rest
  • Sensitivity & specificity of SPECT vs. planar imaging
    • Sensitivity: SPECT > planar
    • Specificity: SPECT = planar
    • Regional localization & quantification: SPECT > planar
  • Candidates
    • 50% of tertiary care, hospital-based pts who aren't able to exercise

13

Coronary Blood Flow Reserve Ratio i.r.t. Adenosine, Dipyridamole, Dobutamine, & Exercise Stress

  • Dobutamine
  • Adenosine & dipyridamole
  • Sensitivity & specificity for pharmacologic stress studies vs. exercise

  • Dobutamine
    • Pharmacologic stress agent that increases coronary blood flow by increasing MOD
    • Increases in blood flow approximate or slightly exceed those achieved during max exercise
  • Adenosine & dipyridamole
    • Preferable agents for pharmacologic stress perfusion imaging
    • Primary coronary artery vasodilators (dipyridamole increases adenosine levels)
    • Increase coronary blood flow by decreasing resistance to perfusion at R2 vessels
    • Increases in blood flow are 4-5x that achieved during max exercise
    • Can cause bronchospasm, so use dobutamine in pts w/ asthma
    • Caffeine blocks the adenosine receptor & inhibits vasodilatoin, so can't have caffeine for 24 hours prior to the test
    • Uptake of radiopharmaceutical at time of max effect of the pharmacologic stress agent reflects peak coronary blood flow
      • Ragedenson: selective adenosine A2A receptor that specifically dilates coronary arteries
  • Sensitivity & specificity for pharmacologic stress studies vs. exercise
    • Similar sensitivity & specificity
    • Exercise is preferred b/c of superoir imaging characteristics & clinical information
    • Ischemic threshold, functional capacity, & symptomatic correlation can be assessed by exercise stress but not pharmacologic stress

14

Predicting Acute Coronary Events & Cardiac Death

  • Pts at low risk for adverse coronary events or cardiac death
  • Pts at high risk for adverse coronary events or cardiac death
  • SPECT perfusion imaging
  • Exercise testing + SPECT perfusion imaging
  • Coronary revascularization w/ coronary bypass surgery or coronary angioplasty
  • Therapies that reduce MI risk
  • Are outcomes improved by increased frequency of revascularizaiton in patients taken directly to the cath lab?

  • Pts at low risk for adverse coronary events or cardiac death
    • Unlikely to benefit from the risk & expense of invasive revascularization therapy (angioplasty or coronray bypass surgery)
    • Better managed medically w/o cardiac cath
  • Pts at high risk for adverse coronary events or cardiac death
    • More likely to benefit from revascularization
    • Better candidates for coronray angiography
  • SPECT perfusion imaging
    • Excellent discrimination power to identify low vs. high risk pts
    • Negative test = low risk of adverse cardiac events (MI or mortality)
    • Positive test = high risk of adverse cardiac events
  • Exercise testing + SPECT perfusion imaging
    • Significant power to differentiate low vs. high risk pts
    • SPECT perfusion imaging adds significant additional prognostic information
    • Low risk exercise test + high risk SPECT = increased mortality risk
    • High risk exercise test + normal SPECT = low mortality risk
    • Intermediate exercise test: SPECT adds substantial power to differentiate mortality risk
  • Coronary revascularization w/ coronary bypass surgery or coronary angioplasty
    • Increases survival in higher risk patients
    • Don't reduce risks of MI
    • Pts w/ moderate to severe abnormal perfusion: at high risk of cardiac death & MI & are more likely to benefit from coronary revascularization
    • Pts w/ mildly abnormal scans: low mortality rish, high MI risk
      • May be better managed medically
  • Therapies that reduce MI risk
    • All medical therapies (aspirin, statins, ACE-Is)
  • Are outcomes improved by increased frequency of revascularizaiton in patients taken directly to the cath lab?
    • No: no significant difference in clinical outcome w.r.t. death or MI
    • Many potentially unnecessary revascularization procedures could be avoided by initially stratifying stable angina pts w/ stress perfusion imaging rather than taking them directly to coronary angiography