Testing in the Diagnosis and Treatment of Coronary Artery Disease

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Testing in the Diagnosis and Treatment of
Coronary Artery Disease

• Jon W. Wahrenberger, MD
• DHMC

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Case 1

• 68 yo man with 2 months exertional chest
  pressure
• Symptoms always relieved with rest
• Two days of symptoms with minimal activity
• Exam BP 160/95 Pulse 82, no JVD, clear lungs,
  soft s4, trace ankle edema
• Resting ECG normal
• Meds Atenolol, Lipitor, metformin
• CRF FH, HTN, smoking, T2DM

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Management?

• Add ASA, NTG, increase BB and
• Exercise stress test
• Nuclear stress test
• Coronary angiography
• Observation

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Case 2

• 23 y.o. single woman with 2 children, recently
  assaulted by boyfriend
• Experiencing frequent episodes of chest
  tightness, dyspnea and lightheadedness
• No exertional symptoms
• Episodes may last 3-4 hours symptoms at time of
  eval.
• Exam BP 120/80, Pulse 105, o/w normal
• ECG Slight sinus tach troponin normal
• Meds BCP, vicodin for back pain
• CRF Tobacco

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Management?

• Order exercise stress test
• Order nuclear stress test
• Refer for coronary angiography
• Counseling and observation

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Physiologic Response to Exercise

• Anticipation
• Increased HR due to vagal withdrawal
• Increased venous return due to sympathetic
  stimulation
• Net increase in resting cardiac output
• Early Exercise
• Increased cardiac output by increased stroke
  volume (Frank-Starling) and HR

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Physiologic Response to Exercise

• Later in exercise
• Increased cardiac output from vagal withdrawal
  and sympathetic stimulation (4-6 fold)
• Vasoconstriction in most of circulatory system
  except exercising muscle
• Decrease in systemic vascular resistance
• Systolic BP increase
• Diastolic BP unchanged or decreases

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Physiologic Response to Exercise

• Post Exercise/Recovery
• Rapid return of hemodynamics to normal
• Vagal reactivation a key component
• Accelerated in trained athletes
• Blunted in patients with CHF

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Overview of Talk

• Exercise stress testing
• Exercise Echo
• MPI
• Testing in Women

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Part 1 Stress Testing

• Diagnosis of CAD
• Prognosis Implications
• Risk assessment after MI
• Evaluation of suitability for transplant
• Hemodynamic evaluation in valvular disease.

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CAD The Gold Standard
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CAD The Gold Standard
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Heart Catheterization Problems

• Cost
• Invasive
• Complications 11000 risk of
• Death
• MI
• Stroke
• Vascular complications
• Others
• Does not provide information on functional
  significance of CAD

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Statistics
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Dreaded Statistics

• Sensitivity True positive rate
• Proportion of patients with disease that will
  have a positive test result
• Sensitivity TP/(TPFN) x 100
• Specificity True Negative Rate
• Proportion of those without the disease that will
  have a negative result
• Specificity TP/(FNTN) x 100

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Probability of CAD
Pre-test Probability of CAD from CASS Trial
Typical Angina Substernal chest pain with 1)
typical quality duration 2) provocation with
exertion or emotional stress 3) relief with rest
and NTG Atypical Angina Chest pain with two of
above qualities Non-Anginal Chest Pain chest
pain with one or none of above
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Stress Testing Implications of Positive Test
Key Point Stress testing offers the most
diagnostic information in those patients at
intermediate risk of having coronary artery
disease.
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Accuracy in Detecting Ischemia Meta Analyses
Source AHA/ACC 2002 Guideline Update for
Exercise Testing Circulation
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Sensitivity vs. Specificity
Source Yanowitz, UpToDate. Electrocardiographic
Changes During Exercise ECG Testing
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ACC/AHAStress Testing in Diagnosing CAD

• Class I
• Adults with intermediate probability of CAD on
  basis of gender, age and symptoms
• Class IIa Patients with vasospastic angina
• Class IIb
• Patients with high or low pre-test probability
• Patients with
• Patients with LVH and
• Class III
• WPW
• Paced rhythm
• Resting ST depression 1 mm
• Complete LBBB

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Stress Testing

• Diagnosis of CAD
• Prognosis Implications
• Risk assessment after MI
• Evaluation of suitability for transplant
• Hemodynamic evaluation in valvular disease

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Prognosis
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Prognosis related to

• Maximal exercise capacity (
• Magnitude of ST segment depression (2mm)
• ST segment elevation
• Number leads with ST depression (5 leads)
• Stage during which ST changes occur (stage 1)
• Attenuated blood pressure response (failure to
  rise 10 mmHg per stage failure to reach SBP of
  130)
• Speed of recovery of heart rate after exercise
  (

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Duke Treadmill Score

• Derived from study of 2842 inpatients with known
  or suspected CAD
• All had stress test and coronary angiogram
• Score calculation
• Treadmill score exercise time 5 x
  (amount of ST-segment deviation in mm) 4 x
  exercise angina index where angina index 0 if
  no exercise induced angina, 1 if exercise induced
  angina occurred, and 2 if angina was reason for
  stopping test

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Duke Treadmill Score
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ST Depression During Recovery
Normal Test
Ischemia during Recovery
Ischemia with Exercise
Rywik, et al. Circulation. 1998972117
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Heart Rate Recovery

• Following exercise HR decreases due to
  sympathetic withdrawal and increasing
  parasympathetic activity

• Expect 20 bmp drop during first minute
• Failure to drop at least 20 bpm associated with
  poor prognosis

Cole, et al. NEJM 19993411351
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Stress Testing in Unstable Angina?
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Recurrent Ischemia and/orST segment shift, or
deep T-wave Inversion, or positive cardiac markers
AspirinBeta-blockersNitrates Antithrombin
regimen GP IIb/IIIa inhibitorMonitoring (rhythm
and ischemia)
Early Invasive strategy
Early Conservative strategy
Immediateangiography
12-24 hourangiography
Patientstabilizes
Recurrentsymptoms/ischemia Heart failure Serious
arrhythmia
Evaluate LV function
Stress Test
EF EF ? .40
Low risk
Follow onMedical Rx
Not low risk
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Classification of Unstable Angina
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ACC/AHAStress Testing for Prognosis

• Class I
• Initial evaluation in suspected or known CAD
• Patients with known or suspected CAD presenting
  with change in clinical status
• Low risk unstable angina patients 8-12 hrs after
  presentation
• Intermediate risk USA pts 2-3 days after
  presentation
• Class IIa
• Intermediate risk USA pts with normal cardiac
  markers, ECG without changes and normal cardiac
  markers 6-12 hrs after onset

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Screening in Asymptomatic Individuals?
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Screening stress testing in asymptomatic
individuals?
Each trial consisted of patients with risk factors
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Rationale for stress testing in asymptomatic
individuals?

• Asymptomatic ST Segment depression predicts
  mortality
• Treatment of silent ischemia improves outcomes
• Atenolol Silent Ischemia Trial (ASIST)
• Asymptomatic Cardiac Ischemia Pilot (ACIP) trial
  

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ACC/AHAStress Testing in Asymptomatic Patients
without Known CAD

• Class I
• None
• Class IIa
• Evaluation of asymptomatic persons with diabetes
  who plan to start vigorous exercise
• Class IIb
• Evaluation of persons with multiple risk factors
  as a guide to risk reduction therapy
• Evaluation of men 45 years and women 55
  years
• Starting vigorous exercise
• Occupations in which impairment may impact public
  safety
• High risk of CAD due to other disease (PVD, CRF)
• Class II
• Routine screening of asymptomatic men or women

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Stress Testing

• Diagnosis of CAD
• Prognosis Implications
• Risk assessment after MI
• Evaluation of suitability for transplant
• Hemodynamic evaluation in valvular disease

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Stress Testing Post MI
Rationale

• Assess functional capacity and ability to perform
  usual tasks at home and at work
• Establish exercise parameters for cardiac rehab
• Evaluate efficacy of medical regimen
• Risk stratify
• Evaluate chest pain occurring post MI
• Reassurance

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Stress Testing Post MI

• Data pertaining to benefit of stress testing in
  current era of reperfusion using thrombolytics
  and percutaneous coronary intervention is
  relatively scant.

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ACC/AHAStress Testing after MI

• Class I
• Should be porformed either in the hospital or
  early after d/c in STEMI patients not selected
  for cardiac cath and without high-risk features
  to assess the presence and extent of inducible
  ischemia
• If baseline ECG abnormalities exist, above stress
  test should be with echo or myocardial perfusion
  imaging
• Class IIa none
• Class IIb
• Exercise testing may be considered before d/c of
  patients recovering from STEMI to guide post d/c
  exercise prescription or to evaluate the
  functional significance of lesions identified at
  coronary angiography
• Class III
• Within 2-3 days of STEMI if reperfusion not done
• Pts with post MI angina, decompensated CHF,
  life-threatening arrhythmias, etc.

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Stress Testing

• Diagnosis of CAD
• Prognosis Implications
• Risk assessment after MI
• Evaluation of suitability for transplant
• Hemodynamic evaluation in valvular disease.

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Exercise Testing with Ventilatory Gas Analysis
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Exercise with Ventilatory Gas Analysis

• Measured parameters
• V02
• V02 Max
• VC02
• Minute ventilation
• Anaerobic threshold

Mancini, et al. Circulation 199183775
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Exercise with Ventilatory Gas Analysis
Peak Oxygen Consumption and Survival in CHF
Mancini, et al. Circulation 199183775
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Exercise with Ventilatory Gas Analysis
Classification of Exercise Capacity in Patients
with Heart Failure based on peak oxygen uptake
and ventilatory anaerobic threshold
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Exercise with Ventilatory Gas Analysis
Functional Status and Cardiac Transplant
Suitability
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Exercise Stress Testing

• More than you really want to know .

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Treadmill vs. Bicycle
Bicycle
Treadmill

• Most popular in Europe
• Less expensive
• Portable
• Less space
• Demanding on thigh muscles

• Most popular in North America
• Flexible protocols
• More accurate measurement of workloads

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Lead Placement
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Stress Testing Safety

• Risk of death or MI about 1 in 2500
• Test can reasonably be performed by
• Physician
• Nurse, technician, etc. with immediate
  availability of supervising physician

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Exercise Protocols
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Stress Testing Contraindications
Absolute
Relative

• Acute MI (within 2d)
• High-risk unstable angina
• Uncontrolled arrhythmias
• Symptomatic severe AS
• Uncontrolled CHF
• Acute PE
• Acute MI or pericarditis
• Acute aortic dissection

• Left main stenosis
• Moderate valvular dz
• Electrolyte imbalance
• Severe hypertension
• Tachy or bradyarrhythmias
• Hypertrophic CM
• Mental or physical impairment
• High-grade AV block

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ST Segment Analysis During Stress Testing
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ECG Analysis
Evaluating the ECG

• PQ junction to determine isoelectric point
• J-point or J-junction
• Point 60 or 80 msec after J-junction
• 60 msec if upsloping
• 80 msec if down

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ECG Analysis
Expected Changes with Exercise

• Increase in p-wave amplitude in inferior leads
• Shortening of PR segment with downsloping in
  inferior leads
• Minimal changes in QRS
• J-junction (J-point) depression, especially in
  lateral leads
• Decrease in T-wave amplitude

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ECG Analysis
Responses in Ischemia

• ST Depression
• ST Elevation
• Normalization

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Implication of Baseline ST Abnormalities

• Further changes not diagnostic when baseline
  changes are due to
• Left ventricular hypertrophy
• Bundle branch block
• Digoxin
• Further changes may be diagnostic when baseline
  changes due to CAD

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ST Segment Depression

• Most common manifestation of ischemia
• Represents electrical gradients between normal
  and ischemic tissue
• Convention for ischemia is 1mm at 80 msec.
  (some use 60 msec)
• Downsloping more predictive than horizontal
• Slowly upsloping depression predictive if 1.5
  mm below PQ junction at 80 msec.

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Rest
Peak Exercise
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ECG Analysis
Surface ECG events coincide with myocardial
action potential events
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ECG Analysis
Action potentials become markedly altered during
ischemia
Normal Voltage during phase 2 plateau identical
in Endo and Epi - no gradient - ST segment
isoelectric
Ischemia both diastolic and systolic currents
of injury occur
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ST Segment Elevation

• When occurring in leads with Q-waves is likely
  due to peri-infarct ischemia

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ST Segment Elevation

• When occurring in leads without Q-waves
• Highly predictive of transmural ischemia
• Unlike depression, correlates with area of
  ischemia
• V2-V4 Anterior
• II, III, AVF Inferior

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ECG Analysis
Action potentials become markedly altered during
ischemia
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Localization of Ischemia by Site of ST Segment
Depression?

• Study of Mark, et al
• 452 patients with single vessel CAD and prior ETT
• ST depression no correlation with site of CAD
• Anterior ST elevation highly correlated with
  LAD disease
• Without Q waves high-grade prox. LAD
• With Q waves Totally occluded LAD

Ann Intern Med. 1987 Jan106(1)53-5.
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Stress Testing Indications for Terminating Test
Absolute
Relative

• Drop in SBP 10 mm Hg with evidence ischemia
• Moderate to severe angina
• Increasing CNS symptoms (ataxia, dizziness, etc.)
• Signs poor perfusion
• Inability to monitor BP
• Patient desire to stop
• Sustained VT
• ST elevation 1 mm

• Drop in SBP 10 mm Hg without ischemia
• ST depression 2mm, horiz. Or downsloping
• Multifocal PVCs, triplets, SVT, heart block
• Fatigue, SOB, wheezing, claudication
• BBB or IVCD similar to VT
• Increasing CP
• Hypertensive response

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Stress Testing

• Diagnosis of CAD
• Prognosis Implications
• Risk assessment after MI
• Evaluation of suitability for transplant
• Hemodynamic evaluation in valvular disease

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Stress Testing in Valvular Disease
Aortic Stenosis Mitral Stenosis Mitral
Regurgitation
Time for Surgery?
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Stress Testing in Valvular Disease
Aortic Stenosis

• Useful in seemingly asymptomatic patients with
  severe aortic stenosis, particularly inactive
  elderly patients.
• Hypotension during exercise in asymptomatic
  patients is a reason to consider aortic valve
  replacement.
• Exercise testing is clearly contraindicated in
  the patient with severe symptomatic AS.

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Stress Testing in Valvular Disease
Mitral Stenosis

• Asymptomatic patients with severe mitral stenosis
  may be considered for surgery if
• excessive heart rate response
• hypotension
• chest pain
• excessive exercise induced pulmonary hypertension
  is seen.

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Stress Testing in Valvular Disease
Mitral Regurgitation

• Stress testing may be helpful in the patient with
  mitral regurgitation, particularly when
  echocardiographic evaluation during exercise
  induces degrees of MR not seen at rest.

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Part 2Exercise Echocardiography
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Exercise Echocardiography

• Logistically performed exactly like standard
  exercise or bicycle test, with addition of
• Baseline (resting) echocardiogram
• Peak exercise echocardiogram
• Alternative stress with dobutamine or a
  vasodilator (adenosine)

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Exercise Echocardiography
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Stress EchocardiographyAdvantages

• Sensitivity and specificity improved over
  exercise testing alone and comparable to MPI
• Portable
• Immediate results
• Less time and cost investment compared to nuclear
  imaging
• Provides information re valve function,etc.

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Stress EchocardiographyDisadvantages

• Interpretation subjective and non-standardized
• Interpretation difficult when resting wall motion
  abnormalities present
• Technical limitations in obese, emphysematous and
  other patients

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Part 3Myocardial Perfusion Imaging
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Myocardial Perfusion Imaging

• Benefits over ordinary exercise testing
• Improved sensitivity and specificity
• Ability to localize ischemia and assess viability
• Similar accuracy compared with stress echo
• Three Methods
• Exercise MPI
• Vasodilator MPI (Adenosine or Dipyridamole)
• Dobutamine MPI

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Myocardial Perfusion Imaging
Vasodilator MPI
Adenosine
Dipyridamole

• Both useful when patient unable to exercise
• Both agents cause coronary vasodilatation,
  working preferentially on normal arteries and
  accentuating flow disparity between normal and
  abnormally perfused myocardium
• Both contraindicated in hypotensive patient
• Both can worsen bronchospasm

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Thallium vs. Technitium
Sestamibi
Thallium

• Potassium analog
• Biologic ½ life 58 hrs
• Concentrates in testes, thyroid, intestines,
  kidneys
• Myocardial extraction 60
• Uptake proportional to blood flow at time of
  injection
• Early images reflect blood flow at time of
  injection
• Late imaging (after 2-24 hrs) represents
  potassium distribution and thus viability

• Biological ½ life 6 hours
• Organ of greatest concentration gallbladder
• Enters myocytes by passive diffusion and binds to
  mitochondria
• Myocardial extraction about 30

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Thallium vs. Technitium
Sestamibi
Thallium

• Lower cost
• Greater evidence base
• Assessment of lung uptake
• Detection of ischemia at rest

• Higher cost
• Better images
• Ability to do gated analysis
• Better Quantification

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SPECT Imaging

• Rotating gamma camera in a circular orbit (180
  degrees) around the patient to acquire multiple
  planar projection images.
• Reconstruction of these planar projection images
  by filtered backprojection.
• Filtering techniques are used to improve imaging
  by correcting for artifacts.
• Tomographic slices are generated perpendicular to
  the anatomical axis of the heart (as in
  echocardiography).

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ECG-Gated SPECT Imaging

• Allows for assessment of global LVEF, regional
  wall motion, and regional wall thickening.
• Usually eight frames per R-R cycle are acquired.
• Limitations
• Tends to estimate LVEF 5-10 lower vs.
  echocardiography.
• Decreased accuracy with irregular HR, low count
  density, increased extracardiac
  radiopharmaceutical uptake, and small LVEF.

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Part 4Stress Testing in Women
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Men and Women are Not the Same!
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Stress Testing in Women

• CAD leading cause of death in women
• Higher mortality after MI than men
• Higher mortality with CABG compared with men

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Testing in Women Meta Analysis
Kwol, et al. Am J Card 199983660
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Stress Testing in Women Limitations

• Lower prevalence of CHD is women than men at any
  age
• Suboptimal performance on treadmill and bicycle
  protocols
• Higher incidence of false positive ST segment
  depression
• Lower pre-test probability of disease
• Greater prevalence of MVP and syndrome X?

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Stress Testing in Asymptomatic Women
20 year Follow-up on Lipid Research Clinics Study
Mora, et al. JAMA. 20032901600
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Alternative to Exercise Testing in Women

• Stress MPI
• Stress Echocardiography

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Stress MPI in Women

• Thallium 201
• Sens 78, Spec 60
• Problems
• Attenuation and scatter caused by breasts
• Smaller ventricular size
• Net increase in false positives in women

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Stress MPI in Women

• Technetium 99m
• Sens 80, Spec. 82
• Requires two injections (rest and stress)
• Two day high dose (25 mCi) protocol shown to
  optimize imaging in women with large breasts
• Specificity increased further with ECG gated wall
  thickening analysis (Spec. 92)

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Conclusion re Stress Testing in Women

• When pre-test probability either extremely high
  (90) or low (
• Among women with intermediate pre-test
  probability of CHD and without resting ST segment
  changes, exercise testing is reasonable
• Diagnostic value of exercise testing increased
  using Duke treadmill score, but prognostic value
  not good in women
• Stress echo or MPI should be considered in those
  with
• Intermediate risk test
• Negative submaximal test
• Baseline ECG abnormalities
• Inability to exercise

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Which Test Should You Choose?
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Comparison of Testing Modalities
Garber, Ann Intern Med 1999130719
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Cost Effectiveness
Men Age 65
Women Age 65
Garber, Ann Intern Med 1999130719
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Summary

• For the majority of patients at intermediate risk
  and without resting ECG changes, exercise stress
  testing is study of choice
• Although ST segment response is the main
  diagnostic tool in stress testing, other factors
  are useful prognostic indicators including
• Exercise ability
• Blood pressure response
• Speed of heart rate recovery

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Summary

• For those with resting ECG abnormalities,
  alternative testing modalities, perhaps more
  accurate but more expensive, include
• Exercise echocardiography
• Myocardial perfusion imaging
• In those with functional limitations alternatives
  tests include
• dobutamine stress echocardiography
• Persantine or adenosine perfusion imaging

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The End