Testing for Coronary Artery Disease by q3f0yOUB

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									     Testing for
Coronary Artery Disease



         John L. Tan, MD, PhD
         North Texas Heart Center
       Presbyterian Hospital of Dallas
Cardiovascular Disease Mortality Trends
                                       United States: 1979-2002

                       520
 Deaths in Thousands




                       500
                       480
                       460
                       440
                       420
                       400
                       380
                       79

                             81

                                  83

                                        85

                                             87

                                                  89

                                                       91

                                                              93

                                                                   95

                                                                        97

                                                                             99

                                                                                  01
                                                       Year


                                             Males       Females
Source: CDC/NCHS.
            Leading Causes of Death
                      United States: 2002
Deaths in Thousands
500                                 494
      434
                                                 Males
400
                                                 Females
          289                       269
300

200

100             69   61                     64    42 39
                           34
  0
      A    B     C   D      E   A   B       D    F   E
 A Total CVD              D Chronic Lower Respiratory Diseases
 (Preliminary)            E Diabetes Mellitus
 B Cancer                 F Alzheimer’s Disease
 C Accidents                            Source: CDC/NCHS
Rate of Myocardial Infarctions
                  700000      650000
Number (Annual)



                  600000

                  500000                                 450000

                  400000

                  300000

                  200000

                  100000

                      0
                           First-time                Recurrent
                              Myocardial Infarction
                                        Heart and Stroke Statistical Update. 2002.
                     Lifetime Risk of CAD
                    60
                                                               Men
                         49                                    Women
Lifetime Risk (%)


                    50

                    40                               35
                                32
                    30
                                                             24
                    20

                    10

                    0
                          >40                          >70
                                     Age (Years)
                                        Lloyd-Jones, DM et al. 1999. Lancet. 353:89
Growing Prevalence of CAD
      Larger pool
        Population   is growing older

      Greater Risks
        Increasing   incidence of
          Obesity
          Diabetes
          Metabolic Syndrome
          Hypertension
     Who Are at Risk?


How Can We Identify Them?
        The
   Framingham
   Score for Risk
     Prediction


 Risk:
 Low                   <10%
 Intermediate         10-20%
 High                  >20%


Greenland and Gaziano, NEJM, 2003
  Framingham Risk Score
50 year-old man           6
Total cholesterol 240     4
Non-smoker                0
HDL 40                    1
SBP 140 mm Hg             1

Framingham Risk Score    12
10-year Risk            10% (Intermediate)
  Framingham Risk Score
45 year-old woman         3
Total cholesterol 240     8
Smoker                    7
HDL 50                    0
SBP 140 mm Hg             3
Framingham Risk Score    21
10-year Risk            14% (Intermediate)
     Limitations of the
  Framingham Risk Score

 Family   History of Premature CAD

 CRP   Levels

 Metabolic   Syndrome
 Elevated hs-CRP as an
Independent Risk Factor




  Ridker et al, NEJM, 2004
                                        Mortality Rates in Adults with
                                           Metabolic Syndrome
                                    NHANES II: 1976-80 Follow-up Study
                           50.0
                                                                                                                    44.1
Deaths/1000 Person Years




                           45.0
                           40.0                                                                                            No MetS or DM
                           35.0                                                                              30.0          MetS w/o DM
                                                                                         28.1             26.1
                           30.0
                                                                                                       21.1                MetS w/DM
                           25.0
                                                                                  16.7              17.1                   DM only
                           20.0                             17.0
                                                                              11.5              14.4
                           15.0                      10.9                                                                  Prior CVD
                                                  6.3                    7.8 8.6                                           Prior CVD and DM
                           10.0         4.3 4.8                    5.3
                                  2.6
                            5.0
                            0.0
                                        CHD Mortality                    CVD Mortality              Total Mortality

                            13 years average follow-up.                                         Source: Circulation 2004;110:1245-50.
          Initial Assessment
   Framingham Risk Score
   Family History of Premature CAD
   CRP Levels
   Presence of the Metabolic Syndrome
     (High triglycerides, Glucose Intolerance, Central Adiposity)

   Presence of Diabetes
    Now What?
  “Fear of God”
Modify Risk Factors

Further Risk Stratify
Available Tests to Detect CAD
       Stress ECG
       Stress Imaging Study
       Ultra-fast CT (EBCT)
       CT Angiography
       Coronary Angiography
       Initial Considerations

   Symptomatic versus Asymptomatic

   Diagnosis versus Prognosis

   Assessment of Risk for CV mortality

   Physiological/Functional versus Anatomical
Patients with Symptoms
  Clinical Classification of Chest Pain
  Typical Angina (definite)
      (1) Substernal chest discomfort with a characteristic quality and
      duration that is (2) provoked by exertion or emotional stress and
      (3) relieved by rest or nitroglycerin

  Atypical Angina (probable)
       Meets 2 of the above characteristics

  Noncardiac Chest Pain
       Meets one or none of the typical angina characteristics

ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999
Pretest Likelihood of CAD in Symptomatic Patients:
  Percent with significant CAD on catheterization

               Nonanginal            Atypical            Typical
               Chest Pain            Angina              Angina

 Age, yrs    Men Women            Men     Women       Men     Women

  30-39        4         2         34       12        76        26

  40-49        13        3         51       22        87        55

  50-59        20        7         65       31        93        73

  60-69        27        14        72       51        94        86
            ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999
Kaplan-Meier Survival in Risk
     Stratified Patients




                  Shaw, et al, AJC, 2000
Exercise Testing
 Clinically Useful Bench Marks of
         Exercise Capacity
1 MET      Basal activity level (3.5 ml O2 comsumed/Kg/min
< 5 METs   Associated with a poor prognosis in patients <65 y/o
5 METs     Marks the limit of ADLs, usual limit immediate post MI
10 METs    Considered average level of fitness
           In patients with angina, no mortality benefit CABG vs
               medical Rx
13 METs    Good prognosis in spite of any abnormal exercise test
               response
18 METs    Aerobic master athelete
22 METs    Achieved by well-trained competitive atheletes
Four-year Mortality Rates with Abnormal
   ETT: Effects of Exercise Capacity


                        47
     50
                                     STAGE 5
     45
                                     STAGE 2-4
     40                              STAGE 1
     35                              STAGE <1
     30
     25       18   20
     20
     15
     10
      5   0
      0                      Weiner, et al, JACC, 1984
Exercise Parameters Associated with
 Advanced CAD or Poor Prognosis
1. Duration of ETT <6.5 METS (<5 METS for women)
2. Exercise HR <120 bpm off b-blockers
3. Ischemic ST segment change at HR <120 bpm or <6.5
      METS
4. ST segment depression >2 mm, especially in multiple
     leads
5. ST segment depression for >6 min in recovery
6. Decrease in BP during exercise
Probability of Significant Disease
    Across Duke TM Scores




                     Alexander, et al, JACC, 1998
    Survival According to Risk Groups
       Based on Duke TM Scores

Risk Group, Score           % of Total        Survival       Mortality, %

Low (5 or greater)                62             0.99               0.25

Moderate (-10 to 4)               34             0.95               1.25

High (-10 or less)                 4             0.79               5.0

Duke TM Score = Exercise time - (5 x ST deviation) - (4 x Treadmill angina)
                  ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999
     Meta-analysis of Exercise Testing
                           Number of Sensitivity   Specificity Predictive
    Grouping                 Studies   (%)            (%)     Accuracy (%)

 Standard exercise test        147          68        77          73
 Without MI                     58          67        72          69
 Without workup bias             3          50        90          69
 With ST depression             22          69        70          69
 Without ST depression           3          67        84          75
 With digoxin                   15          68        74          71
 Without digoxin                  9         72        69          70
 With LVH                       15          68        69          68
 Without LVH                    10          72        77          74
 Overall                                  ~70       ~80
ACC/AHA Guidelines for Exercise Testing, 1997
   The “Ischemic Ladder”
                                             Angina
                                    ECG
                                   Changes
                      Systolic
MVO2




                     Dysfunction

        Diastolic
       Dysfunction




                           Time
Stress Imaging
     Stress Imaging Studies
Stress Modalities   Imaging Modalities
    Exercise          Echocardiography
    Dobutamine        Perfusion Imaging
    Adenosine          –   Nuclear Scan
                        –   Thallium Scan
    (Persantine)
                        –   Sestamibi Scan
                        –   Hybrid Scan
                       MRI
Sensitivity and Specificity of
        CAD Studies
Procedure       Sensitivity (%) Specificity (%)
Exercise Test        68                        77

Stress Echo          76                        88

SPECT                88                        77
                     Lee and Boucher. 2001. NEJM. 344:1840
Advantages of Stress Echocardiography

    1. Higher specificity
    2.   Versatility: more extensive evaluation of
           cardiac anatomy and function
    3. Greater convenience/efficacy/availability

    4. Lower cost
         Advantages of Stress
     Myocardial Perfusion Imaging
1.   Higher technical success rate
2.    Higher sensitivity, especially for one-vessel disease
3.    Better accuracy in evaluating possible ischemia
          when multiple rest LV wall motion
           abnormalities are present
4.    More extensive published database, especially in
          evaluation of prognosis
Patients without Symptoms
  High Grade Stenoses
       Diabetics

Non-flow Limiting Disease
                                   Abnormal Perfusion Scans in
                                     Asymptomatic Diabetics
% Abnormal Stress Perfusion Scan



                                   60

                                   50

                                   40

                                   30

                                   20

                                   10

                                    0
                                               A                      B                      C
                                   A DIAD Study (Wackers et al. 2004. Diabetes Care. 27:1954)
                                   B Rajagopalan et al. (Rajagopalan et al. 2005. J Am Coll Cardiol. 45:43)
                                   C Cedars-Sinai Group (Zellweger et al. 2004. Eur Heart. 25:543)
      Yield of High-Risk Scans in
        Asymtomatic Diabetics
   Subgroup                                    High-risk Scans

Q waves on ECG                                          43%
Abnormal ECG                                            26%
Peripheral Vascular Disease                             28%
LDL >100 mg/dl                                          20%
Two or more risk factors                                17%
    Rajagopalan et al. 2005. J Am Coll Cardiol. 45:43
     Screening of CAD: ADA
        Recommendations

In asymptomatic diabetic patients with:
    Abnormal resting ECG (MI or ischemia)
    Peripheral vascular disease
    Two or more additional CAD risk factors
Patients without Symptoms

Mild CAD Not Detectable
    by Stress Testing
     Myocardial Infarctions
      and Plaque Severity
70                  Burke et al. NEJM. 1997. 336:1276

60
50
40
30
20
10
      2/3        1/6                  1/6
 0
     <50%       50-70%               >70%
            Plaque Severity
                            Outcomes with Mild CAD

                           3    TIMI Trials Meta-analysis         2.8
% Death or Non-fatal MI




                          2.5

                           2
                          1.5             1.3

                           1
                          0.5
                           0
                                    Normal                  Mild Disease
                                                               1-year follow-up
            5-Year Incidence
           of Coronary Death
    9
                     7.8          8.1
    8
    7
    6
    5
%




    4
    3
    2
    1      0.7
         n=763     n=274        n=377
    0
        Normal    <50%          >50%    MONICA Belgian Substudy

                 Stenosis by Angiography
Available Tests to Detect CAD
       Stress ECG
       Stress Imaging Study
       Ultra-fast CT (EBCT)
       CT Angiography
       Coronary Angiography
Coronary Calcium Scoring




             Greenland and Gaziano, NEJM, 2003
  Incremental Value of Coronary
Calcium Scoring to Risk Assessment




    Greenland et al, JAMA, 2004
Sensitivity and Specificity of
        CAD Studies
Procedure       Sensitivity (%) Specificity (%)
Exercise Test        68               77

Stress Echo          76               88

SPECT                88               77

EBCT                80-90            40-50
“Treating the Herd”

    Population
      versus
  Individual Risk
Multi-Detector Computer
 Tomography (MDCT)
     Multi-Detector Computed
      Tomography (MDCT)
 Increased slices per gantry rotation
       (currently 64 slices)

   Faster gantry speed (330 ms/rotation)
       resulting in:
                better spatial resolution (0.4 mm)
                better temporal resolution (165 ms)
MDCT Capabilities
Coronary Angiography with MDCT




           Fuster V, et al. J Am Coll Cardiol. 2005. 46:1209
Coronary Angiography with MDCT




            Raff, et al. J Am Coll Cardiol. 2005. 46:552
       64-Slice CT Angiography: Per
              Segment Analysis
                     Sensitivity (%)       Specificity (%)       PPV (%)        NPV (%)

Leschka, et al              94                    97                 87          99

Leber, et al                80                    97                NR*           NR*

Raff, et al                 86                   95                  66          98

Pugliese, et al             99                   96                 78           99

Mollet, et al               99                   95                  76          99
                                                                          *NR Not Reported
   Leschka, et al. Eur Heart J. 2005. 26:1482; Leber, etl al. J Am Coll Cardiol 2005. 46:147
   Raff, et al. J Am Coll Cardiol. 2005. 46:552; Pugliese, et al. Eur Radiol. 2005 16:1
   Mollet, et al. Circulation 2005. 112(15):2318
       64-Slice CT Angiography: Per
              Patient Analysis
                  Sensitivity (%)   Specificity (%)     PPV (%)        NPV (%)


Raff, et al            86                95                 66          98

Pugliese, et al        100              90                  96          100




                                       Raff, et al. J Am Coll Cardiol. 2005. 46:552
                                       Pugliese, et al. Eur Radiol. 2005 16:1
Detection of “Soft” Plaque
   by CT Angiography




         Fuster V, et al. J Am Coll Cardiol. 2005. 46:1209
Indications for MDCT Angiography
            of the Heart
1.   Facilitation of the diagnostic cardiac evaluation of a patient with
     chest pain syndrome (e.g. chest pains, anginal equivalent, angina).
     Depending on the clinical presentation, the MDCT for coronary
     artery evaluation may precede a perfusion stress test, or it may be
     used to clarify a perfusion stress test that is non-diagnostic,
     equivocal, or is inadequate in explaining the patient’s symptoms.

2.   Facilitation of the management decision of a symptomatic patient
     with known coronary artery disease. (e.g. post-stent, post CABG)
     when the results of the MDCT may guide the decision for repeat
     invasive intervention.

3.   Assessment of suspected congenital anomalies of coronary
     circulation or great vessels.
       Radiation Exposure of
           CAD Studies
                                                   Dose (mSv)
Background          (per year)                        3.5
Chest X-ray                                           0.1
CT of Chest                                           5-7

Procedure
EBCT                                                  ~1
Perfusion Imaging                                     ~10
CT Angiography                                        ~10
Coronary Angiography                                  ~2-3
    Conti, CR. Clin. Cardiol. 2005. 28:450
    Morin RL, et. al. Circulation. 2003. 107:917
Sensitivity and Specificity of
        CAD Studies
Procedure             Sensitivity (%) Specificity (%)
Exercise Test                68                   77
Stress Echo                  76                   88
SPECT                        88                   77
 (40-60% of patients have attenuation defects)

EBCT                       80-90                 40-50
MDCT (per patient analysis)
 16-Slice            85-100                      75-86
 64-Slice            86-100                      90-95
Invasive Coronary Angiography

    ~25% of angiograms performed annually in
    the US are normal
    ~8 million angiograms are performed
    annually in the US at a cost of ~$4,000 per
    procedure
Invasive Coronary Angiography

 Therefore, there are ~2 million angiograms
  performed annually on patients with normal
  coronary arteries
 These procedures expose patients to the
  inherent risks of invasive coronary
  angiography at a cost of ~ $4 billion per year
                Summary
   The incidence and prevalence of CAD is
    growing due to aging of the population
    and to increases in risk factors.

   Global clinical assessment, CRP levels,
    and calcium scoring may help to further
    stratify individual risks.
                Summary
   Stress testing currently remains the
    standard for assessing symptoms.

   Although a negative stress study most
    likely excludes the presence of flow-
    limiting disease (stenosis of >70%), it
    does not exclude the presence of mild to
    moderate disease.
                 Summary
   Mild to moderate disease still confers an
    increase in coronary deaths and
    infarctions.

   Invasive coronary arteriography has been
    the only method of identifying patients
    with mild to moderate disease up to now.
                Summary

   CT angiography will allow for the non-
    invasive identification of at-risk patients
    as having (or not having) underlying
    coronary atherosclerosis.
               Summary

 Exercise   Test
  – Probable more than we do
 Stress   Echocardiogram
  – Lower pre-test probablility population
  – Valvular or other structural heart disease
               Summary

 Stress   Perfusion Scan
  – Higher pre-test probability population
 Cardiac   MRI
  – When above unhelpful and expertise is
    available
                Summary
 Ultra-fast   CT (EBCT)
  – No role in symptomatic patients
 CT   Angiography
  – Will play larger role with ability to image
    coronaries (Triple Rule Out)
 Coronary     Angiography
  – When stress testing is potentially dangerous

								
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