Transcript ASNC women's slides

1
Women and
Coronary Artery Disease (CAD)
Module 3
Diagnosis and Prognosis
2
Supported by an unrestricted
educational grant from
Fujisawa Healthcare, Inc.
3
Diagnosis and Management of
Coronary Artery Disease in Women
• Gender differences: presentation,
manifestation and diagnosis of CAD
• Gender differences in mortality
– 63% of women who die suddenly from CAD had
no prior warning symptoms
– 42% of women vs 24 % of men will die within one
year after myocardial infarction (MI)
• Thus, early recognition of symptoms and
accurate diagnosis of CAD is of great
importance
4
Heart Disease in Women: Lessons
From the Past Decade
• The importance of studying gender-specific
aspects of CAD have helped in the following
clinical dilemmas:
– Presentation of CAD: women are older than men
– Less specific clinical manifestations of CAD in
women
– Greater difficulty in diagnosis: women > men
– More severe consequences on MI when it occurs
in women
5
Screening for Heart Disease
What Tests Should I Undergo to Tell
That I Have Heart Disease?
6
Limited Representation of Women in
Studies of CAD Testing
Women
92
100
Percent of patients
Men
78
80
73
60
40
20
22
27
8
0
ECG
Echo
MPI
Adapted from: Shaw LJ, et al. Coronary Artery Disease
in Women: What All Physicians Need to Know. 1999
7
Are There Gender Differences in
Noninvasive Diagnostic Tests?
Is There a Difference in Diagnostic
Accuracy of Noninvasive Tests?
8
Noninvasive Testing Options
Stress
ECG
Stress
Echo
Stress
MPI
EBCT
PET
MRI
9
Noninvasive Testing in
Symptomatic Women
• Stress electrocardiography (ECG)
• Stress echocardiography (ECHO)
• Stress nuclear
10
Exercise ECG (Treadmill)
• Despite advances in technology, the exercise
ECG remains an important tool in the
diagnosis and prognosis of the patient
suspected of having CAD
• The exercise ECG has an overall sensitivity
of 68% and a specificity of 77% for the
detection of CAD in men
• The sensitivity and specificity of the exercise
ECG in women are about 61% and 70%
respectively
Kwok Y, et al. Am J Cardiol. 1999.
11
ECG Testing in Women
Sensitivity and Specificity
Study, Year
Detry et al, 1977
Weiner et al, 1979
Barolsky et al, 1979
Friedman et al, 1982
Guiteras et al, 1982
Hung et al, 1984
No. of
Women
47
580
92
60
112
92
Sensitivity (%) Specificity (%)
80
76
60
32
79
73
63
64
68
41
66
59
Adapted from Heller GV, et al. Nuclear Cardiology: State of the Art and Future Directions. 1998
12
Gender Differences in Exercise
ECG Testing
•  sensitivity in women >65 years
•  specificity in women on hormone
replacement therapy
•  false-positive results due to
autonomic/hormonal influences
• Digoxin like effect of estrogen
Shaw LJ, et al. CAD in Women: What All Physicians Need to Know. 1999
13
Factors Affecting Accuracy
•
•
•
•
Hormonal status/cyclic variation
Functional capacity
Onboard medications
Adequacy of flow reserve
14
Diagnosis of Noninvasive Tests in
Women
•
•
•
•
ECG
Nuclear
ECHO
Computed tomography
15
Should All Women With Suspected
CAD Have Cardiac Imaging Studies?
• Nuclear
• ECHO
• Positron emission tomography (PET)
16
Incremental Value of Imaging to Exercise
ECG: Women With Abnormal Rest ECG
Stress ECG Alone
Study
Stress
Type
Sensitivity
Specificity
Hung
TM
73
59
Melin
Bike
61
Friedman
TM
Chae
With Imaging
Sensitivity
Specificity
Tl-201
75
91
78
Tl-201
70
93
32
41
Tl-201
75
88
TM
66
60
Tl-201
71
65
Sawada
TM/Bike
29
83
Echo
86
86
Williams
Bike
67
51
Echo
88
84
Masini
Bike – Dipy
72
52
Dipy Echo
79
93
57%
61%
78%
86%
AVERAGE
Imaging
Modality
Douglas PS. Coronary artery disease in women. In: Braunwald E. Heart Disease: A
Textbook of Cardiovascular Medicine. 2001
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Nuclear Imaging in Women
• Myocardial perfusion imaging (MPI)
• Large body of evidence in women
– Gender-specific data available for Tl-201and Tc-99m tracers
– Tc-99m tracers = agent of choice for women due to decrease
attenuation artifacts from breast tissue
– Gated single-photon emission computed tomography
(SPECT) provides post stress ejection fraction and regional
wall motion  helpful to reduce false positives
– IV adenosine/dipyridamole stress provides comparable
overall accuracy in women and men
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Comparative Test Statistics on
Diagnostic Accuracy in Women
ECG (n = 3721)
Echo (n = 296)
Nuclear (Tl-201) (n = 842)
Nuclear (Gated tech) (n = 100)
Sensitivity
Specificity
61%
86%
78%
84%
70%
79%
64%
94%
Kwok Y, et al. Am J Cardiol. 1999
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Diagnostic Specificity:
Tl-201 vs Tc-99m Sestamibi
92%
•
Perfusion imaging
– Regional blood flow
N = 115, P = .0004
•
Robust evidence in women
10 false +
– Gender-specific data for Tl-201
and Tc-99m sestamibi
– Tc-99m sestamibi is agent of
choice for women (reduced
breast attenuation)
21 false +
67%
•
Tl-201
Tc-99m
sestamibi
•
Gated SPECT
– Post-stress EF and regional
wall motion
– Reduce false-positive tests
Pharmacologic stress helpful in
older and obese women
Hachamovitch R. et al. J Am Coll Cardiol. 1996;
Amanullah AM, et al. Am J Cardiol. 1997; Taillefer R, et al. J Am Coll Cardiol. 1997
20
Pharmacologic Stress Testing in a
Community Setting: Women vs Men
Percent of patients referred for MPI who underwent exercise stress vs
pharmacologic stress at Mission Internal Medicine Group, Mission Viejo, CA
(4/21/02 to 8/29/02)
Women (n = 243)
Men (n = 375)
Pharmacologic
34%
Pharmacologic
53%
Exercise
47%
Exercise
66%
Data provided by Greg Thomas, MD, Mission Internal Medicine Group
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Economics of Noninvasive Diagnosis
(END) Study
Multicenter study by Shaw et al compared resource
consumption between 2 patient groups with varying initial
diagnostic testing strategies
11,372 men and women with stable angina
Patients separated into low, intermediate,
and high pretest probability of CAD risk
Direct cardiac
catheterization
(n = 5,423)
MPI (primarily Tc-99m sestamibi),
then selective cardiac catheterization
(n = 5,826)
Shaw LJ, et al. J Am Coll Cardiol. 1999
22
Secondary Analysis of
the END Study Population
Percent of patients
Defect extent with Technetium-99m sestamibi or dual-isotope imaging
100
88
75
80
70
61
60
40
20
20
15
15
8
12
4
10
8
2
3
8
1
0
0
1
2
3
0
1
2
3
Number of areas with perfusion defects
Men (n = 5009)
Women (n = 3402)
Marwick T, et al. Am J Med. 1999
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END Study: Ischemia as Gatekeeper to
Catheterization Laboratory
END Study: Enhanced Diagnostic Strategy in Symptomatic Women
Invasive (n = 3375)
Noninvasive (n = 1263)
0%
45%
22%
23%
32%
20%
20%
58%
40%
60%
80%
100%
Percent of patients
No CAD
1 vessel CAD
2+ vessel CAD
Invasive = cardiac catheterization
Noninvasive = initial stress SPECT plus selective catheterization
Shaw LJ, et al. J Am Coll Cardiol. 1999
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Results of END Study
• MPI with selective catheterization reduced
initial and follow-up care costs at all levels
of pretest clinical risk
• Savings noted by decreasing resource
use in patients with normal MPI results
• Selective catheterization reduced cost
of care while preserving/enhancing
quality of care
Shaw LJ, et al. J Am Coll Cardiol. 1999
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Stress ECHO
• Ultrasound performed
both at rest and during
peak stress
• Stress—exercise
or pharmacologic
• Ischemia defined by
development of wall
motion abnormalities
Courtesy of Howard Lewin, MD, of San Vicente
Cardiac Imaging Center.
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ECHO Testing in Women
• Overall
– Convenient/readily available1,2
– Avoids ionizing radiation2
– Identifies cardiac structure and left ventricular
function (LVF)
• Sensitivity and specificity vs ECG testing1,2
– Increased sensitivity (79%-88%)
– Increased specificity (77%-86%)
1. Williams MJ, et al. Am J Cardiol. 1994
2. Marwick T, et al. J Am Coll Cardiol. 1995
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PET Imaging for CAD in Women
Positron Emission Tomography
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PET Case Study: Patient FF
Stress
Rest
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PET Case Study: Patient FF
Ischemia of Lateral Wall
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The Role of PET for
Evaluating CAD in Women
• Soft-tissue artifacts encountered in SPECT are
eliminated
• Improved image quality due to better resolution than
SPECT
• Ability to quantify coronary blood flow
• Rb-82 perfusion imaging: 98% sensitivity and 95%
specificity for detecting CAD in women
Williams BR, et al. Am J Cardiac Imaging. 1996
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The Role of PET for
Evaluating CAD in Women
• Prognosis of a normal PET study
• ACC 2001: Van Tosh, et al:
– Follow-up at 30 months of 301 women with chest
pain, risk factors for CAD, no prior history of CAD,
and normal PET
– End points: cardiac death, nonfatal MI, PTCA, or
CABG
– Events at 30 months: 0.74% per year
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Electron Beam Computed Tomography
(EBCT)
• Resting study only
• Stationary tungsten target
permits rapid scanning
• Detects coronary
calcification
• Abnormality defined as
presence of any calcium
Courtesy of Howard Lewin, MD, of San Vicente Cardiac
Imaging Center
Diagnostic Accuracy of EBCT
Coronary Calcium Scores by Gender
Subsets
33
100
90
88
88
80
69
Percentage
70
61
60
49
50
48
40
30
20
10
0
Sensitivity
Specificity
Women
Sensitivity
Specificity
Men
Predictive accuracy Predictive accuracy
Women
Men
Devries S, et al. J Am Coll Cardiol. 1995.
Rumberger JA, et al. Circulation. 1995.
Detrano R, et al. Am J Card Imaging. 1996.
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Diagnostic Accuracy of EBCT
• Improved CAD detection and prognostication
through visualization of
– Wall motion
– Perfusion
– Function
35
Prognosis of Noninvasive Tests in
Women
Nuclear
36
Event Rates as Function of MPI With
SPECT Results by Gender
Evanet rate, %
16
14
12
10
Men
Women
8
6
4
2
0
Def normal
Prob normal
Equivocal
Prob abnormal
Def abnormal
Scan interpretation
Hachamovitch R, et al. J Am Coll Cardiol. 1996
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Prognostic Value of Adenosine SPECT
Imaging in 923 Women
8
7.5
7
Event %/ Year
6
Cardiac Death
MI
5
4.1
4
3.5
3
2.4
1.6
2
1
0.8
0.5
0.9
0
Low
Mild
Moderate
Severe
Amanullah AM, et al. Am J Cardiol. 1998
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Technetium-99m SPECT Imaging Predicts
Cardiac Mortality in Women
Ischemia extent and survival by number of vascular territories
Cardiac survival
1.0
0
1
2
0.9
1.0
0 98.5%
1
2
0.9
3
0.8
0.7
0.6
0.8
Women
(n = 3402)
0 0.5 1 1.5 2 2.5 3
Years
80-87%
0.7
3
Men
(n = 4500)
0.6
0
0.5 1
1.5 2
Years
2.5 3
Marwick TH, et al. Am J Med. 1999
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Prognostic Value of MPI
• Exercise MPI provides incremental prognostic
value to risk stratify women and to help in
CAD management1
• Abnormal Tc99m sestamibi SPECT findings
associated with adverse prognosis in both
women and men2
1. Hachamovitch R, et al. J Am Coll Cardiol. 1996
2. Travin MI, et al. Am Heart J. 1997
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Prognosis in Women: Shifting
Strategies for Early Detection
• Gender differences drive outcome differences1
– Baseline characteristics
– Clinical course
– Relative weight of prognostic factors
• Misperception: Coronary artery disease has benign
prognosis in women2
– Results in less aggressive diagnosis and management
• Awareness of higher morbidity/mortality in women3
– Dictates need for early diagnosis and aggressive treatment
– Early aggressive management lowers risk and need for
repeat intervention (eg, Evaluation of Platelet IIb/IIIa Inhibitor
for Stenting)
1. Bedinghaus J, et al. Am Fam Physician. 2001
2. Welty FK. Arch Intern Med. 2001
3. Keller KB, et al. Am J Crit Care. 2000
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Paradigm Shift in Strategies for
Screening Risk in Women
• Symptom presentation1
– Varies in women
– More likely atypical presentation
• Diabetic women
– Worse outcome, often asymptomatic on presentation1,2
– Bias toward undertreatment
• 63% of women with sudden cardiac death have no
prior symptoms3
• If we allow symptoms (current paradigm) to drive
testing and treatment, we will be less than accurate
1. Bedinghaus J, et al. Am Fam Physician. 2001
2. Welty FK. Arch Intern Med. 2001
3. American Heart Association. Women and Cardiovascular Diseases Biostatistical Fact Sheet. 2002
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Prognostic Value of MPI in Women
With Diabetes
Patient characteristics
With diabetes
(n = 1174)
Without diabetes
(n = 5528)
P Value
Age (y)
67 ± 11
65 ± 12
.001
Sex/No. of women
490 (42%)
2079 (38%)
.012
Prior MI
368 (31%)
1370 (25%)
.001
Prior PTCA
210 (18%)
726 (13%)
.001
Prior CABG
233 (20%)
849 (15%)
.001
Hypertension
741 (63%)
2458 (44%)
.001
Hypercholesterolemia
567 (48%)
2375 (43%)
.002
Anginal symptoms
600 (51%)
2488 (45%)
.001
Prescan likelihood of CAD
0.46 ± 0.31
0.38 ± 0.32
.001
Summed stress score
9.5 ± 10.1
7.1 ± 9.4
.001
Summed rest score
3.1 ± 6.6
2.4 ± 5.9
.001
Summed difference score
6.3 ± 7.3
4.6 ± 6.6
.001
Multivessel disease pattern
294 (25%)
892 (16%)
.001
Kang X, et al. Am Heart J. 1999
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Events per year (%)
Prognostic Value of MPI in Women With
Diabetes
10
9
8
7
6
5
4
3
2
1
0
n = 215
Exercise
9.9*
Adenosine
n = 202
n = 95
5.8*
4.8
n = 128
n = 151
n = 289
3.2
2.0
0.7
Normal
SSS <4
*P < .01
Mildly
Moderately
Abnormal to Severely
SSS 4-8
Abnormal
• Event rates rose significantly
as a function of summed
stress score (SSS)
• Diabetics had significantly
higher rate of hard events
versus nondiabetics
• Adenosine and exercise
were valuable tools for risk
stratification and
management of patients with
diabetes (N = 7133)
SSS >8
Kang X, et al. Am Heart J. 1999
44
BARI-2D Clinical Trial
• First BARI trial showed diabetics with CAD survive
longer after initial CABG than after initial PCI
• BARI-2D evaluates early revascularization vs
aggressive medical therapy in patients with type 2
diabetes and CAD
– Multicenter, multidisciplinary, randomized study
– Stress tests (eg, adenosine SPECT) and arteriograms
determine eligibility
• Trial to enroll 2800 patients from 40 centers
– 5-year follow-up
– Repeat stress testing and heart evaluations every 12 months
• VA Cooperative Study / UAB-Iskandrian Core Lab
Feit F, et al. Circulation. 2000
Brooks RC, et al. Curr Opin Cardiol. 2000
45
Diabetes: Prevalence of Subclinical
CAD in Women
The Cardiovascular Health Study
OR
Impaired
New diagnosis
fasting glucose
of diabetes
Known
diabetes
Major ECG changes
1.22
1.47
1.36
Internal carotid thickness
1.54
1.39
2.27
Common carotid thickness
1.24
0.98
2.54
Carotid stenosis >25%
1.08
1.40
2.31
Ankle arm index <0.9
1.24
0.74
3.14
Barzilay JI, et al. Diabetes Care. 2001
SNM Guidelines for Evaluating Women
With Suspected CAD
46
Symptom evaluation,
abnormal rest ECG,
intermediate likelihood of CAD
Caution: age <45,
evaluate comorbidity
Optimize ETT
Consider catheterization
if high risk
Gated SPECT, assess
functional status
No functional
limitations, 5 METS
Functional
limitations
Stratify by EF
Pharmacologic
stress
Diagnostic EF
EF <50%
EF <50%
Ischemia
No ischemia, consider
noncardiac origin
No defects
Catheter
Catheter
Evaluate valvular
disease (via ECHO)
Ischemia
Primary prevention,
modify risk factors
Adapted from: Shaw LJ, et al. Outcomes and Technology Assessment in Nuclear Medicine. 1999
Prognostic Evaluation of Women With
Suspected CAD
47
Clinical evaluation
Low likelihood of
CAD (<15%)
Risk factor
modification
Low
post-ETT
likelihood
Intermediate/high likelihood
of CAD (15% to 85%)
Interpretable
rest ECG
ETT
Uninterpretable
rest ECG
Intermed.high postETT
likelihood
Stress myocardial
perfusion SPECT
Normal or mildly
abnormal with normal
LV function
Moderately to
severely
abnormal
Cardiac
catheterization
Adapted from: Cacciabaudo JM, et al. J Nucl Med. 1998
48
New Paradigm for CAD Testing
Asymptomatic
with risk factors
Low probability:
asymptomatic
screening
Symptom onset
Detection of Subclinical CAD:
Global CAD Burden
High
probability
Intermediate
probability
Subclinical measures:
• A-B index
• Carotid IMT
• EBT-CT
Detection of Obstructive CAD
Cardiac
catheterization
PCI/CABS
Stress
ECG/Echo/SPECT
Anti-ischemic Rx and risk
factor modification
Shaw LJ. ACC 2002
Intermediate – High Likelihood Women 49Wi
Atypical or Typical Chest Pain Symptoms,
Dyspnea, or Reduced Activities
Risk factor
modification
+/or
anti-ischemic Rx
Good exercise tolerance
and normal
rest ECG
Low
post-ETT
likelihood
Exercise
treadmill (TM) testing
Intermediate
risk TM
Normal or mildly
abnormal with
normal LV function
Diabetes, abnormal
rest ECG, or
max exercise capacity <5 METs
Exercise or pharmacologic stress
gated SPECT
Ex capacity >5
METs
Ex capacity <5
METs
Exercise
stress
gated SPECT
Pharmacologic
stress
gated SPECT
Moderateseverely
abnormal
or reduced EF
Cardiac
catheterization
Mieres JH, et al. ASNC VII 2003
50
Beyond Research
• Society educational programs/guideline updates
– Synthesizing research
• Medical literature is immense and changing rapidly—need
strategies for effective/quick dissemination of research
– Create opportunities for clinician education/awareness/
intervention
• Training and educational programs for primary care physicians
including generalists, gynecologists, and cardiovascular
specialists
• Health policy
– Strategies for targeting screening of at-risk women
•  representation of women in NIH-funded/FDA-sponsored
trials—first step
• Should we have a reimbursable/recommended screening test
post-menopause (eg, mammogram)?
51
Conclusions
• Supportive research is unfolding, changing
dynamically
– Dramatic differences in baseline characteristics,
risk factor prevalence, and variability of
management intensity contributing to outcome
differences
– New evidence reveals an array of tests available
for risk assessment in women
– Additional gender-specific evidence is required to
development management strategies aimed at
identification of risk and risk reduction