1. Cardiovascular Disease in Women Module IV: Diagnosis
This slide set was updated April 2008.

2. Diagnosis of Coronary Artery Disease in Women
Drawbacks and Difficulties in Diagnosis
Presentation in Women
Diagnostic Testing Challenges

3. Diagnosis of Coronary Artery Disease in Women
Chest pain is experienced by most women with CHD, but non-chest pain presentations are more common in women than men
Other Presenting Symptoms
Upper abdominal pain, fullness, burning sensation
Shortness of breath
Nausea
Neck, back, jaw pain
Associations
Precipitated by exertion
Precipitated by emotional distress
SLIDE INFORMATION SOURCES: Charney P. Presenting symptoms and diagnosis of coronary heart disease in women. J Cardiovasc Risk 2002; 9: Goldberg RJ, O’Donnell C, Yarzebski J, et al. Sex differences in symptoms presentation associated with acute myocardial infarction: a population-based perspective. Am Heart J 1998; 136:
Coronary artery disease presents more frequently with atypical symptoms in women compared to men (1,2).
Gender, race, and other perceptions may affect physicians’ assessment of whether a patient has CHD. Studies using tapes of actresses reading from a script describing CHD symptoms have shown that physicians are less likely to assess CHD in African American women compared to white women and men, and in women with a “hysterical” style compared to those with a more “business-like” presentation(1).
(1) Charney P. Presenting symptoms and diagnosis of coronary heart disease in women. J Cardiovasc Risk 2002; 9:
(2) Goldberg RJ, O’Donnell C, Yarzebski J, et al. Sex differences in symptoms presentation associated with acute myocardial infarction: a population-based perspective. Am Heart J 1998; 136:
Source: Charney 2002, Goldberg 1998

4. Testing for Ischemic Heart Disease in Women and Factors to Consider
Technique
Assessment
Issues in Women
Angiography
Coronary anatomy
Less focal disease
Coronary CT
Coronary calcification
Less well-validated than other techniques
Echocardiography
Regional wall motion
Reader expertise variable
Nuclear Cardiology
Regional blood flow
Attenuation issues
SLIDE INFORMATION SOURCES: Charney P. Presenting symptoms and diagnosis of coronary heart disease in women. J Cardiovasc Risk 2002; 9: , Greenland P, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain. Circulation 2007; 115:
A variety of tests may be used both for the diagnosis of ischemic heart disease and for risk stratification of known or suspected CHD(1) .
Each of the commonly used methods evaluates a different component of cardiac anatomy or physiology (1) .
Specific aspects of each technique explain the differences in the accuracy for the method and its value for different population groups(1)(2).
Charney P. Presenting symptoms and diagnosis of coronary heart disease in women. J Cardiovasc Risk 2002; 9:
(2) Greenland P, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain. Circulation 2007; 115:
Source: Charney 2002, Greenland 2007

5. Drawbacks of Diagnostic Imaging in Women
Low exercise capacity – likelihood of reaching adequate pressure rate product
Solution: Pharmacologic stress testing
Breast attenuation artifact – higher false positive imaging studies
Solution: Gated acquisition; attenuation correction for nuclear imaging
Solution: Echocardiography
Lower pretest probability of CAD – higher false positive rate
Solution: Integrate clinical variables, risk factors, into decision-making process
SLIDE INFORMATION SOURCE: Claire Duvernoy, M.D., personal communication March 2005.
Source: Duvernoy, personal communication

6. Value of the Exercise ECG in Women77 80 70 68 70 61 60 50 40
Men
SLIDE INFORMATION SOURCE: Kwok Y, et al. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999; 83 :
This meta-analysis found that exercise ECG is less accurate in women than in men (1).
Mechanisms such as digoxin-like effect of estrogen, different catecholamine response to exercise in women, a higher incidence of mitral valve prolapse, and different chest wall anatomy in women have also been proposed as explanations for accuracy differences (1) .
In addition, methods for performing the exercise ECG were developed using men, and the thresholds for abnormal were established almost exclusively in men (1).
(1) Kwok Y, et al. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999; 83 :
Women 30 20 10
Sensitivity
Specificity
Source: Kwok 1999

7. Principles of Nuclear Cardiac Stress Testing
Normal response: Myocardial blood flow demonstrated by injected radioisotopes is increased above the resting condition
Ischemia: With fixed stenoses, myocardial perfusion does not increase with stress in the territory supplied by the stenosed artery, demonstrated by inhomogeneous distribution of the radioisotope
Scar from myocardial infarction: Fixed inhomogeneous distribution of the radioisotope at both rest and with stress
Photons are emitted in all directions from the point of origin
Attenuation of images occurs in obese patients, and from breast tissue
SLIDE INFORMATION SOURCE: Nishimura RA, Gibbons RJ, Blockner JF, Tajik AJ. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005.
Stress may be provided by exercise or pharmacologically (1).
(1) Nishimura RA, Gibbons RJ, Blockner JF, Tajik AJ. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005.
Source: Nishimura 2005

8. Diagnostic Accuracy of Thallium-201 SPECT Myocardial Perfusion Imaging in Men and Women
SLIDE INFORMATION SOURCE: Hansen CL, et al. Lower diagnostic accuracy of thallium-201 SPECT myocardial perfusion imaging in women: an effect of smaller chamber size. J Am Coll Cardiol 1996; 28(:
Hansen et al. compared diagnostic accuracy of Tl-201 SPECT for CAD in 129 normals (60 women, 69 men) and 154 pts w/ CAD (47 women, 107 men)(1).
Overall accuracy of the test was lower in women(1).
When the studies were stratified by the size of the left ventricle, it appeared that size of the left ventricle, rather than gender, was determining factor for accuracy. Women’s tests were less accurate because their hearts were, on average, smaller (1).
The authors attributed this decreased accuracy to a greater effect of image blurring in smaller hearts (1)
(1) Hansen CL, et al. Lower diagnostic accuracy of thallium-201 SPECT myocardial perfusion imaging in women: an effect of smaller chamber size. J Am Coll Cardiol 1996; 28:
P < 0.05
Source: Hansen 1996

9. Sensitivity and Specificity of Dipyridamole SPECT Imaging in Identifying Individual Coronary Stenoses and Multivessel Disease in Women
SLIDE INFORMATION SOURCE: Travin MI, et al. J Nucl Cardiol 2000; 7:
This graphic shows the results for women in a study of 107 unselected pts (58 women, 49 men) who underwent Tc-99 sestamibi SPECT dipyridamole SPECT imaging and cardiac catheterization within a 6 month time period(1).
In this study, the accuracy of dipyridamole sestamibi SPECT imaging was similar. The sensitivity of dipyridamole sestamibi SPECT imaging in detecting disease of the left anterior descending (LAD) artery was better in women(1).
(1) Travin MI, Katz, MS, Moulton AW, et al. J Nucl Cardiol 2000; 7:
Source: Travin 2000

10. Breast Attenuation Image Courtesy of EG DePuey MD
SLIDE GRAPHIC SOURCE: Courtesy of EG DePuey, M.D.
Shown here are short-axis myocardial perfusion images from a female patient which demonstrate decreased uptake in the anterior wall both during stress (first and third rows) and at rest (second and fourth rows), suggestive of a prior anterior wall MI(1).
(1) Image description by Claire Duvernoy, M.D., personal communication, March, 2005.
Image Courtesy of EG DePuey MD

11. Breast Attenuation (continued)
SLIDE GRAPHIC SOURCE: Courtesy of EG DePuey, M.D.
Shown here is the same patient, with perfusion studies divided into end-diastole and end-systole, show that the anterior defect is probably an artifact, because at end-systole, the anterior wall thickens well, and no longer demonstrates decreased uptake(1).
(1) Image description by Claire Duvernoy, M.D., personal communication, March, 2005.
Image Courtesy of EG DePuey MD

12. Principles of Stress Echocardiography
Normal response:
Increased left ventricular contractility
Hyperdynamic wall motion
Ischemia:
New wall motion abnormality with stress
Decreased ejection fraction
Increase in end-systolic volume
Scar from myocardial infarction:
Fixed wall motion abnormality with rest and stress
SLIDE INFORMATION SOURCE: Nishimura RA, et al. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005.
Stress may be provided by exercise or pharmacologically (1).
Dobutamine infusion can be used to assess myocardial viability by using low dose, followed by higher doses of the drug. Viable myocardium demonstrates increased contractility at low doses of dobutamine, followed by decreased contractility at higher doses(1).
(1) Nishimura RA, et al. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005.
Source: Nishimura 2005

13. Principles of Stress Echocardiography
Valvular heart disease evaluation may be performed as well
Need good acoustic window
SLIDE INFORMATION SOURCE: Nishimura RA, et al. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005.
Source: Nishimura 2005

14. Value of Stress Echocardiography Compared to Stress ECG in Women** *
SLIDE INFORMATION SOURCE: Marwick TH, et al. Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women. J Am Coll Cardiol 1995; 26:
This study showed significantly higher specificity and overall accuracy for stress echocardiography as compared to conventional exercise treadmill testing, in a female population(1).
(1) Marwick TH, et al. Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women. J Am Coll Cardiol 1995; 26:
*P < vs. Echo
**Old P < vs. Echo
Source: Marwick 1995

15. Sensitivity and Specificity of Dobutamine Stress Echocardiography for the Diagnosis of CAD in Women*
SLIDE INFORMATION SOURCE: Elhendy A, et al. Gender differences in the accuracy of dobutamine stress echocardiography for the diagnosis of coronary artery disease. Am J Cardiol 1997; 80:
This graph represents the results of a study of 306 consecutive women and men who underwent dobutamine stress echocardiography for evaluation of CAD and coronary angiography within three months(1).
The authors postulated that the greater accuracy of the study in women compared to men might be due to their better response to dobutamine (women more frequently achieved target heart rate), better imaging because of decreased chest wall thickness, and fewer false positives because of thinner myocardium (1).
(1) Elhendy A, et al. Gender differences in the accuracy of dobutamine stress echocardiography for the diagnosis of coronary artery disease. Am J Cardiol 1997; 80:
* Higher in women than in men P < 0.05
Source: Elhendy 1997

16. CHD: Differences in Presentation and Findings in Women Compared to Men
Lower prevalence of MI
More severe CHF
More severe angina
Less angiographic CAD
More ostial lesions
More microvascular dysfunction?
Abnormal vasomotor tone?
More endothelial dysfunction?
SLIDE INFORMATION SOURCE: Jacobs AK. Coronary revascularization in women in 2003: sex revisited. Circulation (3):
Source: Jacobs 2003

17. Cardiac Catheterization Indications for Presumed/Known CAD: ACC/AHA Guidelines
To determine the presence and extent of obstructive coronary artery disease (CAD) when diagnosis … cannot be reasonably excluded by noninvasive testing
To assess the feasibility and appropriateness of revascularization
To assess treatment results … progression or regression of coronary atherosclerosis
SLIDE INFORMATION SOURCE: Scanlon PJ, et al. ACC/AHA guidelines for coronary angiography: executive summary and recommendations. Circulation 1999; 99:
Cardiac catheterization is considered the “gold standard” for the diagnosis of coronary artery disease(1).
(1) Charney P. Presenting symptoms and diagnosis of coronary heart disease in women. J Cardiovasc Risk 2002; 9:
Source: Scanlon 1999

18. Principles of Coronary Calcium (CAC) Scoring by CT
Highly sensitive technique for detecting coronary calcium
Scans are obtained in less than one minute, during one to two breath-holding sequences
Results reported as a coronary calcium score
Highly sensitive for detecting CAD, low specificity, overall accuracy of approximately 70%
African Americans may have less coronary calcification, despite similar risk profiles as whites and more subsequent cardiac events
SLIDE INFORMATION SOURCE: O’Rourke RA, et al. American College of Cardiology/American Heart Association expert consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol 2000; 36: ; Doherty TM. Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors. J Am Coll Cardiol 1999; 35: ; Greenland P, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain. Circulation 2007; 115:
Source: O’Rourke 2000, Doherty 1999, Greenland 2007

19. Sensitivity and Specificity of Electron-Beam Computed Tomography for Detection of Obstructive Coronary Artery Disease in Women
SLIDE INFORMATION SOURCE: Devries S, et al. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol 1995; 25:76-82.
This slide demonstrates data from a study of 70 women and 70 men with suspected coronary artery disease who underwent cardiac catheterization within nine months of electron beam computed topography(1). Of note, although high coronary calcium scores correlate with obstructive CAD, there was little correlation with degree of angiographic disease(1).
Coronary atherosclerosis is more likely to be associated with calcification in men, compared to women. This is because women under the age of 60 years with atherosclerosis do not demonstrate the same patterns of calcification seen in older women and men with CAD(1).
The specificity of EBCT is low, and is lower with advancing age. Because of the lower overall prevalence of CAD in women, false positive rates are higher(1).
(1) Devries S, et al. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol 1995; 25:76-82. ≥
Source: Devries 1995

20. Coronary Calcium (CAC) Scoring by CT Not Routinely Recommended: ACC/AHA Consensus
CAC measurement is not recommended for screening of the general population, or for evaluation of patients at low CHD risk
CAC measurement is not recommended for evaluation of patients with high CHD risk
CAC measurement may be reasonable to evaluate intermediate risk patients (10%-20% 10 year risk of CHD event), because such patients may be reclassified to a higher risk status based on a high coronary calcium score
There is not enough evidence to compare CAC measurement to other methods of cardiac testing at this time
SLIDE INFORMATION SOURCE: Greenland P, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain. Circulation 2007; 115:
Source: Greenland 2007

21. Principles of Cardiac Magnetic Resonance Imaging (CMR) in the Detection of CHD
Static and cine images are obtained using electrocardiographic triggering, often with a short breath-hold of seconds
Myocardial perfusion can be evaluated by injecting gadolinium and continuously scanning as contrast passes through the heart and into the myocardium
Myocardial viability can be assessed by delayed imaging after gadolinium injection; infarcted tissue retains contrast
Magnetic resonance angiography (MRA) of coronary arteries is limited because of the small size of vessels and complex motion during the cardiac cycle
Vasodilators and dobutamine can be used to provide stress imaging
SLIDE INFORMATION SOURCE: Nishimura RA, et al. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005, Hendel RC, et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging. J Am Coll Cardiol 2006; 48:
Source: Nishimura 2005, Hendel 2006

22. Principles of Cardiac Magnetic Resonance Imaging (CMR) in the Detection of CHD
Pacemakers, implantable defibrillators, and certain aneurysm clips are current contraindications (pacemakers and implantable defibrillators are being studied)
Indications evolving, evidence to compare to other modalities for detection of CHD does not currently exist
Ethnic and gender differences in cardiac magnetic resonance imaging have not been investigated
SLIDE INFORMATION SOURCE: Nishimura RA, et al. Noninvasive cardiac imaging: echocardiography, nuclear cardiology, and MRI/CT imaging in DL Kasper, E Braunwald, AS Fauci, SL Hauser, DL Longo, JL Jameson, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York; McGraw Hill, 2005, Hendel RC, et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging. J Am Coll Cardiol 2006; 48:
Source: Nishimura 2005, Hendel 2006

23. Women and CHD: What Test to Order When
For new-onset symptoms, resting, or rapidly worsening symptoms, women should be referred immediately to the emergency department for evaluation
Women with symptoms of acute coronary syndrome should be instructed to call 911, and should be transported to the hospital via ambulance, rather than by friends or relatives
SLIDE INFORMATION SOURCE: Anderson JL, et al. ACC/AHA 2007 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007; 50: e1-157.
Source: Anderson 2007

24. Women and CHD: What Test to Order When
For women at high or intermediate risk of coronary artery disease, consider treadmill echocardiogarphy or nuclear perfusion imaging
For women unable to exercise, consider dobutamine stress echocardiography or adenosine or dipyridamole nuclear imaging
In high risk women with typical symptoms of coronary artery disease, consider referral to a cardiologist
For high risk women, consider cardiac catheterization if symptoms persist despite negative non-invasive imaging
SLIDE INFORMATION SOURCE:SLIDE INFORMATION SOURCE: Anderson JL, et al. ACC/AHA 2007 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007; 50: e1-157, Klocke KJ et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging-executive summary. J Am Coll Cardiol 2003, 42: , Douglas PS, ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress echocardiography, Circulation 2008, 117: , personal communication Claire Duvernoy, M.D., 2005.
Magnetic resonance imaging is also an option, if available (1)
(1) Anderson JL, et al. ACC/AHA 2007 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007; 50: e1-157.
(1)
Source: Anderson 2007, Klocke 2003, Douglas 2008, Duvernoy 2005

25. Women and CHD: What Test to Order When
A stepwise approach beginning with conventional exercise testing may be considered for women who:
Are at low or intermediate risk for coronary artery disease
Are able to exercise
Have an electrocardiogram that can be interpreted during stress testing
An image-enhanced test may be more predictive in women than conventional electrocardiogram stress testing, and may also be more cost effective in women at intermediate risk for CHD
SLIDE INFORMATION SOURCE:SLIDE INFORMATION SOURCE: Anderson JL, et al. ACC/AHA 2007 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007; 50: e1-157, Klocke KJ et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging-executive summary. J Am Coll Cardiol 2003, 42: , Douglas PS, ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress echocardiography, Circulation 2008, 117: , Mieres JH, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation 2005; 111:
Source: Anderson 2007, Klocke 2003, Douglas 2008,Mieres 2005