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The Journal of the Hoffman Heart Institute of Connecticut
November 1997 - Vol.3 No.2
Noninvasive Diagnosis of Coronary Artery Disease in Women
Carolyn M. Kosack, M.D.
Hoffman Heart Institute of Connecticut
Assistant Clinical Professor of Medicine
University of Connecticut Health Center
Introduction
The overall prevalence of coronary artery disease in women is lower than that in men. However
the impact of this disease on women is substantial; in fact, coronary artery disease is the number
one killer of American women. Nearly 500,000 women will die this year from cardiovascular
disease and 250,000 of these deaths can be attributed to coronary artery disease. By age 65
women are nearly as likely as men to suffer a heart attack and are much more likely to die from it.
Women have an 11% higher mortality rate from MI compared to men. They also have a higher
complication and early mortality rate with revascularization procedures. It has been proposed that
the reason for this is that women are older when they present with this disease, tend to have
more severe unstable symptoms and have more comorbidities which further complicate the
course of this disease and contribute to a more adverse outcome. It is therefore critical to be able
to diagnose coronary artery disease accurately in women, prior to the development of more
severe manifestations of this disease, which result in higher risk and poor outcome.
Noninvasive testing for detection of CAD has been studied extensively in the male population.
However, these studies have included too few women to allow meaningful statistical analysis of
the results in women. The noninvasive diagnosis of CAD in women is challenging. Although chest
pain is a frequent symptom in women, the overall prevalence of CAD is lower, therefore
diagnostic tests will have a lower predictive value in a woman than a man. The purpose of this
article is to review what is known regarding noninvasive diagnostic testing in women for CAD and
to recommend a reasonable approach to the diagnosis of CAD in women in 1997.
Clinical Symptoms and Risk Factor Assessment
Studies have shown repeatedly that chest pain is less predictive of significant CAD at
angiography in women. In both the Coronary Artery Surgery Study and the Duke Databank
population, even after adjusting for age and other risk factors, men had a higher rate of significant
CAD for every anginal type; typical, atypical and nonanginal.
The Framingham Heart Study (FHS) was a study of 5,127 patients who presented with chest
pain, clinically assessed to be "angina," as there was no angiography available to confirm the
presence of CAD. In the 26 years of follow-up, chest pain was the most common presenting
symptom in women, occurring 47% of the time compared with only 26% in men. Myocardial
infarction, however, was more common in the men, occurring in 43% vs. 29% of the women, thus
making it appear that women had a better overall prognosis when they presented with "angina."
This study also provided important data on the age dependency of CAD in women, with women
presenting 10 years later with angina and 20 years later with their first myocardial infarction.
Despite the overall good prognosis of the Framingham women with "angina," the women with
myocardial infarction had a much more adverse outcome with an in-hospital mortality of 36% vs.
31% for men, and one year mortality even more astonishingly high; 45% vs. 10% for men. This
raised the question of whether chest pain was different in women and if it was a good predictor of
CAD in women.
Subsequent studies have evaluated the predictive value of chest pain in women. In a
retrospective review of 1000 angiograms in women less than 50 y/o, Welch reported a poor
correlation between chest pain and angiographic evidence of disease. CAD prevalence was only
23% in this group. However, a higher prevalence was noted in older women. At best, clinical
history of angina correlated with angiographic CAD only 51% of the time.
When data were stratified further by risk factors, such as cholesterol levels, significant CAD was
found in women with cholesterol levels greater than 275 mg/dl. Waters et al found additive
predictive value of stratification by risk factors (i.e. hyperlipidemia, hypertension, diabetes
mellitus, smoking and family history). Significant CAD was found in 55% of women with more
than 2 risk factors, but in only 7% of women with less than 2 risk factors.
CASS looked at the quality of chest pain as a presenting symptom in women. It was found that
women with typical angina had a 72% prevalence of significant CAD, women with probable
angina had a 36% prevalence of significant CAD, while women with atypical chest pain had only
a 6% prevalence of disease. Women with typical angina had a 53% chance of having multivessel
or left main disease while those with atypical chest pain had only a 0-3% chance of this. When
age was considered in women with typical angina, the prevalence of significant CAD was 50% in
premenopausal females while it was 90% in postmenopausal females. Hung et al also found that
women presenting with typical angina, probable angina and nonanginal chest pain had a 60%,
30% and 7% prevalence of significant disease respectively.
Douglas et al studied the evaluation of chest pain in women. They stratified according to major
(chest pain, hormonal status, DM, and peripheral vascular disease), intermediate (hypertension,
smoking, and lipoproteins) and minor (age greater than 65, obesity, sedentary lifestyle, and family
history) determinants of the presence of coronary heart disease in women. They found that the
lowest risk (less than 20% likelihood) was in women without any major or no more than 1
intermediate or 2 minor determinants. Highest risk (more than 80% likelihood) was in women with
more than 2 major or 1 major and more than 1 intermediate or minor determinant. Most of the
women in actual practice belong in the moderate risk group, which requires further diagnostic
testing to confirm the presence or define the extent of disease.
In summary, chest pain in women is neither sensitive nor specific in predicting CAD in women.
The highest sensitivity is in women with typical angina, while the highest specificity is in women
presenting with nonspecific symptoms. Additional classification according to risk factors appears
to be useful for improving estimates of pretest probability of disease, but this needs further study.
Exercise ECG
ECG exercise testing is a commonly used diagnostic test for identifying significant CAD with more
than 1mm horizontal or downsloping ST depression being indicative of ischemia. In the 1950s,
Scherlis et al first reported that normal females were more likely to have ECG abnormalities after
exercise. This was confirmed in 1958 by Lepeschelin and Surawicz and again in 1965 by
Austrand. Most studies indicate a higher false positive response on ECG exercise testing in
women hence decreasing the positive predictive value of this test in women.
In 1975, Sketch et al looked at 195 men and 56 women referred for evaluation of chest pain. The
prevalence of significant CAD was significantly higher in the men; 53% vs. 18% for women. There
was a higher false positive result in these women 67% vs. 8% for men. False negative rate,
however, was much lower for the women, 12% vs. 37%. Most studies such as this one have
demonstrated significantly lower accuracy of exercise ECG for women than men. Possible
explanations for the limitations in sensitivity and specificity of ECG exercise testing for the
diagnosis of CAD in women include: lower overall prevalence of disease in women; greater
prevalence of non-coronary causes of chest pain i.e. mitral valve prolapse, angina caused by
vasospasm; a different physiologic response to exercise, with a blunting of catechol response to
exercise in women with CAD and an exaggerated catechol response in women without disease;
digoxin-like effect of estrogen; increased prevalence of baseline ECG abnormalities; and
inadequate exercise duration in women, resulting in less likelihood of achieving an adequate
exercise workload to accurately diagnose the presence of CAD.
Many believed that the lack of utility of ECG stress testing was a function of lower prevalence of
CAD in women. According to Bayes Theorem, given a lower prevalence of disease among a
particular population, a symptom or test will have a lower predictive value for the presence of
disease. Weiner et al looked at this issue using men and women from the CASS population. They
evaluated 1465 men with a 70% prevalence of CAD and 580 women with a 29% prevalence of
CAD. They found a 54% false positive rate in women vs. 12% in men. When subgroups were
matched for age and extent of CAD, there was no gender difference in false positive rate,
concluding that gender differences in ECG exercise testing were due to a difference in disease
prevalence. Barolsky et al then looked at 85 men and 92 women with similar prevalence of
disease (36% vs. 33%) and found a false positive rate of only 23% in men but 53% in women,
implying that a false positive response was not due to difference in disease prevalence, but was
due to a difference in the anatomic or physiologic response to exercise in women.
Hung et al looked at 92 women presenting with chest pain and found that a positive ECG ETT in
women with typical angina, with pre-test probability of 60%, increased the post-test probability of
disease to 79%. In women with non-specific chest pain, a positive ECG ETT did little to change
the pre-test likelihood of the disease. In women with an intermediate pre-test likelihood of disease
(majority of women) neither a positive or negative ECG ETT improved post-test probability of
disease.
In summary, exercise ECG treadmill test is less than perfect in women, with an overall positive
predictive value of 47% and negative predictive value of 81%. Analysis of many studies of
patients with CAD prevalence ranging from 18 to 43%, showed that the false negative rate
ranged from 11 to 33% and the false positive rate ranged from 38 to 67%. Given this high false
positive rate in women, a positive ETT has limited meaning and does little to improve the posttest likelihood of disease except in women with definite angina. The majority of women presenting
in the general population has an intermediate probability of disease and the ECG ETT does little
to improve predictive accuracy, therefore other methods are needed.
Radionuclide Imaging Exercise Radionuclide Angiography:
Early studies using radionuclide ventriculography (RVG) for diagnosis of CAD reported improved
accuracy in the detection of disease in women. Later studies failed to substantiate these findings
and this technique is not widely used at present. In the comparison of exercise LVEF to rest
LVEF, a greater than 5 units increase was considered a normal response while deterioration or
failure to augment LVEF during exercise indicated the presence of CAD. Jones et al looked at
1474 patients with chest pain (496 [25%] were women) and found a definite gender difference,
with a sensitivity and specificity of 82% and 73% respectively in men compared with 78% and
46% respectively in women. Other studies corroborated these findings; however, if the normal
response was redefined as no change or increase in LVEF with exercise, then there was a
significant improvement in the specificity of this test in women to 91%. Finally, Higginbotham et al
looked at the hemodynamic response to exercise in normal women and found that unlike men,
who increase their LVEF with exercise by decreasing their end systolic volume, women increase
their end diastolic volume by 30% with little change in their LVEF with exercise.
Currently, controversy exists as to the sensitivity and specificity of exercise RVG when applied to
women, and until the mechanism of the hemodynamic response to exercise in women is resolved
with further study, exercise RVG should not be used as a tool to diagnose CAD in women.
Myocardial Perfusion Imaging:
In contrast to RVG, studies have shown that the addition of myocardial perfusion imaging (MPI) to
exercise testing increases the sensitivity from 75% to 85% and the specificity from 85% to 95%.
Sensitivity varies according to the extent, location and severity of disease. Because of a lower
prevalence of disease and higher incidence of single vessel disease in women, it might be
thought that MPI would be less sensitive in women than in men and would have a lower
specificity due to breast attenuation. Freedman et al studied 60 women with a 47% prevalence of
documented angiographic CAD. They found when compared to ECG ETT alone, the addition of
planar thallium-201 imaging increased the sensitivity and specificity of exercise stress testing in
women to 75% and 88% respectively. They also found that if fixed anterior defects were
appropriately attributed to breast attenuation the specificity increased even further to 97%. Hung
et al looked at a more diverse group of women with only a 30% prevalence of CAD. Excluding
those with abnormal baseline ECG, those taking medications that could influence the ECG and
patients who were unable to achieve 85% of PMHR, they found the sensitivity and specificity of
ECG ETT alone to be 73% and 59%. With the addition of thallium-201 both the sensitivity and
specificity increased to 75% and 81% respectively. With further identification of fixed anterior
defects as breast attenuation, specificity improved to 91%.
The use of dipyridamole pharmocologic stress testing with planar thallium-201 imaging was
studied in 43 women and 71 men by Kong et al. No significant gender difference was found in the
sensitivity (87 vs. 94%) and specificity (58 vs. 63%). The sensitivity of diagnosing single vessel
disease was statistically significantly lower in women 60% vs. 94% in men. The sensitivity of
detecting multivessel disease was 100% vs. 94% for women and men respectively. The side
effect profile for dipyridamole was higher in women; however, complications such as AV block, MI
or hemodynamic changes were similar. Possible explanation for this was thought to be due to the
difference in the volume of distribution of dipyridamole in women due to fat-to-muscle ratio.
With the development of single photon emission computer tomography (SPECT) imaging, the
sensitivity of MPI was reported to be comparable or better than that of thallium-201 planar
imaging while specificity was comparable or slightly worse. Chae et al studied 243 women with a
67% prevalence of CAD. They found that the overall accuracy of exercise ECG alone was low for
all women, but in women with interpretable ECG, sensitivity was 66% and specificity was 60%,
similar to that with SPECT thallium-201 imaging, 71% and 65%. More importantly, they
addressed not only the diagnosis of CAD but risk stratification of women with CAD as well. They
looked at clinical, exercise and MPI variables to see which were most useful to discriminate
correctly between women with severe left main or triple vessel disease, and women with absent,
single or two vessel disease. They found that only the presence of thallium abnormalities
suggesting multivessel disease and peak exercise heart rate were independent predictors of left
main or three vessel CAD. A model based on these two variables successfully classified 70% of
women into low, medium or high risk, the latter of whom would potentially benefit from more
aggressive management.
With the development of the newer technetium agents, additional benefits in the improvement of
MPI would be appreciated. These agents were of higher energy, thus had more favorable
imaging characteristics. They also afforded the ability to assess left ventricular function with gated
acquisition. This helped in the identification of attenuation artifacts, and thus it increased the
specificity of MPI. There has been only one prospective study comparing the diagnostic accuracy
of thallium-201 to Tc99m sestamibi SPECT in detecting CAD in women. This study was done by
Taillefer et al and was published in JACC in January 1997. The purpose of this study was to
compare the sensitivity and specificity of these two agents in the detection of CAD in 115 women
and to determine if gated SPECT Tc99m sestamibi imaging could further improve diagnostic
accuracy. The overall sensitivities for detecting more than 50% and more than 70% stenoses
were 75.0% and 84.3% for Tl-201 and were 71.9% and 80.4% for Tc99m sestamibi. The
specificity for more than 50% stenosis was 61.9% for Tl-201 and 85.7% for Tc99m sestamibi. For
more than 70% stenosis it was 58.8% and 82.4% for Tl-201 and Tc99m sestamibi, respectively.
When a subset of 34 patients with normal angiograms were added to 30 normal subjects (less
than 5% pretest likelihood of disease) the specificity for lesions more than 70% was 67.2 for Tl201 and 84.4% for Tc99m sestamibi SPECT and 92.2% for Tc99m sestamibi gated SPECT.
Although both Tl-201 SPECT and Tc99m sestamibi SPECT perfusion studies had similar
sensitivity for the detection of CAD in women, Tc99m sestamibi showed a significantly better
specificity which is further enhanced by the use of ECG gated images.
Studies have shown the advantage of MPI in improving the diagnostic accuracy of stress testing
in women. More important, however, than just a yes or no answer to whether CAD is present is
the ability to accurately and economically risk stratify women, thereby being able to identify a
subset of patients who will benefit from further invasive testing and possible revascularization.
A handful of studies, including those from Brown, Staniloff, Ladenhum and Iskandrian, have
shown significant benefits in the use of nuclear techniques, both Tl-201 and Tc99m sestamibi, for
prognosis in patients with chronic CAD. Overall, patients with normal or mildly abnormal nuclear
scans were found to have a low hard event (death or nonfatal MI) rate, while the event rate
increased as the degree of perfusion abnormality increased on the scan. While for diagnostic
purposes, nuclear tests provided the greatest incremental information over clinical and exercise
variables in patients with intermediate probability of disease, for prognostic purposes, nuclear
testing provided the greatest incremental information in those who were already presumed to
have CAD. Hachamovitch et al looked at dual isotope MPI and how it impacted on the prognosis
of this disease in women. Although the prognostic information obtained when nuclear variables
were added to clinical and exercise data was significantly greater in both men and women, the
combination of clinical, exercise and nuclear results actually yielded greater prognostic
information in women than men. This was the first time that a diagnostic or prognostic test for
CAD had been shown to be more effective in women than in men. Hachamovitch also showed
that in patients without known CAD, the hard event rate among women with abnormal scan
results was substantially greater than that of men with abnormal scans, demonstrating superior
discrimination for nuclear scan results in identifying women at high risk. Although this modality
identified low risk women and men equally well, it identified high risk women more accurately than
high risk men and thus was able to risk stratify women more effectively than men.
The prognostic value of Tc99m sestamibi SPECT imaging alone was reviewed by Miller and
Heller, who looked at 214 women and 1262 men with a follow up of two years. They found the
event rate to be low in patients with normal scans, 0.6% in women and 1.4% in men. The event
rate was higher in patients with abnormal scans, 6.9% and 10.9% for women and men
respectively. Travin et al showed that greater numbers of abnormal perfusion defects increased
the rate of cardiac events. Not only did the presence and number of perfusion defects increase
the risk of serious cardiac events, but physicians recognized this risk and performed more cardiac
catheterizations and revascularization procedures in both men and women with greater ischemic
burden as evidenced by more than 3 defects on their nuclear scan. Thirty-nine percent of men
and 49% of women underwent catheterization, and 23% of men and 28% of women underwent
revascularization procedures.
Berman et al studied 598 women and 943 men with 19 month follow up. They also demonstrated
that there was an increased cardiac event rate in association with an increased summed stress
score (number of abnormal segments and degree of abnormality on scan). Low event rate, less
than 1%, was observed in men and women with low SSS. Extensive defects, resulting in high
SSS (more than 8), were associated with an 18% event rate in women, which was significantly
higher than the 5% event rate in men.
The greater risk of an adverse outcome in women with CAD and the difficulties associated with
identification of high risk women on clinical grounds, emphasize the need to identify an effective
noninvasive testing modality to pinpoint women at high risk of future events. The results of these
studies suggest that this need can be met by nuclear myocardial perfusion imaging.
REFERENCES:
1. Beery TA. Gender bias in the diagnosis and treatment of coronary artery disease. Heart and
Lung 1995; 24:427-35.
2. Berman DS, Hachamovitch R. Risk assessment in patients with stable coronary artery disease:
incremental value of nuclear imaging. J Nucl Cardiol 1996; 3:S41-9.
3. Botvinick EH. Stress imaging: current clinical options for the diagnosis, localization, and
evaluation of coronary artery disease. Med Clin North Am 1995; 79:1025-61.
4. Cerqueira MD. Diagnostic testing strategies for coronary artery disease: special issues related
to gender. Am J Cardiol 1995; 75:52D-60D.
5. Curzen N, Patel D, Clarke D, Wright C, et al. Women with chest pain: is exercise testing
worthwhile? Heart 1996; 76:156-60.
6. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med 1996;
334:1311-15.
7. Kuhn FE, Rackley CE. Coronary artery disease in women. risk factors, evaluation, treatment,
and prevention. Arch Intern Med 1993; 153:2626-36.
8. Oettgen P, Douglas PS. Coronary artery disease in women: diagnosis and prevention. Adv
Intern Med 1994; 39:467-84.
9. Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women. N Engl J Med
1993; 329:247-56.
Case Presentation:
Making a Decision to Operate
Bernard Clark, M.D.,
Director, Non-Invasive Cardiology
Hoffman Heart Institute of Connecticut
Associate Professor of Clinical Medicine
University of Connecticut Health Center
The decision to recommend ³mechanical² intervention (angioplasty or surgical revascularization)
is made difficult when the potential benefits are not clear-cut and the risks of the procedure
substantial. The following case presentation illustrates such a situation and highlights some of the
diagnostic and therapeutic dilemmas confronted.
Case Presentation
The patient is a 30-year-old woman with insulin-dependent diabetes mellitus since age 12 who
was admitted to the hospital with chest discomfort and dyspnea. She had noted some shortness
of breath a week earlier with a cough productive of yellow sputum and was treated with an
antibiotic for a presumed bacterial upper respiratory infection. A day prior to admission, she noted
retrosternal chest pressure and worsening dyspnea. The symptoms persisted and intensified
when she attempted to perform housework, prompting a visit to the Emergency Department.
She was born in Puerto Rico and moved to Hartford at age 18. She had apparently been admitted
to hospitals with diabetic ketoacidosis as a child. Two years prior to this admission, she was
admitted to another local hospital with right hemiparesis and mild DKA and was found to have a
small lacunar infarct in the left pontine medullary region. Hypertension and renal insufficiency
were diagnosed and ACE inhibitor therapy was started, along with aspirin. Blood glucose control
was also poor and adjustments were made to insulin dosages. An electrocardiogram and
echocardiogram were normal. She was referred for outpatient follow-up but did not keep regular
appointments.
She is a non-smoker who does not consume alcohol or use drugs. She is married and has two
young children who are well. There was a family history of hypertension and coronary artery
disease. Medications on admission included captopril 12.5 mg. TID, NPH insulin 12 units QAM
and regular insulin 8 units QAM.
Upon arrival in the Emergency Department she became free of chest symptoms with the
administration of nasal oxygen. She was hemodynamically stable. Her exam revealed
bilateral crepitant basilar rales and chest x-ray demonstrated mild pulmonary congestion. The
ECG (inset 1) showed evidence of an age-indeterminate anteroseptal and high lateral myocardial
infarction with ST segment elevation. Initial laboratory work included mildly elevated serum LDH,
and normal serum CK and SGOT. The serum glucose level was 396 mg/dl, serum creatinine 3.3
mg/dl, serum BUN 43 mg/dl, Hb 10.6 gm/dl, Hct 32.6%, WBC 11,100/mm3. Aspirin, furosemide
and metoprolol were administered in the ED and she was admitted to the Cardiology Service. No
rhythm abnormalities were found on continuous monitoring and serial electrocardiograms were
unchanged from admission. Serial cardiac enzyme determinations were within normal limits. An
echocardiogram was performed on admission, which revealed severe hypokinesis to akinesis of
the anterior wall and mid to high interventricular septum and apical dyskinesis with a moderate
reduction in systolic left ventricular function.
The clinical presentation and objective data were consistent with unstable angina and mild leftsided congestive failure in the setting of a previous (possibly recent) myocardial infarction. A noninvasive procedure was elected in light of her diabetic nephropathy and absence of recurrent
symptoms after admission. A dipyridamole thallium test was performed during which she
experienced retrosternal discomfort (5/10 on severity scale) with borderline ST segment
depression on ECG. There was left ventricular dilation with borderline high lung uptake of
thallium. Anterior, anteroseptal and apical hypoperfusion was noted with only minimal
redistribution in the anterior wall at four hours. Because of her clinical response to
pharmacological stress and extensive perfusion abnormalities, cardiac catheterization was
recommended. The coronary circulation was right dominant, with total occlusion of the left
anterior descending artery and severe stenosis of a diagonal branch. The left main, left circumflex
and right coronary arteries had diffuse disease without significant stenosis. There was good
collateral flow from the right system to the occluded LAD. The vessels were of small caliber and
deemed to be suboptimal targets for PTCA or coronary stenting.
Medical management was elected in view of the limited redistribution of isotope, presence of
good collateral flow and the absence of recurrent symptoms. The remainder of her hospital
course was uncomplicated (the serum creatinine transiently elevated to 3.8 mg/dl) and glucose
control was improved. She was discharged on aspirin, metoprolol, topical nitroglycerin patch, iron
sulfate and insulin, and enrolled in the outpatient cardiac rehabilitation program. A serum lipid
profile was obtained with a total cholesterol of 209 mg/dl, HDL 56 mg/dl, LDL 114 mg/dl, and
triglyceride level of 195 mg/dl. Atorvastatin (10 mg QD) was added to her medical regimen.
She noted chest discomfort during her rehabilitation sessions and the beta blocker dose
was increased. Her symptoms progressively worsened over the next two months and she
discontinued regular exercise. She was evaluated by a cardiovascular surgeon who felt that the
lack of significant reversible perfusion abnormalities called into question the potential benefits of
surgical revascularization. In order to assess for severely ischemic but viable myocardium, a
resting thallium study was performed. This study was unchanged from the intravenous
dipyridamole study performed during hospitalization, demonstrating mild late redistribution in the
anterior wall. The beta blocker dose was increased further, but chest discomfort was provoked by
very low levels of exertion, making it difficult to perform her normal daily activities. As her
symptoms had become refractory to treatment, a dobutamine stress echocardiogram was
performed in an attempt to document evidence of myocardial "hibernation" or to provoke
reversible ischemia. The resting images revealed anterior hypokinesis and apical dyskinesis.
During low dose (10 mcg/kg/min) dobutamine infusion, chest discomfort and borderline significant
ST depression developed. The mid to high interventricular septum became akinetic as did the
adjacent anterior wall. These abnormalities resolved after discontinuation of the infusion (inset 2).
This objective documentation of stress-induced reversible ischemia provided confidence in
the potential benefit of successful revascularization and also indicated a need to target the
chronically occluded LAD as well as the diagonal artery. She desired a minimally invasive
procedure and was referred for bypass grafting using the port-access technique. A sequential left
internal mammary graft was implanted to the LAD and diagonal without complications and she
was discharged home on the fourth hospital day. On subsequent outpatient evaluations she
remains free of anginal symptoms and has been compliant with medications and scheduled clinic
visits. Her most recent electrocardiogram demonstrates the return of small R waves in the septal
leads, as well as favorable T wave changes (inset 3).
Discussion
Clinical decision-making entails assessing the relative risks (mortality, morbidity, clinical failure,
and cost) versus the benefits of a proposed therapeutic intervention. The difficulties in arriving at
a best option are amplified when the risks of death and morbidity are substantial. The evaluation
and proper treatment of chest pain syndromes in women have been described in this Journal and
elsewhere(1-3). Women are more likely to present with ³atypical² symptoms and have been
reported to have a higher likelihood of non-specific findings on exercise electrocardiography. For
this reason, alternative modes of diagnosis (radionuclide perfusion scans and echocardiography
with exercise or pharmacological stress) have been evaluated and found to have acceptable
accuracy(4,5). The use of coronary angiography and thrombolytic agents has been less frequent
in women. Furthermore, while mechanical revascularization seems to confer similar long-term
survival rates in men and women, the latter have higher rates of morbidity and perioperative
mortality after surgery and more symptoms after angioplasty(6).
In the present case, the diagnosis of serious coronary artery disease was established on
presentation to the hospital. The central issue of management concerned the potential efficacy of
mechanical revascularization in the setting of prior infarction. Initial non-invasive evaluation
demonstrated evidence of a large area of infarction in the LAD distribution with a modest amount
of viable myocardium in the region. The recurrence and persistence of symptoms despite
alterations in medical therapy led to further evaluation and the dramatic abnormalities on
dobutamine stress echocardiography. This modality has been useful in diagnosing coronary
stenosis, detecting viable but persistently ischemic myocardium, and assisting in risk stratification
of patients with coronary disease(7-10). In addition, the dobutamine stress study provided very
region-specific information indicating that the totally occluded LAD required bypass, as well as the
patent but stenotic diagonal branch.
We have available at the Hoffman Heart Institute both minimally invasive direct coronary artery
bypass grafting (MIDCAB) and minimally invasive surgery using the port-access technique. In the
MIDCAB, the LAD of the beating heart is bypassed through a small incision(11). The port-access
technique allows the heart to be arrested using an endovascular technique to obstruct the aorta
and deliver cardioplegia solution without external cross-clamping(12). The decision to use the
latter technique was based on the need to bypass two vessels. As it happened, the decision was
fortunate, as a long segment of the LAD was intramyocardial, which would have hindered
attempts to use the MIDCAB procedure.
Finally, one cannot over-emphasize the need to aggressively manage coronary risk factors. This
is particularly important in persons with high-risk profiles and/or established coronary artery
disease. Our patient had suffered a cerebrovascular event several years prior to her coronary
event. Unfortunately, her outpatient followup was somewhat casual despite indicators of high risk.
Subsequent to her surgery, she continues to be followed closely to monitor and treat her
metabolic abnormalities (glucose and lipids) and to this point has been compliant with her
treatment regimen.
REFERENCES:
1. Kennedy KA, Kosack CM. Coronary heart disease in women. J Hoffman Heart Inst of CT 1996;
2:2-4.
2. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med 1996;
334:1311-15.
3. Beery TA. Gender bias in the diagnosis and treatment of coronary artery disease. Heart and
Lung 1995; 24:427-35.
4. Curzen N, Patel D, Clarke D, Wright C, et al. Women with chest pain: is exercise testing
worthwhile? Heart 1996; 76:156-60.
5. Cerqueira MD. Diagnostic testing strategies for coronary artery disease: special issues related
to gender. Am J Cardiol 1995; 75:52D-60D.
6. Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women. N Engl J Med
1993; 329:247-56.
7. Botvinick EH. Stress imaging: current clinical options for the diagnosis, localization, and
evaluation of coronary artery disease. Med Clin North Am 1995; 79:1025-61.
8. Perrone-Filardi P, Pace L, Prastaro M, Squame F, et al. Assessment of myocardial viability in
patients with chronic coronary artery disease. Rest-4-hour 201Tl tomography versus dobutamine
echocardiography. Circulation 1996; 94:2712-19.
9. Steinberg EH, Madmon L, Patel CP, Sedlis SP, et al. Long-term prognostic significance of
dobutamine echocardiography in patients with suspected coronary artery disease: results of a 5year follow-up study. J Am Coll Cardiol 1997; 29:969-73.
10. Poldermans D, Mariarosaria A, Fioretti PM, Salustri A, et al. Improved cardiac risk
stratification in major vascular surgery with dobutamine-atropine stress echocardiography. J Am
Coll Cardiol 1995; 26:648-53.
11. Calafiore AM, Teodori G, Di Giammarco G, Vitolla G, et al. Minimally invasive coronary artery
bypass grafting on a beating heart. Ann Thorac Surg 1997; 63(6 Suppl):S72-5.
12. Schwartz DS, Ribakove GH, Grossi EA, Schwartz JD, et al. Single and multivessel portaccess coronary artery bypass grafting with cardioplegic arrest: technique and reproducibility. J
Thorac Cardiovasc Surg 1997; 114:46-52.
Editorial:
Examining the Gender Bias in Evaluating Coronary Disease in Women
Jose Missri, M.D., Chief, Section of Cardiology
Coronary heart disease (CHD) in women has received much attention in the media and in
medical literature because of its recent recognition as the primary cause of death in American
women. Articles have addressed perceived and real gender bias in the way CHD has been
studied and treated in women. Much of the focus has been on how gender differences lead to
discrepancies in how the medical community evaluates risk factors, as well as how symptoms are
interpreted and managed. Women with CHD often experience delays in treatment and referral for
cardiac catheterization, and must overcome obstacles to revascularization and cardiac
rehabilitation. As these issues are in the process of being resolved, the problem of evaluation and
diagnostic testing for CHD in women remains an area that must be specifically addressed,
because improved understanding will have an immediate impact on women¹s health care. In this
issue of the Journal we begin a series of articles that focus specifically on the risk factors,
diagnosis and management of heart disease in women.
Gender discrepancies exist in the evaluation of CHD evaluation of women for several reasons.
The most prominent is the myth perpetuated by the Framingham Study and other studies that
CHD is primarily a man¹s disease. In the Framingham Study, chest pain was interpreted as being
synonymous with CHD at a time when angiographic confirmation was not available. At six years¹
follow up, none of the women initially presenting with chest pain sustained a myocardial
infarction. At 12 years¹ follow up, 70% of the men who initially had chest pain had died of cardiac
disease, while only 31% of the women who initially had chest pain died of cardiac disease. These
data led to decades of physicians believing that chest pain was generally benign in women.
The Coronary Artery Surgery Study (CASS) Registry further demonstrated how poorly chest pain
in women correlated to CHD. In patients referred for cardiac catheterization to evaluate chest
pain, a gender comparison of the incidence of significant coronary artery disease was performed.
In that study, 50% of women with chest pain showed little or no coronary disease on angiogram,
while only 17% of men tested had little or no coronary artery disease. This gender difference was
seen regardless of which coronary risk factors were present. This study forced the realization that
while chest pain is a major indicator of CHD in men, the history of chest pain alone is a poor
predictor of CHD in women. Yet CHD is common in women, reportedly occurring in 1 in 9 women
over the age of 45 years and 1 in 3 women over the age of 65 years, according to data from the
American Heart Association. Of the 250,000 women who die annually from CHD, 60% are over
the age of 65. The late age of CHD presentation in most women relative to men, as well as its
less typical presentation, may contribute to the under appreciation of women¹s heart disease.
The misperception held by the public and the medical profession that CHD is not a woman¹s
problem continues to this day, despite increasing evidence to the contrary. A 1995 Gallup survey
indicated that 80% of women age 45 to 75 years and 32% of primary care physicians did not
know that heart disease was the number one cause of death in American women. This lack of
knowledge about cardiac risk leads to the double problem of women not seeking medical
evaluation for potential cardiac symptoms and physicians not pursuing appropriate diagnostic
testing.
Gender discrepancies in evaluation are compounded by our reliance on diagnostic testing
procedures that have not been validated in women. When diagnostic testing has unacceptable
levels of false-positive and false-negative test results, there is a legitimate lack of confidence in
the results, which prevents the timely referral of women with abnormal findings for invasive
testing and revascularization, leading to excessive morbidity and mortality from CHD.
Noninvasive testing for CHD in women is used to evaluate chest pain syndromes, as well as to
evaluate patients at risk for CHD, regardless of symptoms. Because of the prevalence of CHD in
women and the problems of underrecognition and failure to refer women for invasive testing in a
timely manner, special attention should be given to ensure referral and evaluation of appropriate
patients for revascularization. A greater increase in mortality and morbidity in women following
myocardial infarction and bypass surgery compared to men, coupled with cost constraints, forces
us to make more thoughtful decisions about testing. Our diagnostic tests must address the
appropriate questions: Does this patient have coronary artery disease, and is she likely to benefit
from invasive evaluation and intervention? Noninvasive diagnostic testing for CHD in women
must take into account the sensitivity and specificity of the chosen method in women, as well as
the actual quality of the test at the site where it is being performed. While no test is perfect, the
knowledge and use of the optimal test in local communities is essential in making the correct
clinical decision for female patients. A thorough understanding of the methods of noninvasive
diagnostic testing for CHD and an awareness of how the tests are performed in the community
are essential.
Images in Cardiology:
Ruptured Aortic Root Abscess
Transesophageal echocardiogram (longitudinal view) in a 60-year-old man referred from
another hospital because of S. aureus bacteremia and clinical pericarditis during admission
for inferior wall myocardial infarction. Pericardiocentesis yielded sanguinous fluid. The ultrasound
study demonstrates an echo-free space in the anterior aortic root at the level of right sinus of
Valsalva (curved arrows). An echo-lucent space is present adjacent to the anterior wall of the
ascending aorta and in the pericardial space adjacent to the right ventricular outflow tract (straight
arrows). Within the aortic root ³cavity² was a thin linear region of flow on color Doppler (not
shown) suggesting that the right coronary artery traversed the space.
At surgery, an aortic root abscess (possibly in a right sinus of Valsalva aneurysm) was discovered
with rupture into the pericardial space. The adjacent proximal pulmonary artery segment
appeared to exert some local compression and prevent free bleeding and tamponade. The right
coronary artery was compressed by the abscess cavity. A patch repair and saphenous vein
bypass graft were performed. AV: Aortic Valve; L: Aortic lumen
Paul P. Stroebel, M.D.; John F. DeRossi, M.D.; Gordon C. Eckler, Jr., R.D.C.S.