Images from top: Imatron’s C300EBT Scanner; two Imatron EBT cardiac scans; Varian/GE pet Advance nxi system

Women have made tremendous progress in bringing breast cancer to the forefront of medicine. Now it’s time to do the same for heart disease — which maintains its deadly distinction as the No. 1 killer of women, claiming approximately a half-million women’s lives annually.

Cardiologists believe that number can be reversed by early diagnosis. And imaging modalities are playing a key role in that reversal.

Technology choices may vary from one community to another, but the best choice is to recognize symptoms or the presence of high-risk characteristics — such as family history or diabetes — and the importance of testing. A full range of women including female athletes, pregnant women with heart defects and post-menopausal women are reaping the benefits of imaging technologies to corral coronary disease before it claims another unwitting victim.

Sharonne Hayes, director of Mayo Clinic Women’s Heart Clinic (Rochester, Minn.), says one term that really resonated with the Women’s Health Advisory Group at the American Society of Echocardiography (Raleigh, N.C.) recently was the “womb to tomb” aspect of echocardiography for women, particularly because of the ability to diagnose cardiovascular disease in fetuses. From baby girls to older women, echo is diagnosing female hearts with great accuracy.

“It’s important in young people as they become athletes for screening purposes perhaps, for the pregnant woman who may have heart disease to screen or make sure that she’s capable of having children and then as women move through the life [span] to diagnose valvular disorders and coronary artery disease,” Hayes says. “So truly at every stage in a woman’s life there might be a role for echocardiography, not every woman obviously, but it does touch on the full lifespan.”

Echocardiography, 50 years after its inception, maintains its place as the gold standard for valve disease. “If you look at what is readily available and in use for that type of problem, [its] portability and [use in] acute care, I think echo is superior for and adds value to the standard stress electrocardiogram, which has no imaging,” Hayes says. “One of the reasons echo has come into the forefront is because standard stress testing isn’t as accurate in women as it is in men.”

The false positives in women may be attributable to hormonal effects on the electrocardiogram, rendering it unreliable when doing stress testing on women. The issue of false negatives also enters the picture. “If you have an older woman who can’t exercise as much, she can’t do a maximal stress test on a treadmill, and therefore some kind of imaging modality can reduce that level of false negatives,” Hayes says. “Imaging comes in and corrects both ends of that spectrum.”

The increased use of contrast has made a huge impact on both men and women in diagnosing cardiac problems. Difficult-to-image women are especially diagnostic in a large number of cases, according to Hayes. “In terms of day to day, particularly in the stress area, that’s probably been the biggest leap forward,” Hayes says.

In some people, because of the position of the heart in the chest, the acoustic window can be limited. Sometimes extremely thin women, but more frequently obese women or large-breasted women, can present problems.

Logistical barriers remain with contrast echo. The need to start an IV moves it out of the noninvasive test arena, which is an important differentiation from nuclear testing. However, contrast continues to move echo forward, as does the incorporation of 3D imaging.

“Some labs are doing real-time 3D imaging, so we can see the leaflet tears, the atrial septal defect in three-dimensional method, and that’s the next frontier,” Hayes says. “This may become something that we’re all using and can do in real time. Right now there is still a fair amount of off-time analysis of the images.”

The morphologic aspect benefits greatly from the 3D capability. A surgeon’s ability to see in 3D before going in holds huge appeal. “I don’t think 3D per se is going to change how we diagnose coronary artery disease particularly,” Hayes says. “I think contrast or better myocardial echocardiography is going to be the answer. So there are actually several directions in which echocardiography is moving.”

The possibility that echo will be incorporated as part of a woman’s regular physical exam gets some attention. I don’t see [echo] being in every doctor’s office, but it may in the not-too-distant future be in every cardiologist’s office.”

One area of interest at Mayo Clinic is the use of echo to assess diastolic function (relaxing of the heart) in women. “We’ve had a hard time measuring it and using it in clinical practice,” Hayes says. “Echo as a community has looked much harder at diastology over the past 10 years and has developed a few techniques over the dynamic tissue imaging, which allows us to measure things that are related to this. It appears to be very predictive in terms of who is going to develop heart failure, who is going to have a cardiac event. So I think we’re using echo not just for diagnosis but [increasingly] for prognosis.”

The Care Group uses Siemens’ E.CAM dual-head SPECT technology for cardiac imaging.

With high ultrasound energy pulses to burst microbubbles, doctors work on delivering genes or certain proteins to the heart or muscle. Patients with cardiomyopathy, where there is global dysfunction of the heart, or cases with severe coronary disease where angioplasty or bypass surgery is not an option, or people who are very high risk for such procedures are candidates for the procedure.

“Unfortunately a lot of times women have a slightly higher risk when they go to bypass surgery because their heart arteries are a bit smaller, so technically it can be a bit more challenging in certain people,” Daniel Blanchard, M.D., director of the Cardiac Noninvasive Laboratories (San Diego) and associate professor of medicine at the University of California San Diego says. “So in these people where there’s not a whole lot left from conventional medical treatment or surgery, this is a pretty exciting field that’s in its infancy, but it’s a way to be able to target these drugs rather than give them everywhere.”

Blanchard is among the cardiologists who consider stress echo and stress nuclear complementary. “I don’t think one is innately superior to the other, and multiple studies have shown that,” Blanchard says. “They are slightly different, and my general approach is that since stress echo is easier on the patient, less expensive and takes only an hour instead of several hours, we’ll get a stress echo in most people, unless they have terrible images. In [cases] where they can’t do the stress echo or it’s inconclusive, then we’ll move on to stress nuclear.”

SPECT specifics
Relying on a stress EKG in women is often not enough to effectively diagnose heart disease in women. As a screening tool for at-risk women, single photon emission computed tomography (SPECT) is advantageous for two reasons: The pretest likelihood of disease is lower in younger women and the symptoms aren’t as predictive. In addition, the presentation is sometimes atypical. Depending on a woman’s age, in younger women for instance, it’s less likely the pain is related to coronary disease.

“The reason we add SPECT imaging to the plain old stress testing is to increase the sensitivity of our test and the specificity,” says Mary Norine Walsh, M.D., director of preventive and nuclear cardiology at The Care Group, LLC (Indianapolis, Ind.). “With treadmill exercise testing, sensitivity and specificity are enhanced by adding SPECT perfusion imaging particularly in women.” The Care Group uses Siemens Medical Solutions’ (Malvern, Pa.) E.CAM dual-head SPECT technology.

SPECT increases the ability to diagnose heart disease. In other words, the true positives increase and the false positives decrease. But it’s especially true in women because the pretest likelihood of having the disease is lower in younger women and in those with symptoms but no risk factors. The other anatomic reason is that women have breast tissue that overlies the anterior wall of the heart. “When we use gated SPECT imaging vs. some other type of imaging, we’re better able to sort out whether or not there is an area of true ischemia or scar,” Walsh says.

Higher energy radioisotopes, such as tetrafosmin and sestamibi, have helped overcome breast attenuation problems that were common with the use of thalium-201. The technetium-labeled agents with high-energy photons present images with higher count rates, and this increases accuracy. In addition, gating the study allows the analysis of wall motion.

Gating has been an important tool in differentiating tissue attenuation from true myocardial scarring.

As attenuation correction methods, improved instrumentation and cameras and gating techniques move SPECT forward, tracers also continue to play an integral role in the future of the technology. “The ability of these tracers to accurately identify ischemia is very important,” Walsh says. “The wave of the future for diagnosis really rests, from my way of thinking in the nuclear realm, with new tracer development.”

Cardiac MR moves ahead
Magnetic resonance imaging (MRI) is now available to define viable myocardium, identifying regions of the heart that are dysfunctional at rest but will recover function when revascularized. A large amount of data also exist indicating that MR is very accurate for identifying viable myocardium.

“Particularly in women, the current clinical imaging techniques such as echocardiography which looks at the contractility of the heart and the size of the heart are less valuable and may give inaccurate measures in women,” says Warren J. Manning, M.D., associate professor of medicine and radiology at Harvard Medical School (Cambridge, Mass.) and section chief of noninvasive cardiac imaging at Beth Israel Deaconess Medical Center (Boston). “That’s partly because the female heart is slightly more difficult to image because of intervening breast tissue over the heart and chest wall. MR does not have those limitations.”

The second area where much has been learned in terms of the ability of MR is coronary MRA. Over the last several years, MRA has become widely recognized and practiced as the gold standard for identifying anomalous coronary disease. “More recently, a multi-center study demonstrated that coronary MRA is an accurate method for excluding patients who don’t have any disease or for identifying patients who have multi-vessel disease,” Manning says. “Coronary MRA is not ready today for a screening test for all patients, but in patients for whom multi-vessel disease or no disease is the clinical issue, MR is proving to be an effective tool at experienced centers.”

The introduction of steady-state free precession (SSFP) cine MR techniques has vastly improved the ability of MR to discriminate endocardial borders, increasing the ability to define the myocardium, myocardial mass and contractility.

As MR continues its progress, challenges including education of practitioners and technologists in the practice of cardiac MR remain, because many of the techniques used to image the heart are slightly different and more complex compared with MR imaging of the brain, joints or other parts of the body. Work to educate clinicians in the value of cardiac MR needs to continue as well. In addition, a disconnect between the perceived cost of cardiac MR and the actual reimbursement for cardiac MR studies exists.

“Though cardiac MR is perceived by the general public as being extremely expensive, clinical reimbursement is almost one-third lower than radionuclide studies, so we need to educate the physicians who might consider ordering cardiac MR that in fact it can be relatively cost effective,” Manning says.

An electron beam tomography scan in progress on a GE Imatron scanner seeks to visualize calcified arterial plaque. In the smaller coronary arteries of women, these can be quite clinically significant in determining a woman’s risk of heart attack.

MR will play an increasing role in the future for women who have suspected heart disease or who have defined heart disease. “In the near future, a patient who presents with prolonged atypical chest pain, which may be suggestive of a heart attack, may have a cardiac MR to look for evidence of an infarction,” Manning says. “Cardiac MR can be extremely sensitive for detecting a scar in the myocardium. Similarly, for women who have valvular disease or who have an abnormal heart, the superior accuracy and reproducibility of cardiac MR will allow for closer follow-up of those patients. The conventional imaging techniques of echocardiography and radionuclide imaging have far greater variability. So it’s difficult to distinguish the difference between serial tests. With MR that’s far easier to do.”

Calcium scoring with EBT
Calcium is good for women’s bones, and calcium scoring, identifying calcified plaque in arteries, is good for heart health. A direct relationship exists between atherosclerosis and calcified plaque. People with substantially more than average plaques compared to their peer group are at far higher risk for heart attack and sudden death. Electron beam tomography (EBT) can determine the patients who are vulnerable and at-risk for heart attack through imaging of plaques.

“When you consider that standard risk factor analysis is what is routinely done, measuring cholesterol levels, blood pressure, diabetes, family history [etc.], misses half the people that subsequently have heart attacks and other events,” says Marc Kahn, M.D., medical director of EBT Heart & Body Imaging (Detroit). “This is a modality for the times.” Kahn uses GE Imatron’s (South San Francisco) EBT technology.

Men and women remain different in terms of heart disease. As women age, their rate for heart disease goes up substantially and slightly surpasses what goes on in men. “Prior to [menopause], heart disease does happen, but it’s much rarer,” Kahn says. “Due to the smaller size of women’s coronaries in general, smaller amounts of atherosclerosis are more clinically significant than a similar amount in men, which highlights the need to pick it up earlier. We’re generalizing now, but it takes less atherosclerosis [in women] to cause a problem, and this is the only technology noninvasively that is going to give you an assessment of the total atherosclerotic burden that exists in men or women.”

Kahn says that men and women over 40 who have any inclination to suggest they might have a slight increased risk for heart disease should have this test. “One of the things that is interesting with this test when you sit down with people, you can actually show them pictures of their own heart and show them evidence of disease or not,” Kahn says. “I’m firmly convinced that they can relate to the visual aspects of this in ways that numbers from a cholesterol test never will. I think a lot of the other medical testing is too ambiguous, and many people just don’t relate to it and are more inclined to stop taking their medication, as opposed to people who have had this test and are more inclined to keep on their medication. That’s a very important aspect of this.”

Kahn has added electron beam angiography (EBA), which involves an intravenous injection of contrast to patients who go through a second scan. Not only does it assess the amount of atherosclerosis, but it also provides a look at any serious underlying stenosis related to the plaques.

“What we’re finding is for a lot of doctors who are trained to relate to narrowings, this presents the information in a way they’re more familiar with,” Kahn says. “It’s a little more expensive and a little more time, but it answers just about everything you’d want to know to make a decision about what to do next.”

Approximately 80 EBT scanners are sited across the country. “There are some non-EBT CT scanners that are trying to do the same thing, but there’s no data to substantiate it,” Kahn says. “It’s a much higher radiation dose, and frankly, it’s inaccurate.”

A PET technology
In 2002, the use of PET was approved for determining myocardial viability without the requirement of an inconclusive SPECT scan. Yet, few PET studies are done for the heart. “Over the last several months now, PET is being combined with CT scanning,” says Edward Coleman, M.D., professor of radiology at Duke University Medical Center (Durham. N.C.).

“This is going to have a major impact on cardiac imaging. … The combination of the CT scanning with the coronary calcification scoring, the coronary anatomy provided by contrast injection and myocardial perfusion imaging with PET will be a very powerful technology for evaluating coronary artery disease in the future.”

Coleman adds that much remains to be demonstrated by the combination of these modalities, but a big resurgence of interest is evident in using the combined PET-CT in evaluating the heart.

PET compared with SPECT maintains its advantage of fewer artifacts from attenuation from breast tissue that can be problematic in women. Coleman says that, going forward, cardiac PET procedures will increase. “I think the advantages in women will be slightly greater than that in men as we use this technology in the future,” Coleman says.

Currently, the exact mechanism that PET and combined PET-CT will be used for evaluating coronary artery disease has not been determined. In addition, whether reimbursement will come about for the evaluation of the coronary artery anatomy by intravenous injection of contrast is a hurdle that will have to be overcome before this gains widespread utilization, according to Coleman. “But the initial studies are looking so good that I think that will be something that will be covered by third-party payers in the future,” Coleman says.

A rest study with PET currently costs the patient in the range of $1,800 to $1,900. A stress study runs approximately twice that cost. Coleman uses GE Medical Systems’ (GEMS of Waukesha, Wis.) Advance scanner.

The choice
When it comes to choosing a modality to diagnose the female heart, and determining whether one is truly better than another, The Care Group’s Walsh’s words resonate. “Women need to be diagnosed, and we shouldn’t get lost in arguing over the finer points [of] which test is better.”