Hybrid Imaging: Redefining Women's Heart Health
Women’s cardiac imaging is on the verge of some significant breakthroughs. Fueled by advances in cutting-edge technologies, a number of studies are in the works that look to confirm the benefits of molecular imaging for women; at the same time, improvements in imaging quality should allow cardiologists to see more cardiac disease at an earlier state in both women and men.
The facts are clear when it comes to women and heart disease. Cardiovascular disease (CVD) is the No. 1 killer of American women, as well as Americans over 65. CVD is the leading cause of death globally too, according to The World Health Organization that estimates 17.5 million people died from CVDs in 2005, representing 30 percent of all global deaths. Of these deaths, about 7.6 million are attributed to coronary heart disease.
Because women’s heart attack symptoms often differ from those more typical in men, such as chest pain, cardiac disease is often missed in women. (Women more often experience shortness of breath, nausea, vomiting, and back or jaw pain.) The rates of cardiac disease in women remain stubbornly high compared to declining numbers in men. Many myocardial infarction warning signs are simply not identified by primary care or emergency room physicians attending to women. Also, heart attacks in women are more often fatal than in men—making early diagnosis even more important.
Increasing awareness of how cardiac symptoms can differ among the sexes, coupled with the increased availability of PET/CT and SPECT/CT and their ability to delineate both the anatomic extent and physiological severity of coronary atherosclerosis in one study present a real opportunity for improvement in diagnosis and treatment of women’s cardiac disease.
Unique differences
Detection of coronary disease in women is often hard to detect due to interference of breast issue and breast implants in scanning and the inability to accurately diagnose pre-test symptoms. It is widely known that women show fewer true positive scans than men who undergo SPECT stress testing. Ischemia is often overlooked in women, too.
“There are developments in the PET/CT and SPECT/CT arenas that are beneficial to women, especially since women tend to be under-diagnosed for cardiac disease,” says Gary Heller, MD, director of nuclear cardiology at Hartford Hospital in Hartford, Conn. “Many physicians downplay atypical symptoms in women and women’s cardiac disease isn’t as easy to diagnose with exercise stress testing as men’s disease is. SPECT has better diagnostic ability to catch certain types of coronary disease than exercise stress-testing alone and PET/CT actually has even a higher diagnostic accuracy than SPECT in some of the studies.”
PET/CT’s ability to correct for tissue-related distortion, improved image resolution and the ability to calculate blood flow in the various regions of the heart differentiate it from technologies such as cardiac CT, cardiac MRI, exercise stress tests and SPECT. Daniel Berman, MD, director of cardiac imaging and nuclear cardiology at Cedars-Sinai Medical Center in Los Angeles, Calif., calls PET/CT “the myocardial perfusion imaging test of choice, especially for large-breasted women and women with breast implants.”
Technologies side by side
Cardiologists employ a variety of nuclear and imaging technologies for diagnosing and monitoring coronary artery disease. But because of the differences in the way coronary disease tends to present in women versus men, some of these tests may be leading to the diagnosis of coronary conditions in women that may not previously have been apparent to cardiologists, says Sharmila Dorbala, MBBS, associate director of Nuclear Cardiology at Brigham and Women’s Hospital.
Stress tests, in particular, have been problematic in identifying coronary artery disease in women. “More often than in men, stress tests in women lead to false positive results and we’re not entirely clear on why that is so,” says Marcelo Di Carli, MD, chief of nuclear medicine at Brigham and Women’s. “Some people have hypothesized that it is the effect of sex hormones, but we’re really not sure. The accuracy of non-imaging stress tests is lower than imaging, so we are turning more to imaging when investigating chest pain in both women and men.”
Research at Montefiore Medical Center in New York has shown that 82Rubidium myocardial perfusion PET scans are useful in the subset of women with equivocal SPECT studies because PET/CT demonstrates unequivocal normal perfusion in as much as 77 percent of these patients.
Overall, PET/CT studies the heart at work, revealing coronary artery disease, whether any areas of the heart suffer from impaired blood flow as well as other vital diagnostic information, points out Dorbala. PET/CT offers improved image specificity and diagnostic accuracy. Even more so than SPECT/CT, the reduction of attenuation artifacts is significant in PET/CT, leading to sharper images. PET/CT also may have the advantage in the diagnosis of smaller vessel disease that tends to be more common in women, according to Heller and Dorbala. In addition, PET/CT may offer benefit in diagnosing disease in individuals with smaller hearts; because women are smaller than men, PET/CT offers this gender-based diagnostic advantage, Heller notes.
PET/CT’s ability to display blood flow information also is an advantage in diagnosing Syndrome X, chest pain that is usually associated with decreased blood flow to the heart without coronary artery disease. Syndrome X is far more common in women than men, so any imaging modality that can detect it is beneficial for women who show symptoms of either Syndrome X or coronary microvascular syndrome.
Available evidence shows that myocardial perfusion PET/CT provides an accurate means for diagnosing obstructive coronary artery disease (CAD). PET/CT’s ability to provide changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion provides an advantage over SPECT for multivessel CAD evaluation. Growing evidence suggests that gated myocardial perfusion PET also provides clinically useful risk stratification.
PET/CT has proven useful after an unequivocal or nondiagnostic SPECT study. ER physicians, too, are increasingly ordering tests for chest pain patients with a moderate risk of myocardial infarction (MI). Studies have shown PET/CT can rule out an MI with greater confidence, often avoiding unnecessary hospital admissions. PET/CT is helpful in identifying jeopardized, but still viable, myocardium that can be salvaged via revascularization. PET/CT further offers a superior option over SPECT for morbidly obese patients over 450 pounds.
SPECT/CT, too, is gaining more attention for its superiority in diagnosing women thanks to its attenuation correction and a shorter study time frame than SPECT. Taking a closer look, SPECT/CT reduces the soft-tissue attenuation artifacts that create the false positives in SPECT studies, thus rendering the test more specific. Cardiologists can obtain a calcium score while performing the study, which can provide information about the location and extent of calcified plaque in the coronary arteries. A build up of plaque in the coronary arteries narrows the cardiac arteries over time, constricting blood flow to the heart muscle, which can result in angina as well as heart attack and strokes.
In the research
A number of studies are underway that seek to determine which diagnostic tests are best for women at various stages of risk for coronary artery disease. Heller, who is the past president of the American Society of Nuclear Cardiology, is involved in a study examining the differences in the diagnosis of women with cardiac disease using exercise stress testing and SPECT/CT.
“It’s becoming clear that in the diagnostic hierarchy, SPECT/CT has higher diagnostic accuracy than an exercise stress test and PET/CT has even higher diagnostic accuracy than SPECT/CT. This is being confirmed by [clinical] studies,” says Heller.
A study reported at the fall 2007 meeting of the American Society of Echocardiography reported that stress echocardiography had a better chance of identifying women at high risk for coronary artery disease than traditional stress tests.
The WISE Study research published in the Journal of the American College of Cardiology in January 2006 found that as many as three million women who have coronary heart disease don’t experience build-up of cholesterol plaque into a major blockage. Instead, it spreads throughout the artery wall, a condition known as coronary microvascular syndrome that causes reduced blood flow to the heart along with chest pain. Because the syndrome doesn’t block arteries, it can remain undetected. Coronary microvascular syndrome is linked to Syndrome X and is thought to cause it.
In a study conducted by the Multi-Ethnic Study of Atherosclerosis (MESA) that was published in the Archives of Internal Medicine in December 2007, investigators noted that women’s risk for cardiovascular disease is understated using traditional Framingham risk scores and recommended that women with symptoms or risk factors undergo imaging of their coronary arteries to define heart attack risk. MESA facilities and researchers continue to work on a variety of studies to assess gender, age and ethnic differences in cardiovascular disease.
Research on and awareness of gender differences in the symptoms, diagnosis and treatment of women with cardiac disease followed the publication of an American Heart Association Scientific Statement in 2005 that discussed the important role of noninvasive testing in evaluating women with suspected coronary artery disease. The statement highlighted the benefits of SPECT, cardiac CT, cardiac MRI and carotid intima-media thickness (IMT) and noted that although much more evidence needed to be gathered, that it was fairly clear that women at risk for coronary artery disease are not referred as often for further testing as men.
Future enhancements
Hartford Hospital’s Heller estimates the number of PET/CT studies has increased about 25 percent a year over the past few years. “In the next two to four years, PET/CT will assume a strong role in the diagnosis of coronary disease in women,” he says.
One exciting potential development is a PET/CT study done while the patient is exercising, says Berman. “One drawback of PET/CT currently is that you have to induce stress pharmacologically instead of with exercise, and exercise is generally the preferable method of stress testing,” he says. “But you can’t do it because with 82Rubidium there is a 75-second half-life, so there isn’t enough time to take the measurement.” A new isotope that would be used during exercise stress is being tested in an FDA Phase I test.
Advances in both PET/CT and SPECT/CT are leading to better detection and treatment of coronary artery disease in both men and women. Di Carli believes that a patient-centered approach, rather than a gender-centered approach, is likely to result in the most accurate diagnosis and best treatment path for patients, keeping gender differences in mind. “We have a variety of important tools available to us and it is important to clinically tailor the type of diagnostic test or tests to the specific needs of the patient,” he says. “You would not do the same diagnostic test necessarily on an obese short woman presenting with symptoms of coronary artery disease as you might on a lean woman.”
PET/CT and SPECT/CT offer the opportunity of a comprehensive anatomic and biologic evaluation of the consequences of atherosclerosis in the coronary arteries and myocardium—and perhaps, ultimately, tailoring diagnosis and treatment to the unique needs of women.
The facts are clear when it comes to women and heart disease. Cardiovascular disease (CVD) is the No. 1 killer of American women, as well as Americans over 65. CVD is the leading cause of death globally too, according to The World Health Organization that estimates 17.5 million people died from CVDs in 2005, representing 30 percent of all global deaths. Of these deaths, about 7.6 million are attributed to coronary heart disease.
Because women’s heart attack symptoms often differ from those more typical in men, such as chest pain, cardiac disease is often missed in women. (Women more often experience shortness of breath, nausea, vomiting, and back or jaw pain.) The rates of cardiac disease in women remain stubbornly high compared to declining numbers in men. Many myocardial infarction warning signs are simply not identified by primary care or emergency room physicians attending to women. Also, heart attacks in women are more often fatal than in men—making early diagnosis even more important.
Increasing awareness of how cardiac symptoms can differ among the sexes, coupled with the increased availability of PET/CT and SPECT/CT and their ability to delineate both the anatomic extent and physiological severity of coronary atherosclerosis in one study present a real opportunity for improvement in diagnosis and treatment of women’s cardiac disease.
Unique differences
Detection of coronary disease in women is often hard to detect due to interference of breast issue and breast implants in scanning and the inability to accurately diagnose pre-test symptoms. It is widely known that women show fewer true positive scans than men who undergo SPECT stress testing. Ischemia is often overlooked in women, too.
“There are developments in the PET/CT and SPECT/CT arenas that are beneficial to women, especially since women tend to be under-diagnosed for cardiac disease,” says Gary Heller, MD, director of nuclear cardiology at Hartford Hospital in Hartford, Conn. “Many physicians downplay atypical symptoms in women and women’s cardiac disease isn’t as easy to diagnose with exercise stress testing as men’s disease is. SPECT has better diagnostic ability to catch certain types of coronary disease than exercise stress-testing alone and PET/CT actually has even a higher diagnostic accuracy than SPECT in some of the studies.”
PET/CT’s ability to correct for tissue-related distortion, improved image resolution and the ability to calculate blood flow in the various regions of the heart differentiate it from technologies such as cardiac CT, cardiac MRI, exercise stress tests and SPECT. Daniel Berman, MD, director of cardiac imaging and nuclear cardiology at Cedars-Sinai Medical Center in Los Angeles, Calif., calls PET/CT “the myocardial perfusion imaging test of choice, especially for large-breasted women and women with breast implants.”
Technologies side by side
Cardiologists employ a variety of nuclear and imaging technologies for diagnosing and monitoring coronary artery disease. But because of the differences in the way coronary disease tends to present in women versus men, some of these tests may be leading to the diagnosis of coronary conditions in women that may not previously have been apparent to cardiologists, says Sharmila Dorbala, MBBS, associate director of Nuclear Cardiology at Brigham and Women’s Hospital.
Stress tests, in particular, have been problematic in identifying coronary artery disease in women. “More often than in men, stress tests in women lead to false positive results and we’re not entirely clear on why that is so,” says Marcelo Di Carli, MD, chief of nuclear medicine at Brigham and Women’s. “Some people have hypothesized that it is the effect of sex hormones, but we’re really not sure. The accuracy of non-imaging stress tests is lower than imaging, so we are turning more to imaging when investigating chest pain in both women and men.”
Research at Montefiore Medical Center in New York has shown that 82Rubidium myocardial perfusion PET scans are useful in the subset of women with equivocal SPECT studies because PET/CT demonstrates unequivocal normal perfusion in as much as 77 percent of these patients.
 |
| From left: First two SPECT/CT calcium scoring images courtesy of University of Michigan, Ann Arbor, Mich. Second two PET/CT 13ammonia images courtesy of Technical University of Munich, Munich, Germany. |
PET/CT’s ability to display blood flow information also is an advantage in diagnosing Syndrome X, chest pain that is usually associated with decreased blood flow to the heart without coronary artery disease. Syndrome X is far more common in women than men, so any imaging modality that can detect it is beneficial for women who show symptoms of either Syndrome X or coronary microvascular syndrome.
Available evidence shows that myocardial perfusion PET/CT provides an accurate means for diagnosing obstructive coronary artery disease (CAD). PET/CT’s ability to provide changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion provides an advantage over SPECT for multivessel CAD evaluation. Growing evidence suggests that gated myocardial perfusion PET also provides clinically useful risk stratification.
PET/CT has proven useful after an unequivocal or nondiagnostic SPECT study. ER physicians, too, are increasingly ordering tests for chest pain patients with a moderate risk of myocardial infarction (MI). Studies have shown PET/CT can rule out an MI with greater confidence, often avoiding unnecessary hospital admissions. PET/CT is helpful in identifying jeopardized, but still viable, myocardium that can be salvaged via revascularization. PET/CT further offers a superior option over SPECT for morbidly obese patients over 450 pounds.
SPECT/CT, too, is gaining more attention for its superiority in diagnosing women thanks to its attenuation correction and a shorter study time frame than SPECT. Taking a closer look, SPECT/CT reduces the soft-tissue attenuation artifacts that create the false positives in SPECT studies, thus rendering the test more specific. Cardiologists can obtain a calcium score while performing the study, which can provide information about the location and extent of calcified plaque in the coronary arteries. A build up of plaque in the coronary arteries narrows the cardiac arteries over time, constricting blood flow to the heart muscle, which can result in angina as well as heart attack and strokes.
In the research
A number of studies are underway that seek to determine which diagnostic tests are best for women at various stages of risk for coronary artery disease. Heller, who is the past president of the American Society of Nuclear Cardiology, is involved in a study examining the differences in the diagnosis of women with cardiac disease using exercise stress testing and SPECT/CT.
“It’s becoming clear that in the diagnostic hierarchy, SPECT/CT has higher diagnostic accuracy than an exercise stress test and PET/CT has even higher diagnostic accuracy than SPECT/CT. This is being confirmed by [clinical] studies,” says Heller.
A study reported at the fall 2007 meeting of the American Society of Echocardiography reported that stress echocardiography had a better chance of identifying women at high risk for coronary artery disease than traditional stress tests.
 |
| PET/CT 82Rubidium images and maps from the Siemens Biograph 40 show inferior wall ischemia. Source: Emory University, Atlanta, Ga. |
In a study conducted by the Multi-Ethnic Study of Atherosclerosis (MESA) that was published in the Archives of Internal Medicine in December 2007, investigators noted that women’s risk for cardiovascular disease is understated using traditional Framingham risk scores and recommended that women with symptoms or risk factors undergo imaging of their coronary arteries to define heart attack risk. MESA facilities and researchers continue to work on a variety of studies to assess gender, age and ethnic differences in cardiovascular disease.
Research on and awareness of gender differences in the symptoms, diagnosis and treatment of women with cardiac disease followed the publication of an American Heart Association Scientific Statement in 2005 that discussed the important role of noninvasive testing in evaluating women with suspected coronary artery disease. The statement highlighted the benefits of SPECT, cardiac CT, cardiac MRI and carotid intima-media thickness (IMT) and noted that although much more evidence needed to be gathered, that it was fairly clear that women at risk for coronary artery disease are not referred as often for further testing as men.
Future enhancements
Hartford Hospital’s Heller estimates the number of PET/CT studies has increased about 25 percent a year over the past few years. “In the next two to four years, PET/CT will assume a strong role in the diagnosis of coronary disease in women,” he says.
One exciting potential development is a PET/CT study done while the patient is exercising, says Berman. “One drawback of PET/CT currently is that you have to induce stress pharmacologically instead of with exercise, and exercise is generally the preferable method of stress testing,” he says. “But you can’t do it because with 82Rubidium there is a 75-second half-life, so there isn’t enough time to take the measurement.” A new isotope that would be used during exercise stress is being tested in an FDA Phase I test.
Advances in both PET/CT and SPECT/CT are leading to better detection and treatment of coronary artery disease in both men and women. Di Carli believes that a patient-centered approach, rather than a gender-centered approach, is likely to result in the most accurate diagnosis and best treatment path for patients, keeping gender differences in mind. “We have a variety of important tools available to us and it is important to clinically tailor the type of diagnostic test or tests to the specific needs of the patient,” he says. “You would not do the same diagnostic test necessarily on an obese short woman presenting with symptoms of coronary artery disease as you might on a lean woman.”
PET/CT and SPECT/CT offer the opportunity of a comprehensive anatomic and biologic evaluation of the consequences of atherosclerosis in the coronary arteries and myocardium—and perhaps, ultimately, tailoring diagnosis and treatment to the unique needs of women.