ASNC: Nuclear Cardiology's Future May Lay in Closer Patient Screening

MONTREAL, Sept. 11 -- Nuclear cardiologists are screening asymptomatic patients for risk prevention and for interventional decision-making.

Novel developments in imaging technologies are opening the doors to new applications, including patient screening, and more accurate therapeutic management, said Jamshid Maddahi, M.D., of the University of California at Los Angeles, and Daniel S. Berman, M.D., of the Cedars-Sinai Medical Imaging Center in Los Angeles.

They described some of these advances and their applications here during a symposium sponsored by Bristol-Myers Squibb Medical Imaging, held in conjunction with the annual meeting of the American Society of Nuclear Cardiology (ASNC).

"The field of cardiac imaging has advanced to the point that many people can benefit from it, from the point of view of screening for coronary disease and being able to prevent coronary disease with early pharmacologic interventions," Dr. Maddahi said.

"In patients who are symptomatic, cardiac imaging can help elucidate whether they have enough disease to determine how well they will do if you don't treat or what kind of treatment you need to do: medical treatment versus invasive approaches."

Dr. Maddahi described recent developments in cardiac imaging with pharmacologic stress agents for single photon emission computed tomography (SPECT), perfusion tracers for positron emission tomography (PET), as well as tools for obtaining absolute quantitation of blood flow, improved attenuation correction, and ventricular functional assessment.

Advancements for SPECT

According to Dr. Maddahi, the ideal pharmacologic stress agent would be specific to the adenosine A₂A receptor, thus increasing coronary blood flow without causing undesirable side effects. It would be a potent, selective coronary vasodilator that has little or no effect on blood pressure. It would also have a rapid onset and termination of action and be available in an easy to administer bolus package.

The novel agent regadenoson appears to have at least some of these ideal characteristics, he said. In a phase I trial comparing regadenoson with adenosine for use in SPECT imaging, the two agents provided similar visual and quantitative summed stress, summed rest, and summed difference scores. Multicenter trials with this agent are ongoing.

Advancements for PET

Dr. Maddahi believes that PET will be used increasingly in the future for myocardial perfusion because of the availability of short half-life tracers and fast protocols as well as its ability to provide high resolution, attenuation correction, and absolute quantitation of perfusion. These features mean the test is useful for physiologic assessment and has a high sensitivity and specificity, with particularly high sensitivity for detecting multivessel disease.

Limitations of PET myocardial perfusion imaging are inconvenience and cost. The machines themselves are expensive, and production of isotopes requires either an onsite cyclotron or generator. A new investigational perfusion tracer, however, may help overcome some of these limitations. Currently called BMS-747158-02, the agent has undergone preclinical testing in animals, which have demonstrated some positive features, he said. These include a strong correlation between coronary blood flow and uptake, low redistribution, high myocardial uptake with a good target-to-background ratio, and a high extraction fraction. Importantly, this F-18-labeled agent can be produced in a regional cyclotron and shipped to centers in single dose units, eliminating the need for an onsite cyclotron. Studies in humans are about to commence, and results should be available in the upcoming year.

An important feature of PET for use in MPI is quantitation of blood flow. Traditionally, relative quantitation has been used because absolute quantitation, while available, can be time consuming and tedious to obtain. New technologies are making absolute quantitation easier, and this process has important applications, including the assessment of diffuse disease and balanced ischemia. It can also be used to detect problems with coronary flow reserve in the absence of overt coronary artery disease, provide insight into coronary pathophysiology, help elucidate the effect of drugs and other interventions on coronary circulation, and help assess patients with syndrome X, hypertrophic cardiomyopathy, or transplant vasculopathy.

New technologies are also becoming available that will offer attenuation correction in PET. One of these involves transmission of an image using SPECT or CT. In the near future, said Dr. Maddahi, these various technologies will undergo further scrutiny, and eventually one will be revealed to be the most effective and practical.

Finally, new technologies will provide ventricular functional assessment, allowing for simultaneous measurement of left ventricular ejection fraction and left ventricular volumes as well as evaluation of regional left ventricular wall motion and thickening. Along with attenuation correction, ventricular functional assessment could also help with the identification of attenuation artifacts and improve confidence in the interpretation of results. It can also provide enhanced assessment of myocardial viability and prognosis.

Next, Dr. Berman spoke about advances in CT coronary angiography, cardiac magnetic resonance, and SPECT and emphasized the importance of using new imaging technologies for use in screening patients for early signs of coronary artery disease.

Patient Screening

Given that 40% of patients who die of a heart attack or sudden cardiac death were previously asymptomatic, he said, "the time has come to consider screening for coronary disease. Noninvasive imaging gives us the tools that will enable that." CT, for instance, can be used to obtain a coronary calcium score, which has been shown to correlate with overall plaque burden as well as outcomes.

"Coronary calcium scanning provides us with an opportunity to noninvasively assess atherosclerosis. With hybrid systems available now, many of us will be able to look at coronary calcium and myocardial perfusion imaging simultaneously and get this information," he said. Importantly, coronary calcium score provides prognostic information independent of that provided by traditional risk factor assessments, such as Framingham score, and can be used to determine optimal patient management.

The Glagov phenomenon explains how patients may have an atherosclerotic burden in the presence of little or no stenosis. In early atherosclerosis, there is compensatory expansion of the outer wall of the artery, allowing the lumen to maintain its diameter. Only later, as the atherosclerosis progresses, does the lumen narrow and stenosis begin. As a result, even an angiogram can yield a normal result despite the presence of atherosclerosis. A coronary calcium score can therefore help identify patients with atherosclerosis in the face of a normal angiogram.

Another noninvasive method of identifying subclinical atherosclerosis is via measurement of carotid intima-media thickness. This value can easily be achieved by using an ultrasound probe on the carotid artery of the neck. Absolute thickness carotid intima-media thickness, said Dr. Berman, is a predictor of early atherosclerosis and coronary heart disease events, even though the testing occurs in the neck. It is also predictive of stroke. Serial carotid intima-media thickness studies can demonstrate the progression of thickness, which is also predictive of cardiac events.

CT angiography

CT angiography remains a very young field that is developing quickly. The currently top of the line technology is a 64 slice, dual source machine, but a 256 slice machine is currently in the works, said Dr. Berman. CT angiography allows for visualization of both calcified and non-calcified plaque as well as of stenosis, even without significant calcification. Its high sensitivity and specificity means that high risk coronary artery disease is unlikely to be missed or underestimated. With the fastest scanners, it is possible to perform CT angiography without the use of beta blockers. A limitation, however, is that CT angiography does not allow for the visualization of the lumen in patients with extensive, dense coronary calcium. There is also currently limited information on the prognostic value of this modality.

Cardiac Magnetic Resonance

In contrast to the new technology of CT angiography, cardiac magnetic resonance has been available for over 20 years. Its strengths include no need for ionizing radiation, a high spatial resolution, and higher soft tissue contrast than CT. Weaknesses include technically demanding, long procedures, non-compatibility with pacemakers and implanted cardiac devices (ICDs), and no standardization or quantification of stress perfusion. A new application for coronary magnetic resonance is evaluation of angina in patients with normal coronary arteriograms. In some of these cases, said Dr. Berman, the angina may be associated with a diffuse subendocardial ischemia, which can only be seen if the subendocardial area can be visualized, which it can with coronary magnetic resonance.

SPECT

Dr. Berman described a new SPECT device, called the D-SPECT and manufactured by Spectrum Dynamics, that he believes represents a major advancement in the field. In this unit, the crystal is replaced by a bank of rotating columns. Inside each column is a tungsten collimator and CZT crystal detector. These detectors have a much higher energy resolution than sodium iodide, allowing for the viewing of multiple isotopes. This should improve attenuation correction and reduce scatter. The rotation of the columns creates a wider angle of acceptance and much higher geometric efficiency. As a result, one can reduce acquisition time tenfold and still improve resolution by 50%. Potential applications of this technology, as it develops, include detection of very mild ischemia and serial acquisitions, 10 seconds apart, that offer kinetic information and allow for absolute quantitation of blood flow.

Changes Resulting from New Technologies

Based on these new technologies, Dr. Berman predicted some major changes in how potential coronary artery disease patients are worked up and managed. He believes that calcium scoring will be used to screen low likelihood patients, CT angiography will replace nuclear imaging for intermediate likelihood patients, and nuclear testing will be reserved as the first test only for high likelihood patients who do not require immediate catheterization. Treatment should start to be considered in patients as soon as a coronary calcium score reaches 100, particularly in patients with diabetes or other cardiac risk factors. Patients with critical stenosis revealed by CT angiography should be catheterized. Those with an equivocal CT angiography should go on to nuclear testing to look for ischemia. Patients who start with nuclear testing should receive a CT angiography if the results show mild ischemia, since nuclear testing can underestimate overall atherosclerotic disease burden.

The Association for the Eradication of Heart Attack (AEHA), as part of the Screening for Heart Attack Prevention and Education (SHAPE) initiative, recommends using coronary calcium score and carotid ultrasound to screen for heart attack prevention beginning at age 45 in men and age 55 in women, with the exception of very low risk patients.

According to Dr. Berman, the future will bring with it new imaging techniques that will allow for visualization of entities other than myocardial perfusion. "Anatomy alone and function alone are not sufficient in symptomatic patients many times to determine how to best treat them. As we go forward it's likely that some combination of this kind of testing will be needed," he said.

For instance he is currently investigating using PET/CT for plaque imaging. "In combination with the size of the plaque with CT, we will see the activity of the plaque with PET or SPECT to determine who is at higher risk [of plaque rupture] and better determine who is to be revascularized."

References

1. Hendel R et al. Circulation. 2003;108(suppl 11):2892.