Looking at Coronary Artery Disease from the Inside Out
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Conventional approaches to imaging coronary artery disease leave a fair amount of room for improvement. Molecular imaging technologies, specifically PET/CT and SPECT/CT, are gaining confidence into clinical practice and demonstrating significant improvements in disease diagnosis, risk stratification, patient care and efficiency. ?For example:
- Alegent Health in Omaha, Neb., uses PET/CT to analyze emergent chest pain patients, slashing time and costs from the conventional chest pain model.
- Johns Hopkins University in Baltimore combines SPECT/CT or PET/CT with calcium scoring to better determine the level of intervention required for low to intermediate risk patients.
Current protocols merely scratch the surface of the potential, says Robert Gropler, MD, lab chief of the Cardiovascular Imaging Laboratory at Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis. “Coronary CT angiography, myocardial perfusion PET and SPECT imaging and MRI essentially measure the same biological parameters—coronary anatomy, blood flow, metabolism and cardiac function or a combination thereof. Each brings small improvements, but does not provide new or unique biologic information about coronary atherosclerosis,” Gropler says.
The big bang for molecular imaging will arrive when it effectively tackles a new parameter and assesses the biology of plaque and helps cardiologists determine the likelihood of plaque growth and rupture. There is progress toward the goal, and in the interim, Molecular Imaging Insight visits pioneers across the country to determine how molecular imaging is improving detection, risk stratification and treatment of coronary artery disease.
Embracing new protocols in acute care
Alegent Health is a pioneer in the use of molecular imaging to diagnose coronary artery disease. In 1995, the hospital established a chest pain center to evaluate patients who presented to the ER with chest pain. Rubidium PET myocardial imaging served as the cornerstone of its diagnostic imaging protocol. “At that time, we used PET to exclude coronary artery disease as the reason for the chest pain,” recalls Samuel H. Mehr, MD, director of molecular medicine and imaging.
The molecular imaging approach provides significant advantages over the conventional chest pain model. The conventional protocol requires a 23-hour observation period, serial enzymes and other blood tests. This approach is problematic for two reasons. “It isn’t as accurate as dedicated imaging studies,” reports Mehr. In addition, the conventional protocol is more expensive, and it places a greater workflow burden on staff. The PET protocol can reduce the ER stay from 23 hours to one to two hours, and it reduces personnel costs and requires fewer blood tests and EKGs. In addition, the number of unnecessary, and normal, invasive coronary angiograms is reduced. “It is rare for cardiologists experienced with PET technology to subject normal individuals to invasive testing,” shares Mehr.
Over the next several years, PET technology evolved, and in 2004, Alegent Health deployed a Siemens Biograph PET•CT system. The hybrid system delivers additional benefits with the CT component helping physicians exclude other chest pain etiologies, specifically pulmonary emboli. “With the PET/CT protocol, the hospital converted two studies—a cardiac perfusion PET and CT pulmonary angiogram—into one, using a single PET/CT scan to exclude both coronary artery disease and pulmonary emboli as the cause of the chest pain,” says Mehr. The total number of imaging studies is cut in half, cost-savings are proportional to the decrease in imaging volume and it results in improved quality of patient care.
Emerging trends in follow-up and treatment
Another clinical molecular imaging pioneer, Frank Bengel, MD, director of cardiovascular nuclear medicine at Johns Hopkins University Hospital in Baltimore, has used myocardial perfusion SPECT/CT and PET/CT in conjunction with calcium scoring since 2005. “Unlike with other modalities such as echocardiography, CT angiography or MRI, SPECT/CT and PET/CT provide referring physicians with information about the functional and morphologic aspects of coronary artery disease,” shares Bengel. “Myocardial perfusion imaging detects ischemia as an important marker of risk, which indicates need for invasive workup. The inclusion of calcium scoring in the protocol seems to offer risk stratification even in patients with a normal perfusion scan.”
Myocardial perfusion SPECT/CT, however, may not be ideal for all patients. Obese patients, those who require pharmacologic stress testing and patients with previous inconclusive SPECT data are preferably imaged on the department’s 64-slice PET/CT system. This system offers robust correction for tissue attenuation, a common problem in obese patients, and the overall study time is reduced to 45 minutes. PET/CT protocols resemble SPECT/CT with studies showing that the calcium score complements myocardial perfusion imaging and provides an independent assessment of risk. That is, a patient with a normal myocardial perfusion study but high calcium score is at greater risk for an acute coronary event than a patient with normal results on both tests. Similarly, a patient with an abnormal myocardial perfusion result and a high calcium score is at greater risk than a patient with an abnormal myocardial perfusion study with a normal calcium score.
“Patients with higher risk factors can be treated more aggressively and receive tighter follow-up care,” says Bengel. On the other hand, patients with normal myocardial perfusion results and no coronary calcium can be classified as low risk. “This class of patients may not require expensive long-term medication. Conventional risk factor modification—decreasing fat intake and increasing exercise—may suffice for patients identified as low risk,” notes Bengel. Thus, the molecular imaging protocol may better target treatment and healthcare resources.
Stepping into the future
Molecular pioneers continue to evolve and adapt protocols to new technologies. Later this year, Alegent Health plans to deploy Siemens Biograph mCT, a 128-slice PET/CT system. “In addition to myocardial perfusion imaging, the new system will offer non-invasive coronary CT angiography. It will further reduce patient time in the ER and also decrease costs, and it is expected to improve diagnostic accuracy. The addition of coronary CT angiography [in the molecular imaging protocol] will further reduce the number of imaging studies and allow for more specific treatment protocols,” predicts Mehr. For example, the combination of high-resolution PET and high-resolution CT allows physicians to characterize intraluminal clots as stable or unstable and prescribe the appropriate interventional algorithm for each clot type.
Bengel of Johns Hopkins University also anticipates several improvements in the next year. For example, one disadvantage of SPECT/CT compared to PET/CT is scan speed. Currently, it takes two to three hours to complete a stress and rest myocardial perfusion SPECT/CT study. In contrast, it takes 30 to 45 minutes to acquire the same datasets on a PET/CT system. Bengel expects to decrease SPECT/CT acquisition time to 60 to 90 minutes by employing improved reconstruction methods and new SPECT/CT hardware. “The faster SPECT/CT systems will increase patient convenience while decreasing radiation exposure. In addition, faster throughput will allow us to serve more patients,” notes Bengel.
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Research is progressing on several fronts. PET seems to be well-equipped to handle the challenge. FDG PET imaging illustrates the concept. Gropler explains. “Atherosclerosis is an inflammatory process. It appears the more inflammation in the plaque, the more likely it will grow and rupture. In addition, inflammation is a metabolically active process with increased glucose uptake correlating with the degree of inflammation. Thus, the more active and inflammatory plaque takes up more glucose and lights up on the FDG scan.” The problem is that the method works best in arteries that don’t move, such as the carotids and aorta. “FDG-PET imaging is very difficult in the coronaries for three reasons: they’re small, they move and the images may be obscured by FDG uptake by the heart,” says Gropler.
Vigorous research and development into new probes will offer the solution. New probes will focus on more specific targets such as the surface receptors expressed by active plaque. PET/CT or SPECT/CT could be used to localize the active plaque. “Molecular imaging research is still mostly in the preclinical stage, but it is the next logical step in using imaging to diagnose and risk-stratify patients with coronary artery disease,” asserts Gropler.
Probe research is progressing on others fronts, too, with new cardiac tracers offering more specific data than first-generation tracers. MIBG, for example, is a radiopharmaceutical currently in the development process. It may better assess which ventricular dysfunction patients require an ICD (implantable cardiac defibrillator) than the current standard based on ejection fraction measurement. Other agents under development may more accurately measure myocardial perfusion than existing molecular imaging agents.
Molecular imaging models
Molecular imaging offers viable methods for improving detection, risk stratification and treatment of coronary artery disease. PET/CT and SPECT/CT not only save time, money and unnecessary studies, but also better guide treatment than other modalities. Current options, however, merely scratch the surface. In the future, new tracers could better optimize coronary artery disease imaging by providing critical data about the biology of coronary plaque.
| Changing Standards of Care: Where Molecular Imaging Fits In |
| Cardiac imaging is evolving with molecular imaging poised to play a larger role in detection and diagnosis. Multiple factors including demographics, economics, improved technology and new tracers will all drive change. Cardiologists primarily use two radioisotope-based molecular imaging technologies—SPECT and PET—to diagnose and select treatment decisions for patients with coronary artery disease. Over the last 20 years, cardiac SPECT volume skyrocketed. Currently, 8 million cardiac SPECT studies and several hundred thousand cardiac PET scans are performed annually in the U.S., estimates Daniel Berman, MD, director of cardiac imaging and nuclear cardiology at Cedars-Sinai Heart Institute in Los Angeles. Greater cost scrutiny coupled with the increasing incidence of heart disease fuel the need for greater efficiency and updated standards of care. Efficiency improvements are occurring on two fronts, says Berman. For starters, improved technology and protocols are reducing the average scan time. With new scanners, rest and stress SPECT studies can be completed within 30 minutes. Similarly, more efficient PET protocols drop the average cardiac PET study to 30 minutes. The other half of the efficiency equation is necessity. “In terms of efficiency, we need to make sure that tests are not performed on patients who don’t need them. Currently, a significant fraction of nuclear cardiology studies are performed on patients who don’t need them,” shares Berman. Therefore, appropriate patient selection for imaging procedures is required. The American College of Cardiology (ACC) aims to remedy the situation with updated appropriateness guidelines on nuclear cardiology studies. Berman estimates that nuclear SPECT study volume could drop by 20 percent if appropriateness criteria is implemented and followed nationally. The coronary artery imaging challenge Promoting efficiency in cardiac imaging is a complex challenge. The primary application of cardiac imaging studies is coronary artery disease, which accounts for 90 percent of all cardiac imaging studies. The hitch, however, is that the population of patients at risk for contrary artery disease is very heterogeneous. It ranges from 40-year-old asymptomatic patients with low to moderate risk factors to high-risk 80-year-old patients with diabetes, high cholesterol and hypertension as well as a large group of patients with previous myocardial infarctions, angioplasty or bypass surgeries. It’s fairly clear that appropriate imaging studies differ for each group of patients. “Some imaging studies provide more definitive answers for certain patients,” shares Berman. With further evidence, it’s likely that the mix of cardiac imaging studies will change and be adapted to meet the needs of specific patient populations. For some patients, a CT angiogram produces a clear diagnosis that eliminates the need for downstream testing. Take for example a 50-year-old male with chest pain who presents to the ER without other symptoms of angina. The likelihood of coronary artery disease is about 20 percent, says Berman. “In such cases, a CT angiogram could be more effective than a nuclear study. Current studies suggest that the patient could forego repeat tests for up to seven years if the CT angiogram is normal. On the other hand, a normal nuclear study might require a repeat study in two to three years if the symptoms recur.” That’s because the CT detects any existing plaque. SPECT, on the other hand, targets functionally significant lesions. It takes many years for patients to progress from no significant plaque to functionally significant lesions. In contrast, patients with prior myocardial infarctions may be better served by SPECT or PET than coronary CT angiography. “CT angiography is less useful for patients with existing disease because we know the patient has blockages in certain arteries,” explains Berman. The question centers on the significance of the blockages. “We need more information about these patients. Both SPECT and PET have been shown to be highly effective in risk stratification. Clinical studies show that nuclear scans can help predict which patients will benefit from a revascularization procedure to reduce subsequent cardiac events and improve quality of life.” PET offers the advantage of higher resolution and improved attenuation correction, factors that improve image quality. Researchers are attempting to better determine the best imaging course for each group of patients with several clinical trials comparing the effectiveness of various non-invasive imaging modalities under evaluation by the National Institutes of Health (NIH). For example, the NIH is reviewing a pilot phase of the FABULOUS trial and may approve a larger trial. The study compares the near-term clinical outcomes, quality of life, resource utilization and costs of a coronary CT angiogram-based imaging strategy and a myocardial perfusion SPECT protocol in intermediate-risk patients with stable chest pain syndrome and without known coronary artery disease. As data accumulate and appropriateness criteria are published, Berman predicts the dramatic growth in cardiac SPECT studies will level off, but SPECT will remain viable and valuable for significant segments of the population. Why? As people age, the coronary arteries contain more calcium, reducing the visibility of the lumen by CT and CT is less effective for patients with existing blockages. Incentives at a glance As clinical trials are published, it’s critical that physicians refer to appropriateness criteria and guidelines. Although appropriateness criteria serve as the standard mechanism for updating standards of care, other mechanisms could play a larger role in coronary artery disease imaging in the future. For example, third-party control mechanisms like U.S.-based radiology benefit management (RBM) programs are likely to include cardiac imaging studies in the algorithms used to approve imaging studies. The problem is that these programs are driven by the need to contain costs. Although such programs do save money, studies have not shown that RBM programs improve patient care. Berman believes appropriateness criteria will improve patient care and says it will be most effective for patient care if ordering physicians, rather than external benefits managers, assume control of the imaging decision-making process. Rationale revisited As molecular imaging develops, new standards of care will follow. The need for targeted, more appropriate patient care coupled with the drive for greater efficiency in the healthcare arena compels informed and accelerated clinical adoption. Cardiologists and clinicians need to stay current on molecular imaging protocols via appropriateness criteria and amended guidelines. The end result—improved, more efficient, cost-effective patient care—demands it. |