- Category: FAQ
FAQ: What is CEUS, what are its benefits, and how do I know it’s safe?
New studies show that heart disease, cancer, and serious medical conditions throughout the body may be diagnosed safely, inexpensively, and without ionizing radiation or dye, using a simple “contrast-enhanced ultrasound” (CEUS) scan.
What is CEUS?
It’s simply an “enhanced” ultrasound exam that uses a “contrast agent” to improve the clarity of an ultrasound image. The contrast agent is injected into the patient’s arm vein during the ultrasound exam. As it flows through the bloodstream, it reflects ultrasound waves and lights up the image seen on a television-like screen.
The procedure does not expose patients to ionizing radiation. And ultrasound contrast agents, which do not contain the type of dye that can damage kidneys or other organs, is expelled from the body within minutes.
CEUS reduces misdiagnoses and missed diagnoses, and avoids unnecessary additional testing that would increase risks, costs, and inconvenience to patients. In addition, studies now show that CEUS has a favorable safety profile, is cost-effective, and can change medical outcomes.
Unlike MRI and CT, a simple CEUS scan provides immediate real-time information and may be carried out at a patient’s bedside, in the operating room, and in a variety of other settings. This can be particularly crucial when critically ill patients cannot be moved to an MRI or CT scanner and cannot wait for a diagnosis.
What is CEUS used for?
So far, in the United States, CEUS is FDA-approved for cardiac imaging only. American cardiologists can use CEUS to get a better look at the heart’s left ventricle – the main pumping chamber that squeezes blood out to the rest of the body – and assess the heart's "ejection fraction," a key indicator of how well the heart works.
But cardiologists and radiologists throughout Europe, Canada, Asia and Brazil safely use CEUS to image and diagnose serious medical conditions throughout the body as well as tumors of the breast, liver, kidneys, spleen, ovaries, testicles, lymph nodes, etc. Additional indications are under review by the FDA and, prior to approval, may be used off-label with patient consent if warranted.
What are the advantages of CEUS?
Safety, accuracy, low cost, minimally invasive procedure, and portability.
While other types of diagnostic imaging can be extremely useful tools for diagnosing cardiac abnormalities and are often justified despite their risk and cost, CEUS does differ from other types of diagnostic imaging in a number of ways:
Accurate and reliable diagnoses
Strong safety profile
No ionizing radiation, which may increase a patient’s lifetime risk of cancer. By comparison, SPECT, PET, CT, X-ray and angiography imaging procedures do expose patients to ionizing radiation.
No iodinated dye
No invasive catheterization
No risk of nephrotoxicity.
No anesthesia or sedation.
Fewer redundant, unnecessary downstream tests
Lowers overall costs
CEUS only requires a small amount of an ultrasound contrast agent – ½ to 1 cc, the equivalent to 10-20 drops.
Cheaper equipment -- no “big box” imaging machines or dedicated suites.
Convenient and easy to use
Portable and flexible use. Because ultrasound equipment can often be taken to the patient, CEUS can be used almost anywhere -- including the intensive care unit. This is not true for MRI, SPECT, CT, or PET imaging.
May be used to image a growing number of severely obese patients who often cannot be imaged with other "big box" imaging technology.
Potential for screening, prevention, and ongoing monitoring of care
Widespread international acceptance
Does CEUS work?
Yes. Physicians recently showed that CEUS can improve the accuracy and reliability of ultrasound images, change therapy, avert downstream testing, and ultimately save overall health care costs – to the tune of approximately $122 per patient overall, after considering the cost of the contrast agent. In this study, more than 35% of patients who received contrast during an echocardiogram were found to benefit, either because of procedures avoided, changes in therapy, or both. (Mustafa Kurt, MD, et al., Department of Cardiology, The Methodist Hospital – J Am Coll Cardiol, 2009; 53:802-810, expedited online publication 11 February 2009, © 2009 by the American College of Cardiology Foundation)
In addition, this study showed that clearer ultrasound images led to more accurate diagnoses. For example, initial echocardiograms performed without contrast indicated that a potentially dangerous left ventricular ("LV") thrombus was suspected in 35 patients and was considered “definite” in 3 patients. Subsequently, after a contrast agent was administered, the echocardiogram images were re-analyzed and only 1 of the 35 “suspected” LV thrombi actually existed, while 5 LV thrombi were newly identified. (Mustafa Kurt, MD, et al., Department of Cardiology, The Methodist Hospital – J Am Coll Cardiol, 2009; 53:802-810, expedited online publication 11 February 2009, © 2009 by the American College of Cardiology Foundation)
In Canada, the Ontario Health Technology Advisory Committee, in January 2010, examined the utility of CEUS and concluded that:
- Stress echocardiography with contrast “has a higher diagnostic accuracy” than stress echocardiography without contrast;
- Stress echo with contrast seems to have similar diagnostic accuracy to SPECT (which exposes patients to ionizing radiation);
- The addition of contrast to a suboptimal echocardiogram “significantly improves” the interpretability of the results; and
- There is not a statistically higher mortality rate in patients who receive contrast compared to patients who do not.
What do accreditation bodies think of CEUS?
New accreditation standards for the first time require US echocardiography laboratories to use ultrasound contrast agents to improve suboptimal echocardiograms, unless an alternative imaging plan is in place. These new standards became effective in December 2010 and echo labs that do not comply risk losing ICAEL (the Intersocietal Commission for Accreditation of Echocardiography Laboratories) accreditation.
In addition, the Joint Commission, which accredits health care programs in the US, recently issued a statement urging physicians to use radiation-free ultrasound or MRI scans where feasible instead of radiation-based imaging modalities such as CT, PET or SPECT (nuclear) imaging.
How do I know CEUS is safe?
The safety of ultrasound contrast agents was questioned in 2007, when four deaths were reported out of a total of some 58,000 doses of ultrasound contrast agents. The four deaths occurred in patients who were hospitalized for serious underlying cardiac conditions, and although the causes of these deaths were unclear they were taken seriously by the FDA and the medical community. Accordingly, in 2007, the FDA added boxed” warnings and contra-indications to the package inserts of both of the ultrasound contrast agents sold in the US – Definity and Optison.
However, in May 2008, as new information became available, the FDA modified its mandated labeling changes and modified the new disease state contraindications to warnings. Additional modifications are under review by the FDA and a decision is pending as of this writing.
Meanwhile, the medical community continued to study the safety of CEUS and has now published numerous additional scientific reports showing a favorable safety profile for both products, with no increased mortality or safety signal even among the sickest patients. For example:
One study evaluated the safety of ultrasound contrast agents used in more than 4.3 million patients and showed that those receiving a contrast agent were actually 24% LESS likely to die within 24 hours than patients who did not receive a contrast agent during an ultrasound diagnostic examination. - Main ML et al. Am J Cardiol 2008;102:1742-6
Similarly, the American Society of Echocardiography Multi-Center Registry of 13 sites and more than 66,000 doses showed (a) no deaths, (b) no serious adverse events in hospitalized patients, (c) severe adverse reactions in 8 non-hospitalized patients (0.01%), and (d) anaphylactoid reactions (severe allergic reactions) in 4 patients (0.006%). The authors of the study concluded: The incidence of severe adverse reactions to ultrasound contrast agents is lower than, or similar to, that reported for contrast agents commonly used in other cardiac imaging tests. - Wei K. et al. J Am Soc Echocardiogr 2008;11:1202-1206.
And a meta-analysis of eight controlled observational registry studies, with nearly a quarter million patients, concluded: “the cumulative evidence has suggested that the use of contrast agents for echocardiography is safe and not associated with a greater incidence of myocardial infarction (heart attack)” or death. (Khawaja, et al., “Meta-Analysis of Adverse Cardiovascular Events Associated With Echocardiographic Contrast Agents,” Am J Cardiol 2010; 106: 742-747) In fact, the meta-analysis actually showed lower mortality rates in patients who received ultrasound contrast recipients. According to the senior author, "we did not see any signal that echo contrast was causing any harm." (Heartwire Aug. 13, 2010) And according to Heartwire, this meta-analysis represents "the latest in a number of studies in recent years to suggest no untoward safety hazard from use of echo contrast agents." (Heartwire Aug. 13, 2010)
According to a guest editorial published in the European Journal of Echocardiography:
“(T)he literature does not support the occurrence of systemic, predictable, adverse events during contrast echocardiography. Consequently, to quote Sherlock Holmes: ‘When you have eliminated the impossible, whatever remains, however improbable, must be the truth.’ Thus, contrary to our fears and against odds, contrast echocardiography appears to be safe in humans. We should use it to improve patient care.” (Kaul and Wei, Guest Editorial, European Journal of Echocardiography (2009) 10, 713-15 (http://ejechocard.oxfordjournals.org/content/10/6/713.full.pdf+html))
Why is all of this important?
First the bad news -- Heart disease is the #1 killer in the US
Heart Disease is the #1 cause of death and a major cause of disability in the US -- with one American dying every minute from a coronary event, and countless others suffering the debilitating effects of heart failure and other forms of cardiovascular disease. .
Background: The Center for Disease Control (CDC) reports that heart disease remains the leading cause of death in the U.S. and is a major cause of disability. Figures for 2009 indicate that 785,000 Americans had a new, first time heart attack, and approximately 470,000 will have a recurrent heart attack. About every 25 seconds, an American will have a coronary event, and about one every minute will die as a result.
Thus heart disease remains a serious public health menace even though heart disease declined 30% over the past 10 years – primarily due to improved diets and exercise regimes (often referred to as “therapeutic lifestyle changes”), increased use of prescribed statin drugs, and improved diagnostic imaging.
Second – A Troubling Trend: Increasing use of high-tech diagnostic imaging is detecting cardiovascular disease but also exposes patients to ionizing radiation and increases overall health care costs
Exposure to ionizing radiation can increase a patient's lifetime risk of cancer, and the risk can be cumulative throughout a patient's lifetime.
“Medical imaging is the largest controllable source of radiation exposure to the US population, and its most important determinant is the ordering healthcare provider.” - Science Advisory From the American Heart Association Committee on Cardiac Imaging of the Council on Clinical Cardiology and Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention. Circulation 2009
One troubling example -- Women with breast cancer are often required to undergo serial nuclear-based MUGA scans prior to chemotherapy sessions. The test is important because it provides information on the heart’s ejection fraction – it’s ability to squeeze and pump blood. However, MUGA scans expose patients to cumulative doses of ionizing radiation, which increase the patient’s lifetime risk of cancer.
CEUS is an excellent means of detecting ejection fraction without ionizing radiation.
Another troubling example -- CT scans have come under increasing FDA oversight with reports of massive ionizing radiation overdoses being given to patients in an effort to enhance clarity. More than 400 patients at 8 hospitals, including Cedars-Sinai Medical Center in Los Angeles, were given radiation doses up to 8 times as much as intended.
SPECT imaging also faces a potentially unsolvable shortage of medical isotopes or nuclear tracers. According to the Los Angeles Times (9/20, Forgione) "Booster Shots" blog reported, "The worldwide radiopharmaceutical shortage, as it is called, has affected the ability of doctors to perform cardiac stress tests that use nuclear tracers." The reduced supply of medical isotopes was sharply felt in the US, because the country has failed to construct any new nuclear facilities, according to a reporter with the Allentown Morning Call. Accordingly, some physicians "have turned to MRIs and stress echocardiograms to replace the Tc-99 tests."
Yet, according to the CDC, the use of high-tech diagnostic imaging in emergency rooms (ER) has quadrupled since the mid 1990s. MRI (magnetic resonance imaging), CT (computed tomography; x-rays) or PET (positron emission tomography; nuclear medicine) scans were done or ordered in 14% of ER visits in 2007, which is 4 times as many as in 1996.
What is ICUS?
Following the FDA’s decision to impose boxed warnings on both approved ultrasound contrast agents, a number of cardiologists, radiologists, and other ultrasound professionals around the world came together to advocate for patient interests. In 2008, they launched the only international professional society exclusively focused on CEUS -- the International Contrast Ultrasound Society. ICUS currently has members in 58 countries and has become the strongest and most effective voice for the CEUS field. Membership in ICUS is free, and all members receive weekly email news blasts covering the latest developments in the CEUS field. ICUS also spearheads numerous educational initiatives aimed at the medical and policy communities.