This document addresses use of electron beam computed tomography (EBCT), helical CT and multi-slice spiral CT scanning to detect coronary artery calcium (CAC).  The rapid image acquisition time of these CT scanning techniques eliminates motion artifact related to the beating heart and thus, permits visualization of coronary artery calcium.  In asymptomatic patients, CAC has been investigated as a risk factor for coronary artery disease and has been used to further evaluate patients with known coronary artery disease.    

Note: This document only addresses CT detection of CAC.  Assessment of CAC may also be done in conjunction with CT scanning to visualize the coronary arteries, (referred to as CT angiography, or CCTA).  CCTA is addressed in RAD.00035 Coronary Artery Imaging: Contrast-Enhanced Coronary Computed Tomography Angiography (CCTA) and Coronary Magnetic Resonance Angiography (MRA).

Investigational and Not Medically Necessary:

The use of electron beam computed tomography (EBCT), helical CT or multi-slice spiral (also known as multi-row detector) CT (MSCT) is considered investigational and not medically necessary for the detection of coronary artery calcium, including, but not limited to, the following indications:

• as part of a cardiac risk assessment in asymptomatic or symptomatic patients;
• as a diagnostic test in patients considered at intermediate risk for coronary artery disease, where other cardiac tests have been inconclusive;
• as a diagnostic test in symptomatic patients;
• In conjunction with a coronary CT angiography (CCTA).

General Considerations:
Diagnostic technologies are commonly evaluated according to a sequential three step assessment of analytic validity, clinical validity and clinical utility.  Analytic validity refers to the ability of a CT scan to accurately and reliably detect coronary artery calcium (CAC).  The data is typically reported as a "calcium score," which represents the total atherosclerotic plaque burden.  Clinical validity refers to the relationship between the detected CAC and coronary artery disease.  Finally, clinical utility refers to how CAC scores can be used to improve patient management of coronary artery disease. 

While it is recognized that electron beam or helical CT scans can detect and quantify CAC, the major questions regarding these techniques relate to clinical validity and utility.  For example, in the United States cardiac risk assessment is currently based on the Framingham Risk Score, which is used as the basis for various prevention strategies for coronary artery disease.  The Framingham Risk score is derived from various, easily obtained, clinical and laboratory values, such as age, lipid profile, blood pressure and smoking status. Therefore, a key question is whether an assessment of CAC will improve these traditional risk assessment techniques.  Additionally, it is important to understand how CAC risk assessment will be integrated into overall patient management, particularly in patients considered at intermediate risk. For example, epidemiologic and observational studies may demonstrate that CAC is an independent risk factor for coronary artery disease, but improved risk assessment is not clinically meaningful if this information cannot be used to improve patient management. 

CAC has also been used to evaluate symptomatic patients as an initial test to guide further cardiac function or imaging tests, based on the calcium score.   For example, a low calcium score may be used to rule out coronary artery disease in symptomatic patients, potentially deselecting patients for angiography.  Again, in this setting it is important to understand how measurement of CAC will be integrated into the management of the patient, particularly given the wide variety available of noninvasive diagnostic techniques, ranging from different types of exercise tests, echocardiography and nuclear medicine tests. 

The following discussion is based primarily on review of a variety of consensus documents, scientific statements and guidelines addressing the clinical validity and clinical utility of CT detection of CAC –       

Consensus Reports, Guidelines and Scientific Statements:

1. In 2000, an American College of Cardiology/American Heart Association Expert Consensus paper stated that EBCT measurement of coronary artery calcium is not recommended for diagnosing obstructive coronary artery disease (CAD) because of the imaging device's low specificity (high percentage of false-positive results) or for screening of asymptomatic individuals, because of the lack of incremental value in EBCT screening over other readily available risk assessment methods (O'Rourke, 2000).
   
2. In 2004, the United States Preventive Services Task Force (USPSTF) issued updated recommendations on screening asymptomatic adults for coronary heart disease (CHD) seen in primary care settings. The USPSTF gave a "D"* recommendation against routine screening with EBCT scanning for CAC, for either the presence of severe coronary artery stenosis or the prediction of coronary heart disease (CHD) events in adults at low risk for CHD.
   
   This recommendation was supported by at least fair evidence that screening asymptomatic adults for CHD is ineffective or that harms outweigh benefits. The USPSTF gave an "I"** recommendation to support or reject EBCT scanning for CAC for either the presence of severe coronary artery stenosis or the prediction of CHD events, in adults at increased risk for CHD events. This recommendation was based on insufficient evidence to recommend for or against routinely providing screening services in this patient population (USPSTF, Feb 2004; see the Definitions section for an explanation of the rating system).
   
3. In 2005, the American Heart Association published a consensus statement regarding the role of noninvasive  testing of women with suspected coronary artery disease (Mieres 2006).  The consensus statement considered the incremental value of CAC scores, compared to traditional risk factor assessment, and focused on one observational study that included a large number of women.  The report concluded that additional studies were needed to establish female-specific cut points of CAC scores defining high risk status in women.  The consensus statement offered the following conclusion:
   

   Additional high-quality data are needed from larger cohorts that specifically address CAD outcomes in women to more precisely establish female specific CAC risk cut points and to more precisely quantify the incremental prognostic value beyond the measurement of conventional coronary risk factors.  Until then, consistent with recent consensus statements, CAC testing for CAD risk detection should be limited to clinically selected women at intermediate risk.   

4. In 2006, the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group published appropriateness criteria for cardiac computed tomography, including evaluation of CAC (Hendel, 2006). This report took a consensus approach to the evaluation of test performance of these technologies within specific clinical scenarios. A total of four CT indications addressing CAC were rated as follows:
   For risk assessment in the general population of asymptomatic individuals, CAC measurements were rated:
   

   • Inappropriate for low CHD risk (on Framingham scoring);
   • Uncertain for moderate CHD risk (on Framingham);
   • Uncertain for high CHD risk (Framingham).

   For risk assessment with prior test results when patient is asymptomatic, CAC measurements were rated:

   • Inappropriate if prior calcium score was within the previous 5 years.
     
5. In 2006, the American Heart Association published a scientific statement on the assessment of coronary artery disease by cardiac computed tomography (Budoff, 2006).  Most of the document reviewed the clinical utility of CAC scoring for determining prognosis and diagnosis.  Within this document, there were no Class I* or IIa** recommendations regarding coronary artery calcium detection by CT.  The following IIb recommendations were offered:
   • Patients with equivocal or normal EKG and negative cardiac enzymes;
   • Determination of the etiology of cardiomyopathy;
   • Symptomatic patients with equivocal results of treadmill or functional tests;
   • Asymptomatic patients with intermediate (10-20%) risk of coronary artery disease.
     
6. A 2007 clinical consensus document co-written by the American College of Cardiology Foundation and the American Heart Association provided updated information on CAC measurement (Greenland, 2007).  This document notes that Clinical Expert Consensus Documents concern topics for which, "The evidence base, the experience with the technology and/or the clinical practice are not considered sufficiently well developed to be evaluated by the formal American College of Cardiology/American Heart Association (ACC/AHA) Guidelines process.  Often the topic is the subject of considerable ongoing investigation."  Therefore, this document acknowledged the lack of rigorous evidence addressing the clinical utility of CAC measurement.       
   
   The findings of this expert panel were consistent with the prior AHA scientific statement (Budoff, 2006) in that the Committee judged that it may be reasonable to consider use of CAC measurement in asymptomatic patients with intermediate CHD risk.  This was based on the possibility that such patients might be reclassified to a higher risk status if high CAC scores are found, thereby subsequent patient management may be modified.  However, there was inadequate data to show that changes in patient management result in improved health outcome.  The Committee did not recommend use of CAC measurement in other selected patient groups, such as those with low or high CHD risk (based on the Framingham scoring system).  However, this paper noted, "In general, CAC measurement has not been compared to alternative approaches to risk assessment in head-to-head studies.  Therefore, the question of whether there is evidence that CAC measurement is better than other potentially competing tests for intermediate risk patients for modifying cardiovascular disease risk estimate cannot be adequately answered from the available data."

Conclusions:
The 2006 AHA scientific statement noted that there is growing evidence that CAC scores are an independent predictor of coronary artery disease, (i.e., proof of clinical validity).  However, it is still unknown how this information can be integrated into patient management to improve health outcomes, (i.e., clinical utility).  This gap in the data is reflected by the consensus, rather than evidence-based, approach in developing recommendations and appropriateness criteria.

Clinical Studies:
A literature search focused on studies published since the 2005 review period noted in the 2007 clinical consensus document. (Greenland 2007).   While these studies have further assessed CAC as a risk assessment tool, there are still no studies detailing how this information can be used to improve patient management.  Representative studies are reviewed below.

In 2005, Anand and colleagues published a study specifically evaluating CAC scores as a risk stratification tool in 510 patients with uncomplicated type II diabetes (Anand 2005).  Myocardial perfusion studies were performed in all patients with high CAC scores and in a random sample of the remaining patients.  The patients were followed for a mean of 2.2 years for cardiovascular events.  The authors reported that CAC scores were superior to established cardiovascular risk factors for predicting silent myocardial ischemia and short-term outcome.  It should be noted that the CAC scores were not used to direct patient management.

The MESA Trial (Multi-Ethnic Study of Atherosclerosis) is an ongoing, multi-center, prospective longitudinal study of asymptomatic individuals across four racial/ethnic groups to evaluate the long-term cardiovascular outcomes with a ten year follow-up of 6,772 asymptomatic participants after baseline risk assessment (including CAC measurement).  The MESA study was launched in 2000.

Interim results (median follow-up 3.9 years) suggest that the coronary artery calcium score is a predictor of subsequent clinically significant coronary heart disease and may provide predictive information beyond that provided by standard risk factors, (i.e., the Framingham Risk Score). (Detrano 2008)  The authors reported that after adjustment for standard risk factors, a doubling of the CAC score resulted in a 20% increase in the risk of a major coronary event (myocardial infarction/death from CHD) and a 25% increase in the risk of any coronary event. A limitation of this study was variation in CT acquisition and reading methods across the six study centers.  The authors also caution against using the absolute calcium scores cited in the study and note that ethnic-specific calibrations of CAC scores are needed to adjust for baseline differences between different ethnic groups.  Another limitation of this interim report is the small number of measured clinical events (72 non-fatal MI, 17 fatal coronary events, 73 angina pectoris).

Another study of the MESA cohort (Lakoski, 2007) looked at CAC scores and risk of future coronary events in women.  This MESA cohort study included 3,601 asymptomatic women, age 45 to 84 years, and judged to be at low risk for coronary disease based on FRS.  The authors concluded that the presence of coronary artery calcium in women at low FRS risk was predictive of future coronary heart disease and cardiovascular events.  Compared with women with no detectable coronary artery calcium, low risk women with a CAC score greater than 0 were at increased risk for CHD (HR 6.5, 95%; CI 2.6-16.4) and cardiovascular events (HR 5.2, 95%; CI 2.5-10.8).  Low risk women with advanced coronary artery calcium (CAC score ≥ 300) had a risk of 8.6% for having a cardiovascular event over a 3.75 year period, compared with 0.6% in low risk women with CAC score of 0 and 1.9% in low risk women with CAC score 1-99.

Budoff and colleagues used a large observational data base of 25,253 asymptomatic patients undergoing CAC scoring to develop risk-adjusted multivariable models incorporating CAC scores to predict all cause mortality (Budoff 2007).  The authors reported that the CAC score provided incremental information, in addition to traditional risk factors in the prediction of all-cause mortality.

Conclusions:
Although the above studies suggest that the coronary artery calcium score may be an independent predictor of coronary artery risk, they were not designed to demonstrate an improved clinical outcome, as the result of coronary artery calcium screening.  There is currently no direct evidence that risk stratification using coronary calcium scores improves patient outcomes, i.e., the clinical utility of coronary artery calcium measurement is, as yet, unproven. 

Note:
The presence of extensive coronary artery calcium precludes the use of CT coronary angiogram (CCTA).  Therefore,  an assessment of CAC is often performed in combination with CCTA.  Many of the recently published studies of CAC explore its role in conjunction with CCTA.  These studies are not considered in this document.  CCTA is considered separately in RAD.00035.

Computerized axial tomography, also called CT, CT scan, or CAT scan, is an x-ray technique that uses an x-ray-sensing unit which rotates around the body, along with a computer to create cross-sectional images. The images are generated by a computer synthesis of x-ray transmission data obtained for many different directions in a given plane. Electron beam CT and spiral or helical CT scans are types of CT scans that have very high speeds of image acquisition which eliminate the motion artifact of the beating heart, and thus, permit imaging of coronary artery calcium. Since CAD may remain silent until a major catastrophic event occurs, it has been hypothesized that detection of coronary calcium in asymptomatic patients could provide additional data of cardiac risk, potentially leading to changes in diet, lifestyle, and patient management that potentially could reduce the risk of myocardial infarction (MI).

Computed tomography (CT): an imaging technique that creates multiple cross-sectional images of the body by using special X-rays and computer enhancement to detect disease or abnormalities

Coronary artery disease: a disease characterized by narrowing or blockage of the blood vessels that supply blood to the heart

Electron beam CT (also known as Ultrafast CT): is a type of CT that uses an electron gun rather than a standard x-ray tube to generate x-rays, thus permitting very rapid scanning, on the order of 50-100 milliseconds per image

Framingham Risk Scoring System: the most-commonly used, multi-variable scoring system (in the U.S.) and the most extensively validated quantitative assessment tool for determining an individual's potential risk of developing coronary heart disease and of experiencing a significant coronary event; it includes the following major risk factors: gender, total cholesterol, high-density lipoprotein (HDL) cholesterol, systolic blood pressure (or on treatment for hypertension), cigarette smoking, and age

Helical CT (also known as spiral CT scanning): is a type of CT that creates images at greater speed than conventional CT by continuously rotating a standard x-ray tube around the patient so that data are gathered in a continuous spiral or helix rather than individual slices

Multislice spiral CT (MSCT) also known as mult-row detector CT or MDCT: is a technical evolution of helical CT, and uses CT machines equipped with an array of multiple x-ray detectors that can simultaneously image multiple sections of the patient during a rapid volumetric image acquisition; currently available MDCT machines may have 4, 8, 16, 32, 40 or 64 detectors

Tomograph: an apparatus for moving an x-ray source in one direction as the film is moved in the opposite direction, thus showing in detail a predetermined plane of tissue while blurring or eliminating detail in other planes

Note: According to the USPSTF Task Force ratings on strength of recommendations, the U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms) as follows:
A.— The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.
B.— The USPSTF recommends that clinicians provide [this service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.
C.— The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.
*D.— The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.
**I.— The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that the [service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. (USPSTF, 2004)

According to the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guideline recommendations documents, the following are the definitions of Classifications of Recommendations, as expressed in the ACC/AHA/ESC format:
*Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective.
Class II: Conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/efficacy of a procedure or treatment.
**Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.
***Class IIb: Usefulness/efficacy is less well established by evidence/opinion.
Class III: Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful.  (Hendel, 2006)

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:

When services are also Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Anand DV, Lim E, Hopkins D, et al.  Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy.  Eur Heart J. 2006; 27(6):713-721.
2. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007; 49(18):1860-1870.
3. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008; 358(13):1336-1345.
4. Lakoski SG, Greenland P, Wong ND, et al. Coronary Artery Calcium Scores and Risk for Cardiovascular Events in Women Classified as "Low Risk" Based on Framingham Risk Score: the multi-ethnic study of atherosclerosis (MESA). Arch Intern Med. 2007; 167(22):2437-2442.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Agency of Health Technology Assessment (DAHTA) at German Institute for Medical Documentation and Information (DIMDI). Computed tomography for the measurement of coronary calcification in asymptomatic risk patients [summary]. Technology Assessment. Cologne, Germany; DIMDI; 2006.
2. Mieres JH, Shaw LJ, Arai A et al. Role of non-invasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circ 2005;111:682-96.
3. Budoff MJ, Achenbach S, Blumenthal RS, et al. Assessment of Coronary Artery Disease by Cardiac Computed Tomography. A Scientific Statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circ. 2006; 114:1761-91. Available at: http://circ.ahajournals.org/cgi/reprint/114/16/1761?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Assessment+of+Coronary+Artery+Disease+by+Cardiac+Computed+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT. Accessed on March 23, 2009. Centers for Medicare and Medicaid Services. National Coverage Determination for Computerized Tomography. NCD #220.1. Effective November 22, 1985. Available at: http://www.cms.hhs.gov. Accessed on March 23, 2009.
4. Graham I, Atar D, Borch-Johnsen K, Boysen G, European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG), et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J. 2007; 28(19):2375-2414.
5. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 Clinical Expert Consensus Document on Coronary Artery Calcium Scoring by CT in Global Cardiovascular Risk Assessment and in Evaluation of Patients with Chest Pain: A Report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to update the 2000 Expert Consensus Document on Electron Beam Computed Tomography). J Am Coll Cardiol. 2007; 49:378-402. (Co-published in Circulation. Jan. 23, 2007.) Available at: http://www.acc.org. Accessed on March 23, 2009.
6. Hayes Inc. Hayes Medical Technology Directory. Electron Beam Computed Tomography for Coronary Artery Disease. Lansdale, PA:Hayes, Inc; June 2003. Search updated April 22, 2007. Archived Nov. 12, 2008.
7. Hayes Inc. Hayes Medical Technology Directory. Multi-slice computed tomography for detection of coronary artery disease. Lansdale, PA: Hayes, Inc; July 6, 2004. Reviewed, updated, and unbundled as a detection-specific report July 19, 2007. Search updated July 12, 2008.
8. Hayes Inc. Hayes Medical Technology Directory. Helical Computed Tomography for CAD. Lansdale, PA: Hayes, Inc; February 7, 2000. Search updated Sept. 19, 2006. Archived 2007. Hendel RC, Patel MR, Kramer CM, et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging: A report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions and Society of Interventional Radiology. J Am Col Cardiol. 2006; 48(7).
9. O'Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association expert consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol. 2000; 36(1):326-340. Siemens AG [Web site]. Press release. FDA provides marketing clearance for 64-slice and open CT systems. April 12, 2004. Available at: http://www.medical.siemens.com Accessed on March 23, 2009.
10. U.S. Preventive Services Task Force. Screening for coronary heart disease. Report of the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); February 2004. Available at: http://www.ahrq.gov. Accessed on March 23, 2009. U.S. Preventive Services Task Force (USPSTF). Screening for coronary heart disease: recommendation statement. Ann Intern Med. 2004; 140(7):569-572. Waugh N, Black C, Walker S, et al. National Coordinating Centre for Health Technology Assessment (NCCHTA) Health Technology Assessment. The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: Systematic review. 2006; 10(39):1-60.

1. American Heart Association (AHA) Heart Disease and Stroke Statistics – 2004 Update. 2004a. Available at: http://www.americanheart.org. Accessed on March 23, 2009.
2. Multi-Ethnic Study of Atherosclerosis (MESA) Coordinating Center, University of Washington, Seattle, WA. Available at: http://www.mesa-nhlbi.org/ Accessed on March 23, 2009.
3. National Heart, Lung, and Blood Institute. Facts about Coronary Heart Disease. Available at: http://www.nhlbi.nih.gov. Accessed on March 23, 2009.
4. Radiological Society of North America, Inc. RadiologyInfo™. Cardiac CT for Calcium Scoring. May 23, 2007. Available at: http://www.radiologyinfo.org/en/pdf/ct_calscoring.pdf. Accessed on March 23, 2009.

Cine Computed X-Ray Tomography
Computed Tomography, Electron Beam
Helical CT
High-Speed Computed X-Ray Tomography
Multirow Detector CT (MDCT)
Multislice Spiral CT (MSCT)
Rapid Acquisition X-Ray Computed Tomography
Ultrafast^® Computed Tomography (CT)

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.