The Emerging Role of Cardiac CT and Calcium Scoring in the Diagnosis of CAD

General description of procedure, equipment, technique

What every physician needs to know about coronary artery calcium scoring (CACS) and coronary CT angiography (CCTA):

a. What is a CACS?

Coronary artery calcium scoring (CACS) is an examination for early detection of coronary artery disease (CAD) and improvement of risk stratification for individuals at low-intermediate or intermediate CAD risk.
CACS is a diagnostic tool to determine the presence and extent of calcified plaque in coronary arteries by non-contrast computed tomography (CT) [electron beam computed tomography (EBCT) or multidetector computed tomography (MDCT)].
CACS scores are calculated by the sum of coronary calcified plaque lesions with greater than or equal to the calcium density of 130 Hounsfield units (HU) having an area >=1 mm². This lesion score is measured by the maximal CT number, with 1 for 130-199 HU, 2 for 200-299 HU, 3 for 300-399, and 4 for >=400 HU. Total coronary calcium score is determined by the sum of each of these lesion scores.

b. What is a CCTA?

Coronary CT angiography (CCTA) is a diagnostic tool that has emerged as a promising noninvasive anatomic imaging modality to assess the coronary arteries as well as non-coronary cardiac structural and functional evaluation.
Using contrast-enhanced CT by MDCT scanners, CCTA can provide images of the coronary artery lumen to visualize the presence, extent and severity of coronary artery stenosis. One added benefit of CCTA is to identify not only luminal stenosis but also coronary artery atherosclerotic plaque characteristics such as plaque composition [e.g., noncalcified plaque, mixed plaque (containing noncalcified and calcified) and calcified plaque]. These plaque constituents may contribute to risk prediction of future cardiac events or mortality.
CCTA is also useful for anatomical evaluation of the great vessels, myocardium, pericardium, cardiac chambers and valves. By retrospective ECG gating, CCTA also permits left ventricular (LV) assessment, such as for LV volumes, LV ejection fraction (LVEF) or LV mass.
For the image quality, careful patient selection is needed. Adequate breath holds, low and regular heart rates (normally <= 60 beats per minute) and sublingual nitroglycerin (for coronary vasodilation) are required for patients before CCTA scanning. When needed, an oral and/or intravenous beta blocker can be administered to reach the target heart rate. Patients with significant arrhythmias or who are severely obese are generally poor candidates for CCTA scanning.

Indications and patient selection

In whom should CACS be performed?

Since CACS is useful for risk assessment of future cardiac events or mortality, it should not be performed for low-risk patients. For individuals without prior known CAD, CACS is most useful in patients with moderate risk of 10-year coronary heart disease events, employing commonly used clinical risk algorithms (such as the Framingham risk score). For individuals with prior known CAD, CACS is not endorsed by current societal guidance documents.

In whom should CCTA be performed?

At present, current guidance documents recommend performance of CCTA for symptomatic patients for evaluation of CAD, with no current recommendation for asymptomatic patients. Although several limitation studies demonstrate the benefit of CCTA for asymptomatic patients, the incremental value of CCTA over CACS to assess CAD risk has not been examined. Future studies prospectively examining the incremental prognostic value of CCTA and CCS in asymptomatic patients now appear warranted.

a. Asymptomatic subjects

In asymptomatic subjects without known CAD, CCTA may be useful to exclude CAD for low- and intermediate-risk subjects with reduced LVEF and new-onset or newly diagnosed clinical heart failure. Further, subjects at intermediate pre-test likelihood of CAD may be imaged by CCTA for preoperative coronary artery assessment prior to non-coronary cardiac surgery. Also, asymptomatic patients who have previously undergone percutaneous coronary intervention (PCI) for left main (LM) stenosis with >=3 mm stent may undergo CCTA to evaluate stent patency.

b. Stable symptomatic subjects

CCTA is an accurate diagnostic tool to evaluate CAD in symptomatic patients without known CAD.
Given its high negative predictive value (NPV), CCTA may be a useful test for exclusion of significant CAD and reduction of unnecessary invasive coronary angiography (ICA), i.e., to act as a ‘gatekeeper’ to invasive procedures.
It remains unclear whether CCTA — a test providing anatomic information regarding coronary stenosis– is a more useful diagnostic tool compared with functional stress testing in stable symptomatic patients. An ongoing prospective multicenter trial, called PROMISE, is now underway to investigate whether CCTA improves long-term outcome for patients with stable chest pain compared with functional testing [stress echocardiography, stress single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) or exercise ECG].

c. Symptomatic subjects with acute chest pain

Several prospective multicenter randomized trials have reported the diagnostic utility of CCTA for patients with acute chest pain in the emergency department (ED). CCTA can provide high sensitivity and NPV to rule out acute coronary syndrome (ACS) in low-intermediate risk subjects, and more rapid and cost-efficient care compared to standard of care imaging (e.g., stress testing) in low-risk subjects. CCTA also reduces length of stay and time to diagnosis, with subsequent increased direct discharge rates from ED. This improvement in efficiency is observed with no differences in clinical outcome or missed ACS.

Contraindications

As beta blockers are often used to slow the heart rate in CCTA, caution should be used in patients with a history of reversible airway disease. Beta blockers should not be used in patients with high-grade conduction block or hypotension
As nitroglycerin is often used in CCTA, it should not be used in patients with baseline hypotension, or in patients with recent use of phosphodiesterase inhibitors such as sildenafil due to the potential for inducing hypotension
As iodinated contrast is used for CCTA, CCTA should not be performed in patients with a known anaphylaxis to contrast, unless proper premedication with steroids and Benadryl® are given

Details of how the procedure is performed

Patient preparation includes placement of ECG leads, proper beta blockade for heart rate lowering, and nitroglycerin immediately prior to the CCTA
CCTA can be performed on >= 64-detector row CT scanners in either helical or prospective axial mode
Non-contrast CACS can be performed with only ECG-gating, but does not need administration of beta blocker, nitroglycerin or contrast

Interpretation of results

CACS is useful for predicting future cardiac events in asymptomatic subjects. However, it is also important to manage future risk stratification and downstream medical costs after CACS results. Recently, the prospective EISNER study demonstrated that CACS significantly reduced future CAD risk without increasing medical costs in subjects with CACS, compared to subjects without CACS. In this regard, CACS can not only predict future events, but also may be able to control future health management.
By contrast, CCTA is normally performed for symptomatic subjects to detect or rule out CAD. If significant coronary artery stenosis is identified, invasive coronary angiography (ICA) should be considered. If non-obstructive coronary stenosis is identified, strong management and treatment for CAD risk factors should be considered. However, there is no prospective study to assess medical treatment based on CCTA findings to date. Future studies are warranted.

Performance characteristics of the procedure (applies only to diagnostic procedures)

What is the diagnostic accuracy of CACS?

a. Asymptomatic- compared to ICA

In the asymptomatic population, CACS has high sensitivity, but poor specificity of positive CACS to detect obstructive CAD by ICA. In contrast, CCTA has a high diagnostic accuracy to identify obstructive or non-obstructive CAD compared to CACS.

b. Symptomatic- stable versus acute chest pain

Prior studies have demonstrated high sensitivity, but poor specificity of positive CACS to detect obstructive CAD by ICA among patients with stable chest pain. Conversely, a CACS of 0 provides high specificity but poor sensitivity to identify obstructive CAD >=50% stenosis by invasive coronary angiography (ICA), as seen among patients with acute chest pain. In this regard, CACS might be a gatekeeper to predict obstructive CAD; however, CACS cannot reliably exclude obstructive CAD in subjects with acute chest pain seen in the emergency department.

What is the diagnostic accuracy of CCTA for obstructive CAD?

a. Native coronary arteries

Several previous studies have demonstrated the high diagnostic accuracy of CCTA with sensitivity (91%–99%) and specificity (74%–96%) in subjects without known CAD.
Importantly, CCTA can provide high NPV (97%–99%), to exclude obstructive CAD in symptomatic subjects without known CAD.

b. Stents

CCTA is limited for evaluation of coronary artery stents, given the numerous limitations of CT artifacts, such as motion, beam hardening, and partial volume effects.
Stent size is an important consideration for CCTA use. The ability to assess coronary stents is non-uniform across stents of different sizes. At present, current ACC Appropriate Use Criteria consider it appropriate to use CCTA for asymptomatic subjects who have undergone PCI with >= 3mm stent for evaluation of stent patency.

c. Bypass grafts

Since coronary artery bypass grafts (CABGs) are usually prone to motion artifact, are larger than native coronary arteries, and less frequently possess calcified plaque components, CCTA is a robust test for evaluation of CABG patency.
A recent meta-analysis reported a high diagnostic accuracy of CCTA for CABG patency [sensitivity 97.6%, specificity 96.7%, positive predictive value (PPV) 92.7%, and NPV 98.9%] using CT scanners of at least 16 detector rows.
At present, CCTA appears most useful for the exclusion of CAD in patients without prior known CAD, and also in those with known CAD for evaluation of large intracoronary stents and CABG.

Outcomes (applies only to therapeutic procedures)

What is the prognostic utility of CACS?

The presence and extent of CAC as determined by CACS has been established as a robust predictor of future major adverse cardiac events.
For asymptomatic subjects, several population-based studies have demonstrated the efficacy of CACS for future risk stratification to predict cardiac events.

What is the prognostic utility of CCTA?

The prognostic utility of CCTA-identified CAD has been proven robust by numerous previous studies. The international multicenter CONFIRM study demonstrated the incremental prognostic value of CCTA-identified CAD, with increasing risk identified for measures of nonobstructive or obstructive stenosis, with elevated risk of mortality for individuals with 1-, 2-, 3- vessel CAD.
Further risk stratification by CCTA can be observed when LVEF measured by CCTA is included.
Limited studies demonstrated that the plaque components or extent of plaque assessed by CCTA also may be of prognostic utility.
Significant coronary artery stenosis has been reported in 1%–7% of stable patients with CACS=0, suggesting that CACS may be inadequate to identify overall coronary plaque burden due to the presence of underlying non-calcified plaque components. In patients with CACS=0, patients with non-obstructive or obstructive coronary stenosis experience a higher adverse event rate than patients with no coronary plaque.

Alternative and/or additional procedures to consider

What is the correlation of CCTA to stress tests that identify ischemia?

Several prior studies have demonstrated the relation of anatomically obstructive CAD by CCTA to ischemia presence, as measured by myocardial perfusion SPECT or fractional flow reserve (FFR).
CAD stenosis severity >= 50% on CCTA identifies approximately 20%–50% of individuals with myocardial ischemia on SPECT. Given these results that suggest both reduced specificity and PPV, these findings may indicate a general overestimation of CAD stenosis severity by CCTA.
In this regard, both anatomical and functional assessments by CCTA may be required to more accurately identify individuals with obstructive CAD who have ischemia.

How can one identify the physiologic significance of CAD by CCTA?

Early studies have compared CT perfusion imaging by rest-stress scanning to myocardial perfusion SPECT and rest-stress cardiac magnetic resonance imaging, with promising results. Given the requirement of an additional scan– which will increase the radiation associated with CT — as well as the limited evidence to support its use, caution should be taken before performing CT perfusion.
Employing computational fluid dynamic methods, FFR has been demonstrated as feasible for determination by typically acquired CT scans. This FFR derived from CT (FFR_CT) may allow for assessment of epicardial lesion-specific ischemia, with an early multicenter study demonstrating generally sensitivity, specificity, PPV and NPV comparable to anatomic CAD stenosis alone by CCTA. Future studies will further substantiate the potential role of FFR_CT in clinical practice.

Complications and their management

What is the radiation dose associated with CACS? With CCTA?

Radiation should be considered in patients undergoing non-invasive diagnostic testing, including patients undergoing CACS and CCTA.
Typical radiation doses of CCTA are approximately 10 -15 mSv, which contrasts with the radiation dose of ICA (3 – 5 mSv), SPECT (18-30 mSv) and CACS (0.5 – 1.5 mSv). These doses can be referenced to the annual background radiation from environmental radon, which confers approximately 3 mSv annually.
Recent technological improvements have allowed for significant radiation dose reduction, with radiation doses reported as 1-2 mSv with modern CT scanners.
Optimal CT scan protocols should be performed at the minimum radiation exposure that provides diagnostic image quality.

What’s the evidence?

CACS: Agatston score

Agatston, AS, Jonawitz, WR, Hildner, FJ. “Quantification of coronary artery calcium using ultrafast computed tomography”. J Am Coll Cardiol. vol. 15. 1990. pp. 827-32.

Guidelines

Raff, GL, Abidov, A, Achenbach, S. “Society of Cardiovascular Computed Tomography. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography”. J Cardiovasc Comput Tomogr. vol. 3. 2009. pp. 122-36.

Abbara, S, Arbab-Zadeh, A, Celloster, TQ. “SCCT guidelines for performance of coronary computed tomographic angiography: A report of the Society of Cardiovascular Computed Tomography Guidelines Committee”. J Cardiovasc Comput Tomogr. vol. 3. 2009. pp. 190-204.

Mark, DB, Berman, DS, Budoff, MJ. “ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 expert consensus document on coronary computed tomographic angiography: A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents”. Circulation. vol. 121. 2010. pp. 2509-43.

Taylor, AJ, Cerqueira, M, Hodgson, JM. “American College of Cardiology Foundation Appropriate Use Criteria Task Force; Society of Cardiovascular Computed Tomography; American College of Radiology; American Heart Association; American Society for Cardiovascular Imaging; Society for Cardiovascular Angiography and Interventions; Society for Cardiovascular Magnetic Resonance. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiology, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance”. Circulation. vol. 122. 2010. pp. e525-55.

Meta-analysis and review articles

Carrabba, N, Shuijf, JD, de Graaf, FR. “Diagnostic accuracy of 64-slice computed tomography coronary angiography for the detection of in-stent restenosis: A meta-analysis”. J Nucl Cardiol. vol. 17. 2010. pp. 470-8.

Min, JK, Shaw, LJ, Berman, DS. “The present state of coronary computed tomography angiography a process in evolution”. J Am Coll Cardiol. vol. 55. 2010. pp. 957-65.

Diagnostic accuracy of CCS

Budoff, MJ, Jollis, JG, Doowe, D, Min, JK. “Diagnostic accuracy of coronary artery calcium for obstructive disease; Results from ACCURACY trial”. Int J Cardiol. vol. 166. 2013. pp. 505-8.

Prognostic utility of CACS

Budoff, MJ, Nasir, K, McClelland, RL. “Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis)”. J Am Coll Cardiol. vol. 53. 2009. pp. 345-52.

Blaha, MJ, Budoff, MJ, DeFilippis, AP. “Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study”. Lancet. vol. 378. 2011. pp. 684-92.

Diagnostic accuracy of CCTA

Budoff, MJ, Dowe, D, Jollis, JG. “Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: Results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial”. J Am Coll Cardiol. vol. 52. 2008. pp. 1724-32.

Meijboom, WB, Meijs, MF, Schuijf, JD. “Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study”. J Am Coll Cardiol. vol. 52. 2008. pp. 2135-44.

Multicenter prospective trials in subjects with acute chest pain and CCTA

Hoffmann, U, Bamberg, F, Chae, CU. “Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial”. J Am Coll Cardiol. vol. 53. 2009. pp. 1642-50.

Litt, HI, Gatsonis, C, Snyder, B. “CT angiography for safe discharge of patients with possible acute coronary syndromes”. N Engl J Med. vol. 15. 2012. pp. 1393-1403.

Prognostic utility of CCTA

Min, JK, Dunning, A, Lin, FY. “Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings. Results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 patients without known coronary artery disease”. J Am Coll Cardiol. vol. 58. 2011. pp. 849-60.

Villines, TC, Hulten, EA, Shaw, LJ. “Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: Results from the CONFIRM (Coronary CT angiography evaluation for clinical outcomes: an international multicenter registry)”. J Am Coll Cardiol. vol. 58. 2011. pp. 2533-40.

Min, JK, Shaw, LJ, Devereux, RB. “Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality”. J Am Coll Cardiol. vol. 50. 2007. pp. 1161-70.

Radiation issue

Hausleiter, J, Meyer, T, Hermann, F. “Estimated radiation dose associated with cardiac CT angiography”. JAMM. vol. 301. 2009. pp. 500-7.

Achenbach, S, Goroll, T, Seltmann, M. “Detection of coronary artery stenoses by low-dose, prospectively ECG-triggered, high-pitch spiral coronary CT angiography”. JACC Cardiovasc Imaging. vol. 4. 2011. pp. 328-37.

Functional assessment and CCTA

Blankstein, R, Shturman, LD, Rogers, IS. “Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography”. J Am Coll Cardiol. vol. 54. 2009. pp. 1072-84.

Meijboom, WB, Van Mieghem, CA, van Pelt, N. “Comprehensive assessment of coronary artery stenoses: Computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina”. J Am Coll Cardiol. vol. 52. 2008. pp. 636-43.

Koo, BK, Erglis, A, Doh, JH. “Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study”. J Am Coll Cardiol. vol. 58. 2011. pp. 1989-97.

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