Int J Cardiovasc Imaging (2014) 30:1599–1601 DOI 10.1007/s10554-014-0495-8
COMMENTARY
Screening coronary CT angiography: possibilities and pitfalls Seung Min Yoo • Hwa Yeon Lee • Charles S. White
Received: 11 May 2014 / Accepted: 7 July 2014 / Published online: 16 July 2014 Ó Springer Science+Business Media Dordrecht 2014
Keywords Coronary artery calcium scoring Coronary CT angiography Coronary artery disease Screening Coronary artery calcium scoring (CACS) is a standard imaging tool to predict future cardiac events in asymptomatic subjects with intermediate Framingham risk score (FRS) due to its high accuracy for detecting coronary artery disease (CAD) [1]. In fact, the recently published 2013 guidelines of the AHA/ACC suggest an additional role for CACS in certain asymptomatic patients who are being considered for statin therapy but who are not included in four major statin benefit groups [2]. Notwithstanding these statements, it is undeniable that coronary CTA provides clearer anatomic definition of CAD than CACS and thus may have a role in screening for individuals at risk for CAD. The greatest advantage of coronary CTA over CACS is in visualization of the extent and type of coronary plaque. It has been estimated that CACS identifies only 20 % of total plaque volume that is present histologically [3]. Not only does coronary CTA visualize more of the total plaque amount, but it can provide superior information as to its location, whether the plaque is calcified, non-calcified or mixed, obstructive or non-obstructive and the status of vessel remodeling.
S. M. Yoo Department of Diagnostic Radiology, CHA University Bundang Medical Center, Sungnam, South Korea H. Y. Lee Smile Radiologic Clinic, Seoul, South Korea C. S. White (&) Department of Diagnostic Radiology, University of Maryland, 22S Greene Street, Baltimore, MD, USA e-mail: [email protected]
Coronary CTA may also provide an advantage over CACS in identifying potential precursor lesions of the acute coronary syndrome (ACS), so-called vulnerable plaque [4]. In a cohort of symptomatic patients, Motoyama et al. [4] reported that the CT features of vulnerable plaque include positive remodeling and low attenuation plaque (\30 HU). ACS events were reported in only 0.49 % of patients lacking these features. In contrast, patients with plaques showing positive remodeling and/or low attenuation plaque had a very high hazard ratio of 22.8 for developing ACS compared with those lacking such plaques [4]. A more recently reported coronary CTA finding associated with risk is the so-called ‘‘napkin-ring sign’’, defined as plaque with low-attenuation center surrounded by a rim of higher attenuation. In one study comprising symptomatic and asymptomatic patients, the napkin-ring sign was an independent predictor of ACS, although the sign had a limited sensitivity of 41 % [5]. However, whether any of these findings that are associated with symptomatic patients can be generalized to an asymptomatic screening population is an open question. In addition, coronary CTA has other intrinsic limitations. It cannot reliably discriminate thin-cap fibroatheroma, an important feature of vulnerable plaque from thick-cap fibroatheroma because of limitations of spatial resolution [6]. CT density of a non-calcified plaque may also be altered by different kV settings or the degree of intracoronary enhancement after the contrast injection [7]. Thus, it is difficult to reliably differentiate lipid core from fibrous plaque based on the CT density itself. Other practical limitations to the use of screening coronary CTA instead of CACS include potentially increased radiation exposure, intravenous contrast use, and the concern that it will lead to increased unnecessary downstream testing. However, the gap between coronary CTA and CACS in terms of radiation exposure has been closed due to substantial progress in applying radiation sparing techniques [8, 9]. Thus, radiation
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Int J Cardiovasc Imaging (2014) 30:1599–1601
exposure may not be a major obstacle to adopting coronary CTA as a screening tool in the near future [10]. Use of contrast media is associated with additional cost and potential harm, although the incidence of side-effects secondary to iodine load is low if patients are properly screened [11]. However, the amount of intravenous contrast media can also be reduced by use of lower kV settings (80 or 100 kV) that increase the intrinsic attenuation of iodine [12]. Finally, future applications of CT based fractional-flow reserve, CT perfusion imaging, and coronary contrast opacification gradients may reduce the need for further testing [13–15]. Although multiple observational studies [16–18] of screening coronary CTA have been published, literature directly comparing coronary CTA and CACS in asymptomatic patients is sparse. The recently published study by the CONFIRM investigators showed no incremental prognostic value for coronary CTA over CACS in asymptomatic patients (although there was a slight nonstatistically significant advantage for coronary CTA) [19]. However, generalization of this unfavorable result for coronary CTA to the entire asymptomatic population is limited by the fact that majority of the enrolled patients (48.2 %) had a low FRS, whereas coronary CTA may be more beneficial in patients with mid to high FRS. A separate study from the same registry demonstrated that screening coronary CTA has an incremental benefit in predicting adverse cardiovascular events beyond FRS and CACS in asymptomatic diabetics, a high FRS cohort [20]. In this study, approximately two-thirds and one-fourth of the enrolled patients had subclinical atherosclerosis and obstructive (C50 %) coronary stenosis on coronary CTA, respectively. Furthermore, about one-third of asymptomatic diabetic subjects with a zero calcium score had subclinical coronary atherosclerosis and approximately 10 % had obstructive coronary atherosclerosis. Although a zero calcium score in subjects with low-to-intermediate FRS often indicates an excellent prognosis, this suggests a potential additive effect of coronary CTA in at least one patient group with a zero calcium score [20]. Further high quality preferably randomized studies would be valuable to define populations where screening coronary CTA may be useful. At present, screening coronary CTA cannot be recommended. However, screening coronary CTA may replace or evolve into a complementary approach with CACS in certain populations if there is sufficient evidence of benefit with mitigation of potential harm. Conflict of interest
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None.
References 1. Greenland P, Alpert JS, Beller GA et al. (2010) American College of Cardiology Foundation; American Heart Association.
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2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 56(25):e50–103 Stone NJ, Robinson J, Lichtenstein AH, et al. (2013) ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Nov 7. doi: 10.1016/j.jacc.2013.11.002. [Epub ahead of print] Erbel R, Mo¨hlenkamp S, Kerkhoff G, Budde T, Schmermund A (2007) Non-invasive screening for coronary artery disease: calcium scoring. Heart 93(12):1620–1629 Motoyama S, Sarai M, Harigaya H et al (2009) Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 54:49–57 Otsuka K, Fukuda S, Tanaka A et al (2013) Napkin-ring sign on coronary CT angiography for the prediction of acute coronary syndrome. JACC Cardiovasc Imaging 6(4):448–457 Virmani R, Kolodgie FD, Burke AP et al (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20(5):1262–1275 Cademartiri F, Mollet NR, Runza G et al (2005) Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography. Eur Radiol 15:1426–1431 Mettler FA Jr, Huda W, Yoshizumi TT, Mahesh M (2008) Effective doses in radiology and diagnostic nuclear medicine: a catalog. Radiology 248(1):254–263 Schuhbaeck A, Achenbach S, Layritz C et al (2013) Image quality of ultra-low radiation exposure coronary CT angiography with an effective dose \ 0.1 mSv using high-pitch spiral acquisition and raw data-based iterative reconstruction. Eur Radiol 23(3):597–606 Kim HR, Yoo SM, Rho JY, Lee HY, White CS (2014) MDCT evaluation of atherosclerotic coronary artery disease: What should radiologists know? Int J Cardiovasc Imaging 30(Suppl 1):1–11 El-Hajjar M, Bashir I, Khan M, Min J, Torosoff M, DeLago A (2008) Incidence of contrast-induced nephropathy in patients with chronic renal insufficiency undergoing multidetector computed tomographic angiography treated with preventive measures. Am J Cardiol 102(3):353–356 Komatsu S, Kamata T, Imai A et al (2013) Coronary computed tomography angiography using ultra-low-dose contrast media: radiation dose and image quality. Int J Cardiovasc Imaging 29(6):1335–1340 Koo BK, Erglis A, Doh JH et al (2011) Diagnosis of ischemiacausing 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 58(19):1989–1997 Rochitte CE, George RT, Chen MY et al (2014) Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study. Eur Heart J 35(17):1120–1130 Steigner ML, Mitsouras D, Whitmore AG et al (2010) Iodinated contrast opacification gradients in normal coronary arteries imaged with prospectively ECG-gated single heart beat 320-detector row computed tomography. Circ Cardiovasc Imaging 3(2):179–186
Int J Cardiovasc Imaging (2014) 30:1599–1601 16. Choi EK, Choi SI, Rivera JJ et al (2008) Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol 52(5):357–365 17. Kim KJ, Choi SI, Lee MS, Kim JA, Chun EJ, Jeon CH (2013) The prevalence and characteristics of coronary atherosclerosis in asymptomatic subjects classified as low risk based on traditional risk stratification algorithm: assessment with coronary CT angiography. Heart 99(15):1113–1117 18. Rim JH, Lee HY, Yoo SM, Jung HY, White CS (2013) Carotid Doppler ultrasonography as a surrogate for coronary CT angiography to exclude subclinical coronary atherosclerosis in asymptomatic patients with a negative coronary calcium score. J Clin Ultrasound 41(3):164–170
1601 19. Cho I, Chang HJ, Sung JM et al (2012) Coronary computed tomographic angiography and risk of all-cause mortality and nonfatal myocardial infarction in subjects without chest pain syndrome from the CONFIRM Registry (coronary CT angiography evaluation for clinical outcomes: an international multicenter registry). Circulation 17 126(3):304–313 20. Min JK, Labounty TM, Gomez MJ et al (2014) Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals. Atherosclerosis 232(2):298–304
123
COMMENTARY
Screening coronary CT angiography: possibilities and pitfalls Seung Min Yoo • Hwa Yeon Lee • Charles S. White
Received: 11 May 2014 / Accepted: 7 July 2014 / Published online: 16 July 2014 Ó Springer Science+Business Media Dordrecht 2014
Keywords Coronary artery calcium scoring Coronary CT angiography Coronary artery disease Screening Coronary artery calcium scoring (CACS) is a standard imaging tool to predict future cardiac events in asymptomatic subjects with intermediate Framingham risk score (FRS) due to its high accuracy for detecting coronary artery disease (CAD) [1]. In fact, the recently published 2013 guidelines of the AHA/ACC suggest an additional role for CACS in certain asymptomatic patients who are being considered for statin therapy but who are not included in four major statin benefit groups [2]. Notwithstanding these statements, it is undeniable that coronary CTA provides clearer anatomic definition of CAD than CACS and thus may have a role in screening for individuals at risk for CAD. The greatest advantage of coronary CTA over CACS is in visualization of the extent and type of coronary plaque. It has been estimated that CACS identifies only 20 % of total plaque volume that is present histologically [3]. Not only does coronary CTA visualize more of the total plaque amount, but it can provide superior information as to its location, whether the plaque is calcified, non-calcified or mixed, obstructive or non-obstructive and the status of vessel remodeling.
S. M. Yoo Department of Diagnostic Radiology, CHA University Bundang Medical Center, Sungnam, South Korea H. Y. Lee Smile Radiologic Clinic, Seoul, South Korea C. S. White (&) Department of Diagnostic Radiology, University of Maryland, 22S Greene Street, Baltimore, MD, USA e-mail: [email protected]
Coronary CTA may also provide an advantage over CACS in identifying potential precursor lesions of the acute coronary syndrome (ACS), so-called vulnerable plaque [4]. In a cohort of symptomatic patients, Motoyama et al. [4] reported that the CT features of vulnerable plaque include positive remodeling and low attenuation plaque (\30 HU). ACS events were reported in only 0.49 % of patients lacking these features. In contrast, patients with plaques showing positive remodeling and/or low attenuation plaque had a very high hazard ratio of 22.8 for developing ACS compared with those lacking such plaques [4]. A more recently reported coronary CTA finding associated with risk is the so-called ‘‘napkin-ring sign’’, defined as plaque with low-attenuation center surrounded by a rim of higher attenuation. In one study comprising symptomatic and asymptomatic patients, the napkin-ring sign was an independent predictor of ACS, although the sign had a limited sensitivity of 41 % [5]. However, whether any of these findings that are associated with symptomatic patients can be generalized to an asymptomatic screening population is an open question. In addition, coronary CTA has other intrinsic limitations. It cannot reliably discriminate thin-cap fibroatheroma, an important feature of vulnerable plaque from thick-cap fibroatheroma because of limitations of spatial resolution [6]. CT density of a non-calcified plaque may also be altered by different kV settings or the degree of intracoronary enhancement after the contrast injection [7]. Thus, it is difficult to reliably differentiate lipid core from fibrous plaque based on the CT density itself. Other practical limitations to the use of screening coronary CTA instead of CACS include potentially increased radiation exposure, intravenous contrast use, and the concern that it will lead to increased unnecessary downstream testing. However, the gap between coronary CTA and CACS in terms of radiation exposure has been closed due to substantial progress in applying radiation sparing techniques [8, 9]. Thus, radiation
123
1600
Int J Cardiovasc Imaging (2014) 30:1599–1601
exposure may not be a major obstacle to adopting coronary CTA as a screening tool in the near future [10]. Use of contrast media is associated with additional cost and potential harm, although the incidence of side-effects secondary to iodine load is low if patients are properly screened [11]. However, the amount of intravenous contrast media can also be reduced by use of lower kV settings (80 or 100 kV) that increase the intrinsic attenuation of iodine [12]. Finally, future applications of CT based fractional-flow reserve, CT perfusion imaging, and coronary contrast opacification gradients may reduce the need for further testing [13–15]. Although multiple observational studies [16–18] of screening coronary CTA have been published, literature directly comparing coronary CTA and CACS in asymptomatic patients is sparse. The recently published study by the CONFIRM investigators showed no incremental prognostic value for coronary CTA over CACS in asymptomatic patients (although there was a slight nonstatistically significant advantage for coronary CTA) [19]. However, generalization of this unfavorable result for coronary CTA to the entire asymptomatic population is limited by the fact that majority of the enrolled patients (48.2 %) had a low FRS, whereas coronary CTA may be more beneficial in patients with mid to high FRS. A separate study from the same registry demonstrated that screening coronary CTA has an incremental benefit in predicting adverse cardiovascular events beyond FRS and CACS in asymptomatic diabetics, a high FRS cohort [20]. In this study, approximately two-thirds and one-fourth of the enrolled patients had subclinical atherosclerosis and obstructive (C50 %) coronary stenosis on coronary CTA, respectively. Furthermore, about one-third of asymptomatic diabetic subjects with a zero calcium score had subclinical coronary atherosclerosis and approximately 10 % had obstructive coronary atherosclerosis. Although a zero calcium score in subjects with low-to-intermediate FRS often indicates an excellent prognosis, this suggests a potential additive effect of coronary CTA in at least one patient group with a zero calcium score [20]. Further high quality preferably randomized studies would be valuable to define populations where screening coronary CTA may be useful. At present, screening coronary CTA cannot be recommended. However, screening coronary CTA may replace or evolve into a complementary approach with CACS in certain populations if there is sufficient evidence of benefit with mitigation of potential harm. Conflict of interest
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
None.
References 1. Greenland P, Alpert JS, Beller GA et al. (2010) American College of Cardiology Foundation; American Heart Association.
123
2.
15.
2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 56(25):e50–103 Stone NJ, Robinson J, Lichtenstein AH, et al. (2013) ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Nov 7. doi: 10.1016/j.jacc.2013.11.002. [Epub ahead of print] Erbel R, Mo¨hlenkamp S, Kerkhoff G, Budde T, Schmermund A (2007) Non-invasive screening for coronary artery disease: calcium scoring. Heart 93(12):1620–1629 Motoyama S, Sarai M, Harigaya H et al (2009) Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 54:49–57 Otsuka K, Fukuda S, Tanaka A et al (2013) Napkin-ring sign on coronary CT angiography for the prediction of acute coronary syndrome. JACC Cardiovasc Imaging 6(4):448–457 Virmani R, Kolodgie FD, Burke AP et al (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20(5):1262–1275 Cademartiri F, Mollet NR, Runza G et al (2005) Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography. Eur Radiol 15:1426–1431 Mettler FA Jr, Huda W, Yoshizumi TT, Mahesh M (2008) Effective doses in radiology and diagnostic nuclear medicine: a catalog. Radiology 248(1):254–263 Schuhbaeck A, Achenbach S, Layritz C et al (2013) Image quality of ultra-low radiation exposure coronary CT angiography with an effective dose \ 0.1 mSv using high-pitch spiral acquisition and raw data-based iterative reconstruction. Eur Radiol 23(3):597–606 Kim HR, Yoo SM, Rho JY, Lee HY, White CS (2014) MDCT evaluation of atherosclerotic coronary artery disease: What should radiologists know? Int J Cardiovasc Imaging 30(Suppl 1):1–11 El-Hajjar M, Bashir I, Khan M, Min J, Torosoff M, DeLago A (2008) Incidence of contrast-induced nephropathy in patients with chronic renal insufficiency undergoing multidetector computed tomographic angiography treated with preventive measures. Am J Cardiol 102(3):353–356 Komatsu S, Kamata T, Imai A et al (2013) Coronary computed tomography angiography using ultra-low-dose contrast media: radiation dose and image quality. Int J Cardiovasc Imaging 29(6):1335–1340 Koo BK, Erglis A, Doh JH et al (2011) Diagnosis of ischemiacausing 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 58(19):1989–1997 Rochitte CE, George RT, Chen MY et al (2014) Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study. Eur Heart J 35(17):1120–1130 Steigner ML, Mitsouras D, Whitmore AG et al (2010) Iodinated contrast opacification gradients in normal coronary arteries imaged with prospectively ECG-gated single heart beat 320-detector row computed tomography. Circ Cardiovasc Imaging 3(2):179–186
Int J Cardiovasc Imaging (2014) 30:1599–1601 16. Choi EK, Choi SI, Rivera JJ et al (2008) Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol 52(5):357–365 17. Kim KJ, Choi SI, Lee MS, Kim JA, Chun EJ, Jeon CH (2013) The prevalence and characteristics of coronary atherosclerosis in asymptomatic subjects classified as low risk based on traditional risk stratification algorithm: assessment with coronary CT angiography. Heart 99(15):1113–1117 18. Rim JH, Lee HY, Yoo SM, Jung HY, White CS (2013) Carotid Doppler ultrasonography as a surrogate for coronary CT angiography to exclude subclinical coronary atherosclerosis in asymptomatic patients with a negative coronary calcium score. J Clin Ultrasound 41(3):164–170
1601 19. Cho I, Chang HJ, Sung JM et al (2012) Coronary computed tomographic angiography and risk of all-cause mortality and nonfatal myocardial infarction in subjects without chest pain syndrome from the CONFIRM Registry (coronary CT angiography evaluation for clinical outcomes: an international multicenter registry). Circulation 17 126(3):304–313 20. Min JK, Labounty TM, Gomez MJ et al (2014) Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals. Atherosclerosis 232(2):298–304
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