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Bridging the Detection Gap Chasm of Risk: Where Can Computed Tomography Angiography Take Us?
JACC: CARDIOVASCULAR IMAGING © 2009 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
VOL. 2, NO. 4, 2009 ISSN 1936-878X/09/$36.00 DOI:10.1016/j.jcmg.2009.02.003
EDITOR’S PAGE
Bridging the Detection Gap Chasm of Risk: Where Can Computed Tomography Angiography Take Us? Leslie Shaw, PHD,* Jagat Narula, MD, PHD†
n this issue of iJACC, a large validation series of the prognostic value of significant coronary artery disease (CAD) by cardiac computed tomographic angiography (CTA) is published (1). This new report adds to our understanding of the prognostic accuracy of CTA measurements of obstructive CAD for risk stratification purposes by including a large consecutive series of 1,667 patients. Placing this data within the context of existing CTA data, we observe improved precision in risk stratification and an obvious separation in events between patients with none-mild CAD compared to those with obstructive CAD. The summary meta-analytic rate for obstructive CAD is more than 10-fold higher than that of patients with none-mild CAD. When comparing risk stratification with CTA to that of other imaging modalities, interesting patterns illumine a direction for future developments for this modality (Fig. 1) (2–10). The summary meta-analytic rate for obstructive CAD is higher (11.1%, 5.1% to 22.5%) than for that of significant perfusion (6.2%, 5.9% to 6.5%) or inducible wall motion (7.5%, 5% to 13.4%) abnormalities; highlighting the importance of the burden of CAD as the prominent driver for influencing the hazard for cardiovascular events. For CTA, more extensive, severe, and proximal location of obstructive CAD defines higher CAD event rates (11,12). The totality of interaction of obstructive CAD with ischemia as a modulator of risk is unclear. Further the degree to which overlap exists between extensive CAD and severe
I
From *Emory University, Atlanta, Georgia; and the †University of California-Irvine, Irvine, California.
ischemia is also unclear but remains an important goal for future developments in risk stratification, which will also focus on the interplay between nonischemic CAD to ischemic mild to severe CAD. CTA has tremendous potential due to its ability to define not only obstructive CAD but to examine the burden of nonobstructive atherosclerosis. By examining the current evidence, the summary CAD event rate for CTA-verified none-mild CAD (1.5%, 0.9% to 2.6%) is decidedly higher when compared to that of no perfusion abnormalities (0.6%). The higher event rate with no obstructive CAD on CTA indicates a threshold of risk for significant stenosis (. . .or more extensive atherosclerotic disease) that is higher than that for nonobstructive CAD. This threshold needs to be addressed to define the importance/characteristics of nonobstructive atherosclerosis. An example of this is the very low event rate in individuals with a zero coronary artery calcium score (13,14). A gradient of cardiovascular event risk occurs directly proportional to the extent of calcification (13,14). The lack of correlation between obstructive CAD and coronary calcium, yet its important risk stratification ability, identifies the significant risk burden of nonobstructive atherosclerosis. To that end, one can envision even lower event rates for CTA nonobstructive CAD declining from mild coronary lesions, on the high end of this 1.5% event rate, to a very low-risk for those with no plaque, more closely approximating population norms for risk. Similar to the role of obstructive CAD in defining higher risk status, the characteristics of a nonobstructive plaque should modulate the
Shaw and Narula Editor’s Page
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 4, 2009 APRIL 2009:524 – 6
1-Year Event Rates Study name
N
p value
Pundziute
100
0.01
Min
1,127
<0.001
Gilard
141
<0.001
Gaemperli
220
<0.001
Matsumoto
810
<0.001
Ostrum
2,538
<0.001
Hadamitzky Summary For CTA
1,667
<0.001
6,603
<0.001
Negative Test Results
4.0%
8.0%
No Obstructive CAD 71,463
0.0%
4.0%
8.0%
Normal Perfusion
0.0%
4.0%
8.0%
Normal Wall Motion
50.0%
6.2% (5.9-6.5%)
0.0%
25.0%
50.0%
Abnormal Perfusion
1.0% (0.9-1.2%)
<0.0001
25.0%
Obstructive CAD
0.6% (0.5-0.7%)
<0.0001 0.0%
Echocardiography 17,078 Meta-Analysis
11.1% (5.1-22.5%)
1.5% (0.9-2.6%)
0.0%
SPECT / PET Meta-Analysis
Positive Test Results
7.5% (5.0-13.4%)
0.0%
25.0% 50.0% Abnormal Wall Motion
Figure 1. Meta-Analyses of the 1-Year Event Rates One-year event rates (95% confidence intervals) are presented for no obstructive and obstructive coronary artery disease (CAD) by coronary computed tomography angiography (CTA), and for normal and abnormal stress myocardial perfusion single-photon emission computed tomography (SPECT) and positron emission tomography (PET); data are compiled for SPECT (2), for PET (3,4), and for echocardiography (9,10). The event rates are calculated using a random effects model with significant heterogeneity noted for no obstructive and obstructive CAD (p ⬍ 0.0001). Event types are varied by study including death, myocardial infarction, unstable angina, and/or revascularization.
risk spectrum. We have yet to clearly define the graded change in risk with nonobstructive atherosclerosis that occurs below the obstructive CAD threshold. Additionally, within the nonobstructive atherosclerotic disease subsets, features of high-risk plaque may proffer a substantial risk for downstream acute coronary syndromes (ACS). Preliminary evidence suggests that certain plaque characteristics may be definable with CTA and provide an important link to ACS risk including sudden death (15). Novel gains in risk detection may be realized within nonobstructive atherosclerotic disease subsets to define unique subsets whose risk is equivalent to those with obstructive CAD. The defining of CAD risk equivalent status patients, may blur the prominence of symptoms, obstructive disease or perfusion deficit as signifying risk, but identify risk gradation that occurs across the spectrum of nonobstructive and ob-
structive CAD. Thus, future developments in the field of CTA should focus on improving the granularity of lower and higher risk status including modulation of ischemic risk. A better understanding of the role of CTA in risk detection is fundamental to integrating this modality into every day clinical decision making. Our mandate for the future of cardiac imaging is now to devise strategies to improve the current detection gap that afflicts millions of patients annually in this country and worldwide.
Address for Correspondence:
Jagat Narula, MD, PhD Editor-in-Chief, JACC: Cardiovascular Imaging 3655 Nobel Drive, Suite 630 San Diego, California 92112 E-mail: [email protected]
525
526
Shaw and Narula Editor’s Page
REFERENCES
1. Hadamitzky M, Freißmuth B, Meyer T, et al. Prognostic value of 64-slice coronary computed tomographic angiography for prediction of cardiac events in patients with suspected coronary artery disease. J Am Coll Cardiol Img 2009;2:404 –12. 2. Shaw LJ, Iskandrian AE. Prognostic value of stress gated SPECT in patients with known or suspected coronary artery disease. J Nucl Cardiol 2004;11:171– 85. 3. Lertsburapa K, Ahlberg AW, Bateman TM, et al. Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease. J Nucl Cardiol 2008;15:745–53. 4. Yoshinaga K, Chow BJ, Williams K, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol 2006; 48:1029 –39. 5. Gilard M, Le Gal G, Cornily JC, et al. Midterm prognosis of patients with suspected coronary artery disease and normal multislice computed tomographic findings: a prospective man-
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 4, 2009 APRIL 2009:524 – 6
agement outcome study. Arch Intern Med 2007;167:1686 –9. 6. Gaemperli O, Valenta I, Schepis T, et al. Coronary 64-slice CT angiography predicts outcome in patients with known or suspected coronary artery disease. Eur Radiol 2008;18:1162–73. 7. Matsumoto N, Sato Y, Yoda S, et al. Prognostic value of non-obstructive CT low-dense coronary artery plaques detected by multislice computed tomography. Circ J 2007;71:1898 –903. 8. Pundziute G, Schuijf JD, Jukema JW, et al. Prognostic value of multislice computed tomography coronary angiography in patients with known or suspected coronary artery disease. J Am Coll Cardiol 2007;49:62–70. 9. Shaw LJ, Marwick TH, Berman DS, et al. Incremental cost effectiveness of exercise echocardiography versus SPECT imaging for the evaluation of stable chest pain. Eur Heart J 2006; 27:2448 –58. 10. Metz LD, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a metaanalysis. J Am Coll Cardiol 2007;49: 227–37. 11. Min JK, Shaw LJ, Devereux RB, et al. Prognostic value of multidetector coronary computed tomographic angiogra-
phy for prediction of all-cause mortality. J Am Coll Cardiol 2007;50:1161–70. 12. Ostrom MP, Gopal A, Ahmadi N, et al. Mortality incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol 2008;52: 1335– 43. 13. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography 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. 14. 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; 358:1336 – 45. 15. Motoyama S, Kondo T, Sarai M, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007;50:319 –26.
VOL. 2, NO. 4, 2009 ISSN 1936-878X/09/$36.00 DOI:10.1016/j.jcmg.2009.02.003
EDITOR’S PAGE
Bridging the Detection Gap Chasm of Risk: Where Can Computed Tomography Angiography Take Us? Leslie Shaw, PHD,* Jagat Narula, MD, PHD†
n this issue of iJACC, a large validation series of the prognostic value of significant coronary artery disease (CAD) by cardiac computed tomographic angiography (CTA) is published (1). This new report adds to our understanding of the prognostic accuracy of CTA measurements of obstructive CAD for risk stratification purposes by including a large consecutive series of 1,667 patients. Placing this data within the context of existing CTA data, we observe improved precision in risk stratification and an obvious separation in events between patients with none-mild CAD compared to those with obstructive CAD. The summary meta-analytic rate for obstructive CAD is more than 10-fold higher than that of patients with none-mild CAD. When comparing risk stratification with CTA to that of other imaging modalities, interesting patterns illumine a direction for future developments for this modality (Fig. 1) (2–10). The summary meta-analytic rate for obstructive CAD is higher (11.1%, 5.1% to 22.5%) than for that of significant perfusion (6.2%, 5.9% to 6.5%) or inducible wall motion (7.5%, 5% to 13.4%) abnormalities; highlighting the importance of the burden of CAD as the prominent driver for influencing the hazard for cardiovascular events. For CTA, more extensive, severe, and proximal location of obstructive CAD defines higher CAD event rates (11,12). The totality of interaction of obstructive CAD with ischemia as a modulator of risk is unclear. Further the degree to which overlap exists between extensive CAD and severe
I
From *Emory University, Atlanta, Georgia; and the †University of California-Irvine, Irvine, California.
ischemia is also unclear but remains an important goal for future developments in risk stratification, which will also focus on the interplay between nonischemic CAD to ischemic mild to severe CAD. CTA has tremendous potential due to its ability to define not only obstructive CAD but to examine the burden of nonobstructive atherosclerosis. By examining the current evidence, the summary CAD event rate for CTA-verified none-mild CAD (1.5%, 0.9% to 2.6%) is decidedly higher when compared to that of no perfusion abnormalities (0.6%). The higher event rate with no obstructive CAD on CTA indicates a threshold of risk for significant stenosis (. . .or more extensive atherosclerotic disease) that is higher than that for nonobstructive CAD. This threshold needs to be addressed to define the importance/characteristics of nonobstructive atherosclerosis. An example of this is the very low event rate in individuals with a zero coronary artery calcium score (13,14). A gradient of cardiovascular event risk occurs directly proportional to the extent of calcification (13,14). The lack of correlation between obstructive CAD and coronary calcium, yet its important risk stratification ability, identifies the significant risk burden of nonobstructive atherosclerosis. To that end, one can envision even lower event rates for CTA nonobstructive CAD declining from mild coronary lesions, on the high end of this 1.5% event rate, to a very low-risk for those with no plaque, more closely approximating population norms for risk. Similar to the role of obstructive CAD in defining higher risk status, the characteristics of a nonobstructive plaque should modulate the
Shaw and Narula Editor’s Page
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 4, 2009 APRIL 2009:524 – 6
1-Year Event Rates Study name
N
p value
Pundziute
100
0.01
Min
1,127
<0.001
Gilard
141
<0.001
Gaemperli
220
<0.001
Matsumoto
810
<0.001
Ostrum
2,538
<0.001
Hadamitzky Summary For CTA
1,667
<0.001
6,603
<0.001
Negative Test Results
4.0%
8.0%
No Obstructive CAD 71,463
0.0%
4.0%
8.0%
Normal Perfusion
0.0%
4.0%
8.0%
Normal Wall Motion
50.0%
6.2% (5.9-6.5%)
0.0%
25.0%
50.0%
Abnormal Perfusion
1.0% (0.9-1.2%)
<0.0001
25.0%
Obstructive CAD
0.6% (0.5-0.7%)
<0.0001 0.0%
Echocardiography 17,078 Meta-Analysis
11.1% (5.1-22.5%)
1.5% (0.9-2.6%)
0.0%
SPECT / PET Meta-Analysis
Positive Test Results
7.5% (5.0-13.4%)
0.0%
25.0% 50.0% Abnormal Wall Motion
Figure 1. Meta-Analyses of the 1-Year Event Rates One-year event rates (95% confidence intervals) are presented for no obstructive and obstructive coronary artery disease (CAD) by coronary computed tomography angiography (CTA), and for normal and abnormal stress myocardial perfusion single-photon emission computed tomography (SPECT) and positron emission tomography (PET); data are compiled for SPECT (2), for PET (3,4), and for echocardiography (9,10). The event rates are calculated using a random effects model with significant heterogeneity noted for no obstructive and obstructive CAD (p ⬍ 0.0001). Event types are varied by study including death, myocardial infarction, unstable angina, and/or revascularization.
risk spectrum. We have yet to clearly define the graded change in risk with nonobstructive atherosclerosis that occurs below the obstructive CAD threshold. Additionally, within the nonobstructive atherosclerotic disease subsets, features of high-risk plaque may proffer a substantial risk for downstream acute coronary syndromes (ACS). Preliminary evidence suggests that certain plaque characteristics may be definable with CTA and provide an important link to ACS risk including sudden death (15). Novel gains in risk detection may be realized within nonobstructive atherosclerotic disease subsets to define unique subsets whose risk is equivalent to those with obstructive CAD. The defining of CAD risk equivalent status patients, may blur the prominence of symptoms, obstructive disease or perfusion deficit as signifying risk, but identify risk gradation that occurs across the spectrum of nonobstructive and ob-
structive CAD. Thus, future developments in the field of CTA should focus on improving the granularity of lower and higher risk status including modulation of ischemic risk. A better understanding of the role of CTA in risk detection is fundamental to integrating this modality into every day clinical decision making. Our mandate for the future of cardiac imaging is now to devise strategies to improve the current detection gap that afflicts millions of patients annually in this country and worldwide.
Address for Correspondence:
Jagat Narula, MD, PhD Editor-in-Chief, JACC: Cardiovascular Imaging 3655 Nobel Drive, Suite 630 San Diego, California 92112 E-mail: [email protected]
525
526
Shaw and Narula Editor’s Page
REFERENCES
1. Hadamitzky M, Freißmuth B, Meyer T, et al. Prognostic value of 64-slice coronary computed tomographic angiography for prediction of cardiac events in patients with suspected coronary artery disease. J Am Coll Cardiol Img 2009;2:404 –12. 2. Shaw LJ, Iskandrian AE. Prognostic value of stress gated SPECT in patients with known or suspected coronary artery disease. J Nucl Cardiol 2004;11:171– 85. 3. Lertsburapa K, Ahlberg AW, Bateman TM, et al. Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease. J Nucl Cardiol 2008;15:745–53. 4. Yoshinaga K, Chow BJ, Williams K, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol 2006; 48:1029 –39. 5. Gilard M, Le Gal G, Cornily JC, et al. Midterm prognosis of patients with suspected coronary artery disease and normal multislice computed tomographic findings: a prospective man-
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 4, 2009 APRIL 2009:524 – 6
agement outcome study. Arch Intern Med 2007;167:1686 –9. 6. Gaemperli O, Valenta I, Schepis T, et al. Coronary 64-slice CT angiography predicts outcome in patients with known or suspected coronary artery disease. Eur Radiol 2008;18:1162–73. 7. Matsumoto N, Sato Y, Yoda S, et al. Prognostic value of non-obstructive CT low-dense coronary artery plaques detected by multislice computed tomography. Circ J 2007;71:1898 –903. 8. Pundziute G, Schuijf JD, Jukema JW, et al. Prognostic value of multislice computed tomography coronary angiography in patients with known or suspected coronary artery disease. J Am Coll Cardiol 2007;49:62–70. 9. Shaw LJ, Marwick TH, Berman DS, et al. Incremental cost effectiveness of exercise echocardiography versus SPECT imaging for the evaluation of stable chest pain. Eur Heart J 2006; 27:2448 –58. 10. Metz LD, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a metaanalysis. J Am Coll Cardiol 2007;49: 227–37. 11. Min JK, Shaw LJ, Devereux RB, et al. Prognostic value of multidetector coronary computed tomographic angiogra-
phy for prediction of all-cause mortality. J Am Coll Cardiol 2007;50:1161–70. 12. Ostrom MP, Gopal A, Ahmadi N, et al. Mortality incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol 2008;52: 1335– 43. 13. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography 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. 14. 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; 358:1336 – 45. 15. Motoyama S, Kondo T, Sarai M, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007;50:319 –26.