With all the available therapies at our disposal in cardiology, improved diagnosis and prognosis of patients remains at the forefront of our interests when evaluating patients. Cardiac computed tomographic angiography (CTA) has been proposed as an accurate test that affords the ability to document nonobstructive disease (early atherosclerosis) and enables cardiologists to act earlier in the atherosclerotic process. Traditional work-ups, consisting of stress tests with or without imaging, allow identification of only the person with advanced stenosis, but cardiac CTA can identify both nonobstructive and obstructive coronary artery disease (CAD).

Coronary artery calcium (CAC) scoring has now been documented to accurately identify early atherosclerosis¹ and is embedded in the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 cholesterol and prevention guidelines as a method to determine atherosclerotic risk.^2,3 Risk stratification with CAC is more robust than C-reactive protein or other biomarkers⁴ and is a Class IIa recommendation in the 2010 ACC Foundation/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults.⁵ The 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk states that "(a)ssessing CAC is likely to be the most useful of the current approaches to improving risk assessment among individuals found to be at intermediate risk after formal risk assessment."² CAC has been shown to be the best predictor of future events in the general population,¹ the elderly,⁶ and in persons with diabetes.⁷ Visualizing CAC is associated with improvements in adherence to statin therapy.⁸ Thus, not only can CAC identify who would benefit from anti-atherosclerotic therapies, it can also help identify those who may not need treatment and improve compliance when patients are then instructed to take these therapies. However, even though CAC has been available for 25 years, it is only now being widely used by preventive doctors to identify those patients who may or may not benefit from interventions such as statins and aspirin. Moreover, insurance coverage is still not uniformly offered or applied.

Cardiac CTA is more widely covered by insurance in the United States because it provides a method to assess not only atherosclerosis (plaque burden) but also stenosis. Cardiac CTA has now been shown to be the most accurate method to determine who has obstructive or functionally significant stenosis, affording the highest probability of requiring intervention in the cardiac catheterization laboratory.⁹ Unfortunately, most patients who have undergone invasive coronary angiography after functional testing reveal no obstructive disease. In national registries, only 134,670 of 302,651(44.4%) patients who underwent invasive coronary angiography following nuclear stress tests had obstructive disease.⁹ In the PROMISE (PROspectiveMulticenter Imaging Study for Evaluation of chest pain) trial, 72.1% of patients undergoing invasive coronary angiography after cardiac CTA had obstructive disease, compared with only 47.5% of functional-test-group patients.¹⁰

In a prospective study of patients with stable chest pain, cardiac CTA was found to be more accurate than noninvasive functional testing for detecting significant CAD.¹¹ In this study, 475 patients with stable chest pain and intermediate likelihood of CAD underwent cardiac CTA and stress myocardial perfusion imaging. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30–70% stenosis with fractional flow reserve ≤0.8. Cardiac CTA had the highest diagnostic accuracy, with the area under the receiver operating characteristics curve being 0.91 (95% confidence interval [CI], 0.88–0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had significantly lower diagnostic accuracy (area under the curve: 0.74; CI: 0.69–0.78; sensitivity: 74%; specificity: 73%).

Although cardiac CTA demonstrates a significant improvement in identifying patients with obstructive disease, evaluating the prognostic differences between the testing strategies is of paramount importance. A meta-analysis identified 11 studies (n = 1575) comparing the diagnostic accuracy and 7 studies (n = 216,603) assessing the impact on outcomes of cardiac CTA versus exercise electrocardiography and/or single-photon emission computed tomography (SPECT).¹² The per-patient sensitivity (95% CI) to identify significant CAD was 98% (93–99%) for cardiac CTA versus 67% (54–78%) (p = 0.001) for exercise electrocardiography and 99% (96–100%) versus 73% (59–83%) (p < 0.001) for SPECT. The specificity (95% CI) of cardiac CTA was 82% (63–93%) versus 46% (30–64%) (p = 0.001) for exercise electrocardiography and 71% (60–80%) versus 48% (31–64%) for SPECT. The odds ratio of downstream test utilization for revascularization using cardiac CTA versus exercise electrocardiography and/or SPECT was 2.63 (2.50–2.77, p = 0.001). For nonfatal myocardial infarction (MI) the odds ratio was 0.53 (0.39–0.72, p = 0.001), and for all-cause mortality the odds ratio was 1.01 (0.87–1.18, p = 0.87). This 47% reduction in nonfatal MI using cardiac CTA was similar to the long-term outcomes of a recent prospective randomized study. In this study, 4146 outpatients referred for assessment of suspected angina due to coronary heart disease were randomized to either standard of care plus CTA or standard of care alone. After 1.7 years, the addition of CTA to standard care was associated with a 38% reduction in fatal and nonfatal MI (hazard ratio: 0.62, 95% CI: 0.38–1.01, p = 0.0527). At 3 years, MI was reduced by 50% in the CTA group (p = 0.015).¹³

In a prospective randomized study of cardiac CTA versus nuclear testing, the 2-year event rate for nonfatal MI and death was 1% (6 of 590) for CTA, 2.8% (16 of 565) for SPECT, and 6.6% (36 of 548) for positron emission tomography (p < 0.001).¹⁴ An observational study was performed in 4244 symptomatic patients (mean age 58 ± 9, 62.5% male) without known CAD who underwent CTA (n = 2538) to rule out CAD and were matched to 1706 patients who underwent standard of care in an academic cardiology clinic.¹⁵ During a mean follow-up of 80 ± 11 months, the mortality rate was significantly lower in the CTA group (n = 106, 4.2%) as compared with the control group (n = 184, 10.8%, p < 0.001). Event-free survival was 95.8% and 89.2% in CTA and standard of care groups, respectively. Multivariate analysis demonstrated that undergoing coronary CTA resulted in a risk reduction of 32% (p = 0.0001).

The largest study of stable heart disease patients was the PROMISE study.¹⁰ This study demonstrated a 34% lower event rate of MI and death in the multidetector computed tomography group compared with functional testing in the first year (hazard ratio: 0.66, p = 0.049). However, the difference lost statistical significance by the end of study, demonstrating no advantage of cardiac CTA over functional testing. The secondary endpoint demonstrated that cardiac CTA was associated with fewer catheterizations, showing significantly lower rates of nonobstructive CAD than functional testing (3.4% vs. 4.3%, p = 0.02).

Cardiac CT is very well established in the setting of the emergency department, where it has been shown in multiple studies to be superior to standard of care.¹⁶ Most recently, it has been compared to exercise stress testing and high-sensitivity troponins, saving health care dollars and facilitating discharges in both studies.^17,18

Cardiac CT, as a relatively new modality, continues to develop. Although the mean radiation doses continue to drop, resulting in significantly lower exposure compared with using nuclear testing,¹⁰ it still is a younger modality with less expertise. Thus, randomized trials in expert centers uniformly show prognostic advantages over functional testing while the PROMISE trial (a pragmatic study not requiring expertise in cardiac CTA) demonstrated no long-term differences in outcomes. Clinicians need to be trained, and expert centers will continue to outperform less-experienced operators in both diagnosis and prognosis. Although cardiac CTA has been included in the cardiology training algorithms for fellowship since 2006,¹⁹ not all cardiology training programs offer exposure to this modality. As clinicians continue to be exposed and trained in cardiac CTA, its utility will undoubtedly increase for the evaluation of stable ischemic heart disease, affording the fastest and most accurate noninvasive assessment of CAD available today.

References

1. Budoff MJ, Nasir K, McClelland RL, et al. Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Col Cardiol 2009;53:345-52.
2. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:S49-73.
3. Stone NJ, Robinson JG, 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 2014;63:2889-934.
4. Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 2012;308:788-95.
5. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2010;122:2748-2764.
6. Kavousi M, Elias-Smale S, Rutten JHW, et al. Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study. Ann Intern Med 2012;156:438-44.
7. Kiramijyan S, Ahmadi N, Isma'eel H, et al. Impact of coronary artery calcium progression and statin therapy on clinical outcome in subjects with and without diabetes mellitus. Am J Cardiol 2013;111:356-61.
8. Kalia NK, Cespedes L, Youssef G, et al. Motivational effects of coronary artery calcium scores on statin adherence and weight loss. Coron Artery Dis 2015;26:225-30.
9. Patel MR, Dai D, Hernandez AF, et al. Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J 2014;167:846-52.
10. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015;372:1291-1300.
11. Neglia D, Rovai D, Caselli C, et al. Detection of significant coronary artery disease by noninvasive anatomical and functional imaging. Circ Cardiovasc Imaging 2015;8:e002179.
12. Nielsen LH, Ortner N, Nørgaard BL, et al. The diagnostic accuracy and outcomes after coronary computed tomography angiography vs. conventional functional testing in patients with stable angina pectoris: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging 2014;15:961-71.
13. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet 2015:385;2383-91.
14. Budoff MJ, Li D. Coronary CT angiography again results in better patient outcomes. J Am Coll Cardiol 2014;64:741-2.
15. Budoff MJ, Liu S, Chow D, et al. Coronary CT angiography versus standard of care strategies to evaluate patients with potential coronary artery disease; effect on long term clinical outcomes. Atherosclerosis 2014;237:494-8.
16. Cury RC, Budoff M, Taylor AJ. J Coronary CT angiography versus standard of care for assessment of chest pain in the emergency department. J Cardiovasc Comput Tomogr 2013;7:79-82.
17. Hamilton-Craig C, Fifoot A, Hansen M, et al. Diagnostic performance and cost of CT angiography versus stress ECG—a randomized prospective study of suspected acute coronary syndrome chest pain in the emergency department (CT-COMPARE). Int J Cardiol 2014;177:867-73.
18. Dedic A, Lubbers MM, Schaap J, et al. Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study. J Am Coll Cardiol 2016;67:16-26.
19. Budoff MJ, Achenbach S, Fayad Z, et al. Task Force 12: training in advanced cardiovascular imaging (computed tomography): endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Atherosclerosis Imaging and Prevention, and Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 2006;47:915-20.

Keywords: Aged, Algorithms, Angina Pectoris, Aspirin, Atherosclerosis, Biomarkers, C-Reactive Protein, Calcium, Cardiac Catheterization, Chest Pain, Cholesterol, Constriction, Pathologic, Control Groups, Coronary Angiography, Coronary Artery Disease, Diabetes Mellitus, Electrocardiography, Emergency Service, Hospital, Exercise Test, Follow-Up Studies, Insurance Coverage, Multidetector Computed Tomography, Multivariate Analysis, Myocardial Infarction, Myocardial Perfusion Imaging, Positron-Emission Tomography, Prospective Studies, ROC Curve, Randomized Controlled Trials as Topic, Registries, Risk Assessment, Risk Factors, Risk Reduction Behavior, Standard of Care, Tomography, Emission-Computed, Single-Photon, Troponin, Angina, Stable

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