Chest pain is often the herald of cardiovascular disease and is one of the most common diagnostic challenges encountered by practicing clinicians. Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, despite advances in medical and procedural therapies. Coronary artery disease (CAD) is an important subset of cardiovascular disease that requires timely, accurate, and cost-effective diagnosis. Patients can be classified into low, intermediate, and high pre-test probability of ischemic heart disease groups based on presenting symptoms, history, physical exam findings, ECG changes, and cardiac enzyme profiles. After acute coronary syndrome has been ruled out, the clinician has an abundance of diagnostic options to choose from when aiming to determine the presence of CAD and quantify its extent in these patients. Coronary computed tomographic angiography (CCTA) is an anatomic test that can be used in intermediate-risk patients to provide a diagnostician with these answers quickly.[1][2][3]

While invasive coronary angiography remains the gold standard in the diagnosis of coronary artery disease, CCTA has increasingly become a viable non-invasive alternative. CCTA avoids the risks associated with an invasive procedure, in addition to providing a more expeditious and possibly more cost-effective means of assessing patients at intermediate risk for CAD. Epicardial coronary arteries are moving structures that are typically millimeters in diameter. Because of this, CCTA requires both good spatial and temporal resolution to adequately visualize. Spatial resolution refers to the smallest distance across which two points can be differentiated. Temporal resolution refers to how quickly images of a moving structure can be acquired. Starting with the availability of 64-slice multi-detector CT (64-MDCT) systems, and now with even more modern technologies, CCTA has achieved the temporal and spatial resolution to be able to define the lumen of even distal segments of the coronary artery tree.

Studies assessing the diagnostic performance of CCTA have typically compared its ability to detect significant coronary lesions (blockage of greater than 50%) versus lesions discovered in those same patients on subsequent invasive coronary angiography. Initial studies of 64-MDCT showed a diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of 94%, 97%, 87%, and 99% respectively.  These initial studies typically excluded patients with atrial fibrillation, atrial premature contractions, ventricular premature contractions, prior history of CAD, and inability to tolerate beta-blockade. A study inclusive of these patients had 93% and 97% specificity and negative predictive value at assessing segmental coronary artery stenosis greater than 50%.

CCTA protocols typically involve an initial non-contrast, low-radiation dose phase. This non-contrast portion of the study can yield high-quality data about cardiac anatomical structures that may not be as adequately visualized with other non-invasive imaging modalities, e.g., trans-thoracic echocardiography or cardiac magnetic resonance imaging. This can be particularly useful in diagnosis and management of adult congenital heart disease (CHD). Simple CHD includes an atrial septal defect, patent foramen ovale, ventricular septal defect, and bicuspid aortic valve. Complex CHD can also be with reasonable accuracy, including Ebstein’s anomaly, truncus arteriosus, hypoplastic left heart syndrome, transposition of great arteries, Tetralogy of Fallot, tricuspid atresia. Specifically, with cases of complex CHD, many of these patients benefit from surgical repair and can survive to adulthood. Cardiac CT provides an accurate, timely, and cost-effective means of initial diagnosis and follow-up care in these patients.

Another utility of the non-contrast portion of a CCTA is the ability to calculate a coronary artery calcium (CAC) score. Also known as an Agatston score, a CAC score can be used to risk stratify patients into low, intermediate, and high-risk groups for future development of CAD. CAC scores were thought to be useful in identifying asymptomatic patients where more intensive preventative treatment regimens would be appropriate. Indeed, the most recent (2013) Multimodality Appropriate Use Criteria for the Detection of Stable Ischemic Heart Disease guidelines from the American College of Cardiology and American Heart Association (ACC/AHA) suggested that CAC scoring may be appropriate in select patients who are asymptomatic but at intermediate risk for CAD. However, CAC scoring alone is rarely appropriate in symptomatic patients. By the guidelines, CCTA may be the more appropriate diagnostic tool for symptomatic patients with an intermediate pre-test probability of coronary disease. CAC scores are commonly tabulated during the initial non-contrast phase of a CCTA by assigning a weighted density score to the location of calcium with the highest attenuation (measured in Hounsfield units) and then multiplying by the area of calcification. CAC scores of 0, 1 to 10, 11 to 100, 101 to 400, greater than 400 represent no, mild, moderate, and severe CAD, respectively. Patients with CAC scores of 0 or 1 to 10 have a very low lifetime risk of having an adverse cardiovascular event. However, studies have shown that patients with mild CAC scores of 1 to 10 are at threefold risk of developing CAD compared to patients with CAC scores of zero. These findings have to lead to an additional investigation into the roles of non-calcified coronary artery plaque, rapid atherosclerosis, and plaque destabilization in the development of coronary heart disease.  These additional plaque features are difficult to assess via CAC scoring alone.  This is particularly true in the case of non-calcified coronary artery plaques, which can range from non-obstructive to significantly stenotic.

CCTA can also be applied towards the diagnosis of coronary anomalies.  As with CAD, invasive coronary angiography has been the diagnostic gold standard.  However, with the available temporal and spatial resolution offered by modern CT scanners, CCTA has emerged as a viable non-invasive alternative means of surveying coronary anatomy.  Professional guidelines from the ACC/AHA released in 2008 listed CCTA as a class I indication for initial screening of adult patients with suspected congenital anomalous coronary arteries of ectopic origin.  Coronary anomalies are only present in less than 1% of the population, and their presentations can range from benign, incidental findings, to dramatic, as in the case of sudden cardiac death. Anomalous coronary arteries are classified into three general groups: anomalies of origin and course, intrinsic coronary anatomy anomalies, and artery termination anomalies. In addition to assessment of coronary anatomy, CCTA also allows three-dimensional assessment of the entire heart and spatial arrangements of anomalous coronaries, which can, in turn, provide prognostic information. Newer CCTA applications in the areas of perfusion and fractional flow reserve are on the horizon and are set to expand the diagnostic utility of cardiac CT. Additionally, transcatheter structural invasive procedures are now routinely performed, and these procedures are guided by noninvasive cardiac imaging specifically with CCTA pre-procedurally.[4][5][6][7]

Cardiac computed tomography (CT) is a radiographic test that allows visualization of the heart as a whole and individualized cardiac structures. Common structures of interest include atria, ventricles, pericardium, great cardiac vessels, myocardium, and intra-cardiac valves. CCTA is a contrast-enhanced radiographic assessment of the epicardial coronary arteries. Limited views of cardiac-adjacent pulmonary and osseous structures are also typically obtained in standard cardiac CT windows. Cardiac CT can also be applied in the diagnosis of cardiac anatomical abnormalities, such as CHD and anomalous coronary arteries.

CCTA is a generally accepted means of testing for the presence and severity of coronary artery stenosis. It is an anatomical test that can be used in patients presenting with chest pain who have an intermediate pre-test probability of having obstructive CAD. In these patients, it can be used in place of, or complementary to, functional tests. A CAC score can be obtained during the non-contrast phase of the CCTA, which may be appropriate per the most recent Multimodality Appropriate Use Criteria for the Detection of Stable Ischemic Heart Disease guidelines.  CCTA also maintains a strong recommendation from professional organizations for the diagnosis of a patient with suspected congenital anomalous coronary arteries.[8][9]

Contraindications for CCTA are similar to those encountered during any contrast-enhanced CT scan. Absolute contraindications are a patient history of severe or anaphylactic reaction to iodinated contrast, inability to cooperate with scan protocols, hemodynamic instability, decompensated heart failure, acute myocardial infarction, and renal impairment. Specific thresholds for the definition of renal impairment are deferred to individual performing institutions.  Relative contraindications include pregnancy, inability to tolerate heart-rate slowing medications or nitroglycerin, recent phosphodiesterase inhibitor use, severe aortic stenosis, bronchospastic disease, and patient’s weight and height.

The Society for Cardiovascular Computed Tomography (SCCT) has recommended that, at a minimum, a 64-slice CT scanner be used for CCTA. Dual-head power injection pumps should be utilized to take advantage of biphasic and triphasic injection protocols. Digital images should be stored in the Digital Imaging and Communications in Medicine (DICOM) format. A Picture Archiving and Communication System (PACS) should be available to allow review of the entire image set obtained during the scan.