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.
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.
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.
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.
The SCCT has recommended that CCTAs be performed by technologists adequately trained to perform cardiac CTs, CCTAs, and use of contrast injection devices. One member of the team should be proficient in the insertion of peripheral intravenous (IV) catheters. During image acquisition, a team-member certified in advanced cardiac life support should also be available. Finally a team member, typically, a physician or physician assistant, trained in the administration of beta-blockers and nitroglycerin should also be present during the scan. The interpreting physician should be trained in CCTA according to the respective ACC/AHA Clinical Competence Statement.
The decision to proceed with a CCTA should only be made if the results will affect a patient’s clinical management or prognosis and if there is a reasonable expectation of being able to obtain interpretable images. Review of any possible contraindications should also be performed with subsequent evaluations of the risks versus benefits.
Informed consent should be obtained before the start of the CCTA. The patient should have nothing to eat for 4 hours before the exam and no caffeine for 12 hours before the test. Preferentially, intravenous (IV) access should be obtained in the right antecubital vein with an 18-gauge catheter. This minimizes streak artifact during image acquisition and also allows for the rapid infusion of contrast. Hand veins should be avoided, as this typically requires a 20-gauge or smaller catheter, which can result in slower flow rates. Central lines should not be used unless rated for power injection.
The ideal heart-rate for CCTA image acquisition is typically 60 beats-per-minute or less. An oral beta-blocker is typically administered 1 hour before the test, and this can be supplemented with intravenous beta-blocker administration at the time of the test. Oral metoprolol tartrate 50 mg to 100 mg is typically used as a pre-medication. Alternatives can include oral atenolol, IV esmolol, calcium-channel blockers, and ivabradine.
Nitrates vasodilate coronary arteries and when given 5 minutes before CCTA image acquisition improves visualization of coronary arteries and stenoses. Typically 400 to 800 micrograms of sub-lingual nitroglycerin are used for this effect.
Intra-arterial opacification of approximately 250 Hounsfield units is typically required for diagnostic CCTAs. An injection rate of 5 cc to 7 cc per second is sufficient for most adults to achieve this level, often using a total of 50 cc to 120 cc of iodinated contrast.
Biphasic injection protocols involve the injection of contrast followed by saline. This technique minimizes streak artifact from high concentrations of contrast on the right side of the heart. If images of right-heart structures are also desired, triphasic injection protocols can be used where contrast, contrast-saline, and saline are injected sequentially.
Several techniques can be employed to reduce patient radiation exposure during CCTA while maintaining diagnostic accuracy. Setting a scan range limits radiation exposure to only the structures being examined. In the case of CCTA, the scan range is typically the inferior aspect of the tracheal bifurcation to the lower cardiac border. Tube potential relates to the energy of the x-ray beam used during the CT scan. Typical adult CCTA protocols will use 100 kV to 120 kV. Higher tube potentials result in enhanced tissue penetration and reduced image noise, as the cost of significantly increased radiation exposure. Tube currently relates to the number of photons per unit of time. Increasing tube current can also reduce image noise, which may be necessary for larger patients, but also results in increased radiation exposure. Anatomy-based tube current modulation techniques can selectively adjust tube current when the x-ray beam is directed through less dense tissue, such as lungs, reducing radiation exposure. ECG based tube current modulation uses ECG triggers to reduce tube current during phases of the cardiac cycle where cardiac motion is most prominent, typically early and mid-systole. During these phases motion artifacts are more common, reducing the CCTA’s diagnostic sensitivity.
Newer data acquisition techniques attempt to minimize patient exposure to ionizing radiation while preserving diagnostic accuracy. Prospective ECG triggered acquisition is preferred in patients with controlled heart rates. Using the patient’s ECG, the x-ray tube is only activated during mid-diastole. At sub-optimal heart rates, end-systole can also be used. This results in significant patient radiation exposure reduction at the cost of also reducing the available diagnostic data set. In patients with irregular heart rhythms or high heart rates, retrospective ECG gating can be used. In this technique, data are obtained during the entire cardiac cycle, but images are only generated from pre-determined portions of the cardiac cycle.
Scan protocols for CCTA are fairly standardized. The first image obtained is typically an anterior-posterior scout image that allows determination of the scan range. The next stage involves non-contrast enhanced image acquisition for determination of a CAC. Finally, if the patient’s heart rate is adequately controlled, contrast-enhanced images are obtained using a prospective ECG-gated method, where possible.
CCTA testing centers should be equipped and staffed to manage the rare complication of an anaphylactic response to any of the agents administered during testing. Where specific contrast allergies are noted, standard oral steroid and diphenhydramine pre-test treatments should be prescribed.
CT scans utilize x-rays, which is a type of ionizing radiation that can damage cells on a molecular level. The potential for harm from radiation exposure is cumulative over a patient’s lifetime. Thus, children and young adults are, particularly at risk. Organs with high cellular turnover are also at increased risk for genetic damage from ionizing radiation exposure. Radiation exposure during CCTA should be kept to as low as reasonably achievable to obtain diagnostic results.
CCTA provides another tool in the diagnostician’s armamentarium to discover and manage cardiovascular disease. As a diagnostic modality, CCTA avoids the risks associated with invasive coronary angiography, while also providing a cost-effective, timely, and accurate means of quantifying CAD. Non-contrast portions of the CCTA study can also yield prognostic information, while post-processing techniques such as three-dimensional volumetric formatting can provide insight into the cardiac anatomy. Risks of CCTA include radiation and contrast exposure, but continued refinements of CT technology will likely mitigate these shortcomings in future.