CHAPTER 17: COMPUTED TOMOGRAPHY OF THE HEART

Computed tomography (CT) is a technique that can fully evaluate both cardiac structure and function. Recent advances in imaging allow for evaluation of not only relatively stationary anatomy, such as the thoracic aorta, but also rapidly moving structures, such as the myocardium and coronary arteries. This imparts the ability to noninvasively evaluate for significant coronary artery disease (CAD), myocardial and pericardial abnormalities, and aortic pathology. When combined with electrocardiographic (ECG) gating, freeze-frame images of the heart can be obtained, eliminating most of the motion artifact. This is particularly important in contrast-enhanced CT angiography (CTA) of the coronary arteries and in quantification of coronary artery calcium. Advances in spatial and temporal resolution and image reconstruction software have also helped in the evaluation of cardiac structures such as coronary veins, saphenous vein grafts, atria, ventricles, and pulmonary arteries and veins, helping precisely define their spatial relationships within the cardiovascular system and allowing for a comprehensive assessment of a variety of cardiovascular disease processes. This chapter details the current and future role of cardiac CT for the assessment of cardiovascular physiology and pathology.

Advancements in CT technology have made it possible to noninvasively image the beating heart. Multidetector computed tomography (MDCT) scanners produce images by rotating an x-ray tube around a circular gantry through which the patient advances on a moving table. Improvements in gantry rotation speeds and the development dual source and large detector technologies have reduced effective temporal resolution to less than 100 milliseconds. The coronary arteries move independently throughout the cardiac cycle and even at slow heart rates exhibit significant translational motion of up to 60 mm/s for the right coronary artery (RCA) and 20 to 40 mm/s for the left anterior descending (LAD) and circumflex coronary arteries (Fig. 17–1).^1,2 Image acquisition of less than 50 milliseconds is truly required to completely avoid cardiac motion artifacts.¹

With MDCT systems, temporal resolution may be further improved by selecting specific partial image sector data from different heartbeats and detector rings to reconstruct a complete 240-degree image data set. With retrospective gating, several thousand images can be acquired during a single cardiac study, allowing one to choose images with the least amount of motion-related distortion prior to final image reconstruction.

MDCT scanners using retrospective gating can increase exposure approximately 13-fold.³ Prospective gating during either spiral or nonspiral acquisitions uses ECG-gated image triggering only at specific temporal locations in the cardiac cycle, thereby significantly reducing radiation exposure to more than 3 mSv, with reports as low as less than 1 mSv.⁴ Gating works relatively well at slow heart rates (ie, < 60 beats/min), where the R-R interval is greater than 1000 milliseconds and the fastest imaging protocols may be used. However, at faster heart rates, a 200-millisecond acquisition effectively covers most of the cardiac cycle, thus removing any potential benefit from gating the image acquisition.

Both ventricles are equally well visualized by contrast cardiac computed tomography angiography (CCTA). The combination of ECG gating and image postprocessing permits the reconstruction of multiple data sets at predetermined percentages of the R-R interval throughout the entire cardiac cycle (Fig. 17–2). This multiphase image reconstruction can be displayed in cine mode as in echocardiography or cardiac magnetic resonance (CMR) imaging. Therefore, end-systolic and end-diastolic images can be obtained to assess ventricular volumes and function (see Fig. 17–2).

Both ventricles are well visualized by MDCT, allowing excellent spatial separation between the two structures. Delineation of the epicardial and endocardial surfaces allows accurate and reproducible measurement of left ventricular (LV) and right ventricular (RV) wall thickness and myocardial mass.⁵ LV hypertrophy can be quantified and serially assessed.

Cardiac CT can assess left and right heart hemodynamics as well as regional myocardial wall motion and thickening.^6,7 The cine mode is used to acquire multiple gated images of the right and left ventricles during maximal contrast enhancement (see Fig. 17–2).⁷ This affords accurate and reproducible quantification of LV and RV end-diastolic and end- systolic volumes for the calculation of ejection fraction (EF).⁷ Cardiac CT is comparable to first-pass radionuclide angiography for the calculation of left ventricular ejection fraction (LVEF) in patients with myocardial infarction (MI).⁸

MDCT allows for precise measurements of LV volumes and overall function, which have a close correlation with echocardiography.^5,9,10,11 Compared with CMR, the current gold standard for cardiac functional evaluation, MDCT is an adequate alternative.⁹ Furthermore, MDCT is also a valuable tool in estimating LV wall thickness and mass and revealing segmental wall motion abnormalities, demonstrating good overall agreement with echocardiography and CMR.^5,9,10,11

Ventricular remodeling can be assessed by CT in a method similar to that used by gated blood-pool radionuclide angiography and echocardiography. Computed tomography angiography (CTA) can identify wall thinning and impaired LV thickening in an area of previous MI, and delineate anterior and posterior LV aneurysms and associated mural thrombus (Fig. 17–3).^5,12

RV volume and functional assessment by MDCT is feasible and has good correlation with both radionuclide ventriculography and CMR^5,11 (Fig. 17–4). CT acquisition protocols can be altered to more favorably opacify the right heart when RV volumes are needed, by using a triphasic injection where the initial contrast injection is followed by a blend of saline (60%) and iodinated contrast (40%). When valvular surgery is considered, CT can delineate the important parameters of LV chamber size, wall thickness, and LVEF.^5,12 Congestive heart failure or left atrial enlargement can be complicated by left atrial thrombi. It has been recently suggested that CT could be used as an alternative to transesophageal echocardiography in detecting intra-atrial thrombus.¹³

Coronary Artery Calcification

The presence of coronary artery calcification (CAC) is clearly indicative of coronary atherosclerosis,^14,15 serving as a marker for CAD; but importantly, the severity of angiographic coronary artery stenosis is not directly related to the total CAC. CAC is thought to begin early in life, but it progresses more rapidly in older individuals who have further advanced atherosclerotic lesions.¹⁶ Calcification is an active, organized, and regulated process occurring during atherosclerotic plaque development, where calcium phosphate in the form of hydroxyapatite precipitates in atherosclerotic coronary arteries in a fashion similar to that observed in bone mineralization.^17,18 Although lack of calcification does not categorically exclude the presence of atherosclerotic plaque, calcification occurs exclusively in atherosclerotic arteries and is not found in normal coronary arteries.

The presence and extent of histologically determined plaque area has been compared with the total calcium area in individual coronary arteries derived from autopsied hearts.¹⁴ A strong linear correlation exists between total coronary artery plaque area and the extent of CAC as found in individual hearts (r = 0.93, P < .001) and in individual coronary arteries (r = 0.90, P < .001).

Detection of Coronary Artery Calcification

MDCT imaging protocols vary among different camera systems and manufacturers. Generally, 40 consecutive images, 2.5- to 3-mm thick, are acquired per cardiac study. Calcified lesions are defined as two or three adjacent pixels with a tomographic density of either greater than 90 or greater than 130 HU. Effective pixel size for a reconstruction matrix of 512 × 512 pixels with a common field of view of 26 cm is 0.26 mm². Calcium scoring is usually based on the traditional Agatston method (ie, initial density of > 130 HU). As with electron beam computed tomography (EBCT) scoring, the total coronary artery calcium score (CACS) is calculated as the sum of each calcified plaque over all the tomographic slices.

Noninvasive techniques, such as exercise treadmill testing and myocardial perfusion imaging (MPI), aim to identify patients with abnormal coronary flow reserve either secondary to abnormal microvasculature or advanced epicardial CAD. However, unlike CT, which can detect coronary atherosclerosis at its earliest stages, these techniques can identify only patients with advanced CAD who manifest myocardial ischemia. Although the presence and extent of ischemia can accurately identify asymptomatic individuals at high risk for cardiac events, the very low prevalence of a positive test result (< 5%) precludes the use of these methodologies as primary screening tests for the early detection and treatment of CAD (Fig. 17–5).^19,20

Several studies emphasize the effectiveness of selectively combining stress MPI with CT in the anticipated small (10%) number of asymptomatic patients who will have a high (≥ 400) CACS so as to specifically identify those with silent myocardial ischemia.^20,21 This testing strategy may prove to be optimal based on the known prognostic value of perfusion imaging and the superior sensitivity of CT over the former for detecting preclinical CAD.

Coronary Artery Calcification: Prognostic Implications

Traditional risk factor assessment is routinely used to identify individuals who are at increased risk for developing cardiovascular disease based on standard clinical criteria.²² Given that the development of symptomatic cardiovascular disease occurs almost exclusively in patients with atherosclerosis, it seems advantageous, for the purposes of risk assessment, to use a technique that directly characterizes the presence and severity of atherosclerotic burden, rather than estimating its presence through indirect measures. For example, although there is a clear relationship between the number of cardiac risk factors and the presence and extent of CAC, 40% of men and 30% of women without risk factors in one series had CAC, whereas 26% of men and 36% of women with more than three traditional risk factors did not have any CAC.²³ Importantly, this study and others have confirmed that CAC allows for much more accurate risk stratification than do other risk factors.

The likelihood of plaque rupture and the development of acute cardiovascular events is related to the total atherosclerotic plaque burden.^24,25 There is a direct relationship between the CAC severity, the extent of atherosclerotic plaque, and the presence of silent myocardial ischemia. Many studies have now demonstrated an increased risk of cardiac events in asymptomatic patients who have extensive atherosclerosis and silent ischemia,^19,26,27 Therefore, the CACS could be useful for risk assessment of asymptomatic individuals and potentially guide therapeutics.

Several studies in both symptomatic^28,29 and asymptomatic^{30,31,32,33,34} patients have studied whether the extent of CAC can predict subsequent patient outcomes. In 422 symptomatic patients followed for 30 ± 12 months,²⁸ cardiac events were 10-fold higher in patients with a CACS above the 75th percentile for age (9.5%) versus patients with a CACS below the 25th percentile (0.9%). These results were also adjusted for age, gender, and race. Another study of 288 symptomatic patients referred for coronary angiography²⁹ showed that patients with a CACS of more than 100 had a 3.2-fold higher relative risk of death or MI than those with a lower CACS.

Large trials have reported an approximately 10-fold increased risk with the presence of CAC.^34,35 In one of the largest observational trials to date, Shaw and colleagues³⁶ reported all-cause mortality in 10,377 asymptomatic patients (4191 women and 6186 men) who had a baseline CAC and were then followed for 5.0 ± 3.5 years. Most patients had cardiac risk factors including a family history of CAD (69%), hyperlipidemia (62%), hypertension (44%), and current cigarette smoking (40%). The CACS was a strong independent predictor of mortality, with 43% additional predictive value contained within the CACS beyond risk factors alone. Mortality significantly increased with increasing CACS.

Similarly, in a younger cohort of asymptomatic persons, the 3-year mean follow-up in 2000 participants (mean age, 43 years) showed that coronary calcium was associated with an 11.8-fold increased risk of incident coronary heart disease (P < .002) in a Cox model controlling for the Framingham risk score.³⁷ The Rotterdam Heart Study³⁸ investigated 1795 asymptomatic participants (mean age, 71 years) who had CAC and measured risk factors. During a mean follow-up of 3.3 years, the multivariate-adjusted relative risk of coronary events was 3.1 for calcium scores of 101 to 400, 4.6 for calcium scores of 401 to 1000, and 8.3 for calcium scores greater than 1000, compared with calcium scores of 0 to 100.

Multiple studies have demonstrated that the relationship between CAC and outcomes is similar in men and women and across different ethnic groups.^{39,40,41,42,43} Each of these studies demonstrated that the area under the curve to predict coronary artery events is significantly higher with CAC than either Framingham or Prospective Cardiovascular Munster (PROCAM) risk stratification. Studies comparing predictive capacity of conventional and newer biomarkers for prediction of cardiovascular events consistently demonstrate that adding a number of newer biomarkers (such as C-reactive protein, interleukins, and other proposed risk stratifiers) only changes the C statistic by 0.009 (P = .08).^39,40,44 Small changes such as these in the C statistic suggest limited or modest improvement in risk discrimination. However, CAC scanning has been shown to markedly improve the C statistic, suggesting robust improvement in risk discrimination.

In another study, 9715 individuals underwent CAC imaging and were followed for a mean of 14.6 years. A warranty period was defined as less than a 1% death rate. It was demonstrated that the warranty period in patients with CACS of 0 and low and intermediate risk was almost 15 years, with no significant differences regarding age and sex. A CACS of 0 was associated with a vascular age of 1, 10, 20, and 30 years less than the chronological age of individuals between 50 and 59, 60 and 69, 70 and 79, and 80 years of age and older, respectively. CAC was the strongest predictor of death when compared to both Framingham Risk Score and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III).⁴⁵

Overall, CAC score appears to provide complementary prognostic information to that obtained by the Framingham risk model or other risk assessment methods. Furthermore, multiple studies consistently demonstrate that CAC scanning confers more precise risk prediction than other alternatives such as C-reactive protein or carotid intimal-medial thickness.^39,40,44

Coronary Artery Calcification Progression

Much interest has been directed at using CAC to measure plaque burden and then remeasuring at some point after treatment is applied to assess for progression of disease.⁴⁶ Callister and coworkers⁴⁷ performed one of the first studies to demonstrate a relationship between cholesterol lowering and atherosclerosis progression. There was a significant net increase in mean calcium volume score among individuals not treated with cholesterol-reducing medications (mean change, 52% ± 36%; P < .001). There was a graded response depending on the low-density lipoprotein (LDL) reduction with statin therapy, with those treated to LDL less than 120 mg/dL demonstrating an average diminution of coronary calcium (7% ± 23%) and those treated less aggressively (LDL > 120 mg/dL) showing a calcium volume score increase of 25% ± 22% (P < .001 for comparison with aggressively treated patients).

The Multi-Ethnic Study of Atherosclerosis (MESA) measured baseline CACSs and repeated this measurement after 3.5 years in 5756 patients. Of these, 2948 patients (51%) had a CACS of 0 at onset and were followed for development of incident positive CACS. The percentage developing positive scores was 16%. Another 2808 patients had a detectable CACS at baseline and were followed for progression. Their average rate of progression was 17.5 Agatston units per year. Risk factors associated with CAC progression were older age, male sex, white race/ethnicity, hypertension, higher body mass index, diabetes mellitus, and family history of heart attack. The associations that persisted after adjustment for baseline CAC were body mass index, family history of MI, diabetes mellitus, microalbuminuria, and blood glucose level.⁴⁸

A new post hoc analysis⁴⁹ of eight intravascular ultrasound (IVUS) studies that assessed the effect of medical therapies on serial changes in coronary atheroma burden suggests that there is a paradoxical relationship between calcification of the coronary artery and atheroma volume among individuals treated with statin therapy. This study demonstrates that high-intensity statin therapy promotes coronary calcification despite inducing regression of overall coronary atheroma volume. One interpretation of such results could be that the increase in coronary calcification among patients treated with a statin might be suggestive of coronary plaque stabilization. Therefore, the interpretation of results demonstrating CAC progression in a setting of high-intensity therapy could change from plaque progression to plaque stabilization.

Computed Tomography Angiography

Anatomical Assessment of Coronary Arteries

Assessment of Native Coronary Arteries

The explosive growth of cardiovascular imaging over the past few decades has facilitated the noninvasive detection of CAD. CCTA has the ability to accurately detect luminal stenosis in the coronary arteries and characterize coronary artery plaques. Advances in MDCT technology have resulted in high spatial and temporal resolution capable of detecting coronary atherosclerosis approximating that seen with invasive catheter-based coronary angiography. However, invasive coronary angiography (ICA) carries procedural risk (0.1%-0.2%), as well as high procedural cost.⁵⁰ It has been estimated that approximately up to 40% of patients who undergo coronary angiography have normal angiograms, and many patients with CAD do not require revascularization procedures.^51,52,53 CCTA has the potential to obviate the need for invasive procedures in select patients by demonstrating the absence of significant CAD, as well as improve risk stratification through detection of coronary atherosclerosis, assessment of ventricular function, and provision of information on cardiac structure.

Image Acquisition

MDCT scanners produce images by rotating an x-ray tube around a circular gantry through which the patient advances on a moving table. Pitch is the speed of the table relative to the speed of the gantry rotation, which allows each cross-sectional level of the heart to be imaged during more than one cardiac cycle. The number of image slices acquired during each gantry rotation (4–320) determines the overall duration of the MDCT scan. Developments in MDCT technology have led to the rapid advancement from four-slice MDCT machines in 1998 to 64 slices in 2004 and 256-slice and 320-detector row scanners in 2007. The latest technology contains 0.5-mm-wide detector elements yielding a maximum of 16-cm z-axis coverage. This configuration allows three-dimensional (3D) volumetric whole heart imaging during the diastole of one R-R interval, which opens the possibility of CCTA usage in the settings of higher heart rates and even arrhythmia.⁵⁴ This progression is ongoing, with 640-detector row scanners now citing even less radiation and scanning time, as well as improved image quality.⁵⁵

Cardiac CT is performed with ECG gating in either prospective or retrospective mode. ECG gating synchronizes image acquisition with the cardiac cycle. The optimal phase or interval for image analysis is the period during which the heart is the least mobile (usually end-diastole) and therefore the least degraded by motion artifact. Prospective ECG gating entails scan initiation at a defined interval after the R wave, continues for a prespecified duration, and then stops until the same optimal period is reached in the subsequent cardiac cycle, at which time scanning resumes. Retrospective ECG gating uses continuous acquisition of images throughout the cardiac cycle. The images from multiple consecutive heartbeats are then reconstructed at various percentages of the R-R interval (eg, from 0%-90% of an R-R cycle at 10% intervals). With retrospective gating, several thousand images can be acquired during a single cardiac study, allowing the interpreting physician to select the images with the least amount of motion-related distortion prior to final image reconstruction. Gating is the most advantageous at relatively slower heart rates (< 60 beats/min), where the R-R interval is more than 1000 milliseconds and the fastest imaging protocols may be used.

The coronary arteries move independently throughout the cardiac cycle and, even at relatively slower heart rates (ie, < 70 beats/min), exhibit significant translational motion of up to 60 mm/s for the RCA and 20 to 40 mm/s for the LAD and circumflex coronary arteries (Fig. 17–6).^1,2 The velocity of coronary artery motion increases significantly with increasing heart rates. Image acquisition of less than 50 milliseconds is truly required to completely avoid cardiac motion artifacts.¹ Cardiac motion is minimized with the use of oral and/or intravenous β-blockers prior to scanning, thereby reducing the heart rate and prolonging the time during the cardiac cycle at which coronary artery velocity is low. For individuals without contraindication to β blockade, these drugs are the medication of choice because they not only decrease the heart rate through the reduction of sympathetic tone, but may also reduce the number of premature atrial or ventricular beats, which adversely affect the overall quality of the images. Another crucial element for obtaining high-quality coronary images is to maximally dilate coronary vessels with nitroglycerin through the use of sublingual tablets or spray (Fig. 17–7). Respiratory motion is excluded by performing the scan during a breath-hold.

Coronary CTA requires the intravenous administration of an iodinated contrast medium. Approximately 50 to 100 mL of contrast medium is necessary for adequate coronary artery enhancement. The accurate timing of image acquisition relative to the contrast injection is a major determinant of overall image quality. A test bolus or bolus tracking technique is used to optimize this timing by determining the amount of time necessary to peak enhancement in the aorta.

Advancements in MDCT technology have led to shorter scan times, reduced breath-hold duration, smaller intravenous contrast injections, and decreased motion-related artifacts, resulting in lower radiation exposure and improved diagnostic accuracy.

Image Interpretation

The coronary vasculature on CCTA is evaluated through axial images, multiplanar (coronal, sagittal, or oblique) reformations, and 3D data sets constructed from specific phases during the cardiac cycle (Fig. 17–8). Maximum-intensity projection images allow the evaluation of longer segments of the coronary vessels but can be limited by overlapping structures adjacent to the artery of interest. Curved multiplanar reformations are reconstructed on a plane to fit a curve and allow display of the entire vessel in a single image. 3D volume-rendered images are useful for selecting images with the least motion artifact and for assessing the relationships among different anatomic structures (Fig. 17–9).

The spatial resolution of the image depends on the size of the 3D pixels or volume elements (voxels) that constitute the image. Slice thickness affects the spatial resolution of CCTA. Temporal resolution is determined by the speed of rotation of the gantry around the patient. A temporal resolution of 50 milliseconds or less is desirable for coronary artery imaging. The 64-slice MDCT scans have a spatial resolution of 0.4 mm and temporal resolution of 83 to 165 milliseconds, which limits the sensitivity and diagnostic accuracy for detecting stenosis in vessels less than 1.5 mm in diameter.^56,57 In comparison, invasive angiography has both a superior spatial resolution of 0.2 mm and a temporal resolution of 5 to 20 milliseconds, whereas magnetic resonance angiography has decreased spatial resolution (0.7 mm) compared with MDCT but a better temporal resolution of 20 milliseconds.⁵⁶

Diagnostic Accuracy of Cardiac Computed Tomography Angiography

Although there is still room for improvement in terms of image quality and elimination of artifacts, the diagnostic performance of the CCTA is now well established. A meta-analysis including nine studies totaling 566 patients using scanners with 64 or fewer detectors revealed a per-patient pooled sensitivity of 95% (95% confidence interval [CI] 90%–98%) and specificity of 90% (95% CI 87%-93%) in detecting acute coronary syndromes (ACS) in comparison with ICA.⁵⁸ Another meta-analysis including 16 studies and 1119 patients found sensitivity and specificity of 96% (95% CI 93%-98%) and 92% (95% CI 89%-94%), respectively.⁵⁹ Both studies demonstrate higher diagnostic accuracy for ACS with CCTA than with other previously studied modalities, including exercise treadmill, stress magnetic resonance imaging (MRI), stress nuclear imaging, and stress echocardiography.

Multiple trials have assessed the diagnostic accuracy of 64-slice CCTA compared with ICA.^{60,61,62,63,64} Subsequent meta-analyses have found that in patient-based analysis for the detection of obstructive CAD (> 50% stenosis), 64-slice MDCT had a pooled sensitivity of 94% to 100%, a specificity of 89% to 100%, a positive predictive value (PPV) of 93% to 97%, and a negative predictive value (NPV) of 93% to 100%.^65,66,67,68 These observational results suggest that CCTA has good diagnostic accuracy for the detection of obstructive CAD. This was corroborated by two ensuing multicenter prospective clinical trials: Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY)⁶⁹ and Coronary Artery Evaluation Using 64-Row Multidetector CT Angiography (CORE-64).⁷⁰ The ACCURACY trial enrolled 230 patients with chest pain, who underwent both CCTA and ICA. In a patient-based model, the ability of CCTA to detect obstructive CAD (>70% stenosis) had a sensitivity of 94%, specificity of 83%, PPV of 48%, and NPV of 99%.⁶⁹ The high NPV of CCTA makes 64-slice MDCT a valuable tool in the exclusion of obstructive CAD. Therefore, CCTA is useful in the risk stratification of symptomatic patients and can reduce the need for invasive diagnostic coronary angiography in patients without obstructive CAD. A recent scientific statement from the American Heart Association (AHA) on CCTA concluded that “CT coronary angiography is reasonable for the assessment of obstructive disease in symptomatic patients (class IIa, Level of Evidence: B).”⁷¹

In particular, CCTA is an accurate tool in the assessment of chest pain in patients with intermediate risk of CAD or in patients with uninterpretable or equivocal stress tests.⁷² Other important clinical roles of MDCT include the assessment of congenital heart disease, suspected coronary anomalies, and significant CAD as a cause of new-onset heart failure.

Cardiac Computed Tomography Angiography, Plaque Composition, and Noninvasive Identification of High-Risk Plaques

In contrast to ICA, CCTA can assess the composition of the vessel wall, in addition to characterizing the degree of narrowing of the coronary artery lumen. MDCT can detect coronary plaque extent, distribution, location, and composition. Necropsy and coronary IVUS studies have shown that ICA consistently underestimates the amount of atherosclerotic plaque.^73,74

Most ACS are caused by atherosclerotic plaque rupture, causing sudden luminal thrombosis. Pathological and anatomical features of high-risk or vulnerable plaques have been reviewed extensively in the literature⁷⁵ and in Chap. 32.

These features include presence of large necrotic core, thin fibrous cap, positive remodeling (PR), spotty calcifications (SC), and perivascular inflammation.⁷⁶ Some of these features are identifiable in vivo utilizing various invasive and noninvasive imaging modalities, such as IVUS, optical coherence tomography (OCT) and positron emission tomography (PET).^{77,78,79,80,81,82,83,84,85} In the past decade, noninvasive identification of such features using CCTA has been a major focus of research.

A study by Leber and colleagues⁸⁶ assessed the capability of 64-slice CT to detect and quantify coronary plaques compared with IVUS. For the detection of coronary plaque, 64-slice MDCT had a sensitivity of 84% and specificity of 91%. In addition, 64-slice MDCT showed good correlation with IVUS in determining the mean plaque area (r = 0.73) and mean lumen area (r = 0.81).

In 2007, Motayama and Narula⁷⁷ compared the CCTA plaque features of 38 patients with ACS to 33 patients with stable angina. Presence of PR, low attenuation plaque (LAP) (< 30 HU), and SC were associated with plaque rupture and ACS. In a prospective study by the same authors,⁸⁷ 1059 patients were followed for 27 months after the initial CCTA. The copresence of LAP and PR was associated with a 22.5% chance of ACS, whereas absence of these features was associated with 0.5% event rates. There were no significant differences in the degree of stenosis between the plaques that led to ACS and those that did not. The long-term follow-up (10 years) of this study⁸⁸ showed that ACS occurred in 23.0% of patients with two high-risk features, 10.7% of patients with one high-risk feature, 1.6% of patients with no such features, and 0.6% of patients without any plaque (log-rank P < .0001). The other CT finding suggestive of plaque vulnerability, the so-called “napkin ring” sign, was reported for the first time in 2010.⁷⁸ It was defined as a coronary plaque with a napkin ring–like attenuation pattern and SC (Fig. 17–10). The circumferential outer rim (red dashed line) of noncalcified plaque has a higher CT attenuation in both the noncontrast (A) and contrast-enhanced (B) images as compared to the attenuation within the central part of the plaque. These features of the “napkin ring” sign most likely identify a very similar histological pattern as the thin cap fibroatheroma. The “napkin ring” sign has also been shown to be predictive of events in a study of 895 patients⁸⁰ who had a CCTA and were followed for up to 5 years thereafter. Patients with plaques with no high-risk features had no events, whereas there was a 40% event rate for patients with lesions with the following three high-risk features: “napkin ring” sign, PR, and LAP.

Diagnostic Accuracy of Cardiac Computed Tomography Angiography for the Evaluation of Acute Coronary Syndrome

The diagnostic accuracy of CCTA for the clinical diagnosis of ACS has been investigated in several studies that included more than 3000 patients presenting with acute chest pain to the emergency department.^89,90,91,92 In a prospective study by Rubinshtein and colleagues,⁸⁹ 58 patients (mean age, 56 years; 36% women) with chest pain and initially negative biomarkers in the absence of new ECG changes underwent 64-slice MDCT. Twenty-three patients were found to have obstructive CAD (> 50% luminal narrowing) on CCTA. Of these 23 patients, 20 were subsequently diagnosed with ACS. Thus, 64-slice MDCT was found to have a sensitivity of 100%, specificity of 92%, PPV of 87%, and NPV of 100% for diagnosing ACS in emergency department patients presenting with chest pain. Normal and nonobstructive CCTA results were predictive of a low rate of major adverse cardiovascular events (MACE; 2.8%) and a favorable outcome during a 15-month follow-up period.⁸⁹

The Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT)⁹⁰ study was a larger prospective trial evaluating the role of CCTA in patients presenting to the hospital with possible ACS. Overall, 368 patients (mean age, 53 years; 61% men), were studied from a lower risk population. For CCTA, sensitivity and NPV for ACS were both 100%.⁹³ In addition, this study demonstrated that CCTA independently predicts risk for ACS and has additive value for assessing risk in patients presenting with chest pain, when used in combination with traditional risk factors and clinical estimates of the probability of ACS.⁹³

All trials demonstrated that absence of any coronary atherosclerosis by CCTA, which was observed in about half of the population, has an excellent NPV for presence of ACS. However, presence of significant stenosis by CCTA was only moderately diagnostic for ACS. In combination with the low prevalence of ACS in the acute chest pain population in the emergency department (2%-8%),¹¹ CCTA reveals a low PPV for ACS (~ 35%-50%).

In order to improve the PPV, different strategies have been pursued⁹⁴:

1. Assessment of plaque morphology. As mentioned earlier, CCTA has the potential to visualize select high-risk plaque features. Even though the assessment of such features is not part of current routine clinical practice, a plaque morphology-based score developed by Motayama and Narula resulted in a PPV of 100% for ACS and could potentially enhance the diagnostic accuracy of CCTA in the setting of acute chest pain.²

2. Assessment of LV function. It has been demonstrated that the identification of regional wall motion abnormalities incrementally improves the diagnostic accuracy of CCTA for ACS.⁹⁵ However, this comes at the expense of higher radiation exposure.

3. Physiologic assessment of coronary artery disease by CT perfusion (CTP) or CT fractional flow reserve (FFR; see below). Functional testing, including rest and stress myocardial perfusion, is possible using CTP, but stress testing is not recommended in the acute setting considering the potential adverse effects of stressing a patient with ACS. Similar to the nuclear literature, an incremental value of assessing rest myocardial perfusion by CT has been observed, particularly in improving PPV.^96,97

In summary, the absence of coronary atherosclerosis on CCTA, as observed in 50% of the acute chest pain population, has a NPV of close to 100%. On the other hand, presence of significant stenosis, even though superior to clinical risk score such as thrombolysis in myocardial infarction (TIMI),⁹⁸ has a moderate diagnostic accuracy for ACS. Additional assessment of plaque morphology, LV function or physiological assessment of CAD with CTP perfusion and CT FFR might prove beneficial in improving diagnostic accuracy of CCTA for the assessment of acute chest pain.

Effectiveness of Cardiac Computed Tomography Angiography in the Emergency Department

Because CT has an excellent NPV and can be conducted in a timely manner, it has been hypothesized that CT may allow for rapid assessment of acute chest pain in the emergency department and lead to safe rapid discharge. Based on this hypothesis, three large clinical trials have been conducted.

Litt and colleagues⁹⁹ performed the largest trial of these series. A total of 1370 patients with acute chest pain in the emergency department were enrolled and randomized into CCTA versus standard care in 2:1 fashion in the American College of Radiology Imaging Network–Pennsylvania Department of Health (ACRIN-PA) study. The results met the prespecified safety threshold of below 1% for missed ACS or death during the 30 days follow-up in the CCTA group. Importantly, this study was positive regarding its primary end point establishing CCTA as a safe alternative to traditional ischemia testing, such as MPI and exercise echocardiography, in a cost-effective and time-efficient fashion.

Both the Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment (CT-STAT)¹⁰⁰ and the ROMICAT II¹⁰¹ trials demonstrated that the CCTA-based strategy resulted in a shorter length of stay without lower safety (2.9 vs 6.2 hours for time to diagnosis [CT-STAT] and 23 vs 31 hours for time to hospital discharge [ROMICAT II] for CCTA vs control strategy). These findings were supported by other studies, indicating that the rate of direct discharge from the emergency department increased to about 50% by using a CCTA strategy, while a typical rate of 15% to 25% is observed for standard care.^99,100,101

Prognostic Value of Cardiac Computed Tomography Angiography

CCTA yields independent prognostic information in addition to clinical risk factors in patients with suspected or known CAD.¹⁰² In 100 patients referred for cardiac evaluation, the cardiac event rate in the year following CCTA was 0% in patients without evidence of CAD, 8% in patients with nonobstructive CAD, and 63% when obstructive lesions were present.¹⁰² In patients with chest pain, CCTA can identify obstructive lesions, such as proximal LAD stenosis, as well as the number of vessels with moderate-to-severe stenosis, which predict an increased risk for all-cause mortality.¹⁰³

In a meta-analysis of 11 studies, including a total of 7335 mostly symptomatic patients with suspected CAD followed for a median of 20 months, the presence of any greater than 50% stenosis at CCTA was associated with a 10-fold higher risk of cardiovascular events. In addition, the finding of any CAD inferred a 4.5-fold risk, and each coronary segment involved increased the risk of adverse outcomes by 23%.¹⁰⁴ In the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter (CONFIRM) registry, 27,125 patients underwent CCTA and were followed for a mean follow-up time of 22.5 months. Multivariable analysis demonstrated CCTA measures of CAD severity and LVEF have independent prognostic value. Incorporation of CAD severity had incremental value for predicting all-cause death over routine clinical predictors and LVEF in patients with suspected obstructive CAD.¹⁰⁵

In a more recent analysis of 17,793 patients from the CONFIRM registry, the majority of whom had chronic chest pain, the number of proximal segments with mixed or calcified plaques and the number of proximal segments with 50% or more stenosis were the CCTA parameters with the strongest predictive value for all-cause mortality at a median follow-up of 2.3 years.¹⁰⁶ Evidence of the more long-term prognostic value of CCTA is beginning to accumulate. Hadamitzky and colleagues¹⁰⁷ followed up 1584 patients for a median of 5.6 years and described annual rates of MACE of 0.2% for patients with no CAD and 1.1% in patients with obstructive CAD. In another recent study reporting on a median 6.9-year follow-up period in 218 patients, annual MACE rates were 0.3%, 2.7%, and 6.0% in patients with normal CCTA, nonobstructive CAD, and obstructive CAD, respectively.¹⁰⁸

While CCTA is shown to be an extremely powerful prognostic tool, it has been shown only to improve prognostication for asymptomatic populations with intermediate CACS and is not incremental to CACS for asymptomatic patients with lower or higher CACS levels.¹⁰⁹

CCTA has also shed light on the important prognostic value of nonobstructive CAD. Lin and colleagues¹¹⁰ evaluated 2583 primarily symptomatic (85%) adults (mean age 52.7 years; 58% women) without known CAD or obstructive disease (50% stenosis) on 64-slice coronary CTA. Over a mean follow-up period of 3.1 years, it was demonstrated that the extent of nonobstructive CAD has a strong association with risk for all-cause mortality. The presence of any plaque increased the risk factor–adjusted mortality risk (hazard ratio [HR], 1.98), and risk was increased with multivessel nonobstructive disease (HR of 4.75 for three-vessel nonobstructive disease and HR of 5.12 when five or more segments were involved). Of importance, the increased risk from nonobstructive CAD was also seen in patients with low Framingham Risk Scores (FRS), a patient subset that does not typically qualify for aggressive primary cardiovascular preventive therapies. Similarly, the presence of any plaque demonstrated an improvement in the net reclassification index when compared with risk estimates using the FRS alone. Ahmadi and colleagues¹¹¹ similarly demonstrated in 1102 consecutive symptomatic patients with nonobstructive (< 50%) CAD on coronary CTA, nonobstructive disease independently predicted all-cause mortality. Moreover, mortality incrementally increased according to the type of nonobstructive disease present (mortality given in parentheses): purely calcified plaque (1.4%), partially calcified plaque (3.3%), or noncalcified plaque (9.6%) (P < .001). On the same note, one of the analyses of the CONFIRM registry demonstrated that patients with two or more noncalcified or partially calcified plaques have a prognosis similar to that of patients with one or two obstructive plaques. However, patient with up to seven calcified nonobstructive plaques had an excellent prognosis with a less than 3% event rate in 2.3 years.¹¹²

In summation, the data available to date suggest that (1) the warranty period of a negative coronary CT angiogram appears to extend to at least 5 years, (2) the presence of any CAD and the burden of atherosclerotic changes at CCTA is strongly predictive for MACE and all-cause mortality in those with stable chest pain, and (3) plaque morphology by CT confers incremental prognostic information beyond that provided by percent stenosis alone.

Use of Cardiac Computed Tomography Angiography versus Other Modalities in Evaluation of Patients with Stable Coronary Artery Disease

Three recent randomized prospective studies have evaluated the role of CCTA compared to other commonly used noninvasive modalities for the evaluation of patients with stable CAD.^113,114,115

In a multicenter European study,¹¹³ 475 patients with stable chest pain and low prevalence of CAD underwent CCTA and stress MPI by single-photon emission computed tomography (SPECT) or positron emission tomography, as well as ventricular wall motion imaging by stress echocardiography or CMR for detection of obstructive (> 50%) CAD. CCTA had the highest diagnostic accuracy; the area under the receiver operating characteristics curve was 0.91 (95% CI, 0.88-0.94), with sensitivity of 91%, and specificity 92%.

In the Scottish Computed Tomography of the Heart Trial (SCOT-HEART)^114,116 a total of 4146 patients assessed for new-onset chest pain were randomized to CTA in addition to standard care or to standard care alone. The standard care included documentation of the clinical history of angina pectoris and objective demonstration of exercise-induced myocardial ischemia through exercise stress testing. At 6 weeks, use of CTA reclassified the diagnosis of coronary heart disease in 27% of patients and the diagnosis of angina in 23% of patients. Use of CTA increased the certainty of attributing the patient's symptoms to angina caused by CAD compared with usual care alone (relative risk [RR] 1.79, 95% CI 1.62-1.96). The certainty of diagnosing CAD was also significantly improved (RR 2.56, 95% CI 2.33-2.79). Adding CTA to usual care changed planned investigations and treatment options and was associated with a trend toward a reduction in fatal and nonfatal MI.

The PROspective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial¹¹⁵ randomized a total of 10,003 patients and no prior diagnosis of CAD to a strategy of initial anatomical testing with CCTA or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The study showed no difference in the primary end point, a composite rate of death, MI, major procedural complications or hospitalization for chest pain. However, select secondary end points, including level of radiation exposure and rate of subsequent procedures that did not reveal significant heart disease, favored CCTA.

Assessment of Coronary Bypass Grafts

Saphenous vein grafts are relatively easier to image with CCTA (because of their larger diameter and decreased mobility) compared with native coronary arteries. CCTA has high diagnostic accuracy for evaluating arterial and venous bypass graft stenosis. The diagnostic efficacy of 64-slice MDCT in detecting angiographically significant stenosis in bypass grafts has been demonstrated by several studies, yielding sensitivity ranging from 97% to 100% and specificity ranging from 89% to 100%.^{117,118,119,120} However, the assessment of bypass graft stenosis has several important limitations, namely the image artifacts caused by surgical clips and the presence of extensive coronary calcification in the native coronary arteries. These limitations can particularly hinder the evaluation in distal runoff vessels and nongrafted native coronary arteries.^118,120 The percentage of uninterpretable segments can be as high as 31% with 16-slice MDCT¹²¹ but is significantly reduced, to approximately 2% or less, with 64-slice MDCT.¹²⁰ Furthermore, the percentage of segments of native coronary vessels that cannot be evaluated may be less relevant in the clinical decision-making process because the most extensively calcified vessels are often bypassed.

Therefore, CCTA may be clinically useful for the evaluation of coronary bypass grafts and coronary anatomy in symptomatic patients.^119,120 In the case of reoperation or revascularization, coronary CT angiography may provide critically important information on the status and anatomic location of the bypass grafts. The AHA Scientific Statement on CCTA states, “It might be reasonable in most cases to not only assess the patency of bypass graft but also the presence of coronary stenoses in the course of the bypass graft or at the anastomotic site as well as in the native coronary artery system (class IIb, Level of Evidence: C).”⁷¹ In summary, CCTA using 64-slice MDCT may be appropriate in properly selected patients by providing diagnostic information on the overall patency of the bypass grafts and the presence of significant stenosis without exposure to an invasive diagnostic approach.

Assessment of In-Stent Restenosis

The partial volume effect, or imaging artifacts, caused by the metallic stents limits the overall visibility of the inner lumen of a deployed stent and can potentially reduce the diagnostic accuracy of CCTA for the noninvasive evaluation of in-stent restenosis. Stent location, heart rate, and stent diameter are also important determinants of accuracy and feasibility (Fig. 17–11). The feasibility of stent visualization is approximately 95%, with the remaining 5% being unevaluable or uninterpretable because of the aforementioned factors.¹²² A systematic review of CCTA with 16-slice or more MDCT revealed moderate sensitivity (85%) and high specificity (97%) for the detection of coronary in-stent restenosis when compared with ICA.¹²³ Similarly, a study exclusively comparing 64-slice MDCT with ICA found a sensitivity of 87% and specificity of 98% for the identification of significant in-stent restenosis by CCTA.¹²² In addition, CCTA has the ability to identify stent gaps, which may represent stent fracture or overlap failure and are often associated with in-stent restenosis.¹²⁴ A new method of subtraction CCTA with a long breath-hold (25 seconds) using a 320-row scan was recently shown to improve the diagnostic accuracy of CCTA in detecting in-stent restenosis from 62.7% to 89.5% as compared to ICA¹²⁵ (Fig. 17–12).

Evaluation of Coronary Anomalies

Anomalies of the coronary arteries are reported in 0.3% to 1% of the general population.¹²⁶ Approximately 20% of coronary anomalies can be hemodynamically significant and manifest as arrhythmias, syncope, MI, or sudden death.^127,128 An interarterial course between the pulmonary artery and aorta is the coronary anomaly most commonly associated with sudden cardiac death (Fig. 17–13).¹²⁹

The diagnosis of coronary artery anomalies has previously required ICA; however, in up to 50% of patients, the coronary artery anomalies may be incorrectly classified during invasive angiography.¹³⁰ This misclassification may result from the difficulty in delineating the precise vessel path within a complex 3D geometry using a relatively restricted two-dimensional (2D) view. Coronary CTA has been shown to accurately depict the anomalous vessel origin, its subsequent course, and the relationship to the great vessels.¹²⁸ Two studies comparing CCTA and ICA found that invasive angiography was able to detect 80% of the anomalous origins, but only 53% of the anomalous coronary courses,¹³¹ and resulted in a precise anatomic diagnosis in only 55% of patients.¹³² In a multicenter coronary artery CT registry, CCTA was able to unequivocally demonstrate the origin and the course of the anomalous artery in all patients with equivocal findings on ICA.¹³³ Demonstrating the precise course of an anomalous coronary artery is crucial for determining proper therapeutic options. Therefore, CCTA may be preferable to invasive angiography for the diagnosis of coronary anomalies given its superior diagnostic accuracy.

Physiologic Assessment of Coronary Artery Lesions by Cardiac Computed Tomography Angiography

Rationale

While there is ongoing debate among cardiologists as to whether coronary anatomy or physiology is more important in determining prognosis and impacting treatment decisions, anatomic and functional testing for CAD are often complimentary. Even though the degree of stenosis is one of the factors that partially predicts the presence or absence of ischemia, the association between coronary anatomy and ischemia is poor. For instance, there are lesions causing Ischemia WithOut significant Stenosis (IWOS) and there are lesions that cause significant Stenosis WithOut Ischemia (SWOI).^134,135 Therefore, an ideal diagnostic test would possess the technology that not only can give accurate assessment of the burden of atherosclerosis, location and composition of each plaque, but also determine the physiological consequence of each lesion in the form of presence or absence of ischemia. Two such techniques are CTP and CT FFR. They have allowed us to evaluate both coronary anatomy and physiology.

Techniques for Computed Tomography Myocardial Perfusion Imaging

In order to assess both coronary anatomy and myocardial ischemia using CTP, two separate CT acquisitions are required: one for vasodilator induced stress MPI and one for rest MPI and coronary CTA.¹³⁶ While heart rate is required for the rest acquisition, it is not as stringent for stress MPI because coronary opacification is not necessary or assessed. Typically, a delay ranging from 10 to 30 minutes is currently employed between acquisitions to allow for CT contrast washout and/or reversal of the effects of the pharmacological vasodilator used. For the stress perfusion, peak hyperemia may be achieved with adenosine, dipyridamole, or regadenoson. Regadenoson has can be used with a single injection that results in several minutes of hyperemia. A clinical example of CTP is demonstrated in Fig. 17–14.

Stress-rest perfusion and rest-stress protocols yield similar clinical results. However, rest–stress protocols could lead to more cost effectiveness testing, because the stress portion could be avoided in the rest-stress protocol if no stenosis were identified in the rest images.

Any modern scanner with 64 or more detectors can be used to perform CT MPI, although there are unique considerations for each specific CT platform. Most important is the z-axis coverage. In the 64 MDCT platforms, which require image acquisition over multiple heartbeats, the use of this technique results in nonhomogenous myocardial contrast enhancement resulting from the slight differences in acquisition time of each slab. Even though such heterogeneity does not impact the clinical value of the test, the sufficient z-axis coverage in 320 MDCT eliminates this issue by allowing for a single beat acquisition.

Another important consideration is the estimated effective radiation dose delivered to the patient. Estimated effective dose is significantly dependent on scanner technology and acquisition protocol.¹³⁷ An axial acquisition with prospected ECG gating, as well as reduction in the tube voltage (kV) in nonobese patients and use of a single data set utilizing either a test bolus or bolus tracking are some of the techniques that could lead to reduction in effective radiation dose.

After raw data acquisition, CTP images should be reconstructed with a smooth filter and beam-hardening correction, when available. For optimal image display of myocardial perfusion, the grayscale window width and level are set at approximately 300/150¹³⁸ and multiplanar reformat images are viewed using thick slices (6-8 mm) and average intensity projection of each slab.

Clinical Evidence for Computed Tomography Myocardial Perfusion Imaging

Single-center studies on 64 MDCT were first reported in 2009^139,140 and demonstrated a per-vessel sensitivity and specificity of 86% to 93% and 74% to 91% for CTA-CTP in comparison to ICA-SPECT. These results were followed by other single-center, observational studies evaluating CTP, which demonstrated an accuracy of CTP similar to that of both invasive angiography and functional imaging.^{141,142,143,144,145,146,147,148}

The multicenter, international study Coronary Artery Evaluation using 320-row multidetector computed tomography angiography and myocardial perfusion (CORE 320) followed the previously mentioned single-center studies. This study evaluated 381 patients who underwent CTP and CTA using the 320 MDCT, as well as SPECT MPI and invasive angiography. CTA ≥ 50% demonstrated a sensitivity of 94% and specificity of 64% for detecting obstructive lesions causing defects on myocardial perfusion imaging. There was a modest improvement in specificity with the addition of CTP to CTA.¹⁴⁹ The presence of stenosis by CTA had an area under the curve of 0.82 (0.78–0.85), which improved to 0.87 (0.84–0.89) with the addition of CTP. A subsequent multicenter trial has been conducted using regadenoson for CTP in comparison with SPECT incorporating a variety of different vendors' CTA.^150,151 This study demonstrated that addition of CTP increased the accuracy of CTA for detecting a reversible perfusion defect on SPECT could be improved from 0.69 to 0.85.

Fractional Flow Reserve Computed Tomography: the Fundamentals

Recent advances in the field of computational fluid dynamics (CFD) and advanced imaging-based modeling have allowed for noninvasive calculation of FFR based on static CT images. As applied to typically acquired coronary CT angiograms, these technologies enable noninvasive calculation of FFR without modification of image acquisition protocols, additional imaging or radiation, or need for vasodilators. The details of methods used in calculation of FFR CT have been described elsewhere.^152,153

In general, by using the “Navier-Stokes Equations” of CFD and based on the relationship of mass conservation and momentum balance, coronary artery flow and pressure can be obtained.^{136,153,154,155} Because blood is an incompressible fluid, it can be treated as a newtonian fluid with a relatively constant viscosity in larger vascular beds such as coronary arteries. Clinical evaluation of a true vascular territory such as coronary arteries requires a numerical method to estimate the principle equations and generate a solution, which must be solved simultaneously over many time intervals in a single cardiac cycle, using CFD methods.¹⁵³ Definition of flow boundaries is necessary for construction of the 3D model of coronary arteries and aorta and solving flow equations. These boundaries include the vessel lumen, the root of aorta as the inlet, and the thoracic aorta and the coronary arteries as the outlets.¹⁵⁶ Myocardial wall volume and mass extracted from the coronary CTA data are used to calculate the overall coronary flow under the resting conditions. Total coronary resistance can be calculated using the coronary flow. Using a simulation model of the effect of adenosine on reducing the peripheral resistance of the coronary microcirculation down-stream to the epicardial coronary arteries, maximum hyperemia state is estimated in the FFR CT model.¹⁵⁷ FFR CT can then be obtained by solving the equations of blood flow for velocity and pressure.¹⁵³ Figure 17–15 demonstrates a clinical example of FFR CT with invasive FFR correlation.

Clinical Evidence for Fractional Flow Reserve Computed Tomography to Date

FFR CT technology has been shown to be more accurate than CTA in predicting lesion-specific ischemia, as determined by invasive FFR. To date, three separate multicenter prospective studies have examined the performance of FFR CT using invasive FFR as the gold standard.

The prospective, multicenter international Diagnosis of ISChemia-Causing Stenoses Obtained Via Non-invasivE FRactional FLOW Reserve (DISCOVER-FLOW) trial¹⁵⁸ was the first study to evaluate the accuracy of FFR CT in a prospective fashion. In this study, it was demonstrated that in 103 patients who underwent CTA and invasive FFR measurement, FFR CT was superior to CTA as a predictor of lesion-specific ischemia with higher accuracy, specificity, PPV, and NPV in both per-patient and per-vessel analyses.¹⁵⁸ Specifically, there was a significant improvement in accuracy of CCTA by FFR CT among the 50% to 69% stenosis group. Moreover, it was shown that in the scans with motion artifact, calcium artifact or low signal-to-noise ratio, FFR CT performed significantly better than CTA.

The Determination of Fractional Flow Reserve from Anatomic Computed Tomographic Angiography (DEFACTO) trial¹⁵⁹ was a multicenter study of 252 patients and 407 vessels were investigated by both FFR CT and invasive FFR. The primary end point was to assess the diagnostic accuracy of FFR CT compared to that of invasive FFR. The primary end point of the study was set as having the lower bound of the confidence interval for diagnostic accuracy to be more than 70%, because this represents a 15% increase in diagnostic accuracy over stress echocardiography or MPI when compared to invasive FFR. The per-patient diagnostic accuracy for FFR CT plus CT was 73% (95% CI, 67%-78%), which did not meet the prespecified primary end point. Although the performance of FFR CT did not meet the criteria for the prespecified primary end point, DEFACTO confirmed the superiority of FFR CT over CT alone for the determination of lesion-specific ischemia. The diagnostic accuracy of CTA alone was 64% (95% CI, 58%-70%), and FFR CT showed 9% absolute improvement in the diagnostic accuracy. Importantly, there was a significant improvement in the evaluation of intermediate severity lesions causing 30% to 70% luminal narrowing. DEFACTO also represents the first large-scale demonstration of patient-specific computational models to assess for lesion-specific ischemia from CT images.

The Analysis of Coronary Blood Flow Using CT Angiography: Next Steps (NXT) trial is the third multicenter prospective study that has evaluated the diagnostic performance of FFR CT using invasive FFR as a gold standard.¹⁶⁰ This study evaluated the diagnostic accuracy of an updated iteration of FFR CT and for the first time compared the FFR CT accuracy to ICA in predicting invasive FFR. Two hundred fifty-four patients had a clinically indicated CCTA before ICA. Diagnostic accuracy of FFR CT, CTA, and ICA were compared to invasive FFR. This study compared FFR CT with CCTA and ICA against the reference standard of invasive FFR in patients with CCTA stenosis of 30% to 90%. The area under the receiver-operating characteristic curve of FFR CT was 0.90 (95% CI, 0.87-0.94) versus 0.81 (95% CI, 0.76-0.87) for coronary CTA (P = .0008). The per-patient and per-vessel sensitivity, specificity, PPV, and NPV of FFR CT were superior to CTA for detecting lesion-specific ischemia. FFR CT was also superior in diagnostic accuracy for lesion-specific ischemia compared to diameter stenosis by ICA.

Following the validation of the diagnostic accuracy of FFR CT, it was then necessary to assess the potential impact FFR CT may have on clinical practice and patient outcomes. The Prospective LongitudinAl Trial of FFR CT: Outcome and Resource IMpacts study (PLATFORM) trial was published in the European Heart Journal in 2015. PLATFORM is a multicenter, prospective consecutive cohort study conducted in 11 European sites with a total of 584 patients. The aim of the PLATFORM trial was to compare the accuracy and clinical outcomes of a CCTA/FFR CT–guided approach to assessing stable patients at intermediate risk (20%-80%) of obstructive CAD. Importantly, there were two separate arms of the trial. One arm aimed to evaluate the potential role of CTA/FFR CT as a gatekeeper to the coronary angiography by comparing the rate of nonobstructive disease at the time of ICA in those who simply underwent ICA when referred as compared to those who only underwent ICA following an abnormal CT/FFR CT assessment. The second, noninvasive arm, compared a noninvasive strategy of CTA/FFR CT to a traditional noninvasive assessment, with any chosen ischemia test. The primary end point was the rate of nonobstructive CAD (< 50%) at ICA in the cohort planned for ICA, where CCTA/FFR CT was used as a gatekeeper compared to the arm of direct ICA. The secondary accuracy end point was the rate of nonobstructive CAD at ICA in the noninvasive cohort with standard noninvasive testing as gatekeeper to ICA compared to CCTA/FFR CT as gatekeeper. The clinical outcomes' end point was the rate of MACE and vascular complications as well as resource utilization, change in quality of life, and cumulative radiation exposure. MACE was defined as all-cause mortality, nonfatal MI, and unplanned urgent revascularization.¹⁶¹

With respect to the primary end point, the rate of nonobstructive CAD in the standard-of-care invasive cohort was 73.3% compared to only 12.4% in the CCTA/FFR CT arm (P < .0001). An impressive 61% of CCTA/FFR CT patients had ICA canceled with no resultant adverse events; however, the reported follow-up period was short, at 90 days.¹⁶¹

The comparison of radiation exposure between the groups in PLATFORM was suboptimal. The CCTA radiation exposure was calculated for each individual case or inferred using the median measured value. For all other modalities, predetermined standard values were used; 7 mSv for ICA, 15 mSv for percutaneous coronary intervention, and 14 mSv for MPI.¹⁶¹ The use of standardized values instead of measured values reduces the robustness of the radiation dose comparison, which showed a significantly lower dose in the usual care arm (5.8 mSv) versus the FFR CT arm (8.8 mSv) in the noninvasive cohort. No difference was shown in the invasive cohort with respect to radiation dose.

A cost-effectiveness analysis of the PLATFORM trial demonstrated that among patients in the invasive strategy arm the use of CCTA/FFR CT as a gatekeeper to ICA was considerably less expensive than the usual care arm ($7,343 vs $10,734; P < .0001). By trial design, 100% of patients in the ICA usual care arm proceeded to coronary angiography compared with 61% in the FFR CT arm. Importantly, despite the lower rate of ICA, the rate of coronary revascularization was comparable between the two strategies (28% vs 32%). This important cost analysis seems to suggest that FFR CT is not only more accurate than traditional stress testing for lesion-specific ischemia by FFR but that it is also a cost effective method to determine which patients will benefit from ICA and revascularization.

In the noninvasive arm of the trial, despite the higher rates of ICA (18% vs 12%) and revascularization (10% vs 5%) in the FFR CT cohort, the 90-day cost of care was not significantly different than that in the usual care group ($2,679 vs $2,137; P = .26). Interestingly, there was a greater improvement in quality of life scores in the FFR CT group (19.5 vs 11.4; P = .04), which one could hypothesize may reflect more appropriate physiologically guided revascularization.¹⁶²

Association of Plaque Morphology on Computed Tomography Angiography and Invasive Fractional Flow Reserve: An Emerging Concept in Coronary Atherosclerosis

As mentioned above, the relationship between FFR and luminal stenosis is not perfect,¹⁶³ because there are numerous examples of IWOS and SWOI seen in day-to-day clinical practice and have been reported in various studies.^134,135 Features other than the degree of luminal stenosis, such as lesion length, entrance angle, exit angle, size of the reference vessel, and absolute flow relative to the territory supplied, were originally thought to explain the lesions with IWOS and SWOI.¹⁶⁴ Recently, it has been shown that the presence of high-risk plaque features, especially large LAP, a CTA surrogate for necrotic core, is a strong predictor of FFR-verified ischemia independent of degree of luminal stenosis.^165,166 Local impairment of the vessel to dilate at the site of a large necrotic core may contribute to ischemia independent of the degree of luminal narrowing. A once nonsignificant stenosis with impaired local vasodilatory ability could cause significant functional stenosis when the adjacent segments dilate at the time of maximal hyperemia. The reason for such local inability of vessel to dilate at the site of large necrotic core could be related to reaching the Glagovian limit caused by the presence of significant positive remodeling, presence of significant local endothelial dysfunction at the site of large necrotic core,^{134,167,168,169} or disruption of the local signaling mechanism between intima and smooth muscle cells that is essential for vasodilatation resulting from the presence of large necrotic core.¹³⁵ As a result, FFR-negative lesions are more likely to be devoid of both large necrotic core and severe stenosis. Therefore, FFR may indirectly be a sensitive (but not specific) detector of stenotic plaques with large volume necrotic core.¹³⁵ This might also explain the favorable prognosis associated with negative FFR, given the excellent prognosis of lesions without large necrotic core on CTA.¹³⁵

Aortic Valve Disease

Minimally invasive transcatheter heart valve (THV) interventions have revolutionized the historical paradigm for the treatment of valvular heart disease. Since the first transvenous transcatheter aortic valve replacement (TAVR) performed by Alain Cribier in 2002, TAVR has seen rigorous validation and now broad clinical adoption being considered the first-line treatment for high and extreme-risk patients with severe symptomatic aortic stenosis.^{170,171,172,173,174} In fact, the technique is seeing even further growth in clinical integration in the intermediate-risk population.¹⁷⁵ Along with its rapid adoption in clinical practice, the pretreatment planning has also undergone significant transformation from its early days where sizing and device selection were largely dependent on 2D echocardiography. MDCT is now the primary noninvasive imaging tool for the evaluation of patients prior to TAVR and includes annular sizing, aortic root assessment, provision of coplanar angles to guide implantation, evaluation of suitability of vascular access, and screening for procedural complications.¹⁷⁶

Annulus and Root Assessment

The word annulus comes from the Latin word meaning “ring.” In reality, though, the aortic annulus is an almost uniformly noncircular structure. This was, however, underappreciated historically because of the limitations of 2D imaging. As a result, early THV selection, which was performed with 2D echocardiography, often resulted in deploying a valve that was too small for the annulus, often leading to significant paravalvular regurgitation following valve deployment.^{171,172,177,178} MDCT, with its isotropic voxels and resulting comparable spatial resolution in all reconstructed planes, affords a robust platform to characterize the 3D complex anatomy of the aortic annulus in a granular and reproducible fashion¹⁷⁶ (Figs. 17–16 and 17–17).

The concept of the virtual basal ring, immediately below the hinge point of the aortic valve cusps, was first described by Piazza and colleagues in 2008 as the anatomical correlate of the aortic annulus given that there is no well demarcated anatomical landmark otherwise present.¹⁷⁹ This basal ring can be easily generated in its true short axis using standardized multiplanar reformatting in either a manual or facilitated fashion (see Fig. 17–16). Once generated, various measurements of the annulus can be performed that facilitate device sizing and selection. These include but are not limited to the short and long axes, the perimeter, and the area. In the very early days of CT integration into TAVR practice, it was shown that the mean annular diameter and area measurements^178,180 were the most reproducible across readers and work station platforms. The perimeter, which has been subsequently integrated into THV sizing, was not as stable because of the lack of contour smoothing algorithms across all work stations until recently. Establishing the most reproducible measurements was, however, only a first step toward CT integration. Initial sizing was on the basis of 2D diameters and measurements such as area and perimeter were confounding to the proceduralist and imager.

Sizing algorithms using CT 3D measurements began to appear in 2012. Willson and colleagues proposed area-based sizing for the balloon-expandable Edwards Sapien XT (Edwards Lifesciences, Irvine, CA) with a recommended threshold of 5% to 20% area oversizing to help mitigate the risk of paravalvular regurgitation. This threshold of oversizing needs to be greater for the self-expanding device (Corevalve, Medtronic) given the lower radial force of the device to obviate significant paravalvular regurgitation. Initial experiences with CT sizing for this device were consistently performed on a stable CT work station solution with perimeter smoothing available and, as such, perimeter has become the default measurement for sizing this device. The degree of oversizing recommended based on perimeter is approximately 15% to 30%.^173,181 Importantly, these measurements are performed in late systole when the annulus is the largest. Some have argued the perimeter is impervious to the dynamism of the cardiac cycle¹⁸²; however, these data are primarily derived from bench phantom work and with data derived from cardiac CT, suggesting that the perimeter of the annulus changes throughout the cardiac cycle. This is not surprising because the annulus not only undergoes conformational change but also experiences a degree of stretch. Blanke and coworkers noted that the annular perimeter changes approximately 7% as compared to annular area, which undergoes closer to 15% change over the course of the cardiac cycle.^183,184 These data have been reproduced by others, supporting the importance of consistently measuring the annulus in systole or at least being aware of the dynamic changes in the cardiac cycle when using diastolic measurements for sizing with a systolic sizing algorithm.^185,186 Given the dynamism of the annulus throughout the cardiac cycle, it is still recommended that retrospective ECG gating be performed with peak tube current in late systole.

Sizing Algorithms

Current sizing algorithms for THVs being used in practice are based on systolic area and perimeter measurements of the aortic annulus from MDCT. Typically, the goal of device selection is to place a THV that is larger than the native annulus to help reduce the risk of nonapposition and paravalvular regurgitation.^{177,178,187,188,189,190} The degree of oversizing recommended varies between device platforms and depends on the radial force of the selected device. Balloon-expandable devices, although associated with greater risk for annular injury, require less oversizing to control paravalvular regurgitation while balancing with the potential risk of annular injury that can occur more frequently with these devices. From an imaging perspective, there are important CT findings beyond annular size that are important to identify to help guide the procedure.

Subannular and extensive annular calcium has been shown to be associated with increased frequency and severity of paravalvular regurgitation.¹⁹¹ In addition, in a multicenter registry of patients who experienced annular rupture, Barbanti and colleagues showed that subannular calcification, particularly below the noncoronary cusp,¹⁹² is associated with an increased risk of annular rupture, particularly in conjunction with oversizing greater than 20% by area.^192,193 The identification and evaluation of the subannular zone is now routine and helps determine device sizing and often the type of THV used (Fig. 17–18).

MDCT is also extremely helpful in reducing the risk of coronary occlusion during TAVR. Coronary occlusion is said to occur in 0.66% of TAVR procedures and is associated with a poor clinical outcome. The mechanism of coronary occlusion relates to the native aortic valve leaflet being displaced up toward the coronary ostium. In the early days of TAVR, angiography was the only modality that allowed for prediction of coronary occlusion preemptively and its performance in doing so was modest. CT allows for accurate assessment of both the height of the coronaries as well as the size and capacity of the sinus of Valsalva.¹⁹⁴ In 2013, a registry was published highlighting the preprocedural anatomical findings that help predict the risk of occlusion. The authors collected 42 cases concerning patients who experienced coronary occlusion and had undergone a contrast-enhanced CTA in advance of the procedures. The authors were able to match 27 of these patients to patients who did not experience rupture. They found that left main height of less than 12 mm in conjunction with shallow of Valsalva mean diameter (cusp to commissures) of less than 30 mm was associated with an over five-fold increased risk of coronary occlusion (Fig. 17–19). In addition, a sinus of Valsalva–to–annular ratio of less than 1.25 was also strongly predictive of an increase risk.

Fluoroscopic Angle Prediction with Multidetector Computed Tomography

In TAVR, the proceduralist seeks to use a fluoroscopic angle that allows for the profiling of all three aortic cusps in a single plane. This allows for appropriate device deployment to ensure adequate positioning and reduce the burden of paravalvular aortic regurgitation (PAR). This angle selection can be performed at the time of the procedure through repeated angiographic root injections and perhaps 3D rotational angiograms.^195,196,197 Although this may be effective, it requires repeated contrast injections and, at times, rapid pacing while the spin is being performed, which somewhat limits these techniques. MDCT can provide coplanar angles for valve deployment that correlate with the angles obtained at the time of the procedure. From experience, the aortic root is typically angled a right anterior oblique caudal fashion with rotation to more carinal angulation extending to the left anterior oblique direction. There are, in fact, innumerable angles falling on this S-shaped curve that are coplanar to the root of the aorta, however, because of the limited number of feasible working angles in the hybrid operating room. It has largely become convention to provide angulation at straight anterior-posterior and some varying degrees of caudal or cranial angulation as well as at least on left anterior oblique angle. Preprocedural angle prediction with CT have been shown to correlate well with rapidly paced 3D rotational angiography performed at the time of the procedure¹⁹⁵ when the patient is positioned in a similar fashion for the CT and the ICA.

Reducing the Frequency of Root Injury

Annular injury, manifesting as uncontained or contained root rupture, is a feared complication of transaortic valve implantation (TAVI). Prior to routine integration of cardiac CT, there was the impression that this was a random event associated with balloon-expandable THVs. Through a registry of patients undergoing MDCT prior to TAVI, certain patient- and procedure-related predictors have been identified.^192,193 This registry highlighted that subannular calcification, particularly moderate/severe in grade, was much more common in those patients who experienced annular injury as compared to those who did not. In addition, the authors found that oversizing the annular area by greater than 20% resulted in an incrementally elevated risk. Building on these findings, Hansson performed a more elaborate analysis on the pattern and distribution of calcium using an advance postprocessing algorithm.¹⁹² This analysis confirmed the importance of left ventricular outflow tract (LVOT)/subannular calcification but importantly highlighted that it is really the immediate subannular calcium within 2 mm of the annulus that drives the increased risk. In addition, although most clinical reports have suggested that rupture most commonly occurs below the left main (LM) in an area of relative annular weakness, the calcification is most commonly seen below the noncoronary cusp. These findings have impacted clinical practice with the subannular space now very much being a part of the clinical report and guiding device size selection with the goal of ensuring that annular oversizing is more modest in its presence. Unfortunately, while subannular calcification is an accepted driver of annular rupture, it is also a well-accepted mechanism of paravalvular regurgitation. Protruding nodules of calcification, by preventing THV apposition, often result in PAR, which further complicates device sizing. The appropriate device type and size in the setting of such subannular calcification remains uncertain, but it is imperative that the CT imager understand these potential pitfalls and carefully interrogate and report on the subannular space.

MDCT for Valve in Transcatheter Aortic Valve Replacement

THV deployment within a failing surgical bioprosthesis is becoming an increasingly common procedure for those patients deemed to be at high or excessive surgical risk (Fig. 17–20). This treatment has been shown to be effective at relieving surgical aortic valve replacement (SAVR) valve regurgitation and stenosis with good 30-day and intermediate-term outcomes.^198,199 Although this procedure has shown great promise in its early days, it is not without limitations or complications. Increased THV gradients is the most common complication, with malpositioning probably the second. Although less common, mechanical occlusion of the coronary ostia is a feared complication associated with a high mortality. The role of MDCT in the preprocedural assessment of patients prior to valve-in-valve (VinV) therapy is evolving. Sizing of the THV for the procedure is largely determined by the type and size of the failing surgical valve, with CT being limited to guide device selection in the setting of unknown surgical valve history and to assess the extent of pannus when present. The most important clinical role at present for CT in VinV is to help mitigate the risk of coronary occlusion.

To use anatomical imaging with MDCT to reduce the risk of coronary occlusion with VinV, one must first have an understanding of the mechanism of coronary occlusion with this procedure (which is different than with native TAVI). With native TAVI, coronary occlusion occurs when the native aortic valve leaflet is displaced by the THV and occludes a typically low left main coronary artery. On the other hand, with VinV, the surgical aortic valve leaflets are displaced and wedged between the THV and the surgical bioprosthetic valve struts resulting in the formation of a covered stent in the root of the aorta. If the surgical aortic prosthetic stent struts do not extend above the coronary ostia, if the sinuses are capacious, and if the surgical valve is centrally positioned, coronary occlusion rarely occurs. If, however, the sinuses are shallow and the SAVR valve is canted toward the coronary ostium, then the risk of occlusion is much higher. Importantly, with the anatomical detail afforded by MDCT, one can assess for these at-risk features, including the angulation and positioning of the SAVR valve, which is less easily done with other imaging modalities. Simple modeling of a ring the size of the THV is planned to be implanted at the level of the SAVR valve tips, integrating the tilting/canting of the valve, allowing for an estimation of the risk of coronary occlusion. This methodology allows for the determination of a measure referred to as a “the virtual ring to coronary ostial distance,” or the VTC. Although not yet broadly validated, thresholds of less than 3 mm, 3 to 6 mm, and greater than 6 mm have been proposed as VTC measurement cutpoints to discriminate the risk of coronary occlusion.²⁰⁰

Beyond the Aortic Valve

The success story of TAVR has resulted in a significant amount of interest in the development and validation of transcatheter solutions for other valvular diseases. Given the incidence of mitral regurgitation and the frequency that patients with functional mitral regurgitation in particular are not considered surgical candidates, transcatheter mitral valve replacement (TMVR) has become one of the hottest topics in structural heart disease.^{201,202,203,204} To date, there have been six devices implanted in humans showing promising feasibility and many more undergoing animal testing. Given the years of validation of MDCT to support TAVR, the role of MDCT in TMVR has been evident from day one. Cardiac CT allows for a 3D and granular assessment of the saddle-shaped mitral annulus. In addition, using commercially available postprocessing, the annulus can be reconstructed in a highly reproducible fashion. CT has also allowed us to propose the concept of the D-shaped annulus, truncating the anterior peak at the level of the fibrous trigones, which has been shown to be more conducive for appropriately measuring for device sizing^200,205,206 (Fig. 17–21). Cardiac CT is also able to provide procedural guidance providing coplanar angles of deployment²⁰⁷ similar to TAVR. In the mitral position, the coplanar curve is much steeper than the aortic annular curve. This results in many angles requiring an excessively caudal angulation for use in the hybrid operating room. This is commonly the case to generate an angle coplanar to the commissure-commissure line, with angles parallel to the septal-lateral line being achievable. Puncture site localization is also more complex than with TAVR as deploying the device along an axis oriented perpendicular to the 2D mitral annular plane is very important to ensure device sealing and avoid device migration. As a result, the appropriate access point is commonly not the true apex frequently anterior and anterolateral with substantive interpatient variability.²⁰⁶ CT is also very helpful in determining the appropriateness of other anatomical parameters for the varied transcatheter mitral valve devices. Nodular or extensive mitral annular calcification poses challenges for use of most of the current devices. In addition, the capture and sealing mechanisms are varied among the devices, with some having a tether to the apex and others using barbs/tabs to engage a posterior shelf commonly seen in functional mitral regurgitation.

In a fashion to TAVR, cardiac CT has been shown to be helpful in identifying patients at risk for TMVR-related complications. Annular rupture and coronary occlusion are not of concern, but rather with TMVR, there is a significant concern regarding LVOT obstruction. THVs in the mitral position protrude into the LV cavity, resulting in displacement of the anterior mitral valve leaflet toward the basal septum, leading to remodeling of the outflow tract by elongating the outflow tract into the left ventricle.²⁰⁶ We have proposed that this remodeled LVOT be referred to as the “neo-LVOT,” which can be routinely modeled using basic 3D work station algorithms; these integrate the device size and its positioning into a “postimplant CT,” which will allow a better understanding of the remodeling of the LVOT that will develop following the procedure.²⁰⁸ Clearly, this modeling has many limitations, including an assumption of postimplant device positioning and its inability to predict dynamic LVOT obstruction related to the native mitral valve. In the future, more advance dynamic 3D models from CT, integrating CFD or other computational/simulated approached may allow for a more thoughtful approach to the prediction of the risk of LVOT obstruction post-TMVR.

CT scanning provides excellent visualization of the pericardium and associated lung and mediastinal structures. The low density of epicardial and extrapericardial fat outlines the pericardium and serves as a natural contrast. Therefore, even minimal (4-5 mm) pericardial thickening and calcification is easily detected.²⁰⁹ CT can be useful particularly when visualization of the pericardium is suboptimal with echocardiography. Contrast-enhanced CT can elucidate inflammation of the pericardium and can be diagnostic for pericarditis in the appropriate clinical setting.²¹⁰ In addition, cardiac CT can readily detect pericardial effusion and hematoma and may help distinguish different processes within the pericardial space based on density or attenuation.²¹¹ Cine mode images of the right atrium and right ventricle can also detect diastolic collapse when pericardial tamponade is present.²¹² Enlargement of the superior and inferior vena cavae can be identified when either tamponade or constriction is present.¹⁹⁴ Furthermore, cardiac CT is useful in accurately diagnosing constrictive pericarditis and differentiating it from similar conditions, such as restrictive cardiomyopathy. A pericardial thickness of more than 4 mm in a patient with abnormal rapid early LV diastolic filling is diagnostic of pericardial constriction.²¹³

Congenital abnormalities such as absence of the pericardium or pericardial cyst can also be evaluated with cardiac CT.²¹⁴ CT is currently one of the best techniques for defining the location and extent of pericardial tumors and diagnosing metastatic involvement of the pericardium from mediastinal tumors.²¹⁵

Cardiac CT and MRI have been increasingly used for the assessment of congenital heart disease. Both modalities can be rendered into 3D images that are useful in clarifying the often complex anatomic relationships in patients with congenital heart disease. MRI may be of limited use in critically ill patients because of its relatively long scan time, and it is contraindicated in patients with history of severe claustrophobia and with metallic implants. Despite these limitations, MRI is still preferred over MDCT because it does not involve ionizing radiation or nephrotoxic contrast agents and allows the precise quantification of flow with superior tissue characterization. However, advances in CT image quality, decreases in radiation dose, and the provision of accurate functional information have helped make CT a viable alternative. Furthermore, MRI most often requires significant sedation in children (often necessitating intubation), which is not necessary with the fast study times of CT.

Anomalies of the aortic arch, patent ductus arteriosus, tetralogy of Fallot, and abnormal arteriovenous connections can all be carefully evaluated with cardiac CCTA (Fig. 17–22).²¹⁶ The high spatial resolution of MDCT also permits the evaluation of the atrioventricular valves in conditions such as Ebstein anomaly and tricuspid and mitral valve atresia.²¹⁷ MDCT can also be used to accurately quantify intracardiac shunts as well as cardiac masses.^218,219 Both atrial and ventricular septal defects can be detected and analyzed with CCTA (Fig. 17–23). MDCT evaluation has been used prior to closure device implantation.²²⁰ Arrhythmogenic RV cardiomyopathy is accurately diagnosed based on the characteristic CT findings of an enlarged right ventricle, with a scalloped appearance, trabeculations with low attenuation characteristics, and abundant epicardial adipose tissue.²²¹

The development of four-dimensional (4D) capability has accelerated over the past few years. The heart is a dynamic organ best understood when studied throughout the cardiac cycle. Hence, the development of 4D CT cine angiography (time being the fourth dimension) is a milestone in the clinical application of this technology. It is ideally suited for the complex dynamic dilemmas frequently encountered in congenital heart disease.

In conclusion, the application of CT in evaluating congenital heart disease is feasible and appropriate. In selected cases, CT may be a valuable alternative to MRI for both structural and functional delineation of the anatomic abnormality.

Cardiac neoplasms are rare and have a reported prevalence of 1 to 3 per 10,000 patients in autopsy series.²²² The most common primary cardiac neoplasm is myxoma, which accounts for more than half of all cases.²²² Although the majority of these tumors are benign, there is a 10% mortality associated with myxomas, a 30% mortality with nonmyxoma benign tumors, and 100% mortality within 3 years in all patients with malignant cardiac tumors.²²³ In addition, the clinical course can be complicated by arrhythmias or ventricular dysfunction caused by mass effect or tamponade, which makes prompt diagnosis and management imperative. Echocardiography is usually the first diagnostic test, particularly in patients with tumor-related cardiac symptoms, such as tamponade, heart failure, or systemic emboli. However, CT has expanded the diagnostic capabilities of imaging beyond that of echocardiography. The presence and extent of intracardiac tumors can be well defined with either MDCT or EBCT. In the evaluation of cardiac tumors, MDCT can help differentiate benign from malignant masses and delineate metastatic tumor within the myocardial wall.²²⁴ Given the precise anatomic information afforded by MDCT, presurgical assessment of cardiac neoplasms with MDCT may assist in determining the resectability of tumors and allow planning for the reconstruction of cardiac chambers.

Conventional CT is widely used for diagnosing thoracic aortic aneurysms and dissections.^225,226 With the introduction of MDCT scanners, thousands of images can be acquired within a single breath-hold, and a complete study of the thoracic aorta can be completed in only 10 to 15 seconds. After scan acquisition, 3D reconstructions are produced, which can be rotated and analyzed in multiple views. EBCT can also acquire rapid CT images with elimination of aortic pulsation as a cause of potential artifact.²²⁷

Aortic dissection is readily diagnosed with CTA with greater than 90% accuracy (Fig. 17–24).²²⁶ In a study comparing MDCT, MRI, and 2D echocardiography, CT and MRI were shown to be superior to echocardiography in diagnostic accuracy.²²⁸ CTA can also be used in monitoring of the expansion of thoracic aortic aneurysm over time.²²⁶ In addition, MDCT can diagnose atherosclerotic disease of the aorta, aortic intramural hematoma, penetrating aortic ulcer, sinus of Valsalva aneurysm, and coarctation of the aorta.^225,226

In patients undergoing repeat coronary artery bypass surgery, MDCT scanning has several advantages. CTA may guide the surgical approach by defining the position of the sternum to the right ventricle, establishing patency of existing grafts, and visualizing the aorta, thereby avoiding unnecessary trauma and bleeding.²²⁹

MDCT²³⁰ can diagnose acute and chronic pulmonary thromboembolism (Fig. 17–25). CTA of the pulmonary arteries has replaced nuclear ventilation/perfusion scans as the primary imaging study in the diagnosis of acute pulmonary embolism.²³¹ The cross-sectional view of the main and proximal right and left pulmonary arteries provides clear delineation of the proximal extent of the thrombi, which is essential for successful surgical treatment.²³² Accurate measurement of pulmonary artery size may also help to estimate the severity of pulmonary hypertension.²³³

Triple rule-out (TRO) CTA can evaluate the coronary arteries, pulmonary arteries, aorta, and intrathoracic structures in select patients presenting with acute chest pain of unclear etiology.⁷² Standard 64-slice MDCT scanners can provide high-quality TRO CTA studies by tailoring the injection of iodinated contrast to provide simultaneous high levels of arterial enhancement in the coronary arteries and aorta (> 300 HU) and in the pulmonary arteries (> 200 HU).²³⁴ Radiation exposure is minimized by limiting the imaging window to include from the aortic arch down through the heart, rather than encompassing the entire chest. In addition, the same imaging parameters, such as prospective gating and current modulation, used in CCTA are incorporated into the TRO CTA to limit ionizing radiation doses to between 5 and 9 mSv. New dual-source and whole-heart single-beat scanners allow for further optimization of the timing of image acquisition to allow for straightforward evaluation of both vascular beds with ECG synchronization. When used in the emergency department in appropriately selected patients, TRO CTA can eliminate the need for further diagnostic testing in more than 75% of patients.²³⁴

Lastly, CTA can be used for the noninvasive evaluation of the coronary veins prior to lead placement for a biventricular pacemaker or to assess the pulmonary vein anatomy prior to pulmonary vein isolation with radiofrequency ablation for the treatment of atrial fibrillation.⁷² CTA can also be used in the evaluation of the symptomatic patient after atrial fibrillation ablation to exclude the presence of pulmonary vein stenosis, which can be rapidly progressive and may require further intervention in the postprocedural period.¹⁸⁰

The main historical limitation of MDCT has been the radiation exposure, which used to be two to four times the radiation dose of diagnostic ICA. However, with multiple advancements in technology, there are several effective means of reducing the radiation dose during CCTA to 1 to 3 mSv. The most significant, and routinely available, radiation reduction strategy (up to 79%) can be achieved through prospective ECG-gated or sequential CCTA image acquisition, which involves the use of axial scanning with the tube current on only during prespecified portions of the cardiac cycle, eliminating tube current (milliampere) during nonimaging portions of the cardiac cycle (ie, systole).^3,235 Additionally, radiation exposure can be further minimized by approximately 46% to 53% by decreasing the tube voltage in nonobese (body mass index < 30 kg/m²) patients from 120 to 100 kVp.^236,237 More recently, new iterative reconstruction algorithms have been introduced and validated for use in cardiac CT to allow for significant noise reduction, enabling an uncoupling of tube current and image noise and thereby allowing for significant tube current and dose reduction.²³⁸ All major CT vendors offer similar algorithms, making them the standard algorithm for coronary CT angiography, Finally, new scan acquisition modes employing fast helical pitch technique afforded by dual source dual detector technology allow for rapid scan acquisition and significant dose reduction as a result.²³⁹ Implementation of one or more of these strategies has been shown to consistently reduce radiation exposure to less than 15 mSv²⁴⁰ and can even achieve radiation doses as low as 1 to 3 mSv in suitable patients.

Coronary CTA has undergone significant development and evolution in the past 15 years, since its first description in clinical medicine. From its infancy with 2.5 mm slice acquisition, temporal resolution of 250 milliseconds, and z-axis coverage of 2 cm, modern cardiac CT scanners now offer spatial resolution of 0.5 mm, temporal resolution up to 67 milliseconds, and 16-cm whole heart coverage. In addition to improvements in scanner technology, new CT scan acquisition protocols and software algorithms allow the performance of coronary CTA at significantly lower estimated effective radiation dose exposures than were previously achievable.

The clinical utility of cardiac CT has grown exponentially in conjunction with these technological improvements. While coronary calcium scoring has seen an explosion in validation data, the diagnostic accuracy of coronary CTA is now well established and is considered the noninvasive gold standard for detection and exclusion of anatomical obstructive CAD; this is supported by large-scale robust prognostic data. Recent multicenter randomized clinical trials have shown coronary CT to be a viable alternative to traditional stress testing in the setting of stable chest pain with higher diagnostic certainty. Also, it is associated with lower nonobstructive disease incidence at the time of invasive angiography and a significant trend toward lower rates of downstream MI. Similarly, in the acute setting, coronary CTA has been shown to allow for more rapid discharge than traditional algorithms in a safe and cost-effective fashion. Evolving new applications for the adjudication of the hemodynamic significance of stenosis such as CT myocardial perfusion and FFR CT are now being used in clinical practice. Evaluation of plaque morphology and identification of high-risk plaque features and their prognosis is enhancing the understanding of mechanism of acute events in CAD and might prove very useful clinically in the near future.

Finally, the field of structural heart disease interventions are now increasingly dependent on the spatial resolution and unparalleled anatomical evaluation noninvasively offered by cardiac CT.

We would like to thank Dr. Melissa A. Daubert, Dr. Michael Poon, and Dr. Matthew J. Budoff, who contributed to the previous version of this chapter in the 13th edition.