Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Staging of Renal Cell Carcinoma CT Abdomen and Pelvis Preoperative imaging of RCC provides critical information on staging and serves as a roadmap to the surgeon. Both CT and MRI are comparable in the staging of the primary tumor [15,16]. Some of the advantages of CT include rapid acquisition time, and hence it is often the most commonly used modality for this indication. CT abdomen without and with IV contrast is typically performed for charactering a renal mass as RCC and staging the tumor. However, in patients with contraindications to iodinated contrast, only unenhanced CT may be possible. However, in patients with contraindications to iodinated contrast, only unenhanced CT may be possible, limiting the assessment. MRI abdomen may be useful in this setting, given the superior soft tissue resolution of MRI compared to unenhanced CT.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. There is no relevant literature with high-quality evidence regarding the use of CT of the pelvis in the staging of RCC. Although it is likely that CT pelvis may not offer additional information in most patients with early stage RCC, pelvic imaging can be helpful in patients with more advanced RCC, in whom metastatic spread is suspected [47,48]. If pelvic imaging is indicated in patients with contraindications to iodinated contrast, pelvic MRI may be preferred to unenhanced CT pelvis.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. CT Chest Chest imaging is indicated in the staging of RCC, given that lungs are one of the most common sites of metastases in RCC [5,13]. There is a lack of literature that have directly compared the accuracy of chest CT with chest radiography for detecting pulmonary metastases in the initial staging of RCC. However, limited data have demonstrated that CT is more sensitive than radiography for the detection of pulmonary metastases from RCC [49].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Current literature supports use of IV contrast-enhanced CT chest for detecting pulmonary metastases, especially in patients with large renal tumors [5,13,34,63,64,74,75]. However, in patients with contraindications to iodinated contrast, unenhanced CT chest may be performed because that would be able to detect pulmonary nodules, despite the lack of IV contrast.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. CT Head Most patients with metastases to the central nervous system are symptomatic. Thus, current guidelines from the EAU and NCCN do not support routine imaging of the brain to search for metastases in asymptomatic patients in the initial staging of RCC. Brain imaging should be performed only in cases with suggestive signs or symptoms [5,13]. In symptomatic patients with contraindication to IV contrast, MRI brain without contrast may be helpful.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. CTU CTU There is no relevant literature suggesting that CTU offers any additional benefit over conventional CT of the abdomen in the initial staging of RCC, and thus, this method is not included in the guidelines from the EAU and NCCN [5,13].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT has a limited role in the diagnosis and local staging of RCC [58]. Differentiating renal tumor from background normal renal tissue can be difficult because of renal excretion of FDG. Furthermore, RCC is reported to have variable FDG avidity, limiting its utility. Nakanishi et al [59] reported a 56% sensitivity, a 67% specificity, a 15% positive predictive value, a 57% negative predictive value, and a 65% accuracy for FDG-PET in the staging of RCC. A recent clinical trial from Turkey involving 62 patients with RCC reported an 84% accuracy for contrast- enhanced FDG-PET/CT in staging RCC [60]. However, further studies are warranted before PET/CT can be used in the routine initial staging of RCC. At present, given the paucity of literature to support the use of FDG-PET/CT, the guidelines from the EAU and NCCN do not recommend routine FDG-PET/CT in the initial staging of RCC [5,13].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Fluoride PET/CT Skull Base to Mid-Thigh Preliminary results for other PET tracers are also becoming available. In a small prospective study of 10 patients with metastatic RCC, 18F-NaF PET/CT was found to be significantly more sensitive for the detection of RCC skeletal metastases than Tc-99m bone scintigraphy or CT, with sensitivities of 100%, 29%, and 46%, respectively. CT and Tc-99m bone scintigraphy in this study identified only 65% of the metastases detected by fluoride PET/CT [61]. However, given the paucity of litereature for utility of fluoride PET/CT in the initial staging of RCC, current guidelines from the EAU and NCCN do not support routine fluoride PET/CT to search for metastases in asymptomatic patients in the initial staging of RCC [5,13].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Staging of Renal Cell Carcinoma MRI Abdomen and Pelvis MRI of the abdomen without and with IV contrast is considered to be a reliable method for the staging of RCC and may be of greater benefit in patients with contraindications for iodinated contrast for CT. Various MR sequences, including T2-weighted, chemical shift T1-weighted, contrast-enhanced T1-weighted, and diffusion-weighted images, are typically obtained for the staging of RCC. In a study involving 40 patients with RCC, MRI was reported to have an accuracy of 81% to 86% for T staging [62]. Breath-hold MRI showing lack of perinephric fat involvement is reported to have a high negative predictive value for no perinephric tumor invasion [63].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. In a study of 73 RCCs, Roy et al [64] showed that the presence of a pseudocapsule on MRI had an accuracy of 93% for clear-cell carcinomas in separating T1/T2 tumors from T3a tumors. Lal et al [65] performed a prospective observational study in 50 patients with RCC, comparing MRI with histopathological findings. In this study, MRI was reported to have a 90% agreement with histopathology for detecting perirenal extension and a 97% agreement with histopathology for detecting tumor extension beyond Gerota fascia [65]. Both contrast-enhanced multidetector CT and MRI are helpful in detecting venous involvement, particularly in the main renal vein and the IVC [33,66].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Increased diameter of the IVC and renal vein, presence of tumor signal both inside and outside the vessel wall, altered signal intensity in the vessel wall, presence of flow around the tumor thrombus, and mobility in different phases are some of the MRI features that are helpful in detecting venous involvement [67,68]. Bland thrombus featuring a uniform signal intensity and lack of enhancement after gadolinium can be distinguished from tumor thrombus, which exhibits intermediate or high signal intensity, heterogeneous intensity, and, more reliably, the presence of small vessels. In a recent study involving 81 patients with RCC, MRI was reported to have a 92% sensitivity, an 86% specificity, an 89% positive predictive value, and a 91% negative predictive value for identifying IVC wall invasion [69]. Pitfalls of MRI include the potential for large tumors to compress the vena cava and cause flow-related artifacts. Such artifacts can be reduced with appropriate saturation pulses.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Although MRI of the abdomen with IV contrast is considered in all major guidelines as an adequate method for the staging of RCC, imaging the pelvis for RCC staging is considered optional in the guidelines [5,13]. There is no relevant literature with high-quality evidence regarding the use of MRI of the pelvis in the staging of RCC. Although it is likely that MRI pelvis may not offer additional information in most patients with early stage RCC, pelvic imaging can be helpful in patients with more advanced RCC, in whom metastatic spread is suspected [47,48].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. MRI Abdomen MRI of the abdomen without and with IV contrast is considered to be a reliable method for the staging of RCC and may be of greater benefit in patients with contraindications for iodinated contrast for CT. Various MR sequences, including T2-weighted, chemical shift T1-weighted, contrast-enhanced T1-weighted, and diffusion-weighted images, are typically obtained for the staging of RCC. In a study involving 40 patients with RCC, MRI was reported to have an accuracy of 81% to 86% for T staging [62]. Breath-hold MRI showing lack of perinephric fat involvement is reported to have a high negative predictive value for no perinephric tumor invasion [63].


Staging of Renal Cell Carcinoma


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. MRI Head Most patients with metastases to the central nervous system are symptomatic. Thus, current guidelines do not support routine imaging of the brain to search for metastases in asymptomatic patients in the initial staging of RCC.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Staging of Renal Cell Carcinoma Brain imaging should be performed only in cases with suggestive signs or symptoms [5,13]. In symptomatic patients with contraindication to IV contrast, MRI brain without contrast may be helpful.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. MRU There is no relevant literature suggesting that MRU offers any additional benefit over conventional MRI of the abdomen in the initial staging of RCC, and thus, this method is not included in the guidelines from the EAU and NCCN [5,13].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Radiography Chest The lung is the most common site of metastases in patients with RCC presenting with synchronous metastases. Although the incidence of metastases in RCC <4 cm is low (approximately 1%-2%), it has been reported that 20% to 30% of T1a tumors may have potentially aggressive histologic features. Hence, chest radiography is usually performed in the staging of RCC [13]. However, CT is more sensitive than radiography for the detection of pulmonary metastases from RCC during staging. In addition to a high sensitivity for the detection of pulmonary metastases, chest CT has a high sensitivity for the detection of intrathoracic nodal metastases from RCC. Therefore, in patients with higher risk of pulmonary metastases (such as tumor >4 cm, cN1, presence of systemic symptoms), chest CT is preferred [54,55].


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Staging of Renal Cell Carcinoma


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with chronic chest pain with a high clinical probability of CAD or known ischemic heart disease (IHD), imaging is used to characterize known and unknown IHD. In patients with no known IHD, imaging is valuable in determining and documenting the presence, extent, and severity of obstructive coronary narrowing as well as the presence of myocardial ischemia. Imaging also allows for exclusion of nonocclusive atherosclerotic CAD and/or


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. aHarvard Medical School, Boston, Massachusetts. bPanel Chair, Duke University Medical Center, Durham, North Carolina. cPanel Vice-Chair, Massachusetts General Hospital, Boston, Massachusetts. dUniversity of Michigan, Ann Arbor, Michigan. eUniversity of Virginia Health System, Charlottesville, Virginia; Nuclear cardiology expert. fUniversity of Michigan Health System, Ann Arbor, Michigan. gThe University of Chicago Medical Center, Chicago, Illinois; American College of Physicians. hOregon Health & Science University, Portland, Oregon. iQueen's University, Kingston, Ontario, Canada; Cardiology expert. jUniversity of California San Diego, San Diego, California. kVA Palo Alto Health Care System, Palo Alto, California and Stanford University, Stanford, California. lNaval Medical Center Portsmouth, Portsmouth, Virginia. mMassachusetts General Hospital, Boston, Massachusetts. nWake Forest University Health Sciences, Winston Salem, North Carolina; Society for Cardiovascular Magnetic Resonance. oUniversity of Virginia Health Center, Charlottesville, Virginia; Society of Cardiovascular Computed Tomography. pSpecialty Chair, UT Southwestern Medical Center, Dallas, Texas.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Reprint requests to: publications@acr.org


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD demonstration of abnormalities (eg, congenital or acquired coronary artery anomalies) as well as other etiologies for CAD that can produce chest pain in the absence of coronary obstructive disease.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with known IHD, imaging findings are important in determining the management of patients with chronic myocardial ischemia and can serve as a decision-making tool for medical therapy, angioplasty, stenting, or surgery. Imaging can help understand long-term prognosis and expected benefit from various therapeutic options by evaluating disease location, plaque characteristics, and pre-existing myocardial infarction, as well as determining ventricular function, diastolic relaxation, and end-systolic volume [7].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. OR Discussion of Procedures by Variant Variant 1: Chronic chest pain; high probability of coronary artery disease. No known ischemic heart disease. Initial imaging. Arteriography Coronary Catheter-based selective coronary angiography is historically considered the coronary imaging modality of choice with the highest spatial and temporal resolution. Although only 2-D projection images are obtained (as opposed to 3-D volumes in coronary CTA [CCTA]), selective coronary angiography is considered to be the reference standard for depicting the anatomy and the severity of obstructive CAD and other coronary abnormalities (eg, congenital variants, coronary spasm, dissection, vasculitis) [8]. In addition to visualizing the coronary arteries, the procedure is used to guide percutaneous coronary interventions to the site of the blockage. Hemodynamic relevance of coronary stenosis identified on invasive coronary angiography (ICA) is assessed by measuring fractional flow reserve (FFR) [9,10].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CT Coronary Calcium Coronary artery calcification is an indicator of coronary atherosclerosis presence and can be assessed using ECG- gated noncontrast CT of the heart [11]. There are limited data on the use of CT coronary calcium in symptomatic patients at a high risk for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CCS has been shown to provide value in symptomatic individuals presenting with chest pain for risk assessment for future events [12]. A zero CCS in patients undergoing CT scanning for suspected stable angina has a high negative predictive value (NPV) for the exclusion of obstructive CAD and is associated with a good medium-term prognosis [13].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In one large multicenter study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE] trial) that included patients with stable chest pain and no history of CAD, presence of measurable coronary artery calcification at the baseline was associated with clinical events [14]. A substudy of another larger multicenter trial (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors [CORE-64]) demonstrated that in patients with high probability of CAD and no known CAD, the absence of coronary calcification does not exclude obstructive stenosis [15]. Conversely, a prospective randomized controlled trial (Computed Tomography vs. Exercise Testing in Suspected Coronary Artery Disease [CRESCENT]) showed that in patients with stable chest pain and no known CAD, the presence of a coronary calcium and even a high total coronary artery calcification score is not clearly associated with ischemia [16].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD CT Heart Function and Morphology CT heart function and morphology can provide assessment of ventricular morphology and function as well as assessment of myocardial perfusion and infarction. There are no relevant data published on the use of CT heart for assessment of heart function and regional wall motion abnormalities in patients with chronic chest pain who have a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Several studies have validated stress CT myocardial perfusion against SPECT, stress cardiac MR (CMR), and invasive FFR in patients with suspected or known CAD (no clinical data reported on the presence or absence of chronic chest pain), and it was shown, when combined with CTA, to accurately predict perfusion abnormalities related to atherosclerotic luminal narrowing [19-23].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CTA Chest CTA chest has been shown to be effective in excluding noncardiac causes for chronic chest pain. It has also been shown in some studies to facilitate the diagnosis of acute coronary syndrome and the decision on emergent catheterization, when left ventricular (LV) myocardial ischemia is identified [24]. There is no relevant literature to support non-ECG-gated CTA of the chest in the evaluation of chronic chest pain for the initial evaluation of CAD in patients who are high risk and without known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CTA Triple Rule Out Triple rule out (TRO) is used for diagnosis of acute chest pain and simultaneous assessment of aorta, coronary arteries, and pulmonary arteries. There is no relevant literature to support the use of TRO in patients with chronic chest pain and a high probability of CAD with no known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CCTA obtained in addition to standard of care in patients with stable chest pain with a high pretest probability of CAD has been demonstrated to result in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years compared with standard of care alone [32]. CCTA has been shown to change treatment among 23% of patients in the CCTA arm compared with 5% in the standard-of-care arm with increased use of preventive therapy when atherosclerosis was identified and cancellations of preventive and antianginal therapy with normal coronaries [32].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CCTA and FFR-CT FFR-CT allows for determination of lesion-specific ischemia associated with a coronary arterial narrowing. FFR- CT is performed in conjunction with CCTA [33,34]. FFR-CT has a high diagnostic performance when compared against invasive FFR as the reference standard: 82% specificity and 74% PPV [33].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In a multicenter trial (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]), 5,083 patients demonstrated the prognostic value of CTA with FFR-CT in patients with stable chest pain with a trend to lower major adverse cardiac events and lower cardiovascular death or myocardial infarction with a negative FFR- CT [39].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRA Coronary Arteries Without and With IV Contrast Coronary MR angiography (MRA) does not assess late gadolinium enhancement or viability. MRA coronary arteries can demonstrate lumen narrowing of the proximal coronary arteries. There are limited data on the use of MRA coronary arteries without and with intravenous (IV) contrast in symptomatic patients with a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In a single-center prospective study in patients with suspected CAD, 82% sensitivity, 90% specificity, 88% PPV, and 86% NPV for detecting significant CAD were demonstrated [40].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRA Coronary Arteries Without IV Contrast There is limited data on the use of MRA coronary arteries without IV contrast in symptomatic patients with a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In symptomatic patients with an intermediate or high pretest probability for disease, noncontrast coronary MRA had a patient-based sensitivity of 96%, specificity of 68%, PPV of 79%, and NPV of 93% in the detection of functionally significant CAD as defined by a >90% stenosis or FFR <0.8 on catheter angiography. When added to a comprehensive stress-rest MRI protocol, it had a nonsignificant increase in diagnostic accuracy [42].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function and Morphology Without and With IV Contrast MRI heart function and morphology without and with IV contrast can demonstrate myocardial infarction and ischemia secondary to CAD and can provide assessment of LV wall function.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Areas of myocardial infarction detected on MRI have been shown to be a predictor of mortality and major adverse cardiac events, compared with clinical data, coronary sclerosis at angiography, or LV end-systolic volume index (ESVI) and LV ejection fraction (LVEF) in patients with suspected CAD, even when areas of infarction are small. Even a small area of infarction (<2% of LV mass) was associated with a greater than 7-fold increase in risk for a major adverse cardiac event. Delayed-enhancement MRI in patients without known CAD is associated with lower LVEF and greater LV mass [43].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center observational prospective study with 376 patients with a history suggesting stable CAD but with no history of myocardial ischemia demonstrated that evidence of myocardial infarction on CMR is an independent noninvasive marker of prognosis in stable CAD patients [44] and remains the strongest predictor of adverse events, even after adjustment for significant CAD on angiogram, LVEF, and wall motion abnormality [44,45].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function and Morphology Without IV Contrast MRI heart function and morphology without IV contrast provides assessment of ejection fraction and ventricular volumes including LVEF and ESVI with a higher sensitivity to detect prior myocardial infarct than ischemia.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD There is no relevant literature to support the use of MRI heart function and morphology without IV contrast in the initial evaluation of patients with chronic chest pain and a high probability of CAD with no known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function with Stress Without and With IV Contrast MRI with function/wall motion (dobutamine stress test) and MRI with vasodilator stress perfusion (adenosine/regadenoson stress test) have been used to diagnose hemodynamically significant CAD in patients with an intermediate to high likelihood of having significant stenosis.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Investigations of MRI heart function stress for patients with known CAD indicate that patients with known (70%) or suspected (30%) CAD with inducible LV wall motion abnormalities during dobutamine CMR predict cardiac death and myocardial ischemia [46]. A single-center prospective study focusing on women with known or suspected CAD and variable clinical symptoms demonstrated that, similar to men, dobutamine CMR can identify cardiac risk in women with known or suspected IHD [47]. A single-center study of 815 consecutive patients referred for evaluation of suspected myocardial ischemia over a 10 year period has shown that stress CMR with its protocol including stress and rest myocardial perfusion, ventricular function, and late gadolinium enhancement, effectively reclassifies patient risk beyond standard clinical variables, specifically in patients at moderate to high pretest clinical risk and in patients with established CAD [48].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI heart function stress has a high NPV for adverse cardiac events in patients with known or suspected CAD [46,47]. A meta-analysis of 14 studies has shown that MRI heart function stress has a high NPV for adverse cardiac events, and the absence of inducible perfusion defect or wall motion abnormality shows a similar ability to identify patients with a low risk for adverse cardiac events among patients with known or suspected CAD [49]. The MR- INFORM trial investigated MRI perfusion versus combined invasive angiography with invasive FFR in patients with stable angina and an intermediate to high risk of disease. The study showed that MRI perfusion had noninferior major adverse cardiac events compared with invasive FFR with the added patient benefit of a lower incidence of revascularization [50].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A meta-analysis from pooled studies found that perfusion MRI heart function stress has a sensitivity of 89.1% and a specificity of 84.9% on a patient-based analysis using FFR as a reference, suggesting that stress perfusion MRI remains an accurate test for the detection of flow-limiting stenosis in patients with suspected or established CAD [6].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In another meta-analysis of 37 studies, including 2,191 patients with high CAD prevalence, stress CMR, using either wall motion abnormality or perfusion abnormality technique, demonstrates overall good sensitivity and specificity for the diagnosis of CAD; stress-induced wall motion abnormalities imaging demonstrated a sensitivity of 0.83 and specificity of 0.86 on a patient level (disease prevalence = 70.5%). Stress perfusion imaging demonstrated a sensitivity of 0.91 and specificity of 0.81 on a patient level (disease prevalence = 57.4%) [51].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with known or suspected CAD, the presence of late gadolinium enhancement and stress perfusion defect plus abnormal wall motion are independent predictors of all hard cardiac events [52].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function with Stress Without IV Contrast MRI heart function stress without IV contrast can provide assessment of ventricular function/wall motion abnormalities.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 884 patients with known (70%) or suspected (30%) CAD demonstrated that inducible LV wall motion abnormalities during dobutamine CMR predicts cardiac death and myocardial ischemia [46]. A single-center prospective study focusing on women with known or suspected CAD and variable clinical symptoms demonstrated that, similar to men, dobutamine CMR can identify cardiac risk in women with known or suspected IHD [47].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 208 patients with suspected CAD has demonstrated a high accuracy for detecting wall motion abnormalities related to ischemia with 86.2% sensitivity and 85.7% specificity [53].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 153 patients with suspected or know CAD, with and without chest pain, has demonstrated 83% sensitivity and 83% specificity for detecting a >50% luminal diameter narrowing based on stress- induced abnormal LV contractility [54].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD Nuclear Medicine Ventriculography Stress radionuclide ventriculography includes measurement of the ejection fraction and assessment of regional wall motion at rest and during stress. There is no relevant literature to support nuclear medicine ventriculography in the initial evaluation of patients with chronic chest pain and a high probability of CAD with no known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Rb-82 PET/CT Heart Rb-82 PET/CT heart assesses rest myocardial perfusion and stress LVEF and quantifies rest myocardial blood flow and coronary flow reserve [55,56]. PET/CT has a reported higher accuracy over conventional nuclear techniques, MPI, and viability [55,57]. Rb-82 PET/CT has shown that myocardial perfusion, stress LVEF, and ischemic LV dysfunction are prognostically important in CAD in patients with suspected or known CAD [48]. A single-center prospective study of 510 patients with suspected CAD has shown that Rb-82 PET/CT has demonstrated sensitivity and specificity of 90% and 88% for the detection of obstructive coronary disease compared with ICA [52]. Among patients with suspected CAD, gated Rb-82 PET/CT can also identify a subset of patients with 3-vessel or left main coronary artery CAD [57].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center study of 1,432 patients with known or suspected CAD has shown that the inherent ability of Rb-82 PET/CT to collect LV function data at rest and during peak stress leads to an improved detection of multivessel CAD [58]. LVEF reserve provides significant independent and incremental value to Rb-82 MPI for predicting the risk of left main/3-vessel disease [57] and future adverse events [59].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A multicenter registry study included 7,061 patients with known or suspected CAD who underwent a clinically indicated rest/stress Rb-82 PET MPI (66% of patients had chronic chest pain as the reason for the test). The extent and severity of ischemia and scarring on Rb-82 PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors [60].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. PET/CT and CCTA Hybrid PET scanners use CT for attenuation correction (PET/CT) following completion of the PET study. By coupling the PET perfusion examination findings to a CCTA, PET/CT permits the fusion of complementary anatomic coronary arterial and functional (perfusion) myocardial information and enhances diagnostic accuracy [60]. The results of the combined examinations can more accurately identify patients for revascularization. In a study of 110 consecutive patients with combined stress Rb-82 PET perfusion imaging and CCTA, nearly half of the significant angiographic stenoses (47%) occurred without evidence of ischemia, whereas 50% of normal PET studies were associated with some CCTA abnormality [61].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. SPECT or SPECT/CT MPI Rest and Stress Stress SPECT MPI can identify relative myocardial perfusion defects, indicating the presence of myocardial ischemia and/or infarction. The territory of the perfusion defect identifies the likely coronary artery involved and can usually distinguish between significant single-vessel and multivessel coronary arterial obstructions [62,63].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center study of >900 diabetic patients demonstrated that SPECT MPI has a reported sensitivity of 87% to 89% and a specificity of 73% to 75% for detecting angiographically significant CAD [62]. Another single-center study evaluated 100 consecutive patients referred for SPECT MPI because of either chronic chest pain and no known CAD (55%) or patients with a documented history of myocardial infarction (29%) referred for risk stratification [64]. MPI and poststress and reversible regional wall motion abnormalities on exercise stress Tc-99m- gated SPECT MPI were significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity [64,65].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with typical angina (high pretest likelihood of disease), stress SPECT MPI is useful for estimating the extent (single vessel versus multivessel disease) and severity of coronary stenosis, which has relevance for prognosis, choice among therapeutic options, and advisability of performing coronary arteriography. A meta- analysis including 114 SPECT studies of patients with suspected or established CAD has shown the sensitivity and specificity for the detection of significant CAD and/or myocardial ischemia was 78% and 52%, respectively, with an NPV of 83% [66].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD SPECT and CCTA Hybrid SPECT/CCTA combines the anatomical information provided by CCTA with the functional perfusion evidence of SPECT, resulting in enhanced diagnostic accuracy for detecting significant CAD compared with SPECT and CCTA alone: the sensitivity and specificity of hybrid SPECT/CCTA were 96% and 95%, respectively, compared with SPECT (93% and 79%) and CCTA (98% and 62%) alone [68]. There was 92% agreement on the necessity of revascularization in the treatment decisions based on hybrid SPECT/CCTA versus SPECT and coronary angiography alone [69].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. US Echocardiography Transesophageal Ultrasound (US) echocardiography transesophageal provides assessment of LVEF and ESVI and structural assessment of the heart and ascending aorta. There is no relevant literature to support the use of transesophageal echocardiography in the initial evaluation of patients with chronic chest pain and a high probability of CAD with no known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. US Echocardiography Transthoracic Resting US echocardiography transthoracic resting provides assessment of ejection fraction and ventricular volumes such as LVEF and ESVI with a higher sensitivity to detect prior myocardial infarct than ischemia. Although there is no relevant literature to support transthoracic echocardiography resting in the initial evaluation of patients with chronic chest pain and a high probability of CAD with no known IHD, this modality could be used to assess new wall motion abnormalities that might raise a concern for IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In a meta-analysis of 435 patients (299 with and 136 without angiographically assessed CAD), dobutamine stress contractility echocardiography had 84% accuracy, 86% specificity, and 86% sensitivity for detecting CAD [71].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A meta-analysis of 44 studies including patients with suspected or known CAD indicated that stress echocardiography has a sensitivity of 85% and a specificity of 77% in detection of CAD (defined as >50% coronary artery luminal diameter stenosis) [72].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with suspected or known CAD, inducible wall motion abnormality during dobutamine stress echocardiography is associated with a higher risk for subsequent cardiac events. Patients with negative dobutamine stress echocardiography exhibited a lower event rate [47].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. US contrast-enhanced stress echocardiography improves endocardial visualization. A single-center prospective randomized trial that included 229 patients with suspected or know CAD has demonstrated diagnostic test rates of 100% for contrast-enhanced stress echocardiography [73].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 101 patients with an intermediate to high probability of CAD based on clinical parameters and risk factors has demonstrated that administration of an echocardiography contrast agent (ie, microbubbles) improves endocardial visualization at rest and more so during stress, leading to a more precise interpretation with greater accuracy in evaluating CAD in patients with 2 or more nonvisualized segments and low confidence of interpretation [71,74].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Variant 2: Chronic chest pain; high probability of coronary artery disease. Known ischemic heart disease with no prior definitive treatment. Initial imaging. In this clinical scenario, prior definitive treatment is defined as previous coronary artery angioplasty, stent placement, or coronary arteries bypass graft.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Arteriography Coronary Catheter-based selective coronary angiography is historically considered the coronary imaging modality of choice with the highest spatial and temporal resolution. Although only 2-D projection images are obtained (as opposed to 3-D volumes CCTA), selective coronary angiography is considered useful for depicting the anatomy and the severity of obstructive CAD and other coronary abnormalities (eg, coronary spasm, dissection, vasculitis) [8]. In addition to visualizing the coronary arteries, the procedure is used to guide percutaneous coronary interventions to


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD the site of blockage. LV catheterization and left ventriculography are generally indicated but not always necessary to define ventricular function in patients with known angina and IHD. FFR measurement accurately estimates the functional severity of stenosis in obstructive CAD [75-77].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. The ISCHEMIA trial has shown that, among patients with stable coronary disease and moderate or severe ischemia, there was no evidence that an invasive diagnostic and therapeutic strategy, compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years [78,79].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CT Coronary Calcium There is no relevant literature to support the use of CT coronary calcium in the initial evaluation of patients with chronic chest pain and a high probability of CAD with known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CT Heart Function and Morphology CT heart function and morphology can provide assessment of ventricular morphology and function as well as assessment of myocardial perfusion and infarction. There are no relevant data published on the use of CT heart for assessment of heart function and regional wall motion abnormalities in patients with chronic chest pain who have a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Several studies have validated stress CT myocardial perfusion against SPECT, stress CMR, and invasive FFR in patients with suspected or known CAD (no clinical data reported on presence or absence of chronic chest pain) and was shown when combined with CTA to accurately predict perfusion abnormalities related to atherosclerotic luminal narrowing [19-23].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Patients with suspected or known CAD were evaluated with MPI using cardiac CT either in a single-phase mode for qualitative identification of ischemic myocardium [22] or in a multiphase mode for quantitative assessment of the myocardial blood flow [80].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic infarction can often be differentiated from acute hypoperfusion by myocardial wall thinning or lower attenuation values (low or negative HU) as a result of fat tissue within the scar and/or calcifications [81].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CTA Chest CTA chest has been shown to be effective in excluding noncardiac causes for chronic chest pain narrowing the differential diagnosis and facilitating the appropriate triage for ICA. It has also been shown in some studies to facilitate the diagnosis of acute coronary syndrome and the decision on emergent catheterization, providing information on the ischemic myocardial area by detection of a localized decrease in LV enhancement [24].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. There is no relevant literature to support the use of CTA chest in the initial evaluation of patients with chronic chest pain and a high probability of CAD with known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. CTA Triple Rule Out There is no relevant literature to support the use of TRO in the initial evaluation of patients with chronic chest pain and a high probability of CAD with known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. thresholds of 50% [25]. In the CORE-64 study, the ROC area for cardiac CT was 0.93 using quantitative coronary angiography as the reference standard. CCTA also similarly predicted revascularization within 30 days as invasive angiography (ROC area 0.84 versus 0.82 for CCTA and quantitative coronary angiography, respectively) [30].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. The CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) showed that patients with nonobstructive and obstructive CAD have incrementally higher rates of mortality, whereas the absence of atherosclerosis is associated with a very favorable prognosis [83]. Presence of extensive nonobstructive CAD have higher rates of adverse cardiovascular events than patients with less extensive but obstructive disease (14.5% versus 13.6%), underscoring the prognostic value of plaque burden only available with CCTA [83]. Presence of high-risk plaque features has been shown as an independent predictor of major acute coronary events in patients with nonobstructive CAD [84-87].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients who underwent previous coronary stenting, CCTA can identify in-stent re-stenosis. Andreini et al [88] have demonstrated specificity, PPV, NPV, and diagnostic accuracy for in-stent re-stenosis detection were 91%, 99%, 60% and 91%, respectively. In a meta-analysis conducted by Kumbhani et al [89], the overall sensitivity, specificity, PPV, and NPV for assessable stents were 91%, 91%, 68%, and 98%. No relevant data currently exists on using CCTA for initial evaluation of patients with suspected in-stent re-stenosis with chronic chest pain and a high probability of CAD with known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. FFR-CT FFR-CT allows for the determination of lesion-specific ischemia associated with a coronary arterial narrowing. FFR-CT is performed in conjunction with CCTA [33,34]. FFR-CT is available for native coronary arteries and not available in patients who underwent coronary artery bypass grafts, and it is not available for assessment of stented coronary arteries [33,34]. There is no current data on use of FFR-CT in selected groups of patients with known CAD. In patients with stable chest pain and suspected or established CAD, FFR-CT has a high diagnostic performance when compared against invasive FFR as the reference standard: 82% specificity and 74% PPV [33].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. FFR-CT provides incremental improvement in the accuracy over CCTA alone (84% versus 59%), mitigating the high sensitivity/low specificity tradeoff of CCTA [33]. Another study of patients with suspected and established CAD (no data provided on clinical symptoms) has demonstrated that FFR-CT has correctly reclassified 68% of false-positive patients as true negatives, highlighting the potential role of FFR-CT as a gatekeeper to cardiac catheterization [35,36].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRA Coronary Arteries Without and With IV Contrast Coronary MRA does not include delayed gadolinium enhancement or viability. Coronary MRA can demonstrate lumen narrowing of the proximal coronary arteries. There is limited data on the use of MRA coronary arteries without and with IV contrast in a symptomatic patient with a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In a single-center prospective study in patients with suspected CAD, 82% sensitivity, 90% specificity, 88% PPV, and 86% NPV for detecting significant CAD were demonstrated [40].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. There are no relevant data evaluating MRA coronary arteries without and with IV contrast in symptomatic patients with a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRA Coronary Arteries Without IV Contrast There is limited data on the use of MRA coronary arteries without IV contrast in symptomatic patient with a high probability for CAD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD high sensitivity (88%), moderate specificity (72%), a moderate PPV (71%), and a high NPV (88%) with an AUC of 0.87 for detecting significant coronary artery stenosis were demonstrated [41].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In symptomatic patients with an intermediate or high pretest probability for disease, noncontrast coronary MRA had a patient-based sensitivity of 96%, a specificity of 68%, a PPV of 79%, and an NPV of 93% in the detection of functionally significant CAD as defined by a >90% stenosis or FFR <0.8 on catheter angiography. When added to a comprehensive stress-rest MRI protocol, it had a nonsignificant increase in diagnostic accuracy [42].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function and Morphology Without and With IV Contrast MRI heart function and morphology without and with IV contrast can demonstrate myocardial infarction and ischemia secondary to CAD and can provide assessment of LV wall function. Extrapolation of data on MRI heart function and morphology without and with IV contrast for patients with known CAD is provided below, with a note that no information is available regarding the presence or absence of chest pain in patients included in these studies [70,90-98].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In a multicenter study, assessment of a consecutive 1,560 patients with established or suspected CAD has shown that both LVEF and the amount of myocardial damage are independent predictors of all-cause mortality. Even in patients with near-normal LVEF, significant infarction identifies a cohort with a high risk for early mortality [70].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Demonstration of residual contractile function in dysfunctional segments in response to dobutamine stimulation at cine MRI has been shown to be better than delayed-enhancement MRI alone for prediction of recovery of segmental function 3 months after revascularization [98]. Late gadolinium enhancement MRI can demonstrate the presence, location, and transmural extent of acute and chronic myocardial infarctions [90,95], with a sensitivity of 99% for the detection of acute infarction and 94% for the detection of chronic infarction [95]. Other studies have shown that delayed-enhancement MRI findings can be predictive of the potential for recovery of function in LV dysfunctional segments in chronic IHD [90,94]. Transmural extent of infarction can predict recovery of regional function in dysfunctional segments in patients evaluated before and several months after surgical revascularization [96].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Late gadolinium enhancement with a microvascular obstruction pattern is associated with greater infarct mass, infarction size, and extent of transmurality, lower ejection fraction, more adverse cardiac events early and late, and more severe late LV remodeling [91]. Infarct size at the baseline has proved to be the strongest predictor of adverse long-term LV remodeling [92]. There is a strong linear relation between scar size, LV end-systolic and end-diastolic volumes, and LVEF. Scar size is the strongest predictor of LVEF, independent of scar location and transmurality [97]. Baseline infarct size, infarct heterogeneity, and myocardial salvage are significantly associated with 90-day LVEF [93].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function and Morphology Without IV Contrast MRI heart function and morphology without IV contrast provides assessment of ejection fraction and ventricular volumes including LVEF and ESVI with a higher sensitivity to detect prior myocardial infarct than ischemia. There is no relevant literature to support the use of MRI heart function and morphology without IV contrast in the initial evaluation of patients with chronic chest pain and a high probability of CAD with known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function with Stress Without and With IV Contrast MRI with function/wall motion (dobutamine stress test) and MRI with vasodilator stress perfusion (adenosine/regadenoson stress test) have been used to diagnose hemodynamically significant CAD in patients with an intermediate to high likelihood of having significant stenosis.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Extrapolation of data from MRI heart function and morphology without and with IV contrast for patients with known CAD is provided below with a note that there is no information available regarding the presence or absence of chest pain in patients included in those studies [46,48,49,51,52].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 884 patients with known (70%) or suspected (30%) CAD demonstrated that inducible LV wall motion abnormalities during dobutamine CMR predicts cardiac death and myocardial ischemia [46]. A single-center prospective study focusing on women with known or suspected CAD and variable clinical symptoms demonstrated that, similar to men, dobutamine CMR can identify cardiac risk in women with known or suspected IHD [47]. A single-center study of 815 consecutive patients referred for evaluation of suspected myocardial ischemia over a 10-year period has shown that stress CMR with protocol, including stress and rest myocardial perfusion, ventricular function, and late gadolinium enhancement, effectively reclassifies patient risk beyond standard clinical variables, specifically in patients at a moderate to high pretest clinical risk and in patients with established CAD [48].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD Stress CMR has a high NPV for adverse cardiac events in patients with known or suspected CAD [46,47]. A meta- analysis of 14 studies has shown that MRI heart function stress has a high NPV for adverse cardiac events, and the absence of inducible perfusion defect or wall motion abnormality shows a similar ability to identify patients with a low risk for adverse cardiac events among patients with known or suspected CAD [49].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A meta-analysis from pooled studies found that perfusion MRI heart function stress has a sensitivity of 89.1% and a specificity of 84.9% on a patient-based analysis using FFR as a reference, suggesting that stress perfusion MRI remains an accurate test for the detection of flow-limiting stenosis in patients with suspected or established CAD [6].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Another meta-analysis of 37 studies, including 2,191 patients with high CAD prevalence, stress CMR, using either wall motion abnormality or perfusion abnormality technique, demonstrates overall good sensitivity and specificity for the diagnosis of CAD: stress-induced wall motion abnormalities imaging demonstrated a sensitivity of 0.83 and specificity of 0.86 on a patient level (disease prevalence = 70.5%). Stress perfusion imaging demonstrated a sensitivity of 0.91 and specificity of 0.81 on a patient level (disease prevalence = 57.4%) [51].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with known or suspected CAD, the presence of late gadolinium enhancement and stress perfusion defect plus abnormal wall motion are independent predictors of all hard cardiac events [52].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. MRI Heart Function with Stress Without IV Contrast MRI heart function stress without IV contrast can provide assessment of ventricular function/wall motion abnormalities.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 884 patients with known (70%) or suspected (30%) CAD demonstrated that inducible LV wall motion abnormalities during dobutamine CMR predicts cardiac death and myocardial ischemia [46]. A single-center prospective study focusing on women with known or suspected CAD and variable clinical symptoms demonstrated that, similar to men, dobutamine CMR can identify cardiac risk in women with known or suspected IHD [47].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 208 patients with suspected CAD has demonstrated a high accuracy for detecting wall motion abnormalities related to ischemia with 86.2% sensitivity and 85.7% specificity [53].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center prospective study of 153 patients with suspected or know CAD with and without chest pain has demonstrated 83% sensitivity and 83% specificity for detecting a >50% luminal diameter narrowing based on stress- induced abnormal LV contractility [54]


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Nuclear Medicine Ventriculography Stress radionuclide ventriculography includes measurement of the ejection fraction and assessment of regional wall motion at rest and during stress. There is no relevant literature to support nuclear medicine ventriculography in the initial evaluation of patients with chronic chest pain and a high probability of CAD with no known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Rb-82 PET/CT Heart Rb-82 PET/CT heart assesses rest myocardial perfusion and stress LVEF and quantifies rest myocardial blood flow and coronary flow reserve [55,56]. PET/CT has reported a higher accuracy over conventional nuclear techniques, MPI, and viability [55,57].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. The data cited below for Rb-82 PET/CT heart are for patients with known CAD, but no information is available regarding the presence or absence of chest pain in patients included in those studies.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Gated Rb-82 PET/CT has shown that myocardial perfusion, stress LVEF, and ischemic LV dysfunction are prognostically important in CAD in patients with suspected or known CAD [48]. The inherent ability of Rb-82 PET/CT to collect LV function data at rest and during peak stress seems to result in improved detection of multivessel CAD with LVEF reserve assessment providing significant independent and incremental value to Rb-82 MPI for predicting the risk of future adverse events [59]. An increasing percentage of ischemia on PET-MPI is associated with an increase in the risk of cardiac events and all-cause death [59].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center study of 1,432 patients with known or suspected CAD has shown that the inherent ability of Rb-82 PET/CT to collect LV function data at rest and during peak stress leads to an improved detection of multivessel CAD [58]. LVEF reserve provides significant independent and incremental value to Rb-82 MPI for predicting the risk of left main/3-vessel disease [57] and future adverse events [59].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD A multicenter registry study included 7,061 patients with known or suspected CAD who underwent a clinically indicated rest/stress Rb-82 PET MPI (66% of patients had chronic chest pain as the reason for the test). The extent and severity of ischemia and scarring on Rb-82 PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors [60].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. PET and CCTA Hybrid PET scanners use CT for attenuation correction (PET/CT) following completion of the PET study. By coupling the PET perfusion examination findings to a CCTA, PET/CT permits the fusion of complementary anatomic coronary arterial and functional (perfusion) myocardial information and enhances diagnostic accuracy [60]. The results of the combined examinations can more accurately identify patients for revascularization. In a study of 110 consecutive patients with a combined stress Rb-82 PET perfusion imaging and CCTA, nearly half of significant angiographic stenoses (47%) occurred without evidence of ischemia, whereas 50% of normal PET studies were associated with some CCTA abnormality [61].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. SPECT or SPECT/CT MPI Rest and Stress Stress SPECT MPI can identify relative myocardial perfusion defects, indicating the presence of myocardial ischemia and/or infarction. By acquiring rest and stress perfusion scans, it is possible to demonstrate reversibility (ischemia) or irreversibility (infarction) of a myocardial perfusion defect. The territory of the perfusion defect identifies the likely coronary artery involved and can usually distinguish between significant single-vessel and multivessel coronary arterial obstructions. The magnitude of the abnormality and the presence of high-risk findings also assist in clinical decision making [62,63].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. The data cited below for SPECT or SPECT/CT MPI rest and stress are for patients with known CAD, but no information is available regarding the presence or absence of chest pain in patients included in these studies.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A single-center study evaluated 100 consecutive patients referred for SPECT MPI due to either chronic chest pain and no known CAD (55%) and patients with a documented history of myocardial infarction (29%) referred for risk stratification [64]. MPI and poststress and reversible regional wall motion abnormalities on exercise stress Tc-99m- gated SPECT MPI were significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity [64,65].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with typical angina (high pretest likelihood of disease), stress SPECT MPI is useful for estimating the extent (single vessel versus multivessel disease) and severity of coronary stenosis, which has relevance for prognosis, choice among therapeutic options, and advisability of performing coronary arteriography. A meta- analysis including 114 SPECT studies of patients with suspected or established CAD have shown sensitivity and specificity for the detection of significant CAD and/or myocardial ischemia was 78% and 52%, respectively, with an NPV of 83% [66].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. SPECT and CCTA Hybrid SPECT/CCTA combines the anatomical information provided by CCTA with the functional perfusion evidence of SPECT, resulting in an enhanced diagnostic accuracy for detecting significant CAD compared with SPECT and CCTA alone: the sensitivity and specificity of hybrid SPECT/CCTA were 96% and 95%, respectively, compared with SPECT (93% and 79%) and CCTA (98% and 62%) alone [68]. There was 92% agreement on the necessity of revascularization in the treatment decisions based on hybrid SPECT/CCTA versus SPECT and coronary angiography alone [69].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. US Echocardiography Transesophageal There is no relevant literature to support the use of transesophageal echocardiography in the initial evaluation of patients with chronic chest pain and a high probability of CAD with known IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. US Echocardiography Transthoracic Resting US echocardiography transthoracic resting provides assessment of ejection fraction and ventricular volumes such as LVEF and ESVI with a higher sensitivity to detect prior myocardial infarct than ischemia. Although there is no relevant literature evaluating the use transthoracic echocardiography resting in the initial evaluation of patients with


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Chronic Chest Pain-High Probability of CAD chronic chest pain and known IHD, this modality provides information about wall motion abnormality and left ventricular function which may inform next step management of patients with IHD.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. US Echocardiography Transthoracic Stress US stress 2-D echocardiography depiction of myocardial contractility during rest and stress is used for the evaluation of patients with suspected regional wall motion abnormalities secondary to inducible regional ischemia.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. The data cited below for US Echocardiography transthoracic stress are for patients with known CAD, but no information is available regarding the presence or absence of chest pain in patients included in those studies.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In a meta-analysis of 435 patients (299 with and 136 without angiographically assessed CAD), dobutamine stress contractility echocardiography had 84% accuracy, 86% specificity, and 86% sensitivity for detecting CAD [71].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. A meta-analysis of 44 studies including patients with suspected or known CAD indicated that stress echocardiography has a sensitivity of 85% and a specificity of 77% in detection of CAD (defined as >50% coronary artery luminal diameter stenosis) [72].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. In patients with suspected or known CAD, inducible wall motion abnormality during dobutamine stress echocardiography is associated with a higher risk for subsequent cardiac events. Patients with negative dobutamine stress echocardiography exhibited a lower event rate [47].


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Chronic Chest Pain High Probability of Coronary Artery Disease PCAs. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Syncope

Syncope. Elucidating the underlying cause of a syncopal or presyncopal episode can be challenging. There are numerous potential cardiovascular or neurologic etiologies, many of which rely on appropriate imaging for identification and classification; these include coronary artery disease, aortic disease, and cardiomyopathies. Although the etiology is never discovered in one-third of patients [10], and some causes such as vasovagal syncope are relatively innocuous, others, such as cardiac-related syncope, carry a significant increased risk of death [10-13]. The mainstay of syncope and presyncope assessment is a detailed history and physical examination. The assessment should include measurement of postural changes in blood pressure to diagnose orthostatic-related syncope and a detailed neurologic history and physical examination to exclude symptoms or signs of a separate neurologic process, which would require a different course of evaluation [14]. In addition to a detailed cardiac examination assessing for structural heart disease, certain patient characteristics are associated with an increased risk of cardiac-related syncope and include the following: age >60 years, male gender, known underlying congenital or acquired cardiac disease, palpitations or other cardiac-related symptoms prior to syncopal episode, syncope during exertion, syncope in supine position, low number of prior syncopal episodes, and family history of sudden cardiac death [3].


Syncope

Syncope. Studies have shown that patients with syncope and presyncope have a low yield of 5% to 6.4% of an acute abnormality on head CT, nearly all with external evidence of head trauma or a focal neurological deficit on examination [15-19]. Increasing age has been associated with higher odds for a CT abnormality compared with younger patients with syncope, however, the age cutoffs of >55 [15] or 60 and older [19] have not been validated across studies as independent predictive factors in absence of trauma or neurologic deficit [20]. There is a consensus across multidisciplinary task forces, clinical guidelines, and the ACR Choosing Wisely review that brain CT and MRI should be avoided in uncomplicated syncope [3,8,21]. Cohort studies and a meta-analysis of 12 additional studies reported <1% occurrence of new neurological diagnosis (including stroke) within 30 days from original presentation of syncope or presyncope [4,18,22,23].


Syncope

Syncope. aUniversity of California San Diego, San Diego, California. bUniversity of California San Diego, San Diego, California. cPanel Chair, Duke University Medical Center, Durham, North Carolina. dPanel Chair, University of Iowa Hospitals and Clinics, Iowa City, Iowa. ePanel Vice-Chair, Massachusetts General Hospital, Boston, Massachusetts. fMichigan State University, East Lansing, Michigan; American College of Emergency Physicians. gThe University of Chicago Medical Center, Chicago, Illinois; American College of Physicians. hAlpert Medical School of Brown University, Providence, Rhode Island. iSanger Heart and Vascular Institute, Charlotte, North Carolina; Cardiology expert. jVancouver General Hospital, Vancouver, British Columbia, Canada. kUniversity of California Los Angeles, Los Angeles, California. lGill Heart & Vascular Institute, University of Kentucky, Lexington, Kentucky; Society for Cardiovascular Magnetic Resonance. mUniversity of California Los Angeles, Los Angeles, California; American Academy of Neurology. nHarvard Medical School, Boston, Massachusetts. oNaval Medical Center Portsmouth, Portsmouth, Virginia. pUniversity of California San Diego, San Diego, California. qUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina; American Academy of Neurology. rUniversity of Virginia Health System, Charlottesville, Virginia; Society of Cardiovascular Computed Tomography. sUniversity of Cincinnati Medical Center, Cincinnati, Ohio. tAscension Healthcare Wisconsin, Milwaukee, Wisconsin; Nuclear cardiology expert. uSpecialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia. vSpecialty Chair, UT Southwestern Medical Center, Dallas, Texas.


Syncope

Syncope. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization.


Syncope

Syncope. Reprint requests to: publications@acr.org


Syncope

Syncope. Syncope Although there is conflicting data regarding its utility, multisociety guidelines suggest a resting 12-lead electrocardiogram (ECG) for all patients to detect arrhythmias or abnormality indicative of higher risk for arrhythmia (eg, prolonged QT interval) [7-9,11]. Although additional laboratory, physiologic, and image-based testing can be performed, it is recommended that testing be limited to select patients based on clinical assessment. In most instances, nonfocused additional testing in a patient with syncope or presyncope does not improve diagnostic yield, however, it does increase the hospitalization rate and significantly increases cost, and therefore is not endorsed by any major medical society [3,8,9,20,24].


Syncope

Syncope. All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with contrast also include timing issues and reconstructions/reformats. Only in CTA, however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes.


Syncope

Syncope

Syncope. Syncope


Syncope

Syncope. Discussion of Procedures by Variant Variant 1: Presyncope or syncope. Clinical suspicion for cardiovascular etiology based on history, physical examination, and ECG findings. Initial imaging. CT Head Serial studies of patients with syncope or presyncope have shown that head CT does not influence treatment management in this clinical scenario [15-19].


Syncope

Syncope. CT Heart Function and Morphology There is no relevant literature that examines the use of ECG-gated CT heart in this clinical scenario. CT heart can identify hypertrophic cardiomyopathy and thrombus in the cardiac chambers.


Syncope

Syncope. CTA Coronary Arteries One small retrospective study found that patients with cardiac-related syncope or presyncope had a greater extent and severity of coronary artery disease by coronary CTA (CCTA) compared with those with noncardiac-related syncope and matched patients with chest pain and no syncope [48]. Additionally, anomalous coronary arteries can be a cause of exercise-induced syncope or presyncope, especially in younger patients [49,50]. However, there are no prospective or large retrospective studies assessing the utility of CCTA in patients with syncope or presyncope as the only presenting finding.


Syncope

Syncope. MRI Head There is no relevant literature to support the use of head MRI in this clinical scenario.


Syncope

Syncope. MRI Heart Function and Morphology There is no relevant literature that examines the use of cardiac MRI in this clinical scenario. MRI heart can provide detailed analysis of cardiac function, morphology, and physiology. MRI is a valuable tool in the diagnosis of infiltrative cardiomyopathies that can manifest with episodes of syncope and presyncope including hypertrophic cardiomyopathy [51,52], sarcoid [53,54], myocarditis [55-57], amyloid [58], arrhythmogenic right ventricular dysplasia [58], and nonischemic dilated cardiomyopathy [58,59]. In both ischemic and nonischemic cardiomyopathies, MRI can assess for areas of scarring, which can serve as an arrhythmogenic focus and can lead to syncope or sudden cardiac death [60]. Although not routinely utilized as an initial imaging tool, cardiac MRI could be utilized in stable patients as an alternative to echocardiography when image quality is not diagnostic or optimal.


Syncope

Syncope. Radiography Chest There are no prospective studies that examine the use of chest radiographs in patients with syncope or presyncope. In one large retrospective multi-institution study evaluating syncope and presyncope in 3,686 patients >60 years of


Syncope

Syncope. age, 2,767 (75.1%) had a chest radiograph performed [61]. Of those, 182 (6.6%), had a radiograph interpreted as abnormal. In a smaller retrospective study performed at a single institution, only 4.5% of patients with syncope had an abnormal chest radiograph. However, patients with syncope or presyncope who had abnormal chest radiographs were more likely to have serious adverse events compared with those with normal radiographs [62].


Syncope

Syncope. SPECT or SPECT/CT MPI Rest and Stress There is no relevant literature to support the routine use of a Tc-99m single-photon emission CT (SPECT) or SPECT/CT myocardial perfusion imaging (MPI) rest and stress in most patients with syncope. Limited data from one large retrospective study assessing the use of MPI in 700 patients with syncope of any cause and no known coronary artery disease concluded there was no significant utility for rest and stress testing [63].


Syncope

Syncope. SPECT or SPECT/CT MPI Stress Only There is no relevant literature that examines the use of Tc-99m SPECT or SPECT/CT MPI stress only study in this clinical scenario.


Syncope

Syncope. US Duplex Doppler Carotid Artery Multiple studies have shown no benefit of carotid artery Doppler ultrasound (US) in patients with syncope or presyncope in the absence of neurologic findings or carotid bruit [20,64-66].


Syncope

Syncope. US Echocardiography Transesophageal There is no relevant literature to support the use of a transesophageal echocardiography in the evaluation of syncope or presyncope. Transesophageal echocardiography can further elucidate abnormal findings visualized on transthoracic echocardiogram.


Syncope

Syncope. US Echocardiography Transthoracic Resting Transthoracic resting echocardiography provides a noninvasive assessment of cardiac structure and function. In patients with an abnormal ECG or findings on history or physical examination suggesting a cardiac etiology of syncope or presyncope, transthoracic echocardiography can be used to assess for structural heart disease or to help identify risk factors for malignant arrhythmias and is validated by multiple studies and supported by numerous societies [3,8,67-69]. Possible etiologies include various cardiomyopathies, valvular disease, pericardial disease, and tumors.


Syncope

Syncope. US Echocardiography Transthoracic Stress There are no prospective studies that examine the use of transthoracic stress echocardiography in patients with cardiac etiology for syncope or presyncope. Stress echocardiography can be used to assess for left ventricular outflow obstruction in patients with left ventricular hypertrophy and hypertrophic cardiomyopathy. In both of these populations, outflow tract obstruction is associated with increased future episodes of presyncope and syncope [70,71].


Syncope

Syncope. Variant 2: Presyncope or syncope. Low probability of cardiovascular etiology based on history, physical examination, and ECG findings. Initial imaging. CT Head Serial studies of patients with syncope or presyncope have shown that CT head does not influence treatment management in this clinical scenario [15-19].


Syncope

Syncope. CT Heart Function and Morphology There is no relevant literature that examines the use of ECG-gated CT heart in this clinical scenario.


Syncope

Syncope. CTA Chest There is no relevant literature that examines the use of CTA of the chest in this clinical scenario.


Syncope

Syncope. CTA Coronary Arteries There is no relevant literature that examines the use of ECG-gated CCTA in this clinical scenario.


Syncope

Syncope. Syncope MRI Head There is no relevant literature to support the use of head MRI in this clinical scenario.


Syncope

Syncope. MRI Heart Function and Morphology There is no relevant literature that examines the use of cardiac MRI in this clinical scenario.


Syncope

Syncope. Radiography Chest There are no prospective studies that examine the use of chest radiographs in patients with syncope or presyncope. In one large retrospective multi-institution study evaluating syncope and presyncope in 3,686 patients >60 years of age, 2,767 (75.1%) had a chest radiograph performed [61]. Of those, 182 (6.6%), had a radiograph interpreted as abnormal. In a smaller retrospective study performed at a single institution, only 4.5% of patients with syncope had an abnormal chest radiograph. However, patients with syncope or presyncope who had abnormal chest radiographs were more likely to have serious adverse events compared with those with normal radiographs [62].


Syncope

Syncope. SPECT or SPECT/CT MPI Rest and Stress There is no relevant literature to support the routine use of a Tc-99m SPECT or SPECT/CT MPI rest and stress in most patients with syncope. Limited data from one large retrospective study assessing the use of MPI in 700 patients with syncope of any cause and no known coronary artery disease concluded there was no significant utility for testing [63].


Syncope

Syncope. SPECT or SPECT/CT MPI Rest Only There is no relevant literature that examines the use of Tc-99m SPECT or SPECT/CT MPI rest only study in this clinical scenario.


Syncope


Syncope

Syncope. US Duplex Doppler Carotid Artery Multiple studies have shown no benefit of carotid artery Doppler US in patients with syncope or presyncope in the absence of neurologic findings or carotid bruit [20,64-66].


Syncope

Syncope. US Echocardiography Transesophageal There is no relevant literature that examines the use of transesophageal echocardiography in this clinical scenario.


Syncope

Syncope. sSecac US Echocardiography Transthoracic Resting There is no relevant literature that examines the use of transthoracic resting echocardiography in this clinical scenario, especially if a patient who has syncope or presyncope in the setting of a normal ECG and low probability of a cardiac cause of symptoms [66,69,72,73].


Syncope

Syncope. US Echocardiography Transthoracic Stress There is no relevant literature that examines the use of transthoracic stress echocardiography in this clinical scenario.


Syncope

Syncope. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Syncope

Syncope. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Syncope

Syncope

Syncope. Syncope


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Introduction/Background Chronic chest pain (CCP) with low to intermediate probability of coronary artery disease (CAD) can arise from cardiac and noncardiac etiologies. While there are multiple potential noncardiac causes of CCP, such as costochondritis, arthritic or degenerative diseases, prior trauma, primary or metastatic tumors, pleural disease, or gastrointestinal causes, the scope of this document is focused on evaluating chest pain when a cardiac etiology is the concern.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Multiple imaging tools can be used to evaluate CCP in symptomatic patients with low to intermediate probability for CAD. The imaging modalities available include: (1) multidetector coronary computed tomography angiography (CCTA); (2) stress and rest radionuclide single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI); (3) catheter-based invasive coronary angiography (ICA) with or without ventriculography; (4) chest radiography; (5) stress echocardiography; (6) PET; and (7) cardiac MRI and MR angiography (MRA).


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Special Imaging Considerations Advances in cardiac CT imaging technology have further reduced radiation dose in CCTA examinations [4]. New and available dose-reducing techniques include prospective triggering [5-7], iterative reconstruction algorithms [8], long z-axis coverage, and high-pitch spiral acquisition [9]. However, these newer low-dose techniques may not be available or appropriate for all patients. Although these techniques can reduce patient radiation dose, there may be patients for whom these radiation dose techniques are not optimal. In all cases, the imaging physician must select the appropriate combination of imaging parameters to acquire a diagnostic examination at a radiation dose that is as low as reasonably achievable.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Variant 1: Chronic chest pain, noncardiac etiology unlikely: low to intermediate probability of coronary artery disease. Initial imaging. CTA Coronary Arteries In patients with low to intermediate probability of CAD, multidetector CCTA can be performed for direct coronary artery evaluation. CCTA has been shown to be of value when evaluating patients with CAD because of its high negative predictive value. The use of CCTA has advantages when compared to other testing modalities. CCTA has superior diagnostic accuracy compared to other examinations, may identify high-probability patients


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Reprint requests to: publications@acr.org


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Specifically, recent trials from the Computed Tomography versus Exercise Testing in Suspected Coronary Artery Disease (CRESCENT), the Scottish COmputed Tomography of the HEART (SCOT-HEART), the Prospective Multicenter Imaging Study for Evaluation of Chest Pain trial (PROMISE trial), the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, and COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry (CONFIRM) registry provide additional support for the use of CCTA into the diagnostic algorithm when evaluating patients with chest pain.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. The CRESCENT investigators suggest that the use of CCTA in combination with calcium scoring may allow for a structured protocol that allows a diagnosis to be reached faster with no increase in the referral rate for ICA [20]. The CCTA can also reduce the time to diagnosis and determine which patients need invasive testing [12,13,21- 23]. Specifically in patients in whom angina that is due to CAD was suspected, the SCOT-HEART investigators showed that CCTA clarified the diagnosis by providing added certainty, enabling targeted interventions, and potentially reducing the risk of future myocardial infarction [24].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. The PROMISE investigators evaluated patients with stable chest pain to either CCTA or functional testing. Their work has shown that patients who underwent CCTA had a lower risk of death and lower risk of myocardial infarction (not leading to a fatality) compared to patients who underwent conventional functional testing. The investigators suggest that CCTA can be a safe alternative to functional testing in a low-risk population [25,26].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. CCTA has also provided prognostic information beyond that of clinical risk scores [27]. Data from the CAPP and CONFIRM investigators have provided additional information. The CAPP investigators have shown that patients undergoing CCTA identified significant disease, underwent more revascularizations, less diagnostic testing, and fewer admissions for chest pain [28]. The CONFIRM investigators have also shown that CCTA better predicted risk compared to well-established clinical risk scores and reclassified approximately one [29].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. CT Chest When CAD and other cardiac etiologies of chest pain, such as aortic disease pericardial disease, are suspected, a chest CT may be appropriate.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. SPECT or SPECT/CT MPI Stress SPECT MPI [41] is a central part of the diagnostic pathway when evaluating patients with CCP. A SPECT MPI scan is performed with either exercise-induced or pharmacologically induced stress to demonstrate myocardial perfusion or contraction abnormalities.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Use of stress imaging can be performed rapidly and increasingly through protocol optimization, with lower radiation doses [42]. Patients who undergo SPECT imaging have outcomes similar to CCTA in terms of outcomes [25,43]. In addition, the use of stress MPI improved clinical decision making for chest pain patients [44].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. calcified coronary plaque, does not exclude acute coronary syndrome, significant coronary plaque burden, or plaque, which suggests that additional testing beyond CCS may be needed [48-50].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. US Echocardiography Transthoracic Stress When echocardiography is performed, stress contraction abnormalities are induced by either exercise or inotropic stimulation. In any situation where a SPECT MPI study cannot be performed, an exercise-stress or dobutamine- stress echocardiogram may be substituted [51,52]. Stress echocardiography is used to evaluate for wall motion abnormalities and can provide data regarding flow reserve, which can aid in patient risk stratification [53].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. US Echocardiography Transthoracic Resting In certain cases, if valvular heart disease, hypertrophic cardiomyopathy, or pericardial disease is the primary diagnostic concern, an echocardiogram at rest may be the preferred examination. The use of nonstress echocardiography in patients with stable chest pain when coronary artery disease is suspected may not reveal additional diagnostic information [54].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. MRI Heart MRI is an emerging technology, and its clinical applications to cardiac imaging continue to develop. Currently, stress cardiac MRI and coronary MRA are available to diagnose CAD.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Cardiac MRI without stress can be performed to evaluate valvular heart disease, nonischemic etiologies of chest pain, such as hypertrophic cardiomyopathy, or evaluate for pericardial disease.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Stress cardiac MRI can be performed with dobutamine, adenosine, or dipyridamole. Dobutamine-stress functional cardiac MRI may also play a role in the assessment of chronic CCP [55]. This is especially true when the echocardiographic examination is nondiagnostic. In settings where the study may be adequately monitored, dobutamine-stress functional cardiac MRI provides high sensitivity and specificity for ischemia by the induction of wall motion abnormality [56]. However, adenosine-stress cardiac MRI perfusion imaging is easier to perform and also has been shown to have relatively high sensitivity and specificity for the presence of CAD [56-59]. Dipyridamole-stress MRI can also show ischemia-related wall motion abnormalities, perfusion defects and scar and can help direct revascularization [60].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. MRA Coronary Arteries Coronary MRA is a developing modality to evaluate the coronary arteries. Coronary MRA has been shown to identify severe stenosis, but its sensitivity and specificity for moderate or mild lesions is lower [61,62]. Technological developments may make the use of coronary MRA more widespread and result in shorter acquisition times and improved spatial resolution [63].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Arteriography Coronary ICA may be used if less-invasive imaging was consistent with the presence of significant CAD. However, the use of ICA as a first-line tool to evaluate for CAD in patients who are low to intermediate probability will not have a high diagnostic yield [64], and utilizing noninvasive testing prior to ICA increases the yield of positive ICA [64].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Exercise Treadmill Testing Exercise treadmill testing can be of value in the assessment of patients with low to intermediate probability for CAD. Among patients who are low to intermediate probability, exercise treadmill testing in the acute setting showed a high specificity for detecting CAD with a greater than 50% stenosis [65]. This procedure is not included on the variant table because generally only imaging procedures are assessed for appropriateness in the ACR Appropriateness Criteria documents.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Rb-82 PET/CT Heart PET/CT performed with perfusion agents (rubidium-82 or nitrogen-13-ammonia) may play a role in assessing patients with chronic indeterminate chest pain and who are at low probability to intermediate probability for CAD. Cardiac PET/CT has been shown to provide incremental prognostic value to historical and clinical variables [66], and may be of particular use in patients with equivocal or suboptimal SPECT MPI or echocardiographic results. Compared to SPECT MPI, PET offers higher spatial and contrast resolution and can be used to quantify myocardial blood flow, increasing the specificity of PET compared to SPECT [67].


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Although there are references that report on studies with design limitations, 29 well-designed or good-quality studies provide good evidence.


Chronic Chest Pain Noncardiac Etiology Unlikely Low to Intermediate Probability of Coronary Artery Disease PCAs. Supporting Documents For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Colorectal Cancer Screening

Colorectal Cancer Screening. A number of organizations have issued recommendations for colorectal cancer screening, which are presented as lists of options. Recommendations for average-risk individuals from the United States Preventative Services Task Force include either colonoscopy every 10 years, computed tomographic colonography (CTC) every 5 years, or a stool-based test every 1 to 3 years, depending on the sensitivity of the stool-based test [25]. In addition to these options, the American Cancer Society (ACS) also includes double-contrast barium enema (DCBE) every 5 years in its list of recommended screening tests [26]. The ACS guidelines also separate colorectal cancer screening tools into 2 categories: 1) those that can screen for both adenomatous polyps and cancer (CTC, colonoscopy, and DCBE); and 2) those that are intended to screen for cancer only (fecal occult blood test [FOBT], fecal immunochemical test, and stool DNA test) [26]. The ACS recommends that tests that simultaneously screen for polyps and cancers should be preferred over tests that detect cancers only when resources permit [26].


Colorectal Cancer Screening

Colorectal Cancer Screening. aPrincipal Author, Emory University, Atlanta, Georgia. bCo-author and Panel Chair, University of Wisconsin Hospital & Clinics, Madison, Wisconsin. cGlobal Advanced Imaging, PLLC, Little Rock, Arizona. dUniversity of South Alabama, Mobile, Alabama; American Gastroenterological Association. eNewton-Wellesley Hospital, Newton, Massachusetts. fUniversity of Texas MD Anderson Cancer Center, Houston, Texas; American College of Surgeons. gMallinckrodt Institute of Radiology, Saint Louis, Missouri. hVirginia Tech Carilion School of Medicine, Roanoke, Virginia. iMassachusetts General Hospital, Boston, Massachusetts. jUniversity of Virginia Health System, Charlottesville, Virginia. kMedstar Georgetown University Hospital, Washington, District of Columbia. lDuke University Medical Center, Durham, North Carolina. mPenn State Hershey Radiology, Hershey, Pennsylvania. nLahey Hospital and Medical Center, Burlington, Massachusetts. oBeth Israel Deaconess Medical Center, Boston, Massachusetts. pUniversity of California San Francisco, San Francisco, California. qSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia.


Colorectal Cancer Screening

Colorectal Cancer Screening. Reprint requests to: publications@acr.org


Colorectal Cancer Screening

Colorectal Cancer Screening

Colorectal Cancer Screening. Colorectal Cancer Screening


Colorectal Cancer Screening

Colorectal Cancer Screening. of adenoma or carcinoma), and 3) high risk (individuals with hereditary syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC), or a personal history of ulcerative colitis or Crohn colitis).


Colorectal Cancer Screening

Colorectal Cancer Screening. The ACR practice parameter also includes suggestions regarding the interpretation and reporting of extracolonic findings [28]. To avoid unnecessary further workup and patient anxiety, caution is emphasized when reporting findings that are likely to be of low clinical significance. There is evidence that using structured reporting constructs, such as CT Colonography Reporting and Data System, can decrease workups related to incidental extracolonic findings to <10% [30-32]. Unsuspected extracolonic malignancies and previously unknown aortic aneurysms are detected with CTC examinations in approximately 2% to 3% of patients [30,31,33-36].


Colorectal Cancer Screening

Colorectal Cancer Screening. Regarding barium enema, as utilization of DCBE has declined, training in this modality has also decreased [37], and it is not known if the barium enema data collected from studies performed by radiologists with extensive experience in the technique can be extrapolated to radiologists with lesser experience. For this document, it is assumed procedures are performed and interpreted by experts.


Colorectal Cancer Screening

Colorectal Cancer Screening


Colorectal Cancer Screening

Colorectal Cancer Screening. sensitivities by patient of 85% and 93%, with pooled specificities of 97% [43,44]. Some older studies have shown poorer performance of CTC (sensitivity of 55% to 59%) [45,46]. These discrepant results were likely related to differences in study design, lack of reader training, and CTC technique (eg, no fecal tagging) in these older studies.


Colorectal Cancer Screening

Colorectal Cancer Screening. DCBE DCBE also requires a preprocedural bowel cleansing preparation. The study is performed by administration of a liquid barium-based contrast agent and air-insufflation of the colon via a tube inserted into the rectum. Images are acquired with the patient in different obliquities and at different table angulations ranging from supine to standing. Performance of DCBE is dependent on optimal patient positioning because patient anatomy varies. The


Colorectal Cancer Screening

Colorectal Cancer Screening. perforation rate during DCBE is approximately 1 in 25,000 [56] as compared to 1 in 22,000 for CTC and 1 in 1,000 for diagnostic colonoscopy [38,39].


Colorectal Cancer Screening

Colorectal Cancer Screening. Additional data on the effectiveness of the DCBE for detecting colorectal cancer comes from studies in which the imaging history of patients with colorectal cancer was reviewed. In many of these studies, the risk level of patients undergoing DCBE was not reported. Based on this methodology, the sensitivity of DCBE ranges from 75% to 95% [64-66]. This correlates with a large, population-based study that found the overall rate of new or missed cancers following a DCBE was 22% [67].