Keywords

ACS, acute coronary syndrome, CAD, cardiac magnetic resonance imaging, CCTA, coronary artery disease, coronary computed tomography angiography, diagnostic testing, echocardiography, fractional flow reserve, myocardial perfusion imaging, noninvasive testing, NP, PET, positron emission tomography, single-photon emission computed tomography, SPECT, stable angina

 

Authors

  1. El Hussein, Mohamed Toufic PhD, RN, NP
  2. Fibich, Elio

Abstract

Abstract: Selecting noninvasive diagnostic tests for coronary artery disease can be a daunting task to acute care NPs. This article provides an overview of the pathophysiology of coronary artery disease, relevant noninvasive diagnostic imaging modalities, and an evidence-based approach to guide subsequent diagnostic and therapeutic interventions.

 

Article Content

This article aims to provide a comprehensive overview outlining current noninvasive diagnostic imaging modalities for coronary artery disease (CAD) in patients presenting with acute chest pain. Traditionally, invasive coronary angiography was used early in diagnosing patients with suspected CAD; however, there is evidence that a large percentage of patients presenting with chest pain do not have significant coronary obstruction.1,2 The unnecessary use of invasive diagnostic modalities may lead to serious complications and additional cost. The 2019 European Society of Cardiology (ESC) guidelines for diagnosis and management of chronic coronary syndromes and the 2021 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for evaluation and diagnosis of chest pain recommend using either noninvasive functional or noninvasive anatomical imaging as the initial test to diagnose CAD, except for certain situations discussed later. The ESC and the ACC/AHA guidelines also highlight that clinicians should become familiar with each imaging modality as well as when and why to order them.3,4

  
Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

Pathophysiology

CAD is a pathologic process characterized by obstructive and nonobstructive atherosclerotic plaque formation, commonly made up of fibrous and fatty tissue, in the coronary arteries. The leading cause of CAD is atherosclerosis, in which foam cells, a specific type of macrophage laden with lipids, accumulate in the tunica intima of vessels forming fatty streaks. The accumulated macrophages also stimulate smooth muscle cell proliferation, causing the formation of a fibrous plaque. As the size of the fibrous plaque increases, the diameter of the vessel lumen decreases, leading to myocardial ischemia.5,6 The process of atherosclerosis, and resultant CAD, can be accelerated by various risk factors such as dyslipidemia, diabetes, hypertension, or smoking.3,7 The narrowing and subsequent myocardial ischemia seen in CAD most commonly presents as angina, localized in the chest; however, the chest discomfort may extend to the lower jaw, back, or arms. Patients may describe angina as chest pressure, tightness, or heaviness.3 Chest pain is classified into categories of typical angina, atypical angina, and nonanginal chest pain.3 For angina to be classified as typical, chest pain should meet three criteria: (i) discomfort in the front of the chest (retrosternal) or the shoulder, arm, neck, or jaw and described as constricting; (ii) discomfort is provoked by physical exertion; and (iii) discomfort is relieved by rest or with nitrates within 5 minutes. An individual would be classified as having atypical angina if they met two of these criteria and would be classified as having nonanginal chest pain if they met one or none of the criteria.3,8,9

 

The decision of which diagnostic test to use to determine the cause of chest pain relies primarily on whether the chest pain is acute/unstable or stable. The AHA/ACC guideline established that characteristics including onset, location, intensity, and duration of chest pain distinguish acute chest pain due to ACS compared with chest pain secondary to noncardiac causes.4 History taking is substantial in differentiating between chest pain secondary to CAD and chest pain due to bone or muscle disorders. Asking the patient about a history of chest pain is invaluable, especially if the patient is known to have CAD and experienced ACS in the past.4 Stable chest pain is described as chronic with known and persistent precipitating factors.4 The ESC guidelines further described stable chest pain as a condition with a pattern of transient inducible and reversible ischemia.3

 

The European and American guidelines stipulate their recommendations for diagnosing CAD based on the patient's pre-test probability (PTP) of CAD (see Clinical pre-test probability of obstructive CAD in symptomatic patients).10 The AHA/ACC guideline recommends the use of clinical decision pathways for risk stratification of patients into low-, intermediate-, and high-risk groups.4 The ESC guidelines provide a table of PTP values according to the patient's age, sex, nature of symptoms (that is, typical, atypical, and nonanginal), and presence of dyspnea.3 For example, a 65-year-old male patient presenting with typical angina symptoms would be assigned a PTP of 44% from the ESC table based on their sex (male), age (65 years old), and their presenting chest pain (typical). The same patient presenting with dyspnea as a primary symptom would be assigned a PTP of 27%. Routine testing of patients with a PTP of less than 5% is not recommended. Consideration may be given to pursuing noninvasive diagnostic testing for patients with a PTP of 5% to 15%. Noninvasive testing is recommended for patients with a PTP greater than 15%.3 Proceeding directly to invasive coronary angiography (ICA) without further diagnostic testing is reasonable in patients with a high clinical likelihood of CAD.3 ICA is also recommended in patients with symptoms unresponsive to medical therapy or in patients with typical angina at low levels of exercise.3 In patients where CAD cannot be excluded by clinical assessment alone, noninvasive diagnostic testing to establish a diagnosis and assess the event risk is recommended.11 Noninvasive testing for CAD is divided into two main categories:

 

1. Functional imaging techniques:

 

a. stress echocardiography

 

b. stress cardiac magnetic resonance (CMR)

 

c. myocardial perfusion imaging (MPI): positron emission tomography (PET) and stress single-photon emission computed tomography (SPECT)

 

2. Anatomical imaging techniques, which mainly include coronary computed tomography angiography (CCTA) and computed tomography-based fractional flow reserve (FFRCT)

 

 

Anatomical noninvasive tests are key in ruling out CAD by visualizing lesion(s) or plaques in the coronary arteries. On the other hand, functional tests are primarily used to rule in CAD by providing information on hemodynamically relevant CAD (obstructions greater than 50% of the lumen), such as myocardial ischemia.11 There are also techniques, such as FFRCT, which allow for functional and anatomical imaging. Indications for ordering anatomical imaging include presence of ischemic symptoms (that is, acute chest pain) with high likelihood of normal study findings and the absence of a history of CAD.12,13 Anatomical imaging is useful for making treatment decisions based on the extent of the ischemia, such as whether the ischemia can be treated pharmacologically or if more invasive action must be taken (that is, percutaneous coronary intervention or coronary artery bypass graft surgery).14 Functional imaging is indicated when there is a need to detect the presence and degree of ischemia while also providing useful prognostic information.12,13

 

Functional noninvasive imaging

Stress echocardiography. Stress echocardiography allows a practitioner to assess wall motion abnormalities (WMAs) under rest and stress conditions, indicating any hemodynamic abnormalities brought about by coronary stenosis.11 The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of echocardiography are 64%, 84%, 70%, and 81%, respectively.15 Advantages of using echocardiography are that the test is widely available and can be performed at the bedside, while not exposing the patient to contrast or radiation, and is also able to evaluate ventricular size and function.11 A potential major disadvantage of echocardiography is that it is operator-dependent and has a limited diagnostic value in patients with poor acoustic windows (such as due to body habitus or pulmonary disease).19 Stress during the test can be induced by either exercise (treadmill or bike) or pharmacologic (for example, dobutamine or atropine) means to increase either the force (inotropic) or speed (chronotropic) of the heart's contractions.11 The AHA/ACC and ESC guidelines and the 2014 Canadian Cardiovascular Society (CCS) Guidelines for the Diagnosis and Management of Stable Ischemic Heart Disease recommend ordering echocardiography for patients who present with acute chest pain and an intermediate PTP who require a rapid bedside test.3,4,20

 

Cardiac magnetic resonance. CMR imaging is a functional noninvasive testing modality which evaluates myocardial ischemia under conditions of stress and rest.11 A 2019 meta-analysis by Pontone et al. using invasive FFR as a reference standard found the sensitivity, specificity, NPV, and PPV for CMR to be 87%, 88%, 86%, and 86%, respectively.15 The ESC guidelines suggest considering CMR in patients with suspected CAD when echocardiography with I.V. contrast is inconclusive.3 On top of assessing for ischemia, CMR can also assess the dimensions and function of the right and left ventricles as well as assess for regional WMAs.11 Based on the AHA/ACC and ESC guidelines, CMR is indicated in patients who present with intermediate PTP, acute chest pain, and known CAD.3,4 CMR is useful for cardiac risk stratification in patients with suspected or known CAD. A unique feature of CMR is the ability to characterize tissue and depict myocardial edema and fibrosis using late gadolinium enhancement (LGE). Gadolinium is an I.V. contrast agent that has been shown to have delayed washout in areas of increased extracellular space caused by myocardial cell death or deposits of foreign extracellular material.16 Other potential causes of chest pain, such as myocarditis, sarcoidosis, and hypertrophic cardiomyopathy, can be diagnosed based on the pattern of LGE and edema.17 Contraindications for CMR include claustrophobia, inability to lie flat for long periods of time and perform breath holds, and metal prosthetics or non-MR-conditional devices.11 CMR imaging may also take a long time to acquire and is not always widely available.10 (See Overview of different noninvasive anatomical and functional imaging modalities to assess coronary artery disease.)

 

The Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC 2) was a randomized clinical trial that compared the efficacy and safety of care guided by CMR, MPI, and the United Kingdom National Institute for Health and Care Excellence (NICE) guidelines.18 The CE-MARC 2 included 1,202 participants randomized into three groups: CMR (n = 481), MPI (n = 481), and NICE (n = 240). The study found that using CMR and MPI in patients with a 61% to 90% (n = 389) pretest likelihood of CAD resulted in reduced probability of requiring unnecessary invasive angiography within 12 months compared with those in the NICE group.

 

Myocardial perfusion imaging: Positron emission tomography and single-photon emission computed tomography. PET and SPECT are well-recognized nuclear cardiac imaging tests, also called MPI, used for functional evaluation of myocardial ischemia.11,21 In comparison to ECG, SPECT offers higher sensitivity and specificity when assessing for myocardial ischemia and scarring while also allowing for ventricular size and function assessment.10,22 A benefit to SPECT usage is the practitioner's ability to combine SPECT with CCTA, allowing comprehensive anatomical and functional evaluation.23,24 Overall, PET is significantly more sensitive than SPECT. PET has a sensitivity of 88%, specificity of 86%, NPV of 88%, and PPV of 85%, compared with 71%, 79%, 70%, and 75% of SPECT in the same order.15

 

Among all noninvasive diagnostic testing, PET has the highest diagnostic accuracy and is considered the gold standard for accurate quantification of myocardial blood flow.11 In cases where SPECT and CMR may have limited diagnostic accuracy due to balanced ischemia, such as with three-vessel disease, the availability of a PET scan is instrumental.25 In a comparative study by Bateman et al., PET was significantly more sensitive than SPECT when it came to identifying multivessel coronary disease, 71% compared with 48%, respectively.26

 

A well-known limitation for MPIs is the phenomenon of balanced ischemia where there is homogenous uptake and distribution of the radio tracer/contrast in all segments of the myocardium. Given that the diagnosis of CAD using SPECT and CMR are based around the ability to detect differences in perfusion across the myocardium, balanced ischemia is likely to yield false-negative results due to the uniform distribution of the ischemic burden.27 PET adds an advantage over stress echocardiography by having good image quality in women and individuals with obesity.11 SPECT and PET have certain advantages over CCTA and CMR imaging and are preferred in patients with arrhythmias or severe renal disease as well as in those unable to lie flat for long periods.11 Disadvantages of these imaging modalities are that both SPECT and PET expose patients to radiation; additionally, PET is associated with high costs and cannot be performed with exercise-induced stress, therefore, it is restricted to pharmacologic stress induction.11

 

Based on the AHA/ACC guidelines, PET/SPECT MPI are indicated in patients who present with intermediate PTP and acute chest pain with or without known CAD diagnosis.4 The guidelines suggest that PET is preferred over SPECT in patient with intermediate- to high-risk PTP who present with stable chest pain and no known CAD diagnosis to improve diagnostic accuracy.4

 

Anatomical noninvasive imaging

Coronary computed tomography angiography. CCTA is an anatomical imaging test used to visualize the coronary artery lumen and wall. When used with I.V. contrast, the test has a high sensitivity (96%) and specificity (82%) to detect coronary artery stenosis.10,25 Due to minimal radiation and contrast exposure, CCTA is considered the first-choice imaging test to rule out CAD, particularly in patients with low- to intermediate clinical likelihood of CAD, no previous diagnosis of CAD, and characteristics associated with a good image quality and with a high likelihood of normal study findings.3,4,20,28,29

 

There are several disadvantages and contraindications to the use of CCTA. Due to the usage of a contrast agent, renal disease (estimated glomerular filtration rate less than 60 mL/min) is a relative contraindication to CCTA, as it may result in contrast-induced nephropathy.30 The test cannot be confidently used in individuals with obesity, extensive coronary calcification, a heart rate greater than 80 beats/minute that cannot be lowered pharmacologically, irregular heart rhythms (that is, atrial fibrillation), coronary artery stents, and previous coronary artery bypass grafts.3,7,30 Obesity poses several challenges for accurate CCTA imaging due to the potential size constraints of the machine and the increased noise in the resulting images.30 Extensive coronary calcification also poses issues for accurate imaging, leading to high X-ray attenuation (reduction in intensity).31 Issues regarding the heart rate and irregular heart rhythms go hand in hand, as the best image quality is achieved with a low heart rate (ideally less than or equal to 60 beats/minute) and regular rhythm.32,33 To achieve the ideal heart rate, the NP should consider beta-blockers such as metoprolol or, if there is significant hepatic dysfunction, atenolol, orally or I.V., as first-line pharmacologic intervention.30 The 2016 Society of Cardiovascular Computed Tomography (SCCT) guidelines for CCTA describe two potential approaches to achieve the ideal heart rate: 1) a staggered dosage of metoprolol, ranging from 50 to 100 mg P.O., based on the presenting resting heart rate administered 1 hour prior to the scan, or 2) metoprolol 50 mg P.O. 12 hours prior to the test followed by an additional 50-100 mg P.O. 1 hour prior to the scan; in both cases additional I.V. beta-blockers can be administered if the ideal heart rate has not been achieved.30,34-36 For patients with a CCTA positive for a functionally significant coronary lesion, FFRCT can be used to aid in the clinical decision-making regarding which patients may benefit from invasive evaluation.15

 

In a recently published multicenter, pragmatic, randomized trial, the Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, CCTA was compared with ICA to determine whether it is an accurate alternative.37 The trial included 3,667 patients who had intermediate PTP (10% to 60%) of obstructive CAD and were referred to undergo ICA. The patients were randomly assigned to undergo either CCTA (n = 1,833) or ICA (n = 1,834). Of the 3,667 patients, 3,561 (CCTA, n = 1,808; ICA, n = 1,753) were included in the analysis. The study found that over a 3.5-year follow-up period, major adverse cardiovascular events (that is, cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) occurred in 38 patients (2.1%) in the CCTA group and in 52 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval, 0.46 to 1.07; P = .10). During the same follow-up period, more patients in the CCTA group underwent additional functional tests than those in the ICA group (n = 336 [18.6%] and n = 227 [12.9%], respectively). However, 30 major procedure-related complications were associated with ICA compared with only 7 with CCTA. Furthermore, patients in the CCTA group underwent a lower frequency of coronary revascularization procedures than those in the ICA group, 256 patients (14.2%) to 315 patients (18.0%), respectively. The study concluded that CCTA resulted in no significant differences compared with ICA when it came to the incidence of major adverse cardiovascular events; however, it was associated with a lower risk of major procedure-related complications and revascularization procedures.37

 

The guidelines note that CCTA is contraindicated in patients who present with irregular heart rhythms, significant renal dysfunction, and contrast media allergies.20

  
Overview of differen... - Click to enlarge in new windowOverview of different noninvasive anatomical and functional imaging modalities to assess coronary artery disease

Computed tomography-based fractional flow reserve. FFRCT has become a promising alternative to SPECT and PET, providing practitioners with the functional significance of CAD derived from a CCTA.38 Pijls et al. defined FFR as the maximum blood flow to the myocardium in the presence of a coronary artery stenosis divided by the theoretical normal maximum flow. This calculation gives the practitioner an idea of the maximum myocardial flow that can be achieved despite the presence of coronary stenosis, with an FFR of 1.0 being considered normal.39 Conventional invasively measured FFR only measures the pressure inside a single vessel through a wire and may be measured during ICA.40 FFRCT can calculate the pressure and flow throughout the entire coronary tree through an interactive three-dimensional coronary model and can be determined through CCTA images.40 When interpreting invasive FFR readings, it is recommended that pressure is assessed at least 2-3 cm distal to the stenosis to avoid pressure recovery phenomenon, in which there is an increase in pressure downstream from the stenosis.41,42 Likewise, it is recommended to use the FFRCT value found 1-2 cm distally of the stenosis.40 The Fractional Flow Reserve-Derived from Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain (FORECAST) trial, a randomized controlled trial conducted in the United Kingdom over a 9-month period, concluded that there was not a significant difference in cost between the use of FFRCT and standard ICA; however, the use of FFRCT led to a 22% reduction in the use of ICA.43 The reduced need for invasive testing could result in greater comfort and decreased risk for procedure-related complications and therefore greater quality of life for patients. A primary disadvantage of using FFRCT is the need for high-enough quality CCTA images to use the technique.44,45 As a result of this disadvantage, patients may need to undergo additional or alternative testing to better evaluate lesions if the image quality is not high enough.

 

The AHA/ACC guidelines consider FFRCT imaging a sequential or add-on test.4 Based on these guidelines, it is recommended that the NP orders FFRCT imaging for patients who have an intermediate PTP and coronary artery stenosis of 40% to 90% in a proximal or middle coronary segment on CCTA.

 

Invasive testing

The Task Force on myocardial revascularization of the ESC and European Association for Cardio-Thoracic Surgery (EACTS) state that, for diagnostic purposes, invasive testing (that is, ICA) is only necessary in patients with suspected CAD if noninvasive testing is inconclusive or if noninvasive testing suggests high event risk.46 The 2019 ESC guidelines recommend that for patients who have been determined to have a high clinical likelihood of CAD, symptoms unresponsive to medication or typical angina at low levels of exercise, and initial clinical evaluation suggesting high event risk, early invasive testing without previous noninvasive testing be carried out.3

 

Conclusion

This article presented an updated overview of the noninvasive imaging modalities used to diagnose suspected CAD. The imaging techniques outlined in this paper should be selected based on the patients' presenting symptoms, risk factors, and PTP scores. The local expertise and the availability of each modality should be considered when selecting a noninvasive technique to evaluate symptomatic patients. In addition to following the guidelines, NPs must use their clinical reasoning skills to decide on the best noninvasive procedure for each individual patient.

 

REFERENCES

 

1. Hannan EL, Samadashvili Z, Cozzens K, et al Appropriateness of diagnostic catheterization for suspected coronary artery disease in New York State. Circ Cardiovasc Interv. 2014;7(1):19-27. doi:10.1161/CIRCINTERVENTIONS.113.000741. [Context Link]

 

2. Patel MR, Dai D, Hernandez AF, et al Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J. 2014;167(6):846-852.e2. doi:10.1016/j.ahj.2014.03.001. [Context Link]

 

3. Knuuti J, Wijns W, Saraste A, et al 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-477. doi:10.1093/eurheartj/ehz425. [Context Link]

 

4. Gulati M, Levy PD, Mukherjee D, et al 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines [published correction appears in Circulation. 2021;144(22):e455]. Circulation. 2021;144(22):e368-e454. doi:10.1161/CIR.0000000000001029. [Context Link]

 

5. El Hussein MT, Hakkola J. Management strategies for STE-ACS. Nurse Pract. 2021;46(6):18-26. [Context Link]

 

6. El Hussein M, Hakkola J. Mnemonic to assist in the treatment of NSTE-ACS. Nurse Pract. 2020;45(11):48-55. [Context Link]

 

7. National Institute for Health and Care Excellence. New generation cardiac CT scanners (Aquilion ONE, Brilliance iCT, Discovery CT750 HD and Somatom Definition Flash) for cardiac imaging in people with suspected or known coronary artery disease in whom imaging is difficult with earlier generation CT scanners. 2012. http://www.nice.org.uk/guidance/dg3. [Context Link]

 

8. Diamond GA. A clinically relevant classification of chest discomfort. J Am Coll Cardiol. 1983;1(2 Pt 1):574-575. doi:10.1016/s0735-1097(83)80093-x. [Context Link]

 

9. Genders TS, Steyerberg EW, Hunink MG, et al Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts. BMJ. 2012;344:e3485. doi:10.1136/bmj.e3485. [Context Link]

 

10. Knuuti J, Ballo H, Juarez-Orozco LE, et al The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability. Eur Heart J. 2018;39(35):3322-3330. doi:10.1093/eurheartj/ehy267. [Context Link]

 

11. Boscolo Berto M, Benz DC, Grani C. Noninvasive assessment of coronary artery disease - anatomical versus functional imaging and the marginal role of exercise electrocardiograms. Praxis (Bern 1994). 2020;109(14):1141-1149. doi:10.1024/1661-8157/a003531. [Context Link]

 

12. Hanson CA, Bourque JM. Functional and anatomical imaging in patients with ischemic symptoms and known coronary artery disease. Curr Cardiol Rep. 2019;21(8):79. doi:10.1007/s11886-019-1155-3. [Context Link]

 

13. Karthikeyan G, Guzic Salobir B, Jug B, et al Functional compared to anatomical imaging in the initial evaluation of patients with suspected coronary artery disease: an international, multi-center, randomized controlled trial (IAEA-SPECT/CTA study). J Nucl Cardiol. 2017;24(2):507-517. doi:10.1007/s12350-016-0664-3. [Context Link]

 

14. Schuijf JD, Shaw LJ, Wijns W, et al Cardiac imaging in coronary artery disease: differing modalities. Heart. 2005;91(8):1110-1117. doi:10.1136/hrt.2005.061408. [Context Link]

 

15. Pontone G, Guaricci AI, Palmer SC, et al Diagnostic performance of non-invasive imaging for stable coronary artery disease: a meta-analysis. Int J Cardiol. 2020;300:276-281. doi:10.1016/j.ijcard.2019.10.046. [Context Link]

 

16. Cummings KW, Bhalla S, Javidan-Nejad C, Bierhals AJ, Gutierrez FR, Woodard PK. A pattern-based approach to assessment of delayed enhancement in nonischemic cardiomyopathy at MR imaging. Radiographics. 2009;29(1):89-103. doi:10.1148/rg.291085052. [Context Link]

 

17. Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J. 2005;26(15):1461-1474. doi:10.1093/eurheartj/ehi258. [Context Link]

 

18. Greenwood JP, Ripley DP, Berry C, et al Effect of care guided by cardiovascular magnetic resonance, myocardial perfusion scintigraphy, or NICE guidelines on subsequent unnecessary angiography rates: the CE-MARC 2 randomized clinical trial. JAMA. 2016;316(10):1051-1060. doi:10.1001/jama.2016.12680. [Context Link]

 

19. Tweet MS, Arruda-Olson AM, Anavekar NS, Pellikka PA. Stress echocardiography: what is new and how does it compare with myocardial perfusion imaging and other modalities. Curr Cardiol Rep. 2015;17(6):43. doi:10.1007/s11886-015-0600-1. [Context Link]

 

20. Mancini GB, Gosselin G, Chow B, et al Canadian Cardiovascular Society guidelines for the diagnosis and management of stable ischemic heart disease. Can J Cardiol. 2014;30(8):837-849. doi:10.1016/j.cjca.2014.05.013. [Context Link]

 

21. Askew JW, Chareonthaitawee P, Arruda-Olson AM. Selecting the optimal cardiac stress test. In: Post T, ed. UpToDate. 2022. http://www.uptodate.com. [Context Link]

 

22. Shaw LJ, Berman DS, Picard MH, et al Comparative definitions for moderate-severe ischemia in stress nuclear, echocardiography, and magnetic resonance imaging [published correction appears in JACC Cardiovasc Imaging. 2014;7(7):748]. JACC Cardiovasc Imaging. 2014;7(6):593-604. doi:10.1016/j.jcmg.2013.10.021. [Context Link]

 

23. Benz DC, Gaemperli L, Grani C, et al Impact of cardiac hybrid imaging-guided patient management on clinical long-term outcome. Int J Cardiol. 2018;261:218-222. doi:10.1016/j.ijcard.2018.01.118. [Context Link]

 

24. Pazhenkottil AP, Benz DC, Grani C, et al Hybrid SPECT perfusion imaging and coronary CT angiography: long-term prognostic value for cardiovascular outcomes. Radiology. 2018;288(3):694-702. doi:10.1148/radiol.2018171303. [Context Link]

 

25. Menke J, Kowalski J. Diagnostic accuracy and utility of coronary CT angiography with consideration of unevaluable results: a systematic review and multivariate Bayesian random-effects meta-analysis with intention to diagnose. Eur Radiol. 2016;26(2):451-458. doi:10.1007/s00330-015-3831-z. [Context Link]

 

26. Bateman TM, Heller GV, McGhie AI, et al Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol. 2006;13(1):24-33. doi:10.1016/j.nuclcard.2005.12.004. [Context Link]

 

27. Aziz EF, Javed F, Alviar CL, Herzog E. Triple vessel coronary artery disease presenting as a markedly positive stress electrocardiographic test and a negative SPECT-TL scintigram: a case of balanced ischemia. Heart Int. 2011;6(2):e22. doi:10.4081/hi.2011.e22. [Context Link]

 

28. Benz DC, Grani C, Hirt Moch B, et al. Minimized radiation and contrast agent exposure for coronary computed tomography angiography: first clinical experience on a latest generation 256-slice scanner. Acad Radiol. 2016;23(8):1008-1014. doi:10.1016/j.acra.2016.03.015. [Context Link]

 

29. Cademartiri F, Maffei E, Palumbo A, et al Diagnostic accuracy of 64-slice computed tomography coronary angiography in patients with low-to-intermediate risk. Radiol Med. 2007;112(7):969-981. doi:10.1007/s11547-007-0198-5. [Context Link]

 

30. Abbara S, Blanke P, Maroules CD, et al SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee: endorsed by the North American Society for Cardiovascular Imaging (NASCI). J Cardiovasc Comput Tomogr. 2016;10(6):435-449. doi:10.1016/j.jcct.2016.10.002. [Context Link]

 

31. Halliburton SS, Abbara S, Chen MY, et al SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT. J Cardiovasc Comput Tomogr. 2011;5(4):198-224. doi:10.1016/j.jcct.2011.06.001. [Context Link]

 

32. Brodoefel H, Reimann A, Heuschmid M, et al Non-invasive coronary angiography with 16-slice spiral computed tomography: image quality in patients with high heart rates. Eur Radiol. 2006;16(7):1434-1441. doi:10.1007/s00330-006-0155-z. [Context Link]

 

33. Cademartiri F, Mollet NR, Runza G, et al Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates. Int J Cardiovasc Imaging. 2006;22(1):101-109. doi:10.1007/s10554-005-9010-6. [Context Link]

 

34. Roberts WT, Wright AR, Timmis JB, Timmis AD. Safety and efficacy of a rate control protocol for cardiac CT. Br J Radiol. 2009;82(976):267-271. doi:10.1259/bjr/24574758. [Context Link]

 

35. Sadamatsu K, Koide S, Nakano K, Yoshida K. Heart rate control with single administration of a long-acting b-blocker at bedtime before coronary computed tomography angiography. J Cardiol. 2015;65(4):293-297. doi:10.1016/j.jjcc.2014.07.007.

 

36. Clayton B, Raju V, Roobottom C, Morgan-Hughes G. Safety of intravenous b-adrenoceptor blockers for computed tomographic coronary angiography. Br J Clin Pharmacol. 2015;79(3):533-536. doi:10.1111/bcp.12516. [Context Link]

 

37. Maurovich-Horvat P, Bosserdt M, et alDISCHARGE Trial Group CT or invasive coronary angiography in stable chest pain. N Engl J Med. 2022;386(17):1591-1602. doi:10.1056/NEJMoa2200963. [Context Link]

 

38. Taylor CA, Fonte TA, Min JK. Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J Am Coll Cardiol. 2013;61(22):2233-2241. doi:10.1016/j.jacc.2012.11.083. [Context Link]

 

39. Pijls NH, De Bruyne B, Peels K, et al Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996;334(26):1703-1708. doi:10.1056/NEJM199606273342604. [Context Link]

 

40. Norgaard BL, Fairbairn TA, Safian RD, et al Coronary CT angiography-derived fractional flow reserve testing in patients with stable coronary artery disease: recommendations on interpretation and reporting. Radiol Cardiothorac Imaging. 2019;1(5):e190050. doi:10.1148/ryct.2019190050. [Context Link]

 

41. Toth GG, Johnson NP, Jeremias A, et al Standardization of fractional flow reserve measurements. J Am Coll Cardiol. 2016;68(7):742-753. doi:10.1016/j.jacc.2016.05.067. [Context Link]

 

42. Niederberger J, Schima H, Maurer G, Baumgartner H. Importance of pressure recovery for the assessment of aortic stenosis by Doppler ultrasound. Role of aortic size, aortic valve area, and direction of the stenotic jet in vitro. Circulation. 1996;94(8):1934-1940. doi:10.1161/01.cir.94.8.1934. [Context Link]

 

43. Curzen N, Nicholas Z, Stuart B, et al Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial. Eur Heart J. 2021;42(37):3844-3852. doi:10.1093/eurheartj/ehab444. [Context Link]

 

44. Min JK, Leipsic J, Pencina MJ, et al Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012;308(12):1237-1245. doi:10.1001/2012.jama.11274. [Context Link]

 

45. Norgaard BL, Leipsic J, Gaur S, et al Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. 2014;63(12):1145-1155. doi:10.1016/j.jacc.2013.11.043. [Context Link]

 

46. Sousa-Uva M, Neumann F-J, Ahlsson A, et al 2018 ESC/EACTS guidelines on myocardial revascularization. Eur J Cardiothorac Surg. 2019;55(1):4-90. doi:10.1093/ejcts/ezy289. [Context Link]