Edited by: Gerald A. Meininger, University of Missouri, USA
Reviewed by: Jaw-Wen Chen, National Yang-Ming University School of Medicine, Taiwan; Antonio Francesco Corno, University Sains Malaysia, Malaysia
*Correspondence: Grigorios Korosoglou, Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, 69120, Germany e-mail:
This article was submitted to Vascular Physiology, a section of the journal Frontiers in Physiology.
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Despite advances in the pharmacologic and interventional treatment of coronary artery disease (CAD), atherosclerosis remains the leading cause of death in Western societies. X-ray coronary angiography has been the modality of choice for diagnosing the presence and extent of CAD. However, this technique is invasive and provides limited information on the composition of atherosclerotic plaque. Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have emerged as promising non-invasive techniques for the clinical imaging of CAD. Hereby, CCTA allows for visualization of coronary calcification, lumen narrowing and atherosclerotic plaque composition. In this regard, data from the CONFIRM Registry recently demonstrated that both atherosclerotic plaque burden and lumen narrowing exhibit incremental value for the prediction of future cardiac events. However, due to technical limitations with CCTA, resulting in false positive or negative results in the presence of severe calcification or motion artifacts, this technique cannot entirely replace invasive angiography at the present time. CMR on the other hand, provides accurate assessment of the myocardial function due to its high spatial and temporal resolution and intrinsic blood-to-tissue contrast. Hereby, regional wall motion and perfusion abnormalities, during dobutamine or vasodilator stress, precede the development of ST-segment depression and anginal symptoms enabling the detection of functionally significant CAD. While CT generally offers better spatial resolution, the versatility of CMR can provide information on myocardial function, perfusion, and viability, all without ionizing radiation for the patients. Technical developments with these 2 non-invasive imaging tools and their current implementation in the clinical imaging of CAD will be presented and discussed herein.
Despite major advances in the treatment of coronary artery disease (CAD), it still remains one of the leading causes of death in Western societies (Murray and Lopez,
X-ray coronary angiography is the current clinical gold-standard technique for the detection of CAD. Coronary angiography provides an accurate measure of stenosis. However, this technique is invasive and almost entirely relies on anatomic structure of the vascular lumen (Vallabhajosula and Fuster,
Modern CMR 1.5 & 3.0 Tesla clinical scanners provide high temporal (~40ms) and spatial (<1.0*1.0 mm in plane) resolution for the assessment of cardiac function. The latter is almost 10-fold higher compared to competing nuclear scintigraphy techniques. Although earlier CMR studies had limitations, such as poor slice coverage and low temporal resolution, limiting the detection of CAD, subsequent data demonstrated that CMR compares favorably to SPECT for the detection of myocardial ischemia (Schwitter et al.,
Detection of CAD using CMR is mainly based on the evaluation of the functional significance of coronary artery stenosis during pharmacologic stress testing with either adenosine or dipyridamole, i.e., coronary vasodilators, or dobutamine, which is a synthetic ß-adrenergic stimulator. Using stress CMR, inducible myocardial ischemia can be detected in form of inducible wall motion abnormalities during dobutamine stress or in form of perfusion deficits during vasodilator stress, which both precede the development of ST-segment depression and anginal symptoms in the ischemic cascade (Figure
In a meta-analysis including 14 dobutamine and 24 adenosine stress CMR studies with 754 and 1516 patients, respectively sensitivities and specificities of 83% (95% confidence interval of 79–88%), 86% (95% confidence interval of 81–91%) and of 91% (95% confidence interval of 88–94%) and 81% (95% confidence interval of 77–85%), respectively were reported (Tables
Hundley et al., |
Dobutamine/Atropin | 41 | GE 1.5T | >50 | 83 (86–93) | 83 (36–100) |
Jahnke et al., |
Dobutamine | 40 | Philips 1.5T | ≥50 | 83 (51–97) | 89 (71–97) |
Nagel et al., |
Dobutamine | 172 | Philips 1.5T | ≥50 | 86 (78–92) | 86 (75–93) |
Paetsch et al., |
Dobutamine/Atropin | 79 | Philips 1.5T | >50 | 89 (77–96) | 81 (61–93) |
Paetsch et al., |
Dobutamine | 150 | Philips 1.5T | ≥50 | 78 (67–87) | 88 (78–94) |
Pennell et al., |
Dobutamine | 25 | Picker 0.5T | ≥50 | 91 (71–99) | 100 (29–100) |
Rerkpattanapipat et al., |
Exercise | 27 | GE 1.5T | >70 | 79 (49–95) | 85 (55–98) |
Schalla et al., |
Dobutamine | 22 | Philips 1.5T | >75 | 81 (54–96) | 83 (36–100) |
van Rugge et al., |
Dobutamine | 45 | Philips 1.5T | >50 | 81 (65–92) | 100 (63–100) |
van Rugge et al., |
Dobutamine | 39 | Philips 1.5T | ≥50 | 91 (76–98) | 83 (36–100) |
Pooled data | Dobutamine ± Atropin | 680 | ≥50–75 | 85 (82–90) | 86 (81–91) |
Cury et al., |
Dipyridamole | 47 | GE 1.5T | ≥70 | 87 (74–94) | 89 (80–95) |
Doyle et al., |
Dipyridamole | 199 | Philips 1.5T | ≥70 | 58 (37–77) | 78 (71–84) |
Giang et al., |
Adenosine | 44 | GE 1.5T | ≥50 | 93 (77–99) | 75 (48–92) |
Pennell et al., |
Dipyridamole | 40 | Picker 0.5T | Not specified | 62 (45–77) | 100 (3–100) |
Ishida et al., |
Dipyridamole | 104 | GE 1.5T | ≥70 | 90 (81–95) | 85 (67–94) |
Kawase et al., |
Nicorandil | 50 | Philips 1.5T | >70 | 94 (80–99) | 94 (71–100) |
Klem et al., |
Adenosine | 95 | Siemens 1.5T | ≥70 | 89 (75–97) | 87 (76–95) |
Nagel et al., |
Adenosine | 90 | Philips 1.5T | ≥75 | 88 (75–96) | 90 (77–97) |
Pilz et al., |
Adenosine | 176 | GE 1.5T | >70 | 96 (91–99) | 83 (71–91) |
Plein et al., |
Adenosine | 71 | Philips 1.5T | ≥70 | 96 (88–100) | 83 (52–98) |
Plein et al., |
Adenosine | 92 | Philips 1.5T | >70 | 88 (77–95) | 82 (52–90) |
Sakuma et al., |
Dipyridamole | 40 | Siemens 1.5T | >70 | 81 (58–95) | 68 (43–87) |
Schwitter et al., |
Dipyridamole | 48 | GE 1.5T | ≥50 | 87 (71–95) | 85 (35–93) |
Takase et al., |
Dipyridamole | 102 | GE 1.5T | >50 | 93 (85–98) | 85 (65–96) |
Paetsch et al., |
Adenosine | 79 | Philips 1.5T | >50 | 91 (79–97) | 62 (41–80) |
Pooled data | Vasodilator stress | 1237 | 91 (88–94) | 81 (77–85) |
An example of a patient with inducible wall motion abnormality of the anterior-septal apical wall during peak dobutamine stress CMR is illustrated in Figures
Despite the high diagnostic value and reproducibility of stress CMR (Paetsch et al.,
An example of a patient with an increasing strain abnormality in the anterior-septal wall during dobutamine stress (Figures
Similar to the assessment of wall motion abnormalities, most CMR centers perform visual analysis of perfusion scans for the diagnosis of inducible myocardial ischemia in the clinical routine. In this regard, the transmural extent of a perfusion deficit is determined from dynamic images showing the maximum extent of regional hypoenhancement. Hereby, increase in regional hypoenhancement during adenosine or dypiridamole stress (≥25% increase in hypoenhancement transmurality compared to baseline scans) in at least one myocardial segment, which persists for ≥5 consecutive image frames, is considered as indicative of inducible ischemia (Korosoglou et al.,
Recent studies have also demonstrated the cost-effectiveness of CMR in the clinical routine. Thus, an economic evaluation of the CE-MARC study, which showed that CMR has superior diagnostic accuracy to SPECT (Greenwood et al.,
Estimating the risk for subsequent cardiac events is of paramount importance in patients with known or suspected CAD, because an invasive therapy is warranted for patients with myocardial ischemia who are at high-risk for future events according to current guidelines (Montalescot et al.,
Charoenpanichkit et al., |
6.0 | 353 | Not reported | 31 | 3.1 |
Gebker et al., |
2.1 | 1167 | 48 | 40 | 11.3 |
Jahnke et al., |
2.3 | 513 | 54 | 41 | 4.7 |
Kelle et al., |
3.7 | 1463 | 52 | 30 | 2.9 |
Korosoglou et al., |
2.0 | 1473 | 55 | 20 | 5.9 |
Bertaso et al., |
1.8 | 362 | 43 | 25 | 4.7 |
Bingham and Hachamovitch, |
2.6 | 908 | 49 | 33 | 1.76 |
Bodi et al., |
1.1 | 1722 | Not reported | 41 | 1.15 |
Buckert et al., |
4.2 | 1152 | Not reported | 27 | 3.21 |
Coelho-Filho et al., |
2.5 | 405 | Not reported | 31 | 17.2 |
Doesch et al., |
2.5 | 81 | 100 | 56 | 16.6 |
Ingkanisorn et al., |
1.3 | 135 | 17 | 21 | 30.0 |
Jahnke et al., |
4.8 | 679 | 54 | 48 | 4.1 |
Krittayaphong et al., |
2.9 | 1232 | 12 | 34 | 9.7 |
Lerakis et al., |
0.8 | 103 | 13 | 10 | Non-estimable |
Lo et al., |
3.2 | 203 | 16 | 21 | 7.7 |
Lubbers et al., |
1.8 | 125 | Not reported | 10 | Non-estimable |
Pilz et al., |
1.0 | 218 | 0 | 0 | Non-estimable |
Steel et al., |
1.4 | 254 | Not reported | 29 | 8.04 |
Vogel-Claussen et al., |
1.2 | 27 | 19 | 19 | Non-estimable |
The assessment of myocardial viability using late gadolinium enhancement (LGE) is an established method for the assessment of infarct size and for the risk stratification of patients after acute myocardial infarction and with chronic ischemic heart disease (Gerber et al.,
An example of a patient with a small unrecognized scar of the apical anterior-lateral wall without detectable wall motion abnormality by cine images can be appreciated in Figure
Recent studies also demonstrated the ability of quantitative myocardial deformation assessment using SENC to estimate cardiac outcomes (Korosoglou et al.,
Ongoing clinical trials such as the PROMISE study now aim at comparing functional stress tests such as CMR and echocardiography with anatomical modalities such as CCTA in order to determine which might be better at finding out who has heart disease and will require more testing and treatment (
In addition CCTA is associated with radiation exposure for the patients, which limits its serial applicability, particularly in younger patients (Einstein et al.,
Several studies have demonstrated the ability of CCTA to detect anatomically significant CAD with high negative predictive value and clinically acceptable overall accuracy. Previous studies performed with 16-slice CT scanners, already pointed to the high negative predictive value of the technique (Nieman et al.,
Nieman et al., |
59 | 95 | 86 | 80 | 97 | 90 |
Ropers et al., |
77 | 92 | 93 | 79 | 97 | 93 |
Mollet et al., |
128 | 92 | 95 | 79 | 98 | 94 |
Kuettner et al., |
60 | 72 | 97 | 72 | 97 | 86 |
Dewey et al., |
129 | 82 | 90 | 90 | 95 | 87 |
Overview data | 453 | 72–95 | 86–90 | 72–90 | ≥95 | 86–94 |
Meijboom et al., |
254 | 92 | 93 | 60 | 99 | 93 |
Shabestari et al., |
143 | 92 | 97 | 77 | 99 | 96 |
Leber et al., |
90 | 90 | 99 | 81 | 99 | 99 |
Ropers et al., |
100 | 90 | 98 | 79 | 99 | 98 |
Heuschmid et al., |
51 | 96 | 87 | 61 | 99 | 88 |
Miller et al., |
291 | 75 | 93 | 82 | 89 | n.a |
Overview data | 929 | 75–96 | 87–99 | 60–82 | 89–99 | 88–99 |
Blank et al., |
65 | 95 | 54 | 47 | 96 | n.a. |
Petcherski et al., |
121 | 97 | 97 | 75 | 100 | 97 |
Chao et al., |
104 | 94 | 95 | 78 | 99 | 94 |
Korosoglou et al., |
27 | 89 | 100 | 100 | 95 | 96 |
Dewey et al., |
30 | 78 | 98 | 75 | 99 | 97 |
Li et al., |
454 | 87 | 97 | 98 | 83 | 96 |
Achenbach et al., |
50 | 92 | 98 | 74 | 99 | 95 |
Overview data | 851 | 78–97 | 54–100 | 47–100 | ≥95 | ≥94 |
More recent studies, performed with >64-slice CT scanners confirmed the high negative predictive value of CCTA for the exclusion of anatomically significant CAD (Dewey et al.,
An example of a high-grade proximal LAD lesion using 256-slice CCTA can be appreciated in a male patient with atypical angina using whole-heart (Figure
Currently, an individual patient data meta-analysis is intended within the PROSPERO database, which will include individual patient data originating from studies comparing CCTA to invasive X-Ray angiography (Schuetz et al.,
The cost-effectiveness of CCTA for the diagnostic work-up of patients with suspected CAD was systematically evaluated in a recent meta-analysis (Zeb et al.,
Despite the fact that conventional X-ray coronary angiography still remains the gold standard for detection of CAD, this technique provides limited information on the composition of atherosclerotic plaque (Libby,
Several studies evaluated the ability of atherosclerotic plaque composition assessment by CCTA to estimate cardiac outcomes in patients with suspected or known CAD and clinically stable chest pain syndrome (Pundziute et al.,
Pundziute et al., |
100 | 2.2 | 26 | 58 | 8 | 28.0 |
Gaemperli et al., |
220 | 1.2 | 23 | 51 | 2 | 12.7 |
Carrigan et al., |
227 | 2.3 | 3.5 | 13 | 0.5 | 9.8 |
Gopal et al., |
493 | 3.3 | 1.2 | 6.5 | 0.1 | 16.6 |
Hadamitzky et al., |
1150 | 1.5 | 1.2 | 3.3 | 0.3 | 16.1 |
Aldrovandi et al., |
187 | 2.0 | 5.4 | 24.3 | 1.0 | 34.9 |
Rubinshtein et al., |
545 | 1.5 | 6.4 | 14.5 | 1.0 | 10.9 |
van Werkhoven et al., |
432 | 1.8 | 2.9 | 6.5 | 2.5 | 3.6 |
van Werkhoven et al., |
316 | 1.8 | 2.2 | 6.0 | 1.7 | 3.5 |
Andreini et al., |
1304 | 4.3 | 2.6 | 19.9 | 0 | 4.8 |
Motoyama et al., |
1059 | 2.6 | 0.8 | 22.3 | 0.5 | 22.8 |
Hadamitzky et al., |
2223 | 2.3 | 0.9 | 2.9 | 0.3 | 13.5 |
Pundziute et al., |
100 | 2.2 | 24 | 30 | 0 | n.a. |
Gaemperli et al., |
220 | 1.2 | 23 | 28 | 0 | n.a. |
Ostrom et al., |
2538 | 6.5 | 0.5 | 0.72 | 0.26 | n.a. |
van Werkhoven et al., |
432 | 1.8 | 1.9 | 4.9 | 1.4 | n.a. |
van Werkhoven et al., |
316 | 1.8 | 1.3 | 3.5 | 0.64 | n.a. |
In the recently published CONFIRM registry both lumen narrowing and plaque burden, especially in proximal coronary segments were predictive of cardiovascular mortality in patients with suspected CAD (Hadamitzky et al.,
Fewer studies have investigated the complementary value of cardiac biomarkers to CCTA imaging findings for the estimation of cardiac outcomes so far. Several biomarkers are used in clinical routine together with clinical assessment and 12-lead ECG for the triage of patients with acute coronary syndrome (ACS). In this regard, cardiac troponins were shown to aid the diagnostic classification and risk stratification of such patients (Katus et al.,
C-reactive protein (CRP) on the other hand, was previously proposed as a central mediator in atherosclerotic plaque development and vascular inflammation (Zhang et al.,
Laufer et al., |
hsTnT | 64-slice CT | 615 | HsTnT strongly is associated with CAD in patients without ACS. |
Korosoglou et al., |
hsTnT | 256-slice CT | 124 | HsTnT is closely related to coronary plaque composition. |
Blaha et al., |
hsCRP | 4-slice CT for CAC | 6762 | hsCRP is not associated with coronary calcification. |
Duivenvoorden et al., |
Myeloperoxidase (MPO), hsCRP | 18FDG-PET/CT | 130 | MPO levels are associated with carotid plaque inflammation. |
Andrassy et al., |
HMBG-1 | 256-slice CT | 152 | HMBG1 is associated with the atherosclerotic plaque composition. |
Nakazato et al., |
LDL, HDL and total cholesterol | ≥64-slice CT | 4575 | Non-HDL is associated with non-calcified coronary plaque. |
Voros et al., |
ApoB, HDL, LDL | 64-sl. MDCT IVUS/VH | 60 | ApoB and small HDL particles are associated with larger plaque burden and non-calcified plaque. |
Optimal diagnostic image quality with a minimum dosage of radiation exposure for the patients still represents a major challenge. In this regard, radiation exposure with CCTA still raises concerns among physicians, as it may be associated with non-negligible lifetime attributable risk of breast or lung cancer, particularly in women and in younger patients (Einstein et al.,
In addition, the value of calcium scoring scans as a filter prior to CCTA, in order to identify patients with severe calcification was recently shown to be limited in younger patients with intermediate risk profile. Omitting such calcium scoring pre-scans in younger patients can contribute to further absolute dose reduction of ~0.75–1.0 mSv with cardiac CT studies (Gitsioudis et al.,
Coronary computed tomography angiography and CMR can both be regarded as in the meanwhile clinically well-established techniques for the diagnostic classification and risk stratification of patients with suspected or known CAD. The strengths of CCTA are its ability (1) to non-invasively visualize moving coronary vessels with high spatial resolution, excluding significant CAD with high precision and (2) to assess the composition of atherosclerotic plaque components. Its main limitation is the resultant radiation exposure for the patients, which limits its serial applicability particularly in younger patients. However, scientist, clinicians, and manufacturers managed significant reductions of radiation exposure in this field within the last 5 years. The strength of CMR on the other hand, is its ability to assess inducible wall motion abnormalities and perfusion defects during stress testing aiding the detection of functionally significant CAD. Thus, it represents the optimal technique for the risk stratification of patients with suspected CAD and for guiding revascularization procedures in patients with diagnosed CAD by CCTA or invasive angiography. Current guidelines encourage the liberal use of both CCTA and CMR as first choice modalities for the diagnostic work-up of patients with low and intermediate likelihood for CAD in experienced centers.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.