TY - JOUR
AU - Naito, Hiroshi
AB - Abstract Aims Contrast-enhanced computed tomography (CE-CT) is the gold standard for diagnosing acute aortic syndromes (AAS). Unenhanced computed tomography (unenhanced-CT) also provides specific findings for AAS; however, its diagnostic ability is not well discussed. This study aims to evaluate the potential of unenhanced-CT as an AAS screening tool. Methods and results We retrospectively examined AAS patients who visited our hospital between 2011 and 2021 to validate the diagnostic value of unenhanced-CT alone and along with the aortic dissection detection risk score (ADD-RS) plus D-dimer. Acute aortic syndrome was assessed as detectable using unenhanced-CT with any of the following findings: pericardial haemorrhage, high-attenuation haematoma, and displacement of intimal calcification or a flap. Of the 316 AAS cases, 292 (92%) were detectable with unenhanced-CT. Twenty-four (8%) cases undetectable with unenhanced-CT involved younger patients [median (interquartile range), 45 (42–51) years vs. 72 (63–80) years, P < 0.001] and patients more frequently complicated with a patent false lumen (79% vs. 42%, P < 0.001). Acute aortic syndrome-detection rate with unenhanced-CT increased with age, reaching 98% (276/282) in those ≥50 years of age and 100% (121/121) in those ≥75 years of age. With the ADD-RS plus D-dimer, there was only one AAS case undetectable with unenhanced-CT among patients ≥50 years of age, except for cases with the ADD-RS ≥1 plus D-dimer levels of ≥0.5 μg/mL. Conclusion Acute aortic syndromes in younger patients and patients with a patent false lumen could be misdiagnosed with unenhanced-CT alone. The combination of the ADD-RS plus D-dimer and unenhanced-CT could minimize AAS misdiagnosis while avoiding over-testing with CE-CT. Graphical Abstract Open in new tabDownload slide Graphical Abstract Open in new tabDownload slide Acute aortic syndromes, Aortic dissection detection risk score, D-dimer, Unenhanced computed tomography Introduction Despite recent diagnostic and therapeutic advances, acute aortic syndrome (AAS) is still a life-threatening condition with high mortality rates.1–3 Approximately 40–50% of patients with thoracic AAS died within 48 h of its onset, and the mortality rate after the onset increases by 1–2% per hour.2 Therefore, delay in diagnosis and appropriate treatment could compromise their outcome, and physicians are required to conduct a rapid and accurate diagnosis of AAS.2,3 The typical symptom of AAS is acute onset of severe chest and/or back pain; however, this is not specific to AAS and can mimic pain from other diseases.2,3 Furthermore, ∼20% of patients with AAS do not report typical pain especially elderly patients, and this atypical AAS could result in diagnostic delay.2–6 Contrast-enhanced computed tomography (CE-CT) is a recommended first-line imaging modality for suspected AAS, yielding high sensitivity and specificity; however, this imaging technique is expensive and carries risks of contrast-induced reactions, such as anaphylaxis and nephrotoxicity.3,7 Recently, it has been reported that unenhanced-CT also provides specific findings in >90% of AAS cases, such as the presence of high-attenuation haematoma, displacement of intimal calcification, and displaced intimal flap.8–10 Unenhanced-CT could be a candidate for screening AAS; however, its diagnostic ability and limitations are not well discussed. To address this knowledge gap in the literature, we investigated the diagnostic performance of unenhanced-CT for AAS screening and devised the appropriate use of unenhanced-CT as a screening tool for AAS. Methods Study design Consecutive AAS patients ≥15 years of age who visited our hospital were retrospectively investigated between April 2011 and March 2021. The cases of traumatic aortic dissection and patients complicated with cardiac arrest before undergoing CT were excluded. Patients who underwent either CE-CT or unenhanced-CT were also excluded. All study patients underwent non-electrocardiogram-gated CT using multi-slice CT scanners (BrightSpeed or LightSpeed Ultra, GE Healthcare; Aquilion One, Canon Medical Systems Corporation) with a slice thickness of 5 mm. BrightSpeed, an 8-row multi-slice CT scanner, was mainly used in our study, and its main scanning parameters were as follows: tube voltage, 120 kV and tube current, automatic tube current modulation. Contrast-enhanced CT was performed immediately after unenhanced-CT according to the following institutional protocol. Iodinated contrast material was injected intravenously at a rate of 3–4 mL/s (80–100 mL) using an automated injector. The early and delayed phases were scanned after 25–35-s and 120–180-s injection delay, respectively. Contrast-enhanced CT and unenhanced-CT were independently reviewed by four physicians with >10 years of emergency department experience and one of the reviewers has a certification as a specialist of cardiology. When one or more of the four physicians could not detect AAS with unenhanced-CT, the case was evaluated as AAS undetectable with unenhanced-CT. The following factors were investigated for AAS undetectable and detectable with unenhanced-CT: the baseline characteristics, symptoms associated with AAS, results of blood tests, AAS variants with the status of the false lumen in acute aortic dissection (AAD), Stanford type of dissection, and the aortic dissection detection risk score (ADD-RS).11 Symptoms upon hospital arrival were extracted from physicians’ and nurses’ electronic medical records. Blood sample results closest to the hospital arrival were also extracted from the medical records. The study protocol conformed to the principles of the Declaration of Helsinki and its amendments and was approved by the Hiroshima City Hiroshima Citizens Hospital Ethics Board (reference 2021-34). The need for written informed consent was waived because of the retrospective study design. Definitions Acute aortic syndrome diagnosis was performed by radiologists or vascular surgeons in our hospital based on CT findings in symptomatic patients.2,3 Diagnosis of AAS variants [classic AAD, intramural haematoma (IMH), and penetrating aortic ulcer (PAU)] was based on the 2014 European Society of Cardiology guidelines.3 The status of the false lumen in AAD was classified into three groups (patent, thrombosis, and partial thrombosis) according to the early phase of CE-CT findings.12 Acute aortic syndrome with patent false lumen was defined as AAD patients with patent and partial thrombosis in the false lumen, and AAS without patent false lumen was defined as AAD patients with thrombosed false lumen, IMH, and PAU. The differentiation between AAD with thrombosed false lumen and IMH was based on the presence or absence of intimal tear and high-attenuation haematoma.3 Any dissection involving the ascending aorta was considered Stanford type A dissection, and dissection limited to the descending aorta (distal to the left subclavian artery) was considered Stanford type B dissection.3 Acute aortic syndrome was assessed as detectable with unenhanced-CT when any of the following findings were present: (i) pericardial haemorrhage, (ii) high-attenuation haematoma, (iii) displacement of intimal calcification, and (iv) displacement of intimal flap (Figure 1).13–16 Pericardial haemorrhage was defined as a pericardial effusion with a Hounsfield unit of >50, which suggested bloody density.13 High-attenuation haematoma was defined as a crescent-shaped, hyperattenuating region of the thickened aortic wall.14,15 Displacement of intimal calcification was defined as internal displacement of the calcified aortic wall.15 Displacement of the intimal flap was defined as a linear structure within the aortic lumen with a high density but without calcification or high-attenuation haematoma.15,16 The ADD-RS is a tool based on 12 risk factors organized in three categories (specific high-risk conditions, pain features, and physical examination findings) that allow standardized assessment of the pre-test probability of AAS.11 Based on the ADD-RS, patients were classified into three groups (ADD-RS = 0, low risk; ADD-RS = 1, intermediate risk; and ADD-RS ≥2, high risk of AAS).11 D-dimer test (Sysmex, Kobe, Japan) results of <0.5 μg/mL were defined as negative, and ≥0.5 μg/mL as positive. Figure 1 Open in new tabDownload slide Computed tomography findings of acute aortic syndromes. Left panel indicates unenhanced-CT, and right panel indicates CE-CT in early phase. (A) Pericardial haemorrhage with a Hounsfield unit 58 (arrowhead) in Stanford type A dissection. (B) High-attenuation haematoma (arrowhead) in Stanford type A dissection, which suggests intramural haematoma. (C) The displacement of intimal calcification (arrowhead) in Stanford type A dissection with a low-attenuation thrombosed false lumen, which suggested classic acute aortic dissection. (D) The displacement of an intimal flap (arrowhead) in Stanford type A dissection with a patent false lumen. CE-CT, contrast enhanced computed tomography. Figure 1 Open in new tabDownload slide Computed tomography findings of acute aortic syndromes. Left panel indicates unenhanced-CT, and right panel indicates CE-CT in early phase. (A) Pericardial haemorrhage with a Hounsfield unit 58 (arrowhead) in Stanford type A dissection. (B) High-attenuation haematoma (arrowhead) in Stanford type A dissection, which suggests intramural haematoma. (C) The displacement of intimal calcification (arrowhead) in Stanford type A dissection with a low-attenuation thrombosed false lumen, which suggested classic acute aortic dissection. (D) The displacement of an intimal flap (arrowhead) in Stanford type A dissection with a patent false lumen. CE-CT, contrast enhanced computed tomography. Statistical analyses Data were presented as median [interquartile range (IQR)] for continuous variables and as numbers and percentages for categorical variables. Continuous variables were compared using Mann–Whitney U test, and categorical variables with χ2 or Fisher’s exact test. A receiver operating characteristic (ROC) curve was created to illustrate the diagnostic ability of unenhanced-CT in detecting AAS at each cut-off value of age, and the area under the ROC curve (AUC), with 95% confidence interval (CI), was calculated. All statistical analyses were performed using the R software package (version 4.0.2, R Development Core Team; https://www.r-project.org/). A P-value of <0.05 was considered statistically significant. Results Patient characteristics During the study period, 344 AAS patients visited our hospital, of whom 316 (92%) met the inclusion criteria (Figure 2). The median age was 71 years (IQR, 60–80 years), and 195 (62%) patients were men. Two hundred and thirteen (67%) patients complained of back pain, and 134 (42%) had chest pain, while 22 (7%) had painless AAS. Eighteen of 22 painless AAS patients were of Stanford type A dissection, and 10 patients complained of syncope and 8 had stroke. Four patients with painless Stanford type B dissection did not complain of typical pain; however, they complained of symptoms associated with AAS, including chest discomfort and respiratory distress. Among all AAS patients, 250 (79%) were diagnosed with AAD, 50 (16%) with IMH, and 16 (5%) with PAU. The status of the false lumen in AAD was patent in 68 (22%), thrombosis in 108 (34%), and partially thrombosis in 74 (23%); 145 (46%) patients had Stanford type A dissection. The ADD-RS = 0 was found in 10 (3%) patients, 1 in 157 (50%), and ≥2 in 149 (47%). Among the 316 patients, AAS could be detected in 292 (92%) patients with unenhanced-CT with the following findings: pericardial haemorrhage, 50 (17%); high-attenuation haematoma, 76 (26%); displacement of calcification, 235 (80%); and displacement of the intimal flap, 148 (51%); however, the extent of dissection (beginning and endpoints) was detected only in 203 (70%) patients (Table 1). The details of unenhanced-CT findings are shown in Supplementary material online, S1. Of the 292 patients, 190 (65%), who were detected with AAS on unenhanced CT, showed 2 or more findings suggestive of AAS. Displacements of intimal calcification and intimal flap were the most frequent findings (34%, n = 98). Figure 2 Open in new tabDownload slide A flowchart of participant inclusion. CT, computed tomography. Figure 2 Open in new tabDownload slide A flowchart of participant inclusion. CT, computed tomography. Table 1 Comparisons of patients with undetectable and detectable acute aortic syndromes with unenhanced-computed tomography . All . Undetectable . Detectable . P-value . . n = 316 . n = 24 . n = 292 . . Age, years 71 (60–80) 45 (42–51) 72 (63–80) <0.001 Male, sex 195 (62) 18 (78) 177 (60) 0.119 Hypertension 230 (73) 16 (67) 214 (73) 0.48 Dyslipidaemia 82 (26) 4 (17) 78 (27) 0.34 Diabetes mellitus 20 (6) 1 (4) 19 (6) 1 Current smoker 69 (22) 8 (33) 61 (21) 0.196 Back pain 213 (67) 21 (88) 192 (66) 0.039 Chest pain 134 (42) 5 (21) 129 (44) 0.031 Abdominal pain 38 (12) 5 (21) 33 (11) 0.187 Painless AAS 22 (7) 0 22 (8) 0.39 Syncope 20 (6) 0 20 (7) 0.38 Stroke 15 (5) 0 15 (5) 0.62 D-dimer, μg/mL 6.4 (2.2–21.9)a 4.8 (3.0–13.5)b 6.5 (2.2–22.4)c 0.69 D-dimer <0.5 μg/mL 7 (3)a 1 (5)b 6 (2)c 0.44 AAS variants with the status of false lumen in AAD <0.025 AAD 250 (79) 24 (100) 226 (77)  Patent 68 (22) 15 (63) 53 (18)  Thrombosis 108 (34) 5 (21) 103 (35)  Partial thrombosis 74 (23) 4 (17) 70 (24) Intramural haematoma 50 (16) 0 50 (17) Penetrating aortic ulcer 16 (5) 0 16 (5) AAS with patent false lumen 142 (45) 19 (79) 123 (42) <0.001 Stanford type 0.83  Type A 145 (46) 10 (42) 135 (46)  Type B 171 (54) 14 (58) 157 (54) Aortic dissection detection risk score 0.079  Score 0 10 (3) 0 10 (3)  Score 1 157 (50) 13 (54) 144 (49)  Score 2 132 (42) 7 (29) 125 (43)  Score 3 17 (5) 4 (17) 13 (4) Unenhanced-CT findings suggesting AAS  Pericardial haemorrhage 50 (17)  High-attenuation haematoma 76 (26)  Displacement of intimal calcification 235 (80)  Displacement of intimal flap 148 (51) Extent of aortic dissection could be detected 203 (70) . All . Undetectable . Detectable . P-value . . n = 316 . n = 24 . n = 292 . . Age, years 71 (60–80) 45 (42–51) 72 (63–80) <0.001 Male, sex 195 (62) 18 (78) 177 (60) 0.119 Hypertension 230 (73) 16 (67) 214 (73) 0.48 Dyslipidaemia 82 (26) 4 (17) 78 (27) 0.34 Diabetes mellitus 20 (6) 1 (4) 19 (6) 1 Current smoker 69 (22) 8 (33) 61 (21) 0.196 Back pain 213 (67) 21 (88) 192 (66) 0.039 Chest pain 134 (42) 5 (21) 129 (44) 0.031 Abdominal pain 38 (12) 5 (21) 33 (11) 0.187 Painless AAS 22 (7) 0 22 (8) 0.39 Syncope 20 (6) 0 20 (7) 0.38 Stroke 15 (5) 0 15 (5) 0.62 D-dimer, μg/mL 6.4 (2.2–21.9)a 4.8 (3.0–13.5)b 6.5 (2.2–22.4)c 0.69 D-dimer <0.5 μg/mL 7 (3)a 1 (5)b 6 (2)c 0.44 AAS variants with the status of false lumen in AAD <0.025 AAD 250 (79) 24 (100) 226 (77)  Patent 68 (22) 15 (63) 53 (18)  Thrombosis 108 (34) 5 (21) 103 (35)  Partial thrombosis 74 (23) 4 (17) 70 (24) Intramural haematoma 50 (16) 0 50 (17) Penetrating aortic ulcer 16 (5) 0 16 (5) AAS with patent false lumen 142 (45) 19 (79) 123 (42) <0.001 Stanford type 0.83  Type A 145 (46) 10 (42) 135 (46)  Type B 171 (54) 14 (58) 157 (54) Aortic dissection detection risk score 0.079  Score 0 10 (3) 0 10 (3)  Score 1 157 (50) 13 (54) 144 (49)  Score 2 132 (42) 7 (29) 125 (43)  Score 3 17 (5) 4 (17) 13 (4) Unenhanced-CT findings suggesting AAS  Pericardial haemorrhage 50 (17)  High-attenuation haematoma 76 (26)  Displacement of intimal calcification 235 (80)  Displacement of intimal flap 148 (51) Extent of aortic dissection could be detected 203 (70) Data are presented as the number (column %) of patients or median (interquartile range). CT, computed tomography; AAS, acute aortic syndromes; AAD, acute aortic dissection. a D-dimer was evaluated in 280 patients. b n = 22,. c n = 258. Open in new tab Table 1 Comparisons of patients with undetectable and detectable acute aortic syndromes with unenhanced-computed tomography . All . Undetectable . Detectable . P-value . . n = 316 . n = 24 . n = 292 . . Age, years 71 (60–80) 45 (42–51) 72 (63–80) <0.001 Male, sex 195 (62) 18 (78) 177 (60) 0.119 Hypertension 230 (73) 16 (67) 214 (73) 0.48 Dyslipidaemia 82 (26) 4 (17) 78 (27) 0.34 Diabetes mellitus 20 (6) 1 (4) 19 (6) 1 Current smoker 69 (22) 8 (33) 61 (21) 0.196 Back pain 213 (67) 21 (88) 192 (66) 0.039 Chest pain 134 (42) 5 (21) 129 (44) 0.031 Abdominal pain 38 (12) 5 (21) 33 (11) 0.187 Painless AAS 22 (7) 0 22 (8) 0.39 Syncope 20 (6) 0 20 (7) 0.38 Stroke 15 (5) 0 15 (5) 0.62 D-dimer, μg/mL 6.4 (2.2–21.9)a 4.8 (3.0–13.5)b 6.5 (2.2–22.4)c 0.69 D-dimer <0.5 μg/mL 7 (3)a 1 (5)b 6 (2)c 0.44 AAS variants with the status of false lumen in AAD <0.025 AAD 250 (79) 24 (100) 226 (77)  Patent 68 (22) 15 (63) 53 (18)  Thrombosis 108 (34) 5 (21) 103 (35)  Partial thrombosis 74 (23) 4 (17) 70 (24) Intramural haematoma 50 (16) 0 50 (17) Penetrating aortic ulcer 16 (5) 0 16 (5) AAS with patent false lumen 142 (45) 19 (79) 123 (42) <0.001 Stanford type 0.83  Type A 145 (46) 10 (42) 135 (46)  Type B 171 (54) 14 (58) 157 (54) Aortic dissection detection risk score 0.079  Score 0 10 (3) 0 10 (3)  Score 1 157 (50) 13 (54) 144 (49)  Score 2 132 (42) 7 (29) 125 (43)  Score 3 17 (5) 4 (17) 13 (4) Unenhanced-CT findings suggesting AAS  Pericardial haemorrhage 50 (17)  High-attenuation haematoma 76 (26)  Displacement of intimal calcification 235 (80)  Displacement of intimal flap 148 (51) Extent of aortic dissection could be detected 203 (70) . All . Undetectable . Detectable . P-value . . n = 316 . n = 24 . n = 292 . . Age, years 71 (60–80) 45 (42–51) 72 (63–80) <0.001 Male, sex 195 (62) 18 (78) 177 (60) 0.119 Hypertension 230 (73) 16 (67) 214 (73) 0.48 Dyslipidaemia 82 (26) 4 (17) 78 (27) 0.34 Diabetes mellitus 20 (6) 1 (4) 19 (6) 1 Current smoker 69 (22) 8 (33) 61 (21) 0.196 Back pain 213 (67) 21 (88) 192 (66) 0.039 Chest pain 134 (42) 5 (21) 129 (44) 0.031 Abdominal pain 38 (12) 5 (21) 33 (11) 0.187 Painless AAS 22 (7) 0 22 (8) 0.39 Syncope 20 (6) 0 20 (7) 0.38 Stroke 15 (5) 0 15 (5) 0.62 D-dimer, μg/mL 6.4 (2.2–21.9)a 4.8 (3.0–13.5)b 6.5 (2.2–22.4)c 0.69 D-dimer <0.5 μg/mL 7 (3)a 1 (5)b 6 (2)c 0.44 AAS variants with the status of false lumen in AAD <0.025 AAD 250 (79) 24 (100) 226 (77)  Patent 68 (22) 15 (63) 53 (18)  Thrombosis 108 (34) 5 (21) 103 (35)  Partial thrombosis 74 (23) 4 (17) 70 (24) Intramural haematoma 50 (16) 0 50 (17) Penetrating aortic ulcer 16 (5) 0 16 (5) AAS with patent false lumen 142 (45) 19 (79) 123 (42) <0.001 Stanford type 0.83  Type A 145 (46) 10 (42) 135 (46)  Type B 171 (54) 14 (58) 157 (54) Aortic dissection detection risk score 0.079  Score 0 10 (3) 0 10 (3)  Score 1 157 (50) 13 (54) 144 (49)  Score 2 132 (42) 7 (29) 125 (43)  Score 3 17 (5) 4 (17) 13 (4) Unenhanced-CT findings suggesting AAS  Pericardial haemorrhage 50 (17)  High-attenuation haematoma 76 (26)  Displacement of intimal calcification 235 (80)  Displacement of intimal flap 148 (51) Extent of aortic dissection could be detected 203 (70) Data are presented as the number (column %) of patients or median (interquartile range). CT, computed tomography; AAS, acute aortic syndromes; AAD, acute aortic dissection. a D-dimer was evaluated in 280 patients. b n = 22,. c n = 258. Open in new tab Comparison of patients with undetectable and detectable acute aortic syndrome on unenhanced-computed tomography The comparisons of patients with undetectable and detectable AAS on unenhanced-CT are presented in Table 1. In the undetectable group, the patients were younger [median, 45 (IQR 42–51) vs. 72 (IQR 63–80) years, P < 0.001], with more complaints of back pain (88% vs. 66%, P = 0.039), and less of chest pain (21% vs. 44%, P = 0.031). There was no painless AAS in the undetectable group. All IMH and PAU were diagnosed with unenhanced-CT. AAS with patent false lumen was more frequent in the undetectable group (79% vs. 42%, P < 0.001). Stanford type of dissection and the ADD-RS were not different between the two groups. The extent of a dissection (beginning and endpoints) with DeBakey category of AAS that is undetectable with unenhanced-CT is shown in Supplementary material online, S2. Although undetectable with unenhanced-CT, most patients had complicated extensive aortic dissection. Relationship between age and acute aortic syndrome diagnostic ability of unenhanced-computed tomography In the relationship between age and each unenhanced-CT finding that suggested AAS, high-attenuation haematoma [74 (IQR 67–80) vs. 69 (IQR 58–79) years, P = 0.006] and displacement of intimal calcification [74 (IQR 67–81) vs. 57 (IQR 47–68) years, P < 0.001] could be detected in older patients; however, pericardial haemorrhage [74 (IQR 63–83) vs. 70 (IQR 59–79) years, P = 0.115] and displacement of intimal flap [69 (IQR 59–77) vs. 74 (IQR 61–80) years, P = 0.083] were not related to age. The ROC curves that describe the AAS diagnostic abilities of unenhanced-CT at different ages are presented in Figure 3. Sensitivity refers to the proportion of patients above each cut-off value for the ages among patients with AAS detectable with unenhanced-CT (n = 292), while specificity refers to the proportion of patients below each cut-off value for the ages among patients with AAS undetectable with unenhanced-CT (n = 24). The AUC was 0.92 (95% CI, 0.86–0.98). The cut-off value of 50 years (left upper corner) corresponded to a sensitivity of 0.95 and a specificity of 0.75, and the cut-off value of 75 years corresponded to a sensitivity of 0.41 and a specificity of 1. The AAS detected rate of unenhanced-CT increased with age, reaching 98% (276/282) in those ≥50 years of age and 100% (121/121) in those ≥75 years of age. Figure 3 Open in new tabDownload slide Receiver operating characteristic curves that describe the acute aortic syndrome-diagnostic abilities of unenhanced-computed tomography at different ages. Sensitivity refers to the proportion of patients above each cut-off value for the ages among patients with AAS detectable with unenhanced-CT (n = 292), while specificity refers to the proportion of patients below each cut-off value for the ages among patients with AAS undetectable with unenhanced-CT (n = 24). The AUC was 0.92 (95% CI 0.86–0.98). The cut-off value of 50 years (left upper corner) corresponded to a sensitivity of 0.95 and a specificity of 0.75, and the cut-off value of 75 years corresponded to a sensitivity of 0.41 and a specificity of 1. AAS, acute aortic syndromes; CT, computed tomography; CI, computed tomography; AUC, area under the curve. Figure 3 Open in new tabDownload slide Receiver operating characteristic curves that describe the acute aortic syndrome-diagnostic abilities of unenhanced-computed tomography at different ages. Sensitivity refers to the proportion of patients above each cut-off value for the ages among patients with AAS detectable with unenhanced-CT (n = 292), while specificity refers to the proportion of patients below each cut-off value for the ages among patients with AAS undetectable with unenhanced-CT (n = 24). The AUC was 0.92 (95% CI 0.86–0.98). The cut-off value of 50 years (left upper corner) corresponded to a sensitivity of 0.95 and a specificity of 0.75, and the cut-off value of 75 years corresponded to a sensitivity of 0.41 and a specificity of 1. AAS, acute aortic syndromes; CT, computed tomography; CI, computed tomography; AUC, area under the curve. Diagnostic algorithm for acute aortic syndrome based on the assessment of ADD-RS plus D-dimer and unenhanced-computed tomography findings The diagnostic algorithm for AAS based on the assessment of ADD-RS plus D-dimer and unenhanced-CT findings is presented in Figure 4. Among 280 patients tested for D-dimer, 8 (3%) had ADD-RS = 0, and all 8 (100%) were D-dimer positive. Additionally, 135 (48%) patients had ADD-RS = 1, of whom, 132 (98%) were D-dimer positive. Moreover, 137 patients (49%) had ADD-RS ≥2, of whom, 133 (97%) were D-dimer positive. Twenty-two (8%) patients with AAS were undetectable with unenhanced-CT (ADD-RS = 1 plus D-dimer negative, n = 1; ADD-RS = 1 plus D-dimer positive, n = 11; ADD-RS ≥2 plus D-dimer positive, n = 10); however, there was only one AAS case undetectable with unenhanced-CT among patients ≥50 years of age, except for cases with the ADD-RS ≥1 plus D-dimer positive. Figure 4 Open in new tabDownload slide Diagnostic algorithm for acute aortic syndrome based on the assessment of the aortic dissection detection risk score plus D-dimer and unenhanced-computed tomography findings. D-dimer levels of <0.5 μg/mL were defined as negative, and the levels of ≥0.5 μg/mL were defined as positive. Patients with AAS undetectable with unenhanced-CT were 22 (8%), and of those 6 patients aged ≥50 years, 5 patients (83%) were ADD-RS ≥1 plus D-dimer positive. AAS, acute aortic syndromes; ADD-RS, aortic dissection detection risk score; CT, computed tomography. Figure 4 Open in new tabDownload slide Diagnostic algorithm for acute aortic syndrome based on the assessment of the aortic dissection detection risk score plus D-dimer and unenhanced-computed tomography findings. D-dimer levels of <0.5 μg/mL were defined as negative, and the levels of ≥0.5 μg/mL were defined as positive. Patients with AAS undetectable with unenhanced-CT were 22 (8%), and of those 6 patients aged ≥50 years, 5 patients (83%) were ADD-RS ≥1 plus D-dimer positive. AAS, acute aortic syndromes; ADD-RS, aortic dissection detection risk score; CT, computed tomography. Discussion The major findings of our study were as follows: (i) 92% of AAS cases could be diagnosed with unenhanced-CT, (ii) 8% of AAS especially in younger patients or patients with a patent false lumen could be misdiagnosed with unenhanced-CT alone, and (iii) with the combination of ADD-RS plus D-dimer and unenhanced-CT, there was only one patient who could not be diagnosed for AAS with unenhanced-CT among patients ≥50 years of age, except for those with ADD-RS ≥1 plus D-dimer positive. Contrast-enhanced computed tomography is the gold-standard technique for diagnosing AAS; however, physicians sometimes hesitate to administer contrast medium because of its side effects.3,7 Additionally, not many patients who underwent CE-CT for suspected AAS had AAS, and patients suspected of having AAS tend to be over-tested.17 Recently, it was reported that unenhanced-CT also provides specific findings in >90% of AAS cases, making it a potential candidate for screening AAS; however, the limitations of unenhanced-CT in detecting AAS and the characteristics of patients with AAS that is difficult to diagnose with unenhanced-CT have not been reported.8–10 Hence, we evaluated the diagnostic ability and limitations of unenhanced-CT for AAS diagnosis. In our study population, AAS in 92% of patients could be detected with unenhanced-CT; however, it was undetectable in 8% of patients. Specific findings of unenhanced-CT for AAS are a visualized intimal flap and a thrombosed dissected lumen that appears as a high-attenuation area.14–16 For detecting an intimal flap with unenhanced-CT, atherosclerotic changes in the arterial wall, such as intimal thickening and calcification, mainly caused by chronic hypertension, are required.4,15,18 The aetiologies of AAS are not only atherosclerotic changes in the aortic wall but also connective tissue disorders, such as Marfan syndrome, Ehlers–Danlos syndrome, and familial forms of aortic dissection.3,4 Acute aortic syndrome caused by connective tissue disorders mostly occurs in young individuals and has fewer atherosclerotic changes; therefore, it may be difficult to detect AAS with unenhanced-CT.3,4,18 In this study results, the patients with the displacement of intimal calcification were older than those without. Additionally, a high-attenuation haematoma reflects clotted blood in the dissected lumen typically found in IMH and PAU (AAS without an intimal flap or false lumen and a primary intimal tear), and AAS with a patent false lumen does not show this finding.15,16 Because of these reasons, AAS in younger patients or AAS with a patent false lumen is expected to be difficult to diagnose unless a contrast medium is used. In fact, 8% of AASs undetectable with unenhanced-CT in this study involved younger patients and were more frequently complicated with a patent false lumen. Considering the severity of AAS, this 8% of misdiagnosis is not acceptable. To use unenhanced-CT for AAS screening, we need additional methods to diagnose AAS in the younger population and with a patent false lumen. The ADD-RS is a bedside clinical tool evaluating medical history, pain features, and physical examination of patients with suspected AAS.11 In the large database of the international registry of AAS, 95.7% of patients with AAS were classified into intermediate- and high-risk groups (ADD-RS ≥1).11 AAS in young patients, such as those with Marfan syndrome or familial forms of aortic dissection, are assessed as high-risk conditions in the ADD-RS. Moreover, young AAS patients are more frequently complicated with typical symptoms, such as chest and/or back pain, which are assessed as high-risk pain features in the ADD-RS; therefore, the ADD-RS could aid in the evaluation of AAS in the young population.5,11 D-dimer is known to be a biomarker for screening AAS with high sensitivity. Particularly, AAS with a patent false lumen is more likely to stimulate the clotting cascade, producing positive D-dimer results.19,20 Recently, the combined use of the ADD-RS and D-dimer could be a candidate for diagnostic decisions to rule out AAS without imaging.20–23 According to previous reports, ADD-RS ≤1 plus D-dimer negative can rule out AAS, while ADD-RS ≥1 plus D-dimer positive could consider AAS with high sensitivity.20–23 However, ADD-RS = 0 plus D-dimer positive group and ADD-RS ≥2 plus D-dimer negative group included a small but not a negligible number of AAS cases that require advanced imaging.20–23 Based on these findings, the combination of ADD-RS plus D-dimer and unenhanced-CT may compensate for the limitation of unenhanced-CT for detecting AAS while avoiding over-testing with CE-CT. When evaluating the relationships between age and diagnostic ability of unenhanced-CT, we found that all patients with age ≥75 years could be diagnosed for AAS with unenhanced-CT. Furthermore, with the combination of ADD-RS plus D-dimer and unenhanced-CT, there was only one patient who could not be diagnosed for AAS with unenhanced-CT among patients ≥50 years of age, except for those with ADD-RS ≥1 plus D-dimer positive (the group with a high prior probability). According to our results, the following diagnostic strategy could be stated: 1) ADD-RS = 0 plus D-dimer negative do not need advanced imaging, 2) patients ≥50 years old with ADD-RS = 0 plus D-dimer positive and ADD-RS ≥1 plus D-dimer negative could rule out AAS with unenhanced-CT, and 3) patients <50 years old or ADD-RS ≥1 plus D-dimer positive should undergo CE-CT along with unenhanced-CT. This strategy could reduce over-testing with CE-CT, with only one misdiagnosis of AAS (0.4%). Notably, the mortality rate of AAS increases as time passes. Physicians should not hesitate to perform CE-CT along with unenhanced-CT immediately in those who are highly suspected of having AAS based on their symptoms or those with circulatory failure. Additionally, unenhanced-CT is effective in detecting AAS; however, it cannot clearly evaluate the extent of a dissection (beginning and end points) or visceral ischemia caused by the involvement of aortic branches; therefore, definitive imaging technique with a contrast medium would still be necessary. If AAS is suspected on unenhanced-CT, CE-CT should be performed subsequently. The impact of unenhanced-CT on detecting AAS may be limited especially in patients who are highly suspected of having AAS with typical symptoms; however, it may be useful to rule out AAS with atypical symptoms (e.g., the chief complaints of syncope or stroke), where AAS is not highly probable but cannot be ruled out. There are several limitations to this study. First, this was a single-centre retrospective study and thereby, the clinical conclusion is limited. Second, four physicians independently reviewed CT scans but were not blinded to the results that all study patients had AAS. Our study design may induce an overestimation of the diagnostic ability of unenhanced-CT for detecting AAS; however, patients were classified as AAS-undetectable even if one of the four physicians judged that AAS was not detected with unenhanced-CT to minimize the overestimation. Additionally, all the reviewers were not radiologists. An experienced radiologist or specialist was not always available on the scene for reporting, and the initial management of patients suspected of having AAS was dependant on primary physicians. Hence, emergency physicians reviewed CT scans in our study. Third, because we evaluated only AAS patients, the specificity of unenhanced-CT in AAS diagnosis was not evaluated; however, the specificity of unenhanced-CT in AAS was approximately 80–90% according to previous studies, and this diagnostic accuracy could be well accepted.8–10 In addition, all CT studies were performed without electrocardiogram gating. Pulsation artefact could present as a hypodense curvilinear interface or flap along the aortic wall.7 These artefacts could misidentify the AAS and affect the AAS diagnostic performance with unenhanced-CT. Conclusion Unenhanced-CT could be a candidate for AAS screening; however, younger patients and patients with a patent false lumen could be misdiagnosed. The combination of ADD-RS plus D-dimer and unenhanced-CT could minimize AAS misdiagnosis while avoiding over-testing with CE-CT. Further prospective validation that includes non-AAS patients should be performed to confirm the usefulness of our diagnostic strategy using unenhanced-CT. 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TI - Potential of unenhanced computed tomography as a screening tool for acute aortic syndromes
JO - European Heart Journal. Acute Cardiovascular Care
DO - 10.1093/ehjacc/zuab069
DA - 2021-08-30
UR - https://www.deepdyve.com/lp/oxford-university-press/potential-of-unenhanced-computed-tomography-as-a-screening-tool-for-nHb50bUldr
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -