J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofCardiovascularCT.com
Original Research Article
Coronary competitive reverse flow: Imaging findings at CT angiography and correlation with invasive coronary angiography Minghua Li MDa, Shuyong Liu MDb, Jiayin Zhang MDa,*, Zhigang Lu MDc, Meng Wei MDc, Eun-Ju Chun MDd, Bin Lu MDe a
Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yishan Road, Shanghai 200233, China b Shandong University, School of Medicine, Jinan, China c Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China d Department of Radiology, Seoul National University Bundang Hospital, Seongnam City, Korea e Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
article info
abstract
Article history:
Objective: To study the imaging features of coronary competitive reverse flow and incidence
Received 11 May 2014
of a “reverse attenuation gradient” in coronary CT angiography (CTA) with correlation to
Received in revised form
invasive coronary angiography (ICA).
28 January 2015
Methods: Patients who had undergone coronary CTA and ICA within 2 weeks were retro-
Accepted 28 January 2015
spectively identified in our database and reviewed. All cases with ICA-confirmed
Available online 7 February 2015
competitive reverse flow or chronic total occlusions (CTOs) were included for further analysis. The “reverse attenuation gradient sign” was defined as a reverse intraluminal
Keywords:
opacification gradient of vessels which showed higher opacification in more distal
Computed tomography
compared with proximal segments. ICA findings were recorded and served as the reference
Chronic total occlusion
to identify the clinical implications of this sign.
Coronary angiography
Results: In total, 134 patients (mean age, 68.1 11.3 years; range, 38e90 years; 104 men)
Coronary artery disease
were included in our study. ICA revealed 11 cases of coronary competitive reverse flow and
Coronary collateral vessel
123 cases of CTO. A reverse attenuation gradient sign was present in 9 of 11 patients (82%) with coronary competitive reverse flow and 72 of 123 (59%) chronically occluded coronary arteries. Myocardial bridges, distal collateral filling, as well as direct visualization of collateral connection were all more frequent in cases with coronary competitive reverse flow group compared with cases with a CTO.
Minghua Li and Dr. Shuyong Liu are co-first authors and they contributed equally to this study. This study is supported by National Natural Science Foundation of China (grant number: 81301219), Shanghai Committee of Science and Technology, China (grant number: 13ZR1431400), and National Development Project of Key Clinical Department. Conflict of interest: The authors declare that they have no conflicts of interest. * Corresponding author. E-mail address: [email protected] (J. Zhang). 1934-5925/$ e see front matter ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2015.01.017
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
203
Conclusions: The reverse attenuation gradient sign distal to an upstream coronary severe stenosis indicates the presence of competitive collateral flow. Coronary CTA is able to correctly detect coronary competitive collateral flow and differentiate it from CTOs. ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
1.
Introduction
Coronary competitive reverse flow, also known as “pseudothrombus,” is described as a thrombus-like filling defect seen distally to a severe coronary stenosis at invasive coronary angiography owing to the nonopacified stream from contralateral collaterals.1 It is caused by the flow-limiting upstream severe stenosis and well-established retrograde collaterals.1 The recognition of this phenomenon is of clinical importance to avoid unnecessary revascularization procedures and subsequent complications but can be difficult even at invasive coronary angiography.2,3 The “reverse attenuation gradient sign” is a recently reported sign, which is defined as a reverse intraluminal opacification gradient of vessels distal to the occlusive lesions seen at coronary CT angiography (CTA).4 In contrast to the gradient pattern in normal coronary arteries, which display higher attenuation in proximal segments and gradually decreased attenuation along the vessel,5e7 a “reverse gradient” is present when higher opacification is observed in more distal sites. The reverse attenuation gradient sign is believed to mostly occur in patients with coronary chronic total occlusion (CTO) and to represent retrograde collateral flow.4 However, we assumed that this sign could also be seen in patients with severe coronary stenosis and downstream competitive reverse flow. Therefore, we aimed to systematically study the imaging features of coronary competitive reverse flow and the incidence of reverse attenuation gradient sign in coronary CTA with correlation to invasive coronary angiography.
2.
Methods
2.1.
Patient population
Institutional review board approval was obtained for this retrospective study, and informed consent was waived. We searched our database from January 2011 to December 2013 to identify patients with clinically suspected coronary artery disease who underwent both coronary CTA and invasive coronary angiography. The inclusion criteria were as follows: (1) presence of a nonocclusive lesion with distal competitive coronary reverse flow or presence of a chronic coronary artery occlusion in invasive coronary angiography and (2) an interval of 2 weeks or less between coronary CTA and invasive coronary angiography. Uninterpretable coronary CTA examinations because of poor image quality were excluded.
2.2.
Data acquisition protocol
A 128-slice multidetector CT (Definition AS; Siemens Medical Solutions, Forchheim, Germany) was used for scanning. In
patients with a heart rate >65 beats/min, b-blockers were administrated orally 1 hour before the examination. Nitroglycerin was given sublingually in all patients. A bolus of contrast media (iopamidol; Isovist [370 mg iodine/mL]; Schering AG, Berlin, German) was injected into the antecubital vein at the rate of 4.5 to 5 mL/s, followed by a 20- to 40-mL saline flush by using dual-barrel power injector (Tyco, Cincinnati, OH). The amount of contrast was determined according to the patient’s body weight and scan time. A test bolus was first injected and a region of interest was placed within the ascending aorta to determine a proper delay time, which was defined as 4 seconds plus the time to peak attenuation in the ascending aorta. Retrospectively electrocardiogram (ECG)-gated CTA was performed in patients with heart rates S70 beats/min, with collimation ¼ 128 0.6 mm, reconstructed slice thickness ¼ 0.6 mm, reconstructed slice interval ¼ 0.5 mm, and rotation time ¼ 300 ms. The effective current was 200 mA (ECG-dependent dose modulation technique was applied, full dose during the R-R interval of 40%e70%), and tube voltage was 120 kVp. Prospectively ECG-triggered CTA was performed in patients with a heart rate 0. Coronary CTA diagnosis of coronary competitive reverse flow was made according to the following criteria: (1) presence of the reverse attenuation gradient sign in the vessel segment distal to a severe coronary stenosis and (2) absence of
204
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
obstructive coronary lesion at the junction zone of the proximal end of a segment with reverse attenuation gradient sign. Other parameters and imaging features were also recorded for both coronary competitive reverse flow and CTO lesions as follows: presence of myocardial bridges in the respective vessel, direct visualization of a collateral connection, and distal collateral filling of both competitive reverse flow and CTO lesions. Distal collateral filling was assessed using a 4-point semiquantitative score, as previously introduced by Zhang et al.8 In brief, score 0 ¼ absent filling of the distal epicardial segment of the occluded vessel, score 1 ¼ partial filling of distal epicardial segment with length 3 months estimated from the clinical events or proven by previous angiography. Coronary competitive reverse flow was defined as the interruption of antegrade blood flow distal to a severe stenosis with TIMI grade &1 and having spontaneous restoration of antegrade flow after the revascularization of upstream lesions. The invasive coronary angiography findings served as the reference standard to validate coronary CTA findings. The presence of retrograde collaterals at invasive coronary angiography was recorded for comparison with coronary CTA.
2.5.
were not normally distributed. The Fisher exact test was used to compare proportions. A 2-tailed P < .05 was considered statistically significant.
Statistical analysis
Statistical analysis was performed using commercially available statistical software (SSPS; v13.0; SPSS Inc., Chicago, IL). Quantitative variables were expressed as mean standard deviation. Interobserver agreement was expressed in Cohen kappa value (k) for categorical variables. T-test and 1-way analysis of variance were used for normally distributed data, whereas the Mann-Whitney U test was used for data which
Invasive coronary angiography revealed 11 cases of coronary competitive reverse flow and 123 cases of CTOs. A reverse attenuation gradient sign was present in 9 of 11 patients (82%) with coronary competitive reverse flow and 72 of 123 with CTOs (59%). Unlike the reverse attenuation gradient sign seen in CTOs, which started continuously from the site of occlusion (Fig. 1), the reverse attenuation gradient sign observed in coronary competitive reverse flow usually began from
Table 1 e Demographic data. Characteristic Number of patients Age (y), mean SD Diabetes mellitus Hypertension Smoking Hyperlipidemia Myocardial infarction (>3 mo) Stable angina Unstable angina Silent ischemia Lesion locations LAD RCA LCx Diagonal
n (%) 134 68.1 11.3 59 (44) 77 (57.5) 47 (35.1) 55 (41) 19 (14.2) 49 (36.6) 57 (42.5) 9 (6.7) 57 53 21 3
(42.5) (39.6) (15.7) (2.2)
LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery; SD, standard deviation.
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
205
Fig. 1 e Reverse attenuation gradient sign observed at coronary CTA in patient with RCA total occlusion. (A) Threedimensional MIP image demonstrated a CTO lesion at proximal RCA with well-developed distal collateral. (B) CPR image showed a nonopacified occlusive lesion, which measured 16 mm in length. The attenuation gradient of distal segments was 11 HU/mm, indicating presence of reverse attenuation gradient sign. (C) Invasive coronary angiography confirmed CTO at proximal RCA. (D) Contralateral angiography showed retrograde collaterals. CPR, curved planar reformation; CTA, CT angiography; CTO, chronic total occlusion; MIP, maximum-intensity projection; RCA, right coronary artery.
somewhere distal to the upstream obstructive location. In addition, some cases with very high-grade stenoses revealed a sudden attenuation drop (Fig. 2) distal to the lesion. Comparison to invasive coronary angiography identified the site of sudden attenuation drop to be the watershed between antegrade and retrograde flow. Some coronary CTA features were different between cases with coronary competitive reverse flow and CTOs. The incidence of a myocardial bridge in the respective vessel, the distal collateral filling score, and the frequency of direct visualization of a collateral connection were all higher in cases with coronary competitive reverse flow compared with CTOs, as summarized in Table 2. Regarding the location of vessels with coronary competitive reverse flow, the left anterior descending (LAD) artery was the most frequent site, accounting for 8 of 11 cases (73%; Table 3). All LAD lesions were associated with concomitant myocardial bridge.
3.3. Diagnostic performance of coronary CTA for detecting coronary competitive reverse flow The interobserver agreement for detecting coronary competitive reverse flow was 91% (k ¼ 0.744; P ¼ .011). According to our diagnostic criteria as mentioned previously, coronary CTA managed to correctly detect 9 of 11 (82%) invasive coronary angiographyeconfirmed vessels with coronary competitive reverse flow. Two false-negative cases of competitive reverse flow were misinterpreted in coronary CTA because of the absence of a reverse attenuation gradient sign. Among 123 cases of CTOs, none was misinterpreted as coronary competitive reverse flow at coronary CTA. Therefore, the overall sensitivity, specificity, positive predictive value, and negative predictive value for detecting coronary competitive reverse flow (as opposed to a coronary occlusion) by coronary CTA were 82% (9 of 11), 100% (123 of 123), 100% (9 of 9), and 98.4% (123 of 125), respectively.
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J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
Fig. 2 e Reverse attenuation gradient sign observed at coronary CTA in patient with LAD subtotal occlusion and competitive collateral flow. (A) Three-dimensional MIP image of left coronary artery demonstrated a subtotal occlusion at proximal LAD and interruption of antegrade flow at middle LAD. (B) 3D-MIP image of right coronary artery demonstrated retrograde collateral flow from AM. (C) CPR image showed an occlusive lesion at proximal LAD, which measured 5 mm in length. The lumen opacification had a sudden drop at the watershed point (white arrowhead ) between antegrade and retrograde flow. Please note the absence of any obstructive lesion at that point. The attenuation gradient of distal segments was 21 HU/mm, indicating presence of reverse attenuation gradient sign. (D) Invasive coronary angiography confirmed subtotal occlusion at proximal LAD and absence of antegrade flow at middle LAD. (E) Contralateral angiography showed retrograde competitive collaterals from AM. (F) Poststenting angiography revealed recovery of antegrade flow at middle LAD once the proximal lesion had been treated. AM, acute marginal; CTA, CT angiography; CPR, curved planar reformation; LAD, left anterior descending; MIP, maximum-intensity projection.
4.
Discussion
This study revealed 2 major findings: (1) the reverse attenuation gradient sign distal to an upstream coronary severe stenosis indicates the presence of competitive collateral flow and (2) coronary CTA is able to correctly detect coronary competitive collateral flow and differentiate it from CTOs. Competitive collateral flow, also known as pseudothrombus, is described as a thrombus-like filling defect seen distally to a severe coronary stenosis at invasive coronary angiography owing to the nonopacified stream from contralateral collaterals.1 It is caused by the flow-limiting upstream severe stenosis and well-established retrograde collaterals.1 The recognition of this phenomenon is of clinical importance to avoid unnecessary revascularization procedures but can be difficult even at invasive coronary angiography. Although coronary CTA is considered to have high diagnostic accuracy for characterization of coronary stenosis in com-
parison with invasive coronary angiography and intravascular ultrasonography,11,12 its value of identifying this entity has not been fully recognized. This study for the first time established the diagnostic criteria for detection of competitive reverse flow according to coronary CTA findings and revealed high diagnostic accuracy compared to invasive coronary angiography validation. It is of potential clinical significance and enables the noninvasive diagnosis of coronary competitive reverse flow before invasive coronary angiography is performed. The comprehensive understanding of the reverse attenuation gradient sign is fundamental for an accurate diagnosis. In line with a previous study in patients with a chronic occlusion,4 the reverse attenuation gradient sign was also observed in cases with severe stenosis and downstream competitive collateral flow. In general, the reverse attenuation gradient sign distal to a severe coronary stenosis correlates to the reverse competitive flow as confirmed by invasive
207
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
Table 2 e Imaging features of competitive reverse flow and CTO. Feature
Competitive reverse flow (n ¼ 11)
CTO (n ¼ 123)
P value
9/11 (81.8) 11.7 12.4 8/11 (72.7) 3.1 1.1 14.3 5.9 3 (2e3) 6/11 (54.5)
72/123 (58.5) 3.1 12.8 8/123 (6.5) 2.1 0.6 11.8 4.1 2 (2e3) 14/123 (11.4)
.13 .035
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofCardiovascularCT.com
Original Research Article
Coronary competitive reverse flow: Imaging findings at CT angiography and correlation with invasive coronary angiography Minghua Li MDa, Shuyong Liu MDb, Jiayin Zhang MDa,*, Zhigang Lu MDc, Meng Wei MDc, Eun-Ju Chun MDd, Bin Lu MDe a
Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yishan Road, Shanghai 200233, China b Shandong University, School of Medicine, Jinan, China c Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China d Department of Radiology, Seoul National University Bundang Hospital, Seongnam City, Korea e Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
article info
abstract
Article history:
Objective: To study the imaging features of coronary competitive reverse flow and incidence
Received 11 May 2014
of a “reverse attenuation gradient” in coronary CT angiography (CTA) with correlation to
Received in revised form
invasive coronary angiography (ICA).
28 January 2015
Methods: Patients who had undergone coronary CTA and ICA within 2 weeks were retro-
Accepted 28 January 2015
spectively identified in our database and reviewed. All cases with ICA-confirmed
Available online 7 February 2015
competitive reverse flow or chronic total occlusions (CTOs) were included for further analysis. The “reverse attenuation gradient sign” was defined as a reverse intraluminal
Keywords:
opacification gradient of vessels which showed higher opacification in more distal
Computed tomography
compared with proximal segments. ICA findings were recorded and served as the reference
Chronic total occlusion
to identify the clinical implications of this sign.
Coronary angiography
Results: In total, 134 patients (mean age, 68.1 11.3 years; range, 38e90 years; 104 men)
Coronary artery disease
were included in our study. ICA revealed 11 cases of coronary competitive reverse flow and
Coronary collateral vessel
123 cases of CTO. A reverse attenuation gradient sign was present in 9 of 11 patients (82%) with coronary competitive reverse flow and 72 of 123 (59%) chronically occluded coronary arteries. Myocardial bridges, distal collateral filling, as well as direct visualization of collateral connection were all more frequent in cases with coronary competitive reverse flow group compared with cases with a CTO.
Minghua Li and Dr. Shuyong Liu are co-first authors and they contributed equally to this study. This study is supported by National Natural Science Foundation of China (grant number: 81301219), Shanghai Committee of Science and Technology, China (grant number: 13ZR1431400), and National Development Project of Key Clinical Department. Conflict of interest: The authors declare that they have no conflicts of interest. * Corresponding author. E-mail address: [email protected] (J. Zhang). 1934-5925/$ e see front matter ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2015.01.017
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
203
Conclusions: The reverse attenuation gradient sign distal to an upstream coronary severe stenosis indicates the presence of competitive collateral flow. Coronary CTA is able to correctly detect coronary competitive collateral flow and differentiate it from CTOs. ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
1.
Introduction
Coronary competitive reverse flow, also known as “pseudothrombus,” is described as a thrombus-like filling defect seen distally to a severe coronary stenosis at invasive coronary angiography owing to the nonopacified stream from contralateral collaterals.1 It is caused by the flow-limiting upstream severe stenosis and well-established retrograde collaterals.1 The recognition of this phenomenon is of clinical importance to avoid unnecessary revascularization procedures and subsequent complications but can be difficult even at invasive coronary angiography.2,3 The “reverse attenuation gradient sign” is a recently reported sign, which is defined as a reverse intraluminal opacification gradient of vessels distal to the occlusive lesions seen at coronary CT angiography (CTA).4 In contrast to the gradient pattern in normal coronary arteries, which display higher attenuation in proximal segments and gradually decreased attenuation along the vessel,5e7 a “reverse gradient” is present when higher opacification is observed in more distal sites. The reverse attenuation gradient sign is believed to mostly occur in patients with coronary chronic total occlusion (CTO) and to represent retrograde collateral flow.4 However, we assumed that this sign could also be seen in patients with severe coronary stenosis and downstream competitive reverse flow. Therefore, we aimed to systematically study the imaging features of coronary competitive reverse flow and the incidence of reverse attenuation gradient sign in coronary CTA with correlation to invasive coronary angiography.
2.
Methods
2.1.
Patient population
Institutional review board approval was obtained for this retrospective study, and informed consent was waived. We searched our database from January 2011 to December 2013 to identify patients with clinically suspected coronary artery disease who underwent both coronary CTA and invasive coronary angiography. The inclusion criteria were as follows: (1) presence of a nonocclusive lesion with distal competitive coronary reverse flow or presence of a chronic coronary artery occlusion in invasive coronary angiography and (2) an interval of 2 weeks or less between coronary CTA and invasive coronary angiography. Uninterpretable coronary CTA examinations because of poor image quality were excluded.
2.2.
Data acquisition protocol
A 128-slice multidetector CT (Definition AS; Siemens Medical Solutions, Forchheim, Germany) was used for scanning. In
patients with a heart rate >65 beats/min, b-blockers were administrated orally 1 hour before the examination. Nitroglycerin was given sublingually in all patients. A bolus of contrast media (iopamidol; Isovist [370 mg iodine/mL]; Schering AG, Berlin, German) was injected into the antecubital vein at the rate of 4.5 to 5 mL/s, followed by a 20- to 40-mL saline flush by using dual-barrel power injector (Tyco, Cincinnati, OH). The amount of contrast was determined according to the patient’s body weight and scan time. A test bolus was first injected and a region of interest was placed within the ascending aorta to determine a proper delay time, which was defined as 4 seconds plus the time to peak attenuation in the ascending aorta. Retrospectively electrocardiogram (ECG)-gated CTA was performed in patients with heart rates S70 beats/min, with collimation ¼ 128 0.6 mm, reconstructed slice thickness ¼ 0.6 mm, reconstructed slice interval ¼ 0.5 mm, and rotation time ¼ 300 ms. The effective current was 200 mA (ECG-dependent dose modulation technique was applied, full dose during the R-R interval of 40%e70%), and tube voltage was 120 kVp. Prospectively ECG-triggered CTA was performed in patients with a heart rate 0. Coronary CTA diagnosis of coronary competitive reverse flow was made according to the following criteria: (1) presence of the reverse attenuation gradient sign in the vessel segment distal to a severe coronary stenosis and (2) absence of
204
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
obstructive coronary lesion at the junction zone of the proximal end of a segment with reverse attenuation gradient sign. Other parameters and imaging features were also recorded for both coronary competitive reverse flow and CTO lesions as follows: presence of myocardial bridges in the respective vessel, direct visualization of a collateral connection, and distal collateral filling of both competitive reverse flow and CTO lesions. Distal collateral filling was assessed using a 4-point semiquantitative score, as previously introduced by Zhang et al.8 In brief, score 0 ¼ absent filling of the distal epicardial segment of the occluded vessel, score 1 ¼ partial filling of distal epicardial segment with length 3 months estimated from the clinical events or proven by previous angiography. Coronary competitive reverse flow was defined as the interruption of antegrade blood flow distal to a severe stenosis with TIMI grade &1 and having spontaneous restoration of antegrade flow after the revascularization of upstream lesions. The invasive coronary angiography findings served as the reference standard to validate coronary CTA findings. The presence of retrograde collaterals at invasive coronary angiography was recorded for comparison with coronary CTA.
2.5.
were not normally distributed. The Fisher exact test was used to compare proportions. A 2-tailed P < .05 was considered statistically significant.
Statistical analysis
Statistical analysis was performed using commercially available statistical software (SSPS; v13.0; SPSS Inc., Chicago, IL). Quantitative variables were expressed as mean standard deviation. Interobserver agreement was expressed in Cohen kappa value (k) for categorical variables. T-test and 1-way analysis of variance were used for normally distributed data, whereas the Mann-Whitney U test was used for data which
Invasive coronary angiography revealed 11 cases of coronary competitive reverse flow and 123 cases of CTOs. A reverse attenuation gradient sign was present in 9 of 11 patients (82%) with coronary competitive reverse flow and 72 of 123 with CTOs (59%). Unlike the reverse attenuation gradient sign seen in CTOs, which started continuously from the site of occlusion (Fig. 1), the reverse attenuation gradient sign observed in coronary competitive reverse flow usually began from
Table 1 e Demographic data. Characteristic Number of patients Age (y), mean SD Diabetes mellitus Hypertension Smoking Hyperlipidemia Myocardial infarction (>3 mo) Stable angina Unstable angina Silent ischemia Lesion locations LAD RCA LCx Diagonal
n (%) 134 68.1 11.3 59 (44) 77 (57.5) 47 (35.1) 55 (41) 19 (14.2) 49 (36.6) 57 (42.5) 9 (6.7) 57 53 21 3
(42.5) (39.6) (15.7) (2.2)
LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery; SD, standard deviation.
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
205
Fig. 1 e Reverse attenuation gradient sign observed at coronary CTA in patient with RCA total occlusion. (A) Threedimensional MIP image demonstrated a CTO lesion at proximal RCA with well-developed distal collateral. (B) CPR image showed a nonopacified occlusive lesion, which measured 16 mm in length. The attenuation gradient of distal segments was 11 HU/mm, indicating presence of reverse attenuation gradient sign. (C) Invasive coronary angiography confirmed CTO at proximal RCA. (D) Contralateral angiography showed retrograde collaterals. CPR, curved planar reformation; CTA, CT angiography; CTO, chronic total occlusion; MIP, maximum-intensity projection; RCA, right coronary artery.
somewhere distal to the upstream obstructive location. In addition, some cases with very high-grade stenoses revealed a sudden attenuation drop (Fig. 2) distal to the lesion. Comparison to invasive coronary angiography identified the site of sudden attenuation drop to be the watershed between antegrade and retrograde flow. Some coronary CTA features were different between cases with coronary competitive reverse flow and CTOs. The incidence of a myocardial bridge in the respective vessel, the distal collateral filling score, and the frequency of direct visualization of a collateral connection were all higher in cases with coronary competitive reverse flow compared with CTOs, as summarized in Table 2. Regarding the location of vessels with coronary competitive reverse flow, the left anterior descending (LAD) artery was the most frequent site, accounting for 8 of 11 cases (73%; Table 3). All LAD lesions were associated with concomitant myocardial bridge.
3.3. Diagnostic performance of coronary CTA for detecting coronary competitive reverse flow The interobserver agreement for detecting coronary competitive reverse flow was 91% (k ¼ 0.744; P ¼ .011). According to our diagnostic criteria as mentioned previously, coronary CTA managed to correctly detect 9 of 11 (82%) invasive coronary angiographyeconfirmed vessels with coronary competitive reverse flow. Two false-negative cases of competitive reverse flow were misinterpreted in coronary CTA because of the absence of a reverse attenuation gradient sign. Among 123 cases of CTOs, none was misinterpreted as coronary competitive reverse flow at coronary CTA. Therefore, the overall sensitivity, specificity, positive predictive value, and negative predictive value for detecting coronary competitive reverse flow (as opposed to a coronary occlusion) by coronary CTA were 82% (9 of 11), 100% (123 of 123), 100% (9 of 9), and 98.4% (123 of 125), respectively.
206
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
Fig. 2 e Reverse attenuation gradient sign observed at coronary CTA in patient with LAD subtotal occlusion and competitive collateral flow. (A) Three-dimensional MIP image of left coronary artery demonstrated a subtotal occlusion at proximal LAD and interruption of antegrade flow at middle LAD. (B) 3D-MIP image of right coronary artery demonstrated retrograde collateral flow from AM. (C) CPR image showed an occlusive lesion at proximal LAD, which measured 5 mm in length. The lumen opacification had a sudden drop at the watershed point (white arrowhead ) between antegrade and retrograde flow. Please note the absence of any obstructive lesion at that point. The attenuation gradient of distal segments was 21 HU/mm, indicating presence of reverse attenuation gradient sign. (D) Invasive coronary angiography confirmed subtotal occlusion at proximal LAD and absence of antegrade flow at middle LAD. (E) Contralateral angiography showed retrograde competitive collaterals from AM. (F) Poststenting angiography revealed recovery of antegrade flow at middle LAD once the proximal lesion had been treated. AM, acute marginal; CTA, CT angiography; CPR, curved planar reformation; LAD, left anterior descending; MIP, maximum-intensity projection.
4.
Discussion
This study revealed 2 major findings: (1) the reverse attenuation gradient sign distal to an upstream coronary severe stenosis indicates the presence of competitive collateral flow and (2) coronary CTA is able to correctly detect coronary competitive collateral flow and differentiate it from CTOs. Competitive collateral flow, also known as pseudothrombus, is described as a thrombus-like filling defect seen distally to a severe coronary stenosis at invasive coronary angiography owing to the nonopacified stream from contralateral collaterals.1 It is caused by the flow-limiting upstream severe stenosis and well-established retrograde collaterals.1 The recognition of this phenomenon is of clinical importance to avoid unnecessary revascularization procedures but can be difficult even at invasive coronary angiography. Although coronary CTA is considered to have high diagnostic accuracy for characterization of coronary stenosis in com-
parison with invasive coronary angiography and intravascular ultrasonography,11,12 its value of identifying this entity has not been fully recognized. This study for the first time established the diagnostic criteria for detection of competitive reverse flow according to coronary CTA findings and revealed high diagnostic accuracy compared to invasive coronary angiography validation. It is of potential clinical significance and enables the noninvasive diagnosis of coronary competitive reverse flow before invasive coronary angiography is performed. The comprehensive understanding of the reverse attenuation gradient sign is fundamental for an accurate diagnosis. In line with a previous study in patients with a chronic occlusion,4 the reverse attenuation gradient sign was also observed in cases with severe stenosis and downstream competitive collateral flow. In general, the reverse attenuation gradient sign distal to a severe coronary stenosis correlates to the reverse competitive flow as confirmed by invasive
207
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 2 0 2 e2 0 8
Table 2 e Imaging features of competitive reverse flow and CTO. Feature
Competitive reverse flow (n ¼ 11)
CTO (n ¼ 123)
P value
9/11 (81.8) 11.7 12.4 8/11 (72.7) 3.1 1.1 14.3 5.9 3 (2e3) 6/11 (54.5)
72/123 (58.5) 3.1 12.8 8/123 (6.5) 2.1 0.6 11.8 4.1 2 (2e3) 14/123 (11.4)
.13 .035
