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Multidetector Computed Tomography Coronary Angiography forthe Assessment of Coronary In-Stent Restenosis

Daniele Andreini, MD*, Gianluca Pontone, MD, Saima Mushtaq, MD, Mauro Pepi, MD,and Antonio Luca Bartorelli, MD

The investigators conducted a review to evaluate the diagnostic performance of multide-tector computed tomography (MDCT) for coronary stent evaluation. The prespecifiedinclusion criteria selected prospective or retrospective human studies published in English.Studies that did not report raw numbers of diagnostic accuracy for the detection of in-stentrestenosis were excluded. The data from 24 studies are reported, 6 performed with old-generation scanners (4-, 16-, and 40-slice MDCT) and 18 performed with 64-slice MDCTor dual-source MDCT. With old-generation MDCT, up to 18% of coronary stents weremissed, the rate of nonevaluable stents ranged from 2.6% to 23.5%, and the overallfeasibility and diagnostic accuracy were 90.4% and 90%, respectively. With 64-sliceMDCT, no stent was missed, and the overall feasibility and diagnostic accuracy were 90.4%and 91.9%, respectively. Advancements in MDCT and stent technologies may furtherreduce the number of nonassessable stents and improve diagnostic performance. © 2010
Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:645–655)
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Invasive coronary angiography (ICA) is the most de-endable imaging modality for detecting in-stent restenosisISR).1 With the introduction of multidetector computedomography (MDCT), coronary computed tomographic an-iography has emerged as a new tool for diagnosing coro-ary artery disease and conducting patient follow-up. Cor-nary computed tomographic angiography with 16- and0-slice scanners has �90% sensitivity and specificity forhe detection of significant coronary stenosis (luminal di-meter �50%).2,3 Studies performed using 64-slice MDCTr dual-source MDCT (DSCT) have shown an improvementn diagnostic performance for the detection of significantoronary stenosis on per segment and a per patient analysesue to greater spatial and temporal resolution.4 However,looming artifacts caused by metallic stent struts may stillmpair the visualization of stent lumen and the quantifica-ion of luminal narrowing.5 Our aim was to perform atructured review of all studies that assessed the diagnosticerformance of MDCT for the detection of coronary ISR.

ethods

Our prespecified inclusion criteria selected prospectiver retrospective human studies published in English. Studieshat did not report raw numbers of diagnostic accuracytrue-positive, true-negative, false-positive, and false-nega-ive rates) for the detection of ISR were excluded. Using ourredetermined criteria, we searched Medline combining theearch terms “computed tomography,” “coronary stent,”restenosis,” and “angiography” and included reports pub-

Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Caratterecientifico, Department of Cardiovascular Science, University of Milan,ilan, Italy. Manuscript received July 28, 2009; revised manuscript re-

eived and accepted October 14, 2009.*Corresponding author: Tel: 39-02-58002577; fax: 39-02-58002283.

DE-mail address: [email protected] (D. Andreini).

002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved.oi:10.1016/j.amjcard.2009.10.046

ished through May 2009. The studies were performedainly in patients referred for ICA because of suspected

SR (angina, positive results on electrocardiographic [ECG]tress testing or myocardial perfusion imaging), with thexception of 4 studies performed in asymptomatic pa-ients.5–8 The overall feasibility of stent evaluation on

DCT (the ratio of evaluable segments to the total numberf segments) was measured. We assessed the overall sensi-ivity, specificity, positive predictive value, negative predic-ive value, and accuracy of MDCT for the detection of ISR

50% from a segment-based analysis against the standardf findings on ICA.

esultsTechnology and data acquisition: High spatial and

emporal resolution is needed to evaluate coronary arteries,articularly in case of stented vessels.9,10 Therefore, ICA ishe gold standard technique for ruling out ISR. In the late990s, MDCT with retrospective ECG gating was intro-uced.11 This technology, characterized by thinner and mul-iple sections and lower pitch factors (table feed/gantryotation) consists of a continuous spiral scan of the heartith simultaneous ECG recording. This translates intoigher spatial and temporal resolution that allows the eval-ation of stented segments.

The main technical factors that influence diagnostic per-ormance are the number of slices, slice thickness, gantryotation time, scanning parameters, heart rate during thecan, the type of contrast injection protocol, and postpro-essing analysis2,5–7,8,12–30 (Tables 1 and 2). A progressivencrease in the number of slices from 4 up to 40 allowed aontemporaneous increase in spatial resolution from 1.25 to.5 mm, providing promising results in ISR detection.2,12–16

The temporal resolution of old-generation scanners wasurther improved in the mid-2000s with the introduction of4-slice multidetector computed tomographic scanners and
SCT.5–8,17–30 Moreover, in addition to detector improve-
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646 The American Journal of Cardiology (www.AJConline.org)

ents, these scanners were equipped with much faster gantries,esulting in effective temporal resolution up to 83 ms.24,25,30

However, matrices with such thin layers required veryigh tube current and voltage,5–7,17–23,26–30 translating toadiation exposure increases.31,32 The studies using 64-lices scanners included in this review reported effective-ray doses ranging from 10 and 20.5 mSv.5–8,17–23,26–29

everal strategies have been proposed to reduce radiationose, such as modulation dose protocols, dual-source scan-ing, and prospective ECG gating.25,31,32 With the latterechnique, the table remains stationary while the x-ray tubeotates around the patient and is advanced for the subse-uent scan only when data acquisition is completed. Thisllows a reduction of up to 5.7 mSv without impairingiagnostic accuracy for ISR detection.25,29

Several studies demonstrated that heart rate has anmportant impact on the diagnostic performance of

DCT.33,34 Although the heart rate limit depends on theemporal resolution of the scanner used,35,36 a target heartate �65 beats/min is always desirable. This was achievedith � blockers administered orally 60 to 90 minutes before

he scan,6,7,17,18,20,21,23,26,27,30 intravenously immediatelyefore,5,6,17,19,23,28–30 or both.5,6,7,17–21,23,26–30 Image qual-ty has also been shown to improve with nitroglyce-in,17,19,20,25,30 and therefore, some investigators adminis-ered sublingual nitrates immediately before scans tochieve maximum coronary vasodilatation.17,19,20,25,30

With regard to the contrast injection protocol, no differenceas found between the “bolus-tracking technique,”5–8,18–29

aster and more reliable, and the “test bolus technique.”17,30

ith regard to postprocessing analysis, image data setsere analyzed in all studies using reconstruction protocols

nd vessel analysis (Figure 1). To improve stent visibilitynd to decrease artifacts, dedicated kernels can be used.econstruction kernels are mathematical calculations ap-lied to raw data that control low contrast detectability andpatial resolution in the reconstructed images.37 Although amooth kernel is suitable for the evaluation of the vesselumen, vessel wall, and surrounding tissue, the visualizationf high-density structures such as stents requires a sharpernel37,38 (Figure 2). Indeed, this was used for ISR evalua-ion in almost all studies reported in this review.5–8,18–21,23–30

Finally, 3 different methods were used to determinatehe degree of ISR: qualitative, semiquantitative, anduantitative. With the qualitative technique, significant ISRdiameter reduction �50%) was visually detected.6,7,17,19

ith the semiquantitative method, a 4-point scale rangingrom 1 (patent stent lumen) to 4 (stent occlusion) wassed.5,8,18,20,23,25–28,30 In the quantitative measurement, theercentage of stenosis was calculated as the ratio betweenhe diameters, measured in the short axis, of the narrowertent lumen and of the proximal and distal reference seg-ents.6,18,21,22,24,28,29 However, no significant differenceas reported in the accuracy of the qualitative and quanti-

ative method.

Diagnostic performance of 4-, 16-, and 40-sliceDCT: Two of 6 studies included in the present review

howed that multidetector computed tomographic scannersf this generation were unable to correctly identify all stent

segments. Indeed, up to 18% of stents were not recognizedTab

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Table 2Technical background, data acquisition, and effective doses of 64-slice computed tomography for the detection of in-stent restenosis

Study Journal Manufacturer Source No. of Slices/Slice Thickness

(mm)

GantryRotation

Time(ms)

TubeCurrent(mA)

TubeVoltage(kVp)

�Blockade/Nitrates

ECG Gating ModulationDose

ContrastAgent

Protocol

SharpKernel

Type of Analysis EffectiveRadiation

Dose(mSv)

Rixe et al(2006)17

EHJ Siemens Single 32 � 2/0.6 330 850 120 OR,IV/yes

Retrospective Yes (34patients)

Test bolus No Qualitative NR

Van Mieghemet al(2006)18

Circ Siemens Single 32 � 2/0.6(43 patients)

330 900 120 OR/no Retrospective No Bolus tracking Yes Semiquantitative/quantitative

15.2–21.4

Rist et al(2006)5

AR Siemens Single 32 � 2/0.6 330 850 120 IV/no Retrospective Yes Bolus tracking Yes Semiquantitative 8–10

Oncel et al(2007)19

Rad Siemens Single 32 � 2/0.6 330 900 120 IV/yes Retrospective No Bolus tracking Yes Qualitative NR

Ehara et al(2007)20

JACC Siemens Single 32 � 2/0.6 330 800 120 OR/yes Retrospective No Bolus tracking Yes Semiquantitative 12.1

Cademartiri etal (2007)21

JACC Siemens Single 32 � 2/0.6 330 900 120 OR/no Retrospective No Bolus tracking Yes Quantitative 15–20Toshiba Single 64/0.5 400 712 120 Retrospective No Yes

Carabba et al(2007)22

AJC Philips Single 64/0.6 400 600–850 120 No/no Retrospective No Bolus tracking No Quantitative 12.8 � 2.3

Das et al(2007)23

Rad Siemens Single 64/0.6 370 750–850 120 OR,IV/no

Retrospective No Bolus tracking Yes Semiquantitative NR

Schuijf et al(2007)8

Rad Toshiba Single 64/0.5 400–500 350 120 No/no Retrospective Yes Bolus tracking Yes Semiquantitative 10–15

Pugliese et al(2008)24

Heart Siemens Dual 32 � 2/0.6 330 412 120 No/no Retrospective Yes Bolus tracking Yes Quantitative 12.1–16.7

Oncel et al(2008)25

AJR Siemens Dual 32 � 2/0.6 330 390 120 No/yes Prospective No Bolus tracking Yes Semiquantitative 12.3

Carbone et al(2008)26

ER Siemens Single 32 � 2/0.6 330 800 120 OR/no Retrospective No Bolus tracking Yes Semiquantitative 15.0

Manghat et al(2008)27

AJC GE Single 64/0.6 350 900 120 OR/no Retrospective No Bolus tracking Yes Semiquantitative NR

Hecht et al(2008)6

AJC Philips Single 64/0.6 — 600–1,000 120–140 OR,IV/no

Retrospective No Bolus tracking Yes Qualitative/quantitative

13–18

Nakamura etal (2008)7

IJC GE Single 64/0.6 350 300–750 120 OR/no Retrospective Yes Bolus tracking Yes Qualitative NR

Andreini et al(2009)28

AJC GE Single 64/0.6 350 650 120 IV/no Retrospective Yes Bolus tracking Yes Semiquantitative/quantitative

NR

Pontone et al(2009)29

JACC GE Single 64/0.6 350 700 120 IV/no Retrospective Yes Bolus tracking Yes Quantitative 5.7Prospective Yes Yes 20.5

Pflederer et al(2009)30

AJC Siemens Dual 64 � 2/0.6 330 400 120 OR,IV/yes

Retrospective Yes Test bolus Yes Semiquantitative 14.8 � 4.8

AJR � American Journal of Roentgenology; AR � Academic Radiology; Circ � Circulation; EHJ � European Heart Journal; IJC � International Journal of Cardiology; Rad � Radiology. Otherabbreviations as in Table 1.

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n these studies, as well as in other studies not included inhis review because of the exclusion criteria.3,13,15 The rea-ons were mainly motion artifacts and severe calcifications.herefore, analysis was performed on the correctly identi-ed stents only.

Table 3 lists the percentage of nonevaluable coronarytented segments and the diagnostic accuracy parameterseported in the 6 published studies that investigated theiagnostic performance of 4-, 16-, and 40-slice MDCT. The

igure 1. (A) MDCT (volume rendering) showing stents (arrows) implanteultiplanar reconstruction of the left main coronary artery (LM) and LCX s

D) stent segments. LAD � left anterior descending coronary artery.

igure 2. (A) MDCT (volume rendering) showing multiple stents (arrows)oronary artery (LCX). (B) The blooming effect caused by the metallic stC) Use of a dedicated sharp kernel reduces the blooming effect, with a s

able 3iagnostic performance of 4-, 16-, and 40-slice computed tomographic scy multidetector computed tomography)

tudy Journal No. of Patients/No. of Stents

Not Evaluabl(%)

ademartiri et al (2005)2 AJC 51/76 2.6 (2/76)aspar et al (2005)12 JACC 65/111 4.5 (5/111)azzarotto et al (2006)13 JCM 24/34 23.5 (8/34)

oon et al (2007)14 IMJ 37/47 4.2 (2/47)efer et al (2007)15 ER 50/69 7.2 (5/69)edeschi et al (2008)16 JCM 72/90 21 (19/90)otal 299/427 9.6 (41/427

NPV � negative predictive value; PPV � positive predictive value. Ot

ate of coronary stents classified as not evaluable because of l

oor image quality ranged from 2.6% and 23.5%.2,12–16 Theverall feasibility of MDCT was 90.4%. Image qualityas impaired mainly by motion artifacts related to pa-

ients’ inability to hold their breath or refrain from chestovement. These were the reasons for uninterpretable

tented segments in 100% of the cases in a study byademartiri et al2 and in 40% of the cases in a study byaspar et al12 and represented the first cause of noneva-

uability in a study by Kefer et al.15 This is due to the

first diagonal branch (D1) and left circumflex coronary artery (LCX). (B)stent patency, confirmed by short-axis view of the proximal (C) and distal

ed in the proximal segment and first marginal branch of the left circumflexders adequate stent luminal visualization with multiplanar reconstruction.nt improvement in stent luminal visualization.

for the detection of in-stent restenosis (using stents correctly identified

nsitivity(%)

Specificity(%)

PPV(%)

NPV(%)

Accuracy(%)

(5/6) 98 (67/68) 83 (5/6) 98 (67/68) 97 (72/74)(9/17) 88 (78/89) 45 (9/20) 91 (78/86) 82 (87/106)(21/23) 67 (2/3) 95 (21/22) 50 (2/4) 88 (23/26)(5/7) 97 (37/38) 83 (5/6) 95 (37/39) 93 (42/45)(12/18) 98 (50/51) 92 (12/13) 89 (50/56) 90 (62/69)(14/17) 96 (52/54) 87 (14/16) 94 (52/55) 93 (66/71)(66/88) 94 (286/303) 80 (66/83) 93 (286/308) 90 (352/391)

reviations as in Table 1.

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649Review/MDCT for ISR Assessment

ausing longer scan times requiring that patients holdheir breath longer.

Another cause of impaired quality was the high-densityrtifacts generated by metallic stent struts.12 Three studiesound that stent diameter may influence the evaluation oftent lumen on MDCT.14–16 In a study by Tedeschi et al,16

nly 1 of 9 stents (11%) with diameters �3 mm was judgedvaluable, compared with 60 of 81 stents (74%) with diam-ters �3 mm. In a study by Soon et al,14 all nonevaluabletents had diameters �3 mm. Similarly, in the study byefer et al,15 nonevaluable stents were of significantly

maller diameters. In the latter study, nonassessable stentsad thinner struts (87 vs 110 �m). As listed in Table 3, theverall diagnostic accuracy of the 6 studies included in this

able 4iagnostic performance of 64-slice computed tomography and dual-sourc

tudy Journal No. ofPatients/No.

of Stents

Not Evaluable(%)

Sensitivity(%)

ixe et al(2006)17

EHJ 64/102 42 (43/102) 86 (6/7)

an Mieghemet al(2006)18

Circ 70/162 — 100 (10/10)

ist et al(2007)5

AR 25/46 2 (1/46) 75 (6/8)

ncel et al(2007)19

Rad 30/39 0 (0/39) 89 (17/19)

hara et al(2007)20

JACC 81/125 12 (15/125) 91 (20/22)

ademartiri etal (2007)21

JACC 182/192 7 (14/192) 95 (19/20)

arrabba et al(2007)22

AJC 41/87 0 (0/87) 84 (11/13)

as et al(2007)23

Rad 53/110 2.7 (3/110) 97 (31/32)

chuijf et al(2007)8

Rad 50/76 14 (11/76) 100 (6/6)

ugliese et al(2008)24

Heart 100/178 5 (9/178) 94 (37/39)

ncel et al(2008)25

AJR 35/48 15 (7/48) 100 (17/17)

arbone et al(2008)26

ER 41/74 19.5 (21/74) 75 (12/16)

anghat et al(2008)27

AJC 40/114 9.6 (11/114) 85 (17/20)

echt et al(2008)6

AJC 67/132 0 (0/132) 94 (16/17)

akamura etal (2008)7

IJC 49/75 14.6 (11/75) 67 (2/3)

ndreini et al(2009)28

AJC 100/179 5 (9/179) 87 (34/39)

ontone et al(2009)29

JACC 80/48* 8 (4/48) 92 (11/12)80/66† 6 (4/66) 73 (8/11)

flederer et al(2009)30

AJC 112/150 10 (15/150) 84 (16/19)

otal 1,300/2,003 9.6 (178/1,841) 89.7 (296/33

* Prospective ECG gating.† Retrospective ECG gating.Abbreviations as in Tables 1 to 3.

eview was 90%. As shown in the study by Kefer et al,15 (

tent diameter plays a significant role in the correct evalu-tion of stent patency.

In conclusion, most of the studies using 4-, 16-, and0-slice MDCT reported high overall feasibility for thevaluation of stent patency. However, some studies notncluded in this review because of the exclusion criteriahowed more relevant rates of nonevaluable stents: 46%106 of 232) in a study by Gilard et al3 and 77% (50 of 65)n a study by Schuijf et al.39

Feasibility and imaging quality of 64-slice MDCT andSCT: Table 4 lists the percentages of nonevaluable coro-ary stented segments reported in the 18 published studieshat investigated the diagnostic performance of 64-slice

DCT and DSCT. With the exception of a very high rate

uted tomography for the detection of in-stent restenosis

Specificity(%)

PPV(%)

NPV(%)

Accuracy(%)

8 (51/52) 86 (6/7) 98 (51/52) 97 (57/59)

1 (55/60) 67 (10/15) 100 (55/55) 93 (65/70)

2 (34/37) 67 (6/9) 94 (34/36) 89 (40/45)

5 (19/20) 94 (17/18) 90 (19/21) 92 (36/39)

3 (82/88) 77 (20/26) 98 (82/84) 93 (102/110)

3 (147/158) 63 (19/30) 99 (147/148) 93 (166/178)

7 (73/74) 92 (11/12) 97 (73/75) 96 (84/87)

8 (66/75) 77 (31/40) 98 (66/67) 91 (96/107)

0 (52/52) 100 (6/6) 100 (52/52) 100 (58/58)

2 (128/130) 77 (37/48) 98 (128/130) 98 (165/169)

4 (29/31) 89 (17/19) 100 (29/29) 96 (46/48)

6 (32/37) 71 (11/14) 89 (32/36) 83 (44/53)

6 (68/79) 61 (17/28) 96 (68/71) 83 (85/103)

4 (85/115) 39 (16/46) 99 (85/86) 77 (101/132)

2 (56/61) 29 (2/7) 98 (56/57) 91 (58/64)

8 (128/131) 92 (35/38) 96 (128/133) 95 (162/170)

4 (30/32) 85 (11/13) 97 (30/31) 93 (41/44)6 (49/51) 80 (8/10) 94 (49/52) 92 (57/62)5 (110/116) 73 (16/22) 97 (110/113) 93 (126/135)

2 (1,294/1,399) 72.5 (296/408) 97.4 (1,294/1,328) 91.9 (1,590/1,729

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n 2006 by Rixe et al,17 the rate of coronary stents classifiedn the other studies as not evaluable because of poor imageuality ranged from 0% to 19.5%.5–8,17–30 The overall fea-ibility of MDCT was 90.4%.

The main reasons for impaired image quality and stentssessment were high-density artifacts generated by metal-ic stent struts, followed by motion artifacts related to pa-ients’ inability to hold their breath or refrain from chestovement, misalignment of slices due to heart rate varia-

ion or premature beats, and blooming effects due to vesselalcifications.

Some investigators evaluated stent and patient character-stics that may have a negative impact on image quality with

DCT. A number of stent characteristics, such as diameter,ype, strut thickness, material, cell shape, and the complex-ty of the interventional procedure (bifurcation or overlap-ing stenting) were evaluated. Almost all studies showedhat stent diameter plays a major role in the evaluation of thetent lumen. In a study performed at our institution, weound a significant increase in evaluability in stents withiameters �3 mm compared to those with diameters �3m. Accordingly, the mean diameter of evaluable stentsas significantly larger than that of nonevaluable stents.28

ixe et al17 confirmed these findings, showing that the meaniameter of evaluable stents was significantly larger than theiameter of nonevaluable stents (3.28 vs 3.03 mm). Twotudies performed by Oncel et al,19,25 the first with 64-slice

DCT19 and the second with DSCT,25 and a study byarbone et al26 showed a significant difference in the per-

igure 3. (A,B) Multidetector computed tomographic multiplanar reconstrucenerated by metallic stent struts (arrows) that prevent the correct evaluultiplanar reconstructions of 2 overlapping stents implanted in the proxima

ate variations during the scan.

entage of evaluable stented segments between �3-mm- d

iameter stents and �3-mm-diameter stents. In a study byflederer et al,30 the mean diameter of stents classified asssessable (3.30 mm) was significantly higher than that oftents classified as nonassessable (3.0 mm); in the sametudy, multivariate analysis showed that diameter was sig-ificantly associated with stent assessability. Finally,ugliese et al,24 using DSCT, demonstrated that all stentslassified as not evaluable had diameters �2.75 mm, con-rming the key role of stent size.

Two studies evaluated the effect of strut thickness ontent evaluability, demonstrating a significant reduction inrtifacts with thinner stents (�100 �m).17,28 The influencef stent material on image quality was assessed by Oncel etl,25 who found that the cobalt-chromium alloy producedewer metal artifacts than did other materials.

The finding that stent luminal visibility greatly variesepending on the stent type was also reported in an in vitrotudy by Maintz et al.37 Using a 64-slice MDCT, theyhowed that all types of stents made of cobalt-chromiumlloy had luminal visibility �66%. In another in vitro studyerformed with DSCT and using all 4 different type ofernel reconstruction protocols, Maintz et al40 confirmedhe influence of stent material on image quality, showinghat the mean luminal diameter was highest with stentsade using magnesium (WE43) and lowest with thoseade using tantalum. A study by Schuijf et al8 showed that

mage quality was significantly lower in overlapping stentshan in stents without overlap. Finally, no significant dif-erence was found between stents with open or closed cell

the left anterior descending coronary artery showing high-density artifactsf the proximal stent lumen. (C,D) Multidetector computed tomographiccoronary artery showing artifacts due to slice misalignment caused by heart

tions ofation ol right

esigns in the 2 studies that evaluated this feature.20,28

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Two studies performed with 64-slice MDCT showedigher feasibility when the heart rate during the scan was60 versus �60 beats/min.17,28 In our study, heart rate was

lso a predictor of better feasibility on multivariate analysis.lso, the study by Schuijf et al8 confirmed this finding,

howing that the mean heart rate in the interpretable stentsas significantly lower than that in the noninterpretable

tents (55 vs 72 beats/min). In contrast, the 2 studies per-ormed with DSCT showed no significant difference be-ween �70 and �70 beats/min during the scan. This wasikely due to the increased temporal resolution of this typef scanner in comparison to single-source scanners.24,25

In conclusion, concerning stent characteristics that maynfluence stent image quality, the role of stent diameter isritical, as shown by almost all studies included in thiseview. The role of strut thickness is still controversial, withtudies in which this parameter affected stent assessmentnd other studies that found no impact. However, it ismportant to note that in the latter studies, the cutoff foristinguishing thin from thick strut stents was higher (110s 120 or �140 vs �140 �m).8,30 The role of stent materialas been demonstrated by in vitro studies and confirmed byhe study of Oncel et al.25 Finally, high-density artifactsenerated by metallic stent struts are more evident in over-apping stents.18 Concerning patient characteristics, heartate during the scan has a fundamental role on stent imageuality, as in the case of native coronary arteries.8,17,28 Figure

igure 4. (A) MDCT (volume rendering) of 2 stents implanted at the bifuranch (M1). (B) Multiplanar reconstruction shows stent patency. (C) Multiplanar reconstruction showing moderate ISR of the proximal stent s

oronary artery (RCA) subocclusion distal to the stent. (E) MDCT (volumeescending coronary artery (LAD), the proximal LCx, and the intermediateM � left main coronary artery.

shows 2 cases of nonevaluable stents due to high-density M

rtifacts generated by metallic stent struts and to the mis-lignment of slices related to heart rate variability.

Diagnostic accuracy of 64-slice MDCT and DSCT: The006 consensus of the American Heart Association deemed

between the left circumflex coronary artery (LCx) and the first marginalvolume rendering) of 1 stent in the proximal right coronary artery. (D)t (arrow), severe ISR of the distal stent segment (arrowhead), and rightng) showing 3 stents implanted at the trifurcation between the left anterior(IR). (F) No evidence of ISR is visible with multiplanar reconstruction.

able 5ntraobserver and interobserver agreement for multidetector computedomographic evaluation of in-stent restenosis reported in the studieserformed with older-generation scanners, 64-slice computedomography, and dual-source computed tomography

tudy Journal IntraobserverAgreement (�)

InterobserverAgreement (�)

ademartiri et al (2005)2 AJC NR 0.75aspar et al (2005)12 JACC NR 0.88an Mieghem et al (2006)18 Circ 0.84 0.72ist et al (2007)5 AR NR 0.53efer et al (2007)15 ER 1 0.86hara et al (2007)20 JACC 0.92 0.85arrabba et al (2007)22 AJC 0.82 0.78oon et al (2007)14 IMG NR 0.90edeschi et al (2008)16 JCM 0.85 0.80ugliese et al (2008)24 Heart 0.87 0.78ncel et al (2008)25 AJR 0.96 0.93arbone et al (2008)26 ER NR 0.79ndreini et al (2009)28 AJC NR 0.81

Abbreviations as in Tables 1 and 2.

rcationDCT (egmenrenderiramus

DCT unsuitable for coronary stent evaluation (class III,

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evel of evidence C).41 This statement was based on studieserformed with 16- and 40-slice scanners.2,12–16 Studieserformed with the newer 64-slice scanners, thanks to theirigher spatial and temporal resolution, showed high feasi-ility and diagnostic accuracy for the evaluation of coronary

igure 5. (A,B) Multidetector computed tomographic multiplanar reconstruoronary artery. (C,D) ICA of the same artery. (E) IVUS image of the naithin the stent lumen (from 12 to 6). (F) Corresponding short-axis multiardiol.28

igure 6. Multidetector computed tomographic multiplanar reconstructiomplantation of a polymeric bioabsorbable everolimus-eluting stent, and attructure is not radiopaque. Note the radiopaque markers that are embedd

tents and the diagnosis of ISR.5–8,17–30 w

Table 4 lists the diagnostic accuracy of 64-slice MDCTnd DSCT in the detection of ISR in evaluable stents. Theverall diagnostic accuracy of stent evaluation on MDCTas 91.9%. Of note, totally occluded stents were more

asily recognized by MDCT. Indeed, all total occlusions

owing ISR (arrows) of a bare-metal stent implanted in the proximal rightrestenotic site showing neointimal hyperplasia as hypoattenuating tissue

r computed tomographic image. Reproduced with permission from Am J

e left anterior descending coronary artery at baseline (PRE), after theup (FU). The stented vessel contour is clearly delineated because the stente stent ends (arrows). Courtesy of Professor Patrick W. Serruys.

ction shrrowestdetecto

n of thfollow-

ere correctly detected in these studies. Four studies

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howed that stent diameter, besides reducing evaluability ofhe stent lumen, has a critical impact on diagnostic accu-acy.24,26–28 This may have a negative impact on the evalu-tion of stents deployed in distal vessels or side branches. Inur study,28 diagnostic accuracy parameters were higher in3-mm-diameter stents compared to �3-mm-diameter

tents, with significant differences in specificity, positiveredictive value, and negative predictive value. Moreover,n multivariate analysis, stent diameter was the only pre-ictor of better diagnostic accuracy. Similarly, in �3-mm-iameter stents compared to �3-mm-diameter stents, accu-acy was significantly higher in the study by Carbone et al,26

ensitivity and negative predictive value were higher in atudy by Manghat et al,27 and sensitivity was also higher inhe study by Pugliese et al.24

Two studies showed a significant role of strut thicknessn the ability of MDCT to detect ISR.26,28 With regard totent material, our study showed diagnostic accuracy of00% for all parameters and higher sensitivity for cobalt-hromium alloy stents compared to stainless steel stents,robably because of their smaller strut thickness (60 to 80m).28

A study by Nakamura et al7 showed higher diagnosticccuracy in stents located in the proximal left anterior de-cending coronary artery and in patients with low bodyass indexes.Finally, the complexity of the interventional procedure

bifurcation or overlapping stenting) may affect the accu-acy of ISR detection. Indeed, Pugliese et al24 showed lowerpecificity and positive predictive value in patients treatedith complex procedures. Our study confirmed this finding.his is likely due to the larger amount of metal at the ostiumf the side branches and at overlapping sites in complexrocedures. No difference in diagnostic accuracy in relationo index vessel, lesion location, stent cell shape, and heartate during the scan was found by any study.

The ability of MDCT in determining the significance ofoderate ISR is limited.21 Indeed, intravascular ultrasound

IVUS) and fractional flow reserve may better assesshether this type of lesion is of clinical significance. Figure 4

hows 3 case examples of coronary stent evaluation byDCT. Table 5 lists intraobserver and interobserver agree-ent values for multidetector computed tomographic eval-

ation of ISR reported in the studies included in this review.ith the exception of Rist et al5 study, the � coefficient was

ood for intraobserver (0.82 to 1.00) and interobserver (0.72o 0.93) agreement.2,5,12,14–16,18,20,22,24–26,28

Only 2 studies compared MDCT to IVUS for the quan-itative analysis of coronary stents.18,28 In the first study,an Mieghem et al18 analyzed the diagnostic accuracy for

SR detection of 16-slice MDCT in 27 patients and of4-slice MDCT in 43 patients scheduled for follow-up ICAfter left main coronary artery stenting. In a subgroup of 50atients, IVUS evaluation was also performed. These inves-igators demonstrated a good correlation between MDCTnd IVUS measurements of stent area and diameter (corre-ation coefficients of 0.73 and 0.78, respectively), with aignificant overestimation of stent diameter by MDCT onland-Altman analysis (mean difference 0.22 � 0.44 mm).

n the 11 patients with sufficient luminal narrowing to
ompare IVUS to MDCT, the correlations were moderate (
or quantifying the degrees of diameter and area stenosisr � 0.65 and r � 0.55 respectively).

In our study, we analyzed the diagnostic accuracy of4-slice MDCT for the detection of ISR in 100 patientscheduled for ICA because of suspected ISR.28 A subgroupf 24 patients underwent IVUS evaluation. We found aignificant correlation between MDCT and IVUS measure-ents of stent diameter and area (r � 0.75 and r � 0.76

espectively) and a good correlation of stent diameter andrea at the maximum luminal narrowing site in the presencef ISR (r � 0.92 and r � 0.82, respectively). The underes-imation of stent dimension by MDCT compared to IVUSeasurements (for diameter, mean difference 0.22 mm, p �

.012; for area, mean difference 1.48 mm2, p �0.0001) wasikely due to the blooming effect of metallic stent struts andarge calcifications. This artifact makes the stented vesselrtificially thicker on MDCT, subtracting a small portion ofhe stent lumen from the measurement. In contrast, theinimal underestimation of measurements performed at theaximal luminal narrowing site by MDCT compared to

VUS (for diameter, mean difference 0.01 mm, p � 0.42;or area, mean difference 0.72 mm2, p � 0.01) was likelyelated to the small luminal dimension that is proximal tohe imaging technique resolution.

The current limitations of the method do not affect thessessment of ISR percentage narrowing on MDCT. Indeed,he correlation between the percentage of stenosis calcu-ated by the 2 methods using the ratio of diameters and areasas high (r � 0.94 for diameter percentage of stenosis, r �.90 for area percentage of stenosis). Thus, this study indi-ates that 64-slice computed tomography may be a reliableodality for quantitative measurements of coronary stents,

ven when evaluation is not limited to the left main coro-ary artery. The better results of our study compared tohose reported by Van Mieghem et al18 in terms of theorrelation between the percentage of stenosis calculated byDCT and IVUS may be explained by the use of an

ld-generation, 16-slice scanner in a subgroup of their pa-ients. In conclusion, a slight underestimation of lesioneverity is the more frequent finding with MDCT. Figure 5hows a case of ISR detected by MDCT and confirmed byCA and IVUS.

iscussionClinical implications: The noninvasive evaluation of

oronary stents is an attractive clinical challenge. Indeed,CA is not an ideal routine follow-up strategy because of themall risk for complications associated with its invasiveature and significant cost. However, the widespread use ofrug-eluting stents in ever more complex lesions, multives-el coronary artery disease, and critical anatomic locationsnd the knowledge that ISR has a negative impact on theong-term survival of patients42 underscore the need for aeliable diagnostic technique to assess stent patency. Com-ared to ICA, MDCT is a noninvasive approach definitelyreferred by patients, with a shorter preparation time thatoes not expose personnel to radiation. The results of recenttudies have shown moderate sensitivity and very goodpecificity,43 suggesting that stent evaluation by MDCT toule out ISR still has some problems. Stent-related factors
thick struts, stent size, and stent material) and scanning

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ethods (number of detectors, kernel) have a negative im-act on diagnostic performance. Nevertheless, the sensitiv-ty and specificity of MDCT are superior to those reportedith ECG stress testing44 and myocardial perfusion imagingith nuclear techniques and contrast echocardiography.45,46

oreover, we must acknowledge that multidetector com-uted tomographic technology is advancing very rapidly,ogether with the levels of experience at different centers.ombined technologies such as positron emission tomog-

aphy/computed tomography and single photon-emissionomputed tomography/computed tomography that associatenatomic and functional evaluation of ISR may furthermprove diagnostic accuracy. At the same time, stent ad-ancements have brought to the clinical arena new devicesith thinner struts and innovative materials that alreadyemonstrated to significantly reduce the proportion of stentsot assessable using MDCT. A recent report of the clinicalfficacy and safety of a polymeric bioabsorbable drug-elut-ng stent (Figure 6)47 is another indication that the metalrtifacts caused by previous stents may be overcome byechnology evolution. Finally, the significant reduction ofadiation exposure obtained by new scan acquisition proto-ols is minimizing a clear disadvantage associated withDCT.

Future directions: The most recent generation of 256-nd 320-slice multidetector computed tomographic scan-ers, introduced at the end of 2008, can greatly reduce theime for data acquisition and, thus, breath-hold duration,vercoming the issue of breath holding and further reducingotion artifacts and those related to heart rate variation

uring the scan. Moreover, the newest high-definition scan-ers, which have spatial resolution similar to that of ICA,ay significantly reduce high-density artifacts generated byetallic stent struts, allowing correct evaluations even of

mall-diameter stents and stents implanted in coronary ves-els with large calcifications. Finally, the significant reduc-ion of x-ray doses from the new scanners will likely in-rease the use of this imaging modality for the follow-up ofatients treated with coronary stenting.

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multidetector computed tomography coronary angiography for the assessment of coronary in-stent...

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