Follow-Up of Coronary Artery Bypass Graft Patency byMultislice Computed Tomography

Emilio Chiurlia, MD, Mila Menozzi, MD, Carlo Ratti, MD, Renato Romagnoli, MD,and Maria Grazia Modena, MD

Fifty-two consecutive asymptomatic patients with atotal of 166 bypass grafts were investigated by 16-slice computed tomography (CT) 15 � 5 days beforeinvasive coronary angiography. Overall, 165 grafts(99.4%) were assessable with multislice CT (MSCT).Coronary angiography showed that 111 grafts (67%)were patent and 54 (33%) were occluded. Of thepatent grafts, 22 had high-grade stenoses. MSCT cor-rectly classified 111 grafts as patent and 54 as oc-cluded. Of the patent grafts, 16-slice CT correctlydetected 21 bypass stenoses (95%). These resultsyielded 100% sensitivity and specificity of 16-slice CTfor detecting bypass grafts occlusion and 96% sensi-tivity and 100% specificity for detecting high-gradestenoses in patent grafts. �2005 by Excerpta Med-ica Inc.

(Am J Cardiol 2005;95:1094–1097)

Coronary angiography is the gold standard to eval-uate the status of grafts, but it is an invasive

procedure that includes x-ray exposure, requires hos-pitalization, and includes a (small) risk for complica-tions.1,2 These disadvantages make use of coronaryangiography less attractive as a diagnostic method forthe evaluation of early and late postoperative graftspatency. Electron beam computed tomography (CT)and magnetic resonance imaging have been investi-gated for noninvasive coronary artery and bypass graftimaging.3–5 However, neither of these approaches hasresulted in an accurate diagnostic procedure that iswidely accepted. Multislice CT (MSCT) with 4 rowsof detectors has shown promising results, despite alarge percentage of nonassessable bypass grafts due toinadequate spatial and temporal resolution and to ascan time of approximately 40 seconds.6 Our aim wasto compare the newest generation of cardiac MSCTscanners that permit the simultaneous acquisition ofup to 16 submillimeter slices per rotation, with con-ventional angiography for the evaluation of graft oc-clusion and the presence of significant coronary ste-noses.

• • •From January to May 2004, 52 consecutive asymp-

tomatic patients (45 men and 7 women; mean age 63years, range 35 to 84) with a total of 166 bypass grafts

(117 venous and 49 arterial grafts) were investigatedby 16-slice CT 15 � 5 days before invasive coronaryangiography. The mean time between bypass opera-tion and MSCT investigation was 95 months (range 36to 168). Only patients in sinus rhythm and stableclinical condition, without implanted pacemakersand contraindications to the administration of iodin-ated contrast agent, were included in the study. Allpatients gave their written informed consent, andthe ethics committee of our university approved thestudy protocol.

Each patient was placed within the gantry of amultidetector row CT scanner (LightSpeed Ultra 16,GE Healthcare, Waukesha, Wisconsin) in a supineposition. Leads were attached for simultaneous elec-trocardiographic and image recording, which is nec-essary for inter-related image reconstruction. Our im-aging protocol consisted of the following steps. First,a noncontrast coronal view of the chest was obtainedto determine the position of the heart, define the scanvolume for further imaging, and recognize eventualcoronary calcification. Then, the patient contrast agenttransit time was measured from the injection into aperipheral vein of a 20-ml bolus of contrast agent(Iomeron 350, Bracco Ltd., Milan, Italy) to the in-crease in density within the ascending aorta. At last,the volume data set for coronary bypass imaging wasacquired in spiral mode with the simultaneous acqui-sition of 16 parallel slices using the algorithm of 180°multislice cardiac interpolation, during the intrave-nous injection of 120 ml of contrast agent at a rate of3.5 ml/s. Scan parameters were as follows: detectorcollimation 16 � 0.625, tube current 440 mA, andtube voltage 120 kVp. Depending on patient heart

From the Departments of Cardiology and Radiology, University ofModena and Reggio Emilia, Policlinico Hospital, Modena, Italy. Dr.Chiurlia’s address is: Via del Pozzo 71, 41100 Modena, Italy.E-mail: emiliochiurlia@virgilio.it. Manuscript received October 13,2004; revised manuscript received and accepted December 20,2004.

FIGURE 1. Volume rendering images before (A) and after (B) theautomatic removal of large cardiac chambers. Three patentgrafts, a left IMA (LIMA) graft and 2 saphenous vein grafts(SVGs), are visible simultaneously.

1094 ©2005 by Excerpta Medica Inc. All rights reserved. 0002-9149/05/$–see front matterThe American Journal of Cardiology Vol. 95 May 1, 2005 doi:10.1016/j.amjcard.2004.12.067

frequency, the scanner adapted table speed and as aconsequence the spiral pitch. Patients with heart rates�65 beats/min received metoprolol 5 to 10 mg intra-venously immediately before MSCT examination. Allimages were acquired during inspiratory breath hold(20 to 25 seconds) and reconstructed with a slicethickness of 0.6 mm and an interslice gap of 0.6 mmusing retrospective electrocardiographic gating at dif-ferent R-to R-wave intervals (from 35% to 95% inincrements of 10%). Finally, images were transferredto an offline dedicated Advantage Workstation (ver-sion 4.1) equipped with CardIQ software (GE Health-care) for image editing. For each graft and coronarytree segment, we selected the R- to R-wave interval

that allowed the best image quality.MSCT data sets were displayed in a 3-di-mensional volume rendering fashion andwith multiplanar reformation. MSCT im-ages were evaluated by 2 independent ra-diologists blinded to the conventional cor-onary angiographic findings.

Cardiac catheterization and contrast-enhanced x-ray coronary angiographywere done according to standard tech-niques. Multiple views of the coronaryarteries were obtained and stored on aCD-ROM.

The MSCT images were evaluatedby 2 independent radiologists experi-enced in cardiac CT and blinded to theangiographic results. Bypass grafts wereconsidered occluded if they were notidentified in cross-sectional images and3-dimensional images. Significant ste-noses of bypass grafts were defined asluminal diameter stenoses �50% on thebasis of cross-sectional images and mul-

tiplanar 3-dimensional images. Analysis of all angio-grams was performed by 2 independent experiencedcardiologists, who scored arterial and venous grafts byflow, in accordance with the system used in theThrombolysis In Myocardial Infarction Trial.7 Grades0 or 1 were taken as occluded grafts and all others aspatent grafts. A lesion was considered to be a signif-icant stenosis if the mean diameter reduction in 2orthogonal planes was �50%.

The sensitivity, specificity, and accuracy for thedetection of bypass graft patency and the presence ofsignificant stenosis was evaluated using conventionalcontrast angiography as a reference. The concordancebetween observers for the detection of coronary ste-nosis by MSCT was calculated using Cohen’s � value.

All patients completed MSCT examinations with-out complications. The average investigation time was15 minutes, although reconstruction took a further 20minutes. The average heart rate during the scan was 58� 6 beats/min. The total scan time was 19 � 2seconds. Overall, 165 of the possible 166 grafts wereassessable with MSCT. One graft was excluded fromanalysis because of numerous metal clips along itscourse. Of the 165 assessable bypass grafts, 117(71%) were saphenous vein grafts; 46 (28%) wereinternal mammary artery (IMA) grafts, including 37left IMA grafts and 9 right IMA grafts; and 2 were radialartery grafts. Of the 117 saphenous vein grafts, 47 wereto the left anterior descending artery, 25 to the obtusemarginal artery, 29 to the right coronary artery, 11 to thediagonal branch, 7 to the left circumflex coronary artery,and 7 to the posterior interventricular branch. Of theIMA grafts, there were 5 sequential bypasses to thediagonal branch and left anterior descending coronaryartery; the remaining were single grafts to the leftdescending anterior artery in 30 patients, to the diag-onal branch in 9 patients, and to the right coronaryartery in 2 patients. The 2 radial artery grafts were tothe obtuse marginal artery. Coronary angiography of

FIGURE 2. (A) A volume rendering image shows the occlusion (arrow) of saphe-nous vein grafts. (B) In the postcontrast transverse image, the occlusion of the sa-phenous vein grafts (arrow) is clearly seen.

FIGURE 3. A volume rendering image shows 2 significant steno-ses (arrows) in the middle segment of a saphenous vein graft tothe left anterior descending coronary artery; farther up, stentplacement (asterisk) is shown.

BRIEF REPORTS 1095

the bypass grafts showed that 111 bypass grafts (67%)were patent and that 54 (33%) were occluded (42saphenous vein grafts, 10 IMA grafts, and 2 radialartery grafts). Of the patent grafts, 89 were free ofsignificant stenoses, and 22 (19 saphenous vein grafts,2 left IMA grafts, and 1 right IMA graft) had high-grade stenoses. In 15 patients, the stenosis was local-ized in the graft itself, and in 7 patients, the stenosiswas in the region of the distal anastomosis. MSCTcorrectly classified 111 grafts as patent (Figure 1) and54 as occluded (Figure 2). Of the patent grafts, MSCTcorrectly detected 21 of the 22 bypass stenoses (Fig-ures 3 and 4); the only false-negative stenosis waslocalized at distal anastomosis. These results yieldedsensitivity and specificity of 100% of MSCT for de-tecting bypass graft occlusion and sensitivity of 96%and specificity of 100% for detecting high-grade ste-noses in patent grafts. The interobserver agreementbetween the 2 readers was excellent (� � 0.82, 95%confidence interval 0.76 to 0.87).

• • •The newest generation of MSCT scanners permits

the simultaneous acquisition of up to 16 submillimeterslices per rotation, and these scanners have greaterspatial and temporal resolution compared with previ-ous scanners.8 So far, only 1 study has used this newtechnology compared with conventional angiographyfor bypass evaluation, yielding images of adequatequality in all examinations.9 Compared with the datareported by Ropers et al,10 in this study, the number ofbypasses that could be evaluated increased from 62%to 74%, combined with improved diagnostic accuracyfor the detection of the stenosis. Our study confirmsthe excellent image quality of the new scanners. Only1 of the 166 grafts was not eligible for analysis be-cause of numerous metal clips along its course.

Despite these encouraging results, several limita-tions of our study need to be addressed. First, to obtaingood image quality, all patients with heart rates �65

beats/min received � blockers intravenously immedi-ately before the MSCT examination. This strategy isnot applicable to patients with chronic obstructivepulmonary disease. However, this is a minor limita-tion that concerns particularly native coronary arter-ies; bypass grafts, because of their size and relativeimmobility, are less affected by heart rate. In ourstudy, few grafts had extensive calcific deposits ormetal artifacts. The lower frequency of clip artifacts inour study may have also been influenced by differentsurgical techniques. Finally, we need to underline themajor drawback of retrospectively electrocardiograph-ically gated MSCT data acquisition: its large radiationexposure, which has been reported at between 6.7 and13.0 mSv.11 However, by reducing the tube outputduring heart phases that are not likely to be targeted bythe electrocardiographically gated reconstruction, adose reduction of 48% is possible.12

Even with these technical limitations, our studyshows that the newest generation of MSCT scannersallows the very accurate assessment of graft patencyand provides relevant information concerning thepresence of significant obstructive disease in bypassgrafts.

1. Ryan TJ. The coronary angiogram and its seminal contributions to cardiovas-cular medicine over five decades. Circulation 2002;10:752–756.2. Kennedy JW. Complications associated with cardiac catheterization and an-giography. Cathet Cardiovasc Diagn 1982;8:5–11.3. Achenbach S, Moshage W, Ropers D, Nossen J, Bachmann K. Noninvasive,three-dimensional visualization of coronary artery bypass grafts by electron beamtomography. Am J Cardiol 1997;79:856–861.4. Rubinstein RI, Askenase AD, Thickman D, Feldman MS, Agarwal JB, HelfantRH. Magnetic resonance imaging to evaluate patency of aortocoronary bypassgrafts. Circulation 1987;76:786–791.5. Langerak SE, Vliegen HW, de Roos A, Zwinderman AH, Jukema JW, KunzP, Lamb HJ, van Der Wall EE. Detection of vein graft disease using high-resolution magnetic resonance angiography. Circulation 2002;105:328–333.6. Engelmann MG, von Smekal A, Knez A, Kurzinger E, Huehns TY, Hofling B,Reiser M. Accuracy of spiral computed tomography for identifying arterial andvenous coronary graft patency. Am J Cardiol 1997;80:569–574.

FIGURE 4. Curved multiplanar reconstruction (A) and corresponding conventional coronary angiography (B) confirm the presence ofmultiple stenoses (arrows) in the middle segment of the venous graft; farther down, stent placement (asterisk) is shown.

1096 THE AMERICAN JOURNAL OF CARDIOLOGY� VOL. 95 MAY 1, 2005

7. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT,Francis CK, Hillis D, Ludbrook P. Thrombolysis In Myocardial Infarction (TIMI)Trial, phase I: a comparison between intravenous tissue plasminogen activatorand intravenous streptokinase. Clinical findings through hospital discharge. Cir-culation 1987;76:142–154.8. Pannu HK, Flohr TG, Corl FM, Fishman EK. Current concepts in multi-detector row CT evaluation of the coronary arteries: principles, techniques.Radiographics 2003;23:S111–S125.9. Kuettner A, Trabold T, Schroeder S, Feyer A, Beck T, Brueckner A, Heus-chmid M, Burgstahler C, Kopp AF, Claussen CD. Noninvasive detection ofcoronary lesions using 16-detector multislice spiral computed tomography tech-nology: initial clinical results. J Am Coll Cardiol 2004;44:1230–1237.

10. Ropers D, Ulzheimer S, Wenkel E, Baum U, Giesler T, Derlien H, MoshageW, Bautz WA, Daniel WG, Kalender WA, et al. Investigation of aortocoronaryartery bypass grafts by multislice spiral computed tomography with electrocar-diographic-gated image reconstruction. Am J Cardiol 2001;88:792–795.11. Hunold P, Vogt FM, Schmermund A, Debatin JF, Kerkhoff G, Budde T,Erbel R, Ewen K, Barkhausen J. Radiation exposure during cardiac CT: effectivedoses at multi-detector row CT and electron-beam CT. Radiology 2003;22:145–152.12. Jakobs TF, Becker CR, Ohnesorge B, Flohr T, Suess C, Schoepf UJ, ReiserMF. Multislice helical CT of the heart with retrospective ECG gating: reductionof radiation exposure by ECG-controlled tube current modulation. Eur Radiol2002;12:1081–1086.

Do Statins Increase the Risk ofIdiopathic Polyneuropathy?

Jeffrey L. Anderson, MD, Joseph B. Muhlestein, MD, Tami L. Bair, BS, Steven Morris,Aaron N. Weaver, MD, Donald L. Lappé, MD, Dale G. Renlund, MD,

Robert R. Pearson, BS, Kurt R. Jensen, MS, and Benjamin D. Horne, MStat, MPH

A recent European case-control study suggested thatstatins increase the risk for polyneuropathy, a rare butserious neurologic condition. This risk was assessed in272 patients with idiopathic polyneuropathy and 1,360matched controls in the Intermountain Health Care elec-tronic database. It was found that statin use beforediagnosis was not significantly greater in patients thancontrols (odds ratio 1.30, 95% confidence interval 0.3 to2.1, p � 0.27), nor were doses different between pa-tients and controls. �2005 by Excerpta Medica Inc.

(Am J Cardiol 2005;95:1097–1099)

Hydroxymethylglutaryl CoA reductase inhibitors (sta-tins) have become the dominant lipid-lowering

pharmacotherapy.1,2 Accumulating clinical trial datasupport the benefit of statins for chronic secondary andhigh-risk primary prevention.3–5 Statins recently havebeen shown to benefit patients when begun early afteracute coronary syndromes.6,7 Simvastatin is now avail-able in the United Kingdom from pharmacies on a non-prescription basis. Recent National Cholesterol Educa-tion Program Adult Treatment Panel III guidelines havebeen revised to allow the targeting of lower low-densitylipoprotein cholesterol levels (i.e., �70 mg/dl) in high-risk patients.8,9 Thus, statin use and doses are expected tocontinue to increase through prescription and futureover-the-counter use.

• • •With widespread statin use, there is growing con-

cern about rare but severe adverse reactions (e.g.,myopathy, rhabdomyolysis) as well as less severe butmore common reactions (e.g., low-grade myopathy

with normal creatine kinase levels).2,10,11 A recentDanish case-control study12 linked statin use withidiopathic polyneuropathy (IPN), which has not beenpreviously recognized as a potential hazard of statintherapy. This study followed smaller, earlier reports ofan association of neuropathy with statin use.13–18 Itwas suggested that statins might induce IPN by alter-ing nerve function by excessive depletion of choles-terol, a ubiquitous component of nerve cell mem-branes.12 Statins also co-inhibit the synthesis ofubiquinone, a key mitochondrial respiratory chain en-zyme, potentially disturbing neuronal energy produc-tion and use, inducing neuropathy.15

Polyneuropathy is not listed as a potential adversereaction to statin therapy in current product labeling,nor was it recognized as a potential side effect by arecent expert clinical advisory on statin safety.2 Thus,the finding of an association of statins with IPN, iftrue, might importantly affect the assessment of statinsafety as well as an understanding of the pathophysi-ologic mechanisms of IPN. Therefore, we tested thehypothesis that statin use predisposes to IPN in theIntermountain Health Care (IHC) database.

After receiving institutional and corporate consentfor the study, a search of the IHC electronic databasewas performed to find patients with an initial diagno-sis of IPN within the past 4 years. The IHC databasecontains records of all admissions to any of the 23IHC hospitals, located in Utah and its neighboringstates. It also contains records of outpatient visits tohospital-affiliated IHC clinics and physicians, and, inrecent years, has provided a link to prescription infor-mation from IHC pharmacies, which are preferentiallyused by IHC health insurance plan enrollees (1.2 millioncovered lives). The following codes, registered fromApril 2000 to April 2003, were sought: progressiveidiopathic neuropathy (International Classification ofDiseases, 9th Revision, codes 356.4 and 356.8), drug-induced polyneuropathy (code 357.6), or unspecifiedIPN (code 356.9). To eliminate cases of possible sec-ondary polyneuropathy, patients were excluded if they

From the Cardiovascular Department, LDS Hospital, IntermountainHealth Care; and the University of Utah School of Medicine, Salt LakeCity, Utah. This study was partially supported by the Deseret Founda-tion, Salt Lake City, Utah. Dr. Anderson’s address is: LDS Hospital,Cardiology Division, 8th Avenue and C Street, Salt Lake City, Utah84143. E-mail: jeffrey.anderson@ihc.com. Manuscript received Oc-tober 4, 2004; revised manuscript received and accepted December27, 2004.

1097©2005 by Excerpta Medica Inc. All rights reserved. 0002-9149/05/$–see front matterThe American Journal of Cardiology Vol. 95 May 1, 2005 doi:10.1016/j.amjcard.2004.12.068