Potential intrinsic error of noninvasive coronary angiography

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1 Journl of Crdiovsculr Mgnetic Resonnce (2005) 7, Copyright D 2005 Tylor & Frncis Inc. ISSN: print / X online DOI: /JCMR CORONARY ANGIOGRAPHY Potentil intrinsic error of noninvsive coronry ngiogrphy SEBASTIAN KELLE, M.D.,* JÜRGEN HUG, M.D., UWE KÖHLER, PH.D., ECKART FLECK, M.D., nd EIKE NAGEL, M.D. Deprtment of Internl Medicine/Crdiology, Germn Hert Institute Berlin, Berlin, Germny Purpose. With current noninvsive techniques compromises hve to be ccepted for coronry imging, e.g., prtil coverge of the coronry rtery tree. The im of the study ws to estimte the potentil intrinsic error of prtil coverge from dtbse of invsive ngiogrms. Methods nd Results. The locliztion nd severity of coronry rtery stenoses nd, if percutneous coronry intervention (PCI) ws performed, the blloon nd stent size were extrcted from lrge dtbse of 21,335 selective coronry ngiogrms. Of stenoses with 50% dimeter reduction, 31.4% were locted in distl segments nd minor side brnches, constituting 28.8% of interventionl tretment. In 5% of ptients undergoing their first invsive ngiogrm, the most proximl relevnt stenosis ws found in distl segment or minor side brnch. Most interventions (83.5%) were performed in min coronry rtery segments. Conclusion. Coronry rtery stenoses were found nd interventionl tretment performed in ll coronry segments. Therefore, noninvsive coronry imging of only proximl nd medil segments nd mjor side brnches is n indequte strtegy for complete dignosis or s guide to therpeutic decisions. However, the currently vilble noninvsive techniques llow the detection of relevnt stenoses in 95% of ptients with suspected coronry rtery disese (CAD) to prepre for further invsive dignostic nd therpeutic plnning. Key Words: Mgnetic resonnce imging; Computed tomogrphy; Coronry disese; Angiogrphy 1. Introduction to quntify loss of coronry rtery stenoses by noninvsive coronry ngiogrphy. The current stndrd of reference in the dignosis of CAD is invsive coronry ngiogrphy, which is, by definition, invsive, requires the dministrtion of contrst gents, nd 2. Methods is burdened with rdition. Despite the vilbility of noninvsive tests to identify 2.1. Ptients ptients with coronry rtery disese, lrge number of The locliztion nd severity of coronry rtery stenoses nd, ptients referred to coronry ngiogrphy re found not to if PCI ws performed, the blloon nd stent size were hve significnt coronry rtery stenoses (1 3). extrcted from lrge dtbse of 21,335 selective coronry Mgnetic resonnce coronry ngiogrphy (MRCA) (4 ngiogrms from 14,473 consecutive ptients. Of these, 4,138 7), electron-bem computed tomogrphy (EBCT) (8, 9), (28.6%) women nd 10,335 (71.4%) men (63.7 ± 9.7 yers; nd multislice computed tomogrphy (MSCT) (10 12) rnge 15 to 98 yers), who underwent crdic ctheteriztion hve been suggested s noninvsive imging tools for erly t the Germn Hert Institute Berlin (= group A) from dignosis nd monitoring of coronry rtery disese. November 1997 through October 2003 were retrospectively reviewed. However, since these techniques hve lower sptil nd temporl resolution in comprison to invsive ngiogrphy Indictions to perform coronry ctheteriztions were in nd my only prtilly cover the coronry rtery tree, precise ccordnce with the relevnt guidelines (13). knowledge of locliztion nd severity of coronry rtery PCI with or without stent implnttion ws performed in stenoses could be helpful to optimize interprettion of 12,280 ptients, 3,757 women (30.6%), nd 8,523 (69.4%) men. noninvsive ngiogrms. The totl group ws nlyzed for: sex, coronry rtery The im of the current report is to extrct informtion from stenosis locliztion nd dimeter reduction in percent, locliztion of PCI, nd luminl size of the blloon or stent used sufficiently lrge dtbse of invsive coronry ngiogrms for PCI in millimeters. Stenoses in coronry rtery bypsses were excluded. When the dimension of the blloon or stent differed t the sme locliztion or severl blloons with different Received 2 August 2004; ccepted 23 October *Address correspondence to Sebstin Kelle, M.D., Deprtment of sizes were used, the lrgest size ws entered into the dtbse. Internl Medicine/Crdiology, Germn Hert Institute, Augustenburger Pltz 1, Berlin 13353, Germny; Fx: ; with coronry rtery stenoses who underwent their first in- For more detiled nlysis, subgroup of 352 ptients E-mil: kelle@dhzb.de vsive ngiogrphy due to suspected CAD, crdiomyopthy, D 2005 Tylor & Frncis Inc. 401 Order reprints of this rticle t

2 402 or preopertive ssessment of vlvulr disese ws nlyzed. This group, 110 (31.2%) women nd 242 (68.8%) men, ws consecutively extrcted from the pst 2 yers, since more specific informtion on these ptients ws vilble from the electronic dtbse. No risk fctors or primry medicl history were nlyzed Coronry ngiogrphy Coronry ngiogrphy ws performed using the stndrd Judkins technique (14). Coronry ngiogrms were visully evluted by three independent experienced observers ccording to the clinicl review process. Locliztion nd percent luminl dimeter reduction were documented for ny coronry rtery with stenosis. Significnt coronry rtery stenosis ws defined s luminl dimeter reduction of 50%. Fifteen coronry rtery segments were defined in modified form ccording to the recommendtions of the Americn Hert Assocition (AHA) (15) (Fig. 1). In ddition to the modified AHA guidelines, the segments were ctegorized into five groups:. proximl min segments: 1; 5; 6; 11. medil min segments: 2; 7; 13. distl min segments: 3; 8; 15. mjor side brnches: 9; 12. minor side brnches: 4; 10; 14 Kelle et l. In order to determine whether smll or distl segments re involved in the erly CAD process, the subgroup ws dditionlly nlyzed for the most proximl relevnt coronry rtery stenosis ( 50% dimeter reduction) using the five-group scle, beginning t the origin of the coronry rtery. For this nlysis it ws not relevnt whether we found nother significnt stenosis distl to the most proximl rtery stenosis. The progression from proximl to distl ws defined s: proximl segments, followed by mjor side brnches, medil segments, distl segments, nd minor side brnches Sttisticl nlysis The chi-squre test ws used for comprison of vribles s pproprite, Student s t-test for nlysis of vrince. A difference ws considered sttisticlly significnt if the two-side probbility of the observed result, under the null hypothesis, ws p Sttisticl nlysis ws performed using the softwre pckge SPSS (version 9.0). Figure 1. Modified system of coronry rtery segments ccording to AHA clssifiction (15) nd subdivision of coronry rteries into 15 segments. Right coronry rtery (RCA): segments 1 (proximl), 2 (medil, including right ventriculr brnch), 3 (distl), 4 [A V node rtery, posterolterl brnch (PLV) nd posterior descending rtery (PDA)]. Left min stem (LM): segment 5. Left nterior descending rtery (LAD): segments 6 (proximl), 7 (medil), 8 (distl), 9 [first digonl brnch (D1)], 10 [ll septl brnches (S1; S2; S3), second (D2), nd third (D3) digonl brnch]. Left circumflex rtery (LCX): segments 11 (proximl), 13 (medil), 15 (distl), 12 [first mrginl obtuse brnch (M1) nd rmus intermedius], 14 [second (M2) nd third (M3) obtuse mrginl brnch nd PLV of LCX]. Grey scle is used to show the clssifiction into five groups. For ech coronry segment re shown from left to right: percentge of ll stenoses = 25%, stenoses 50%, nd PCIs performed.

3 Noninvsive Coronry Angiogrphy 403 Figure 2. Locliztion of first coronry rtery stenoses 50% fter origin of coronry min segments in ptients who underwent first crdic ctheteriztion (ptients with CAD: 352). 3. Results A totl of 92,333 coronry rtery stenoses were documented nd 75.3% (n = 69,564) were considered to show 50% dimeter reduction. These higher grdes of stenoses were found more frequently in men (men: 63.0 ± 27.0) in comprison to women (men 60.7 ± 26.6); p < In ptients with suspected or known coronry rtery disese, lrge numbers of nonsignificnt nd significnt stenoses were found in ll coronry segments (Fig. 1). Even Figure 3. Locliztion of significnt stenoses nd interventions. though tendency towrds proximl nd medil segments ws found for stenoses 50%, 30.9% of ll stenoses 50% were locted in mjor or minor side brnches. We found no gret difference in lesion locliztion between men nd women. Distl segments contribute n dditionl 16.1% of stenoses 50%. Only 5% of ptients who underwent first coronry ngiogrphy hd stenoses 50% in distl segments or minor side brnches, without more proximl stenosis in proximl or medil min segment or mjor side brnch (Fig. 2). A totl number of 13,661 coronry interventions (PCI or stent implnttion) were documented. Interventions were Tble 1. Blloon/stent size (mm) compred to modified clssifiction of coronry rtery segments, ccording to AHA clssifiction Blloon/stent size in mm Treted in % Coronry rtery segment According to Fig. 1 b Coronry rtery Proximl RCA RCA Medil RCA, RVB Distl RCA 3 * * * 8.2* PLV/PDA 4 * * * * 3.1 LM 5 * * * * 1.0* 1.0 LM Proximl LAD 6 * * * 9.4* 38.3 LAD Medil LAD 7 * * * 16.1 Distl LAD 8 * * * * 7.7 D1 9 * * * * * 4.0* S1-3, D * * * * * * 1.1* Proximl LCX 11 * * * * 5.0* 26.2 LCX M1 12 * * * * 4.5* Medil LCX 13 * * * 8.0* M2-3, PLV 14 * * * * 3.8* Distl LCX 15 * * * * 4.9 Totl in % 0.1* * * Cumultive in % In some cses originl dt were not in relevnt quntity in every box of tble (empty boxes); they were summrized nd rounded. [From Ref. (15).] b Figure 1 demonstrtes modified system of coronry rteries ccording to AHA clssifiction.

4 404 done in 12,280 ptients [3,757 women (30.6%) nd 8,523 men (69.4%)]. Gender distribution of interventions ws similr to the distribution of included women nd men of ll ptients. Interventionl tretment ws performed in ll coronry segments (Fig. 1). The size in millimeters of the blloon or stent used for PCI for ll coronry rtery segments is shown in Tble 1. The gret mjority of interventions (92.3%) re performed with blloons or stents of 2.5 mm nd 83.5% of PCIs re performed in min coronry rtery segments. Figure 3 shows the locliztion of significnt stenoses nd interventions for the five groups of coronry rtery segments. 4. Discussion From lrge dtset of invsive coronry ngiogrms nd PCIs, we were ble to drw the following observtions, which re relevnt for users of noninvsive imging techniques to optimize their imging strtegies: 1. Significnt numbers of coronry rtery stenoses cn be found in ll coronry segments with tendency towrds loction in the proximl nd medil segments. Mjor nd minor side brnches contribute more thn 30% of significnt stenoses. 2. Only 5% of ptients who undergo first ctheteriztion hve relevnt coronry rtery stenoses only in distl segments or minor side brnches % of PCIs re performed in min coronry rtery segments. 4. More thn 90% of interventions re performed in coronry rteries with vessel size of 2.5 mm or more. Our observtions hve significnt influence on noninvsive imging strtegies since noninvsive imging my be used for severl resons, requiring different degrees of ccurcy. The imging technique is used to decide on the therpy regimen. This requires ccurte informtion on the existence, loction, distribution, nd quntifiction of disese. Such n pproch requires detection nd quntifiction of stenoses within the full coronry rtery tree, since more thn 30% of significnt stenoses cn be found in mjor or minor side brnches. In ddition, since interventions re lso performed in distl min segments (20.8%) nd mjor nd minor side brnches (16.5%), visuliztion nd quntittive ssessment of these lesions would be necessry. However, since interventions re minly performed with blloon/stent sizes of 2.5 mm nd only 7.7% of PCIs re performed with smller devices, one might rgue tht the sptil resolution used in invsive ngiogrphy (pproximtely mm) might currently not be fully required for noninvsive imging. Indeed, other observers found tht the bsolute number of new lesions ws high in distl coronry segments but low in Kelle et l. segments with dimeters < 2 mm. Their conclusion ws tht ngiogrphic follow-up studies should nlyze coronry segments t ll loctions but my neglect segments with dimeters smller thn 2 mm (16, 17). The imging technique is used to decide whether or not to proceed to invsive ngiogrphy. This requires ccurte informtion on the existence or bsence of significnt disese only. Agin, full coverge of the whole coronry rtery tree is the only imging strtegy tht would llow complete exclusion of disese. However, only 5% of ptients present with stenoses only in their distl min segments or minor side brnches nd 95% of ll other ptients hve t lest one significnt stenosis in proximl or medil min segment or mjor side brnch. The decision whether or not to proceed to invsive ngiogrphy could be bsed on the visuliztion of proximl nd medil min segments nd mjor side brnches only. This strtegy would result in n intrinsic error of pproximtely 5% Limittions of current imging techniques Severl noninvsive methods hve been suggested for visuliztion of the coronry rteries. MRCA, EBCT, nd MSCT re rpidly evolving techniques nd hve been exmined in lrger trils nd reported to be useful for the detection or exclusion of significnt coronry rtery disese. Ech of those modlities hs its specific dvntges nd disdvntges Mgnetic resonnce coronry ngiogrphy While mgnetic resonnce (MR) clerly hs the dvntge, in comprison to computed tomogrphy (CT) techniques, of relying on mgnetiztion nd thus not requiring rdition or contrst gents, the disdvntge is the reltively low signlto-noise rtio. Wheres this cn be compensted for by longer exmintion times, such prolongtion of imging time requires not only crdic gting (similrly to CT), but lso suppression of brething motion, which is performed with either breth holding or nvigtor lgorithms, which determine nd correct for the position of the diphrgm immeditely before dt cquisition (18 20). Especilly the nvigtor pproch hs the dvntge of chieving very high sptil resolution nd reducing the cquisition time per hert bet to below 100 ms, which my be required to fully suppress coronry rtery motion even if imging is restricted to mid-distole (20, 21). In the literture dignostic ccurcy rtes rnging from 38% to 90% re reported for single center studies (4, 5, 22) nd 72% for recent multi-center tril (5). However, in ll these studies the investigtors restricted themselves to the more proximl portions of the coronry rtery tree. Sptil resolution rnged from mm to mm in most studies (5, 6, 23). Thus, ccording to the specifictions set forth in the current study, the pper by Kim et l. (5) concludes tht specific group of ptients (those with triple vessel disese) cn be relible

5 Noninvsive Coronry Angiogrphy detected since t lest one of the stenoses in these ptients cn be found with the locl coverge described. Crdic mgnetic resonnce (CMR) hs the dvntge of simultneous functionl ssessment. The generl question is, if the visuliztion of the coronry rteries lone is cliniclly importnt or even solely, the evlution of functionl consequences of ischemi would be sufficient. Currently, the mjor therpeutic decisions (PCI, implnttion of stent, ortocoronry bypss) re bsed on coronry ngiogrms nd the presence of tretble coronry stenoses. We believe tht the detection of ischemi rther thn the current possible noninvsive visuliztion of the coronry rteries nd quntifiction of stenoses cn help to mke tretment decision. Future studies need to cover lrger proportions of the coronry rtery tree, especilly mjor side brnches. This will be chieved by using sequences with higher signl-to-noise rtio, better motion compenstion, higher field strength (e.g., 3 Tesl), nd intrvsculr contrst gents Electron-bem computed tomogrphy EBCT is method with high sptil resolution ( mm) nd signl-to-noise rtio. The min disdvntges re its limited vilbility nd the difficulty of visulizing stenoses in clcified res of the coronry rtery tree. However, smll vessel dimeters (< 1.5 mm) were found to led to flse-positive findings (9). Dignostic ccurcy hs been reported to be 70% (8); however, 20 25% of coronry rtery segments could not be evluted (8, 24). Thus, the technique my be suited to mking decision whether or not to proceed to invsive ngiogrphy but not ble to prove or exclude significnt coronry rtery disese. However, since nondignostic segments my be found in proximl or medil prts of the coronry rtery tree, the intrinsic error is vrible nd depends on the number of visible segments Multislice computed tomogrphy The enormous dvnces in hrdwre for MSCT hve encourged its ppliction for coronry rtery imging. Mjor limittions re high rdition nd reltively long cquisition durtion per hert bet round ms (12), depending on the equipment. Methods to further shorten this time led to n even higher rdition nd my lso increse the durtion of the breth hold which is lredy between 20 nd 35 seconds depending on hert rte nd imging volume (10). However, continuous X-ry rdition during systole nd distole with MSCT leds to n exposure of pprox. 9 msv or more (EBCT: 1.5 msv). A new technique, which reduces the current of the X-ry during systole, cn lower the rdition exposure (25). Another limittion is motion rtifcts, especilly of the rpidly moving right coronry rtery (RCA) nd coronry clcifictions, which mke lrge number of coronry segments unevluble (26, 27). Dignostic ccurcy hs been reported to be between 58% nd 78% (10 12); gin round 30% of coronry rtery segments hd to be excluded from the nlyses (12, 28). Premediction with orl ß-blockde to minimize motion rtifcts nd improved sptil resolution seem to permit higher ccurcy in the detection of coronry rtery stenoses (11, 29). Thus, the technique my lso be suitble to mke decision whether or not to proceed to invsive ngiogrphy but not to prove or exclude significnt coronry rtery disese. However, the high number of nondignostic segments cuses n intrinsic error dependent on the loction of these segments Limittions A potentil limittion of the current study my be the ptient popultion, since ll ptients hd n indiction for crdic ctheteriztion. Thus, the results cnnot be trnsferred to group with lower pretest probbility. A further potentil limittion is the visul ssessment of the coronry ngiogrms without quntittive determintion. The ccurcy of such visul ssessment depends on the experience of the observers nd is pproximtely 90% within our qulity control progrm. The number of stenoses t distl position t coronry rtery tree could be interpreted too low, becuse of high grde stenosis t proximl or medil locliztion. Some investigtors would conclude segment 4 to be mjor side brnch; we cquired this segment s minor side brnch. In this study we did not ssess the impct of MRCA sptil resolution nd imge contrst for evlution of smll nd distl vessels. However, from the dt obtined, we my conclude tht for the utiliztion of MRCA s screening method for tretble CAD the detection of stenoses in vessels greter thn 2 mm in size is sufficient. For the purpose of stenosis quntifiction in vessels with dimeter s smll s 2 mm, the sptil resolution would hve to be round 0.2 mm in ll three dimensions (30). Potentilly, this cn be dvised with MRCA; however, current vilble methods usully result in sptil resolution of pproximtely mm (31). No direct determintion of vessel size ws performed; however, n estimtion of vessel size cn be devised from the blloon or stent used for PCIs. For interventionl tretment, usully stent with slightly lrger dimeter thn the vessel itself is chosen (32). In study with quntittive determintion of vessel size, stent size ws 10 20% lrger thn tht of the rtery (33). Thus, mild overestimtion of vessel size my be ssumed with the reported pproch. 5. Conclusion 405 Imging strtegies with noninvsive modlities cn be dpted to the size of vessels nd distribution of coronry

6 406 rtery lesions. The decision whether or not ptient with suspected CAD should proceed to invsive ngiogrphy cn be relibly mde from visuliztion of proximl nd medil min segments nd mjor side brnches, yielding n intrinsic error of only 5%. This pproch, however, cnnot be used to detect or exclude disese or mke tretment decision. References 1. Chitmn BR, Bourss MG, Dvis K, Rogers WJ, Tyrs DH, Berger R, Kennedy JW, Fisher L, Judkins MP, Mock MB, Killip T. Angiogrphic prevlence of high-risk coronry rtery disese in ptient subsets (CASS). Circultion 1981; 64(2): Miller TD, Roger VL, Hodge DO, Hopfenspirger MR, Biley KR, Gibbons RJ. Gender differences nd temporl trends in clinicl chrcteristics, stress test results nd use of invsive procedures in ptients undergoing evlution for coronry rtery disese. J Am Coll Crdiol 2001; 38(3): Enriquez-Srno M, Klods E, Grrtt KN, Biley KR, Tjik AJ, Holmes DR Jr. Seculr trends in coronry therosclerosis-nlysis in ptients with vlvulr regurgittion. 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