Dimensions in Humans

Transcription

1 2294 Determinnts of Norml Coronry Artery Dimensions in Humns Wing-Hung Leung, MB, MRCP; Michel L. Stdius, MD; nd dwin L. Aldermn, MD Downloded from by on November 12, 218 Bckground. Studies of norml humn coronry dimensions hve been performed primrily in postmortem herts. We evluted the influence of ge, body hbitus, nd regionl myocrdil mss on coronry dimensions in living ptients with norml coronry vessels. Methods nd Results. Arteriogrphiclly norml coronry ngiogrms were nlyzed from the following groups of subjects: group 1 (ge, yers) consisted of 3 post-crdic trnsplnt ptients with donor herts from mle subjects ged yers, group 2 (ge, yers) consisted of 12 post-crdic trnsplnt ptients with donor herts from mle subjects ged yers nd 26 mle subjects investigted for typicl chest pin, nd group 3 (ge, yers) consisted of 26 mle subjects investigted for typicl chest pin. All ngiogrms were performed fter sublingul nitroglycerin. Mesurements of the dimensions of the left min, proximl left nterior descending, proximl left circumflex, nd proximl right coronry rteries were mde using computer-ssisted edge-detection lgorithm. The regionl myocrdil mss supplied by ech vessel ws derived from echocrdiogrphiclly derived totl left ventriculr mss nd semiquntittive ngiogrphic territory scoring system bsed primrily on the number nd length of its terminl nutrient brnches. Conclusions. Liner regression nlysis showed tht coronry vessel cross-sectionl re nd totl coronry cross-sectionl re increse with regionl myocrdil mss nd decrese linerly with ge. Multivrite regression nlysis reveled tht regionl myocrdil mss nd ge were independent predictors of cross-sectionl re for ech vessel nd for the totl coronry cross-sectionl re. We speculte tht ge-relted decline in physicl ctivity, in prt, my be responsible. (Circultion 1991;84: ) A ccurte description of the extent of coronry therosclerosis is predicted on the understnding of the norml coronry ntomy. However, studies of the luminl dimensions of truly norml coronry rteries re limited. Although severl studies hve evluted the dimensions of postmortem coronry rteries,1-4 few studies hve been performed using quntittive coronry rteriogrphic techniques in living ptients with presumbly norml rteries.5,6 Previous studies hve shown tht pthologicl conditions such s hypertension tht substntilly increse left ventriculr mss re ssocited with incresed epicrdil coronry vessel size.7-9 There re lso postmortem observtions nd niml studies suggesting tht the mount of myocrdium supplied by coronry vessel is correlted with the size of tht From the Division of Crdiovsculr Medicine, Stnford University Medicl Center, Stnford, Clif. Supported in prt by Reserch Fellowship Awrd (W.-H.L.) from the Stnford-Asi Medicl Fund (SAMFUND). Address for reprints: dwin L. Aldermn, MD, Division of Crdiovsculr Medicine, Stnford University Medicl Center, 3 Psteur Drive, Stnford, CA Received October 3, 199; revision ccepted July 23, proximl vessel.3,1 Other reports show lrger coronry vessel size for the mle sex reltive to the femle.5 Intrinsic vsculr pthology such s therosclerosis generlly tends to nrrow vessel lumens. It is the purpose of this study to nlyze determinnts of epicrdil coronry vessel size in subjects selected to void pthologicl conditions tht could directly or indirectly ffect coronry dimensions. In the present study, we use territory scoring system for the semiquntittive ngiogrphic estimte of regionl coronry vessel distribution. Mesurement of coronry vessel distribution nd echocrdiogrphic ssessment of totl left ventriculr mss permits evlution of the reltion of proximl coronry rtery dimensions to regionl left ventriculr mss. In ddition, the influence of ge nd body hbitus on coronry dimensions determined by quntittive coronry rteriogrphy re evluted in living ptients with norml coronry vessels. Methods Selection of Subjects ntirely norml coronry ngiogrms bsed on visul ssessment of bsence of ny luminl irregu-

2 Downloded from by on November 12, 218 lrities were reviewed from 94 mle subjects. The ngiogrms were divided into three ge groups: group 1, ge yers; group 2, ge yers; nd group 3, ge yers. The sources of coronry ngiogrms for the different ge groups were s follows. Group 1. To obtin coronry ngiogrms of young mle subjects without history of crdic disese, the ngiogrms of 3 post-crdic trnsplnt ptients with donor herts from mle subjects ged yers were nlyzed. Angiogrms from trnsplnt subjects were performed with men intervl postllogrft surgery of 38±9 dys s prt of prospective study of posttrnsplnt coronry rtery disese. Informtion on body hbitus (weight nd height) ws obtined from donor reltives. Group 2. This included 12 post-crdic trnsplnt ptients with donor herts from men ged yers nd 26 men (ged 35-54) investigted for typicl chest pin. The crdic trnsplnt subjects were similrly studied with men of dys fter trnsplnttion. The ngiogrphic results from the trnsplnt nd typicl chest pin ptients were combined becuse comprison of the coronry dimensions of the 12 post-crdic trnsplnt ngiogrms nd 26 ngiogrms from ptients with typicl chest pin showed no significnt differences. Group 3. This included 26 men (ged yers) investigted for typicl chest pin. All subjects with typicl chest pin (in groups 2 nd 3) hd either norml or equivocl exercise stress test results. Subjects (or donor subjects) with systemic hypertension, left ventriculr hypertrophy, vlvulr hert disese, crdiomyopthy, or history of other crdic disese were excluded becuse such ptients my hve pthologiclly different coronry rtery dimeters.235,7-9 Only mle subjects were included in this study becuse of the well recognized sex difference in coronry dimensions5 nd the lck of sufficient number of norml-ppering coronry ngiogrms from femle subjects for ll ge rnges. Adequte echocrdiogrphic exmintions were obtined in 77 of the 94 (82%) subjects (87% of group 1, 79% of group 2, nd 81% of group 3). Stndrd prsteml nd picl views were used. According to the recommendtions of the Americn Society of chocrdiogrphy,"1 the thickness of the posterior wll nd interventriculr septum, the left ventriculr end-distolic nd end-systolic dimensions were mesured. The left ventriculr mss ws derived from n ntomiclly vlidted formul12: left ventriculr mss (g) = 1.4[(LVDD + PW+ VS)3-(LVDD)3] -13.6; where LVDD is left ventriculr end-distolic dimension, PW is posterior wll thickness, nd VS is ventriculr septl wll thickness. Subjects with echocrdiogrphic evidence of left ventriculr hypertrophy bsed on wll thickness mesurements were excluded from the study. Crdic Ctheteriztion All ngiogrms were performed using 5-7-inch intensifier modes nd were reviewed s suitble for Leung et l Determinnts of Coronry Dimensions 2295 nlysis by quntittive coronry rteriogrphy. All ptients gve written informed consent for coronry ngiogrphy. Selective coronry rteriogrphy ws performed using the percutneous femorl pproch. Sublingul nitroglycerin (.4 mg) ws given 2-3 minutes before the contrst injections used for quntittion to minimize the effect of vrying vsomotor tone on vessel lumen dimeters. Ptients received nitroglycerin before quntittive ngiogrphy, irrespective of whether the ptient ws studied erly fter trnsplnttion or for evlution of typicl chest pin. Ptients with suspected coronry spsm bsed on prior clinicl or electrocrdiogrphic evidence were not included in this protocol becuse of potentil need for ergonovine chllenge. Ctheters of known dimeters were used for clibrtion.13 Multiple projections including crnil nd cudl ngulted views were obtined for ll ptients. Quntittive Coronry Artertiogrphy Dimeters of the left min coronry rtery (LMCA), proximl left nterior descending rtery (plad), proximl left circumflex rtery (plcx), nd proximl right coronry rtery (prca) were mesured. Coronry segments tht were proximl to mjor digonl or mrginl brnches were selected for quntittion. Only coronry segments tht best visulized the vessel in elongted profile of t lest.5 cm in length were quntitted nd used for nlysis. In generl, to void vessel overlp, the crnil left nterior oblique view ws chosen for plad, cudl right nterior oblique view for LMCA nd plcx, nd left nterior oblique view for prca. Coronry cinengiogrphic films were nlyzed by computer-ssisted edge detection by using 35-mm cine film trnsport mechnism mounted on movble stge (Vngurd Instruments, Melville, N.Y.).14 Single end-distolic cine frmes, identified by n electrocrdiogrm-triggered mrk on the frmes nd selected for optiml coronry vessel opcifiction, were focused nd mgnified (x 3.5). Coronry segments were centered in the imge field, nd the imge ws digitized with video processor (model 5524, De Anz Systems, Fremont, Clif.) controlled by Hewlett-Pckrd 21 computer (Andover, Mss.). The digitized imge ws displyed on grphic computer terminl linked to light pen. The mrgins of either the ctheter or coronry segment were trced mnully using the light pen. Using these lines s initil serch loctions, the utomtic edgefinding lgorithm drew nd smoothed the edges, defining the edge s the pek of the first derivtive of the gry-scle density grdient, perpendiculr to the long xis of the ctheter or vessel s estimted from the initil mnul trcings. When the computer lgorithm ws unble to resolve vessel boundries in res of noise or vessel crossings, mnul editing of short segments of boundry with the light pen ws used to correct the computer-generted boundry. At no time did the length of mnully entered mrgin exceed 2% of the totl length of the qun-

3 2296 Circultion Vol 84, No 6 December 1991 DF1NMON OF TRRITORY SCOR FORTRMNATING VSSLS (Dbgonl% Rms, Mnrginls, Pos lterls, RCA d LCX Terminticn) LAO O~ Bse RAO CCd~ Apex t A 11 LwW(': Medu : > 2r ilr todl 1 is 'I t S lrj d1)*: Abx fth Oid.c 13rd c Ilfith sm tnn J1 Distl LOX lql_ Apex Downloded from by on November 12, 218 FIGUR 1. Coronry rtery mp used for teritory scoring illustrtes proximl coronry segments quntitted nd potentil terminting nutrient brnches used to clculte tenitory scores. LMCA, left min coronry rtery; prca, proximl right coronry rtery; plcx, proximl left circumflex rtery; plad, proximl left nterior descending rtery. titted segment. After the light pen indicted the segment fiducil (strting) nd end points, the men dimeter of the segment ws computed from perpendiculrs constructed through the length of computer-generted center line. The men dimeter of the segment ws then used for nlysis. Becuse only norml coronry rteries were included, we ssumed tht the rtery cross section ws round nd clculted coronry cross-sectionl re from dimeter s rd'. 4. The totl coronry cross-sectionl re ws defined s the sum of cross-sectionl res of plad, plcx, nd prca. Determintion of Regionl Myocrdil Teritory Size nd Regionl Left Ventriculr Mss To evlute the reltion between proximl coronry rtery size nd the regionl left ventriculr mss supplied by the vessel, semiquntittive ngiogrphic territory score ws ssigned to proximl coronry segment bsed on the number of its distl terminl brnches nd their reltive length. The coronry vessels re divided into conduit nd nutrient vessels. All terminting vessels re ssumed to be potentil nutrient rteries. Figure 1 shows coronry rtery mp used for the territory scoring scheme illustrting the proximl coronry segments quntitted nd the potentil terminting brnches. In this mp, n rcde, referred to s the trioventriculr groove segments, connects the distl right nd left circumflex rteries. The posterior descending nd three potentil posterolterl brnches rise from this rcde. These brnches cn rise either from the right coronry rtery or the left circumflex rtery, depending on the dominnce of the circultion. Hence, terminl brnches for the plad include 'Number In p h Issrto,ysoey 1to 3) ss~gnedtormin wesse v FIGUR 2. Illustrtion showing definitions of teritory scores for terminting vessels. RCA, right coronry rtery; LCX, left circumflex rtery; LAO, left nterior oblique; RAO, right nterior oblique. digonl brnches, the distl left nterior descending segment, nd the left nterior descending septl brnches. Terminl brnches of the prca include the posterior descending nd potentil posterolterl brnches. Terminl brnches of the plcx include the obtuse mrginl brnches, distl left circumflex rtery segment (if it is the terminting segment), nd potentil posterolterl brnches. The extent of myocrdil territory supplied by nutrient vessel is bsed on the reltive size of the vessel nd is judged by the length of the terminl vessel in n ngiogrphic projection tht best elongtes the segment, lthough some considertion is given to the lterl spred of the terminting smll brnches. Terminting vessel length nd corresponding territory is ssigned numericl vlue of 3, 2, 1, or corresponding to lrge, medium, smll, or bsent for ll segments on the coronry mp tht supply left ventriculr myocrdium (i.e., right ventriculr mrginl nd tril brnches re excluded). A lrge territory is subtended by terminl segment extending more thn two-thirds of the distnce from bse to pex of the left ventricle (see Figure 2). A medium territory is subtended by terminl segment extending from one third to two thirds of the bse-to-pex length. A smll territory is subtended by terminl segment extending less thn one third of the bse-topex length. Very smll twigs tht extend less thn one fifth of the bse-to-pex length re typiclly thin nd inconspicuous nd re considered bsent. Sizing of the distl left nterior descending coronry rtery is bsed on the left nterior descending termintion: A lrge vessel wrps round the pex, medium stops t the pex, nd smll termintes well before reching the pex of the left ventricle. The rmus intermedius vessel territory, if present, is not included in either plad or plcx territory score. The totl septl territory is ssigned three points nd llocted to the plad.

4 Leung et l Determinnts of Coronry Dimensions 2297 Downloded from by on November 12, 218 prca LAO Ciw x ULMCA.pLCX RAOCc RCA LAD Rrnus LCX Posteulodeucndng:2 Septs : stObtuse m n : 1 +2 lt Posro :1 1slDlgo :2 2nd Obse m,nri :1 2nd Pooltr :2 2nd DWo l: rd Obse m Wnl :1 RCA :1 3rdDDigonl :1 Dlsll LCX DsIW LAD :3 Totl RCA: 6(23%) Totl LAD :11 (42%) Totl Rm :4(15%) To LX: 5(2 ) To LV: 26 (1%) LM A*: 2 (77%) Numbem In pemr re lte frwons comn lhmuo s ofltl sst teltd dydm cw d by totl LV trrl wrycous FIGUR 3. Illustrtion showing ssignment of teritory scores nd computtion of teritory frctions in coronry ngiogrm. LAO, left nterior oblique; RAO, right nterior oblique; prca, proximl right coronty rtery; LMCA, left min coronry rtery; plad, proximl left nterior descending rtery; plcx, proximl left coronry rtery. The territory score of proximl vessel is the sum of the scores of its terminl brnches, which is n estimte of the summed length of the brnches. Territory scores of the LMCA, plad, plcx, nd prca were ssessed. The LMCA territory score is the sum of scores of plad, plcx, nd the rmus intermedius. The totl left ventriculr territory score is the sum of scores of LMCA nd prca. The territory frction for ech vessel is defined s (territory score of the vessel divided by totl left ventriculr territory score x 1%). Figure 3 shows n illustrtion of the territory scoring method in coronry ngiogrm. The regionl left ventriculr mss supplied by vessel is defined s totl left ventriculr mss multiplied by territory frction of the vessel. Reproducibility of the territory scoring system ws ssessed from pired blinded observtions of 36 coronry ngiogrms red by two experienced individuls. Sttisticl Anlysis Dt re expressed s the men with the stndrd devition s the index of dispersion. Student's unpired t test ws used for compring two groups of unpired dt. Anlysis of vrince ws used if more thn two groups of unpired dt were compred. Correltions between vribles were ssessed using univrite liner regression nlysis nd Person's correltion coefficient. Multivrite regression nlysis ws performed to test dependence of coronry dimensions on ge, body surfce re, nd vsculr territory.15 Differences were considered significnt when confidence limits exceeded 95% (p<.5). Results Regionl Left Ventriculr Mss The men left ventriculr mss (left ventriculr mss divided by body surfce re) of the study popultion ws 21±37 g (98+21 g/m2). There were no significnt differences in left ventriculr mss between the three ge groups (group 1, g; group 2, 199±35 g; group 3, 24±39 g) or between the herts of trnsplnt recipients nd subjects with typicl chest pin in group 2 (2+ 37 versus g). No significnt differences were found in body weight, height, nd body surfce re between the three ge groups or between the trnsplnt donors nd norml subjects in group 2. The men territory score for ll subjects ws (rnge, 1-25) for the LMCA; (rnge, 5-14) for the plad; (rnge, 1-14) for the plcx, nd (rnge, 1-9) for the prca. The LMCA territory score is more thn the sum of the plad nd plcx territory scores, reflecting inclusion of rmus intermedius territory. The territory frction for the LMCA ws 75+8% (rnge, 55-95%); for the plad ws 42±8% (rnge, 19-67%); for the plcx ws 29±1% (rnge, 6-52%), nd for the prca ws 2±7% (rnge, 4-41%). Comprison of territory scores nd territory frctions by different observers in TABL 1. Comprison of Two Blinded Redings of Myocrdil Territory Scores nd Territory Frctions in 36 Coronry Angiogrms Men of territory scores (territory frctions) for ll SD of subject by subjects subject differences Coefficient Observer 1 Observer 2 between observer 1 nd observer 2 of vrition* plad (n=36) 1.6 (43.1) 1.5 (43.7) 1.42 (4.72) 13% (11%) plcx (n=36) 7.6 (3.4) 7.4 (3.7) 1.8 (4.14) 14% (13%) prca (n=36) 6.6 (26.5) 6.5 (26.8) 1.28 (2.96) 19% (11%) All vessels (n=18) 8.3 (33.3) 8.1 (33.7) 1.26 (3.95) 15% (11%) Numbers in prentheses represent vlues for territory frctions. plad, proximl left nterior descending rtery; plcx, proximl left circumflex rtery; prca, proximl right coronry rtery; SD, stndrd devition. *Coefficient of vrition is SD of subject by subject differences divided by men territory score or men territory frction.

5 2298 Circultion Vol 84, No 6 December 1991 TABL 2. Men Coronry Cross-sectionl Ares nd Totl Coronry Cross-sectionl Are for Different Age Groups Men CSA (mm2) Group LMCA plad plcx prca TCSA (mm2) Group 1 (15-34 yers) ±+7.34 Group 2 (35-54 yers) * * Group 3 (55-74 yers) ±3.65* * *t 8.11±3.12* 23.47±5.83*t CSA, cross-sectionl re; TCSA, totl coronry cross-sectionl re; LMCA, left min coronry rtery; plad, proximl left nterior descending rtery; plcx, proximl left circumflex rtery; prca, proximl right coronry rtery. *p<.5 vs. group 1. tp<.5 vs. group 2. Downloded from by on November 12, pired observtions showed tht the overll coefficients of vrition (stndrd devition of subject by subject differences/men vlue) were 15% nd 11%, respectively (Tble 1). Regionl left ventriculr mss ws clculted by multiplying the territory frction by the echocrdiogrphiclly mesured totl left ventriculr mss in those subjects with vilble dt. Regionl left ventriculr mss for the LMCA ws 152±33 g (rnge, g); for the plad ws g (rnge, g); for the plcx ws g (rnge, 9-11 g), nd for the prca ws 4±14 g (rnge, 8-74 g). Quntittive Coronry Arteriogrphy Tble 2 shows the totl coronry cross-sectionl re nd men cross-sectionl re of ech vessel for the three ge groups. There is progressive decrese with ge in the totl coronry cross-sectionl re nd cross-sectionl res of the LMCA, plad, plcx, nd prca. Compred with group 1 (ge, yers) ptients, the group 2 (ge, yers) nd group 3 (ge, yers) ptients hd smller totl coronry cross-sectionl res (p<.5 for both groups). The difference between group 2 nd group 3 ws lso significnt (p<.5). There ws no significnt difference in totl coronry cross-sectionl re between the trnsplnt nd nontrnsplnt subjects in group 2 (26.97±7.4 versus 28.12±7.83 mm2). Tble 3 nd Figures 4, 5, nd 6 show the reltion between the men vessel cross-sectionl re nd totl coronry cross-sectionl re nd ge, regionl or totl left ventriculr mss, body weight, body height, nd body surfce re. Totl left ventriculr mss hd strong positive correltion with TCSA (r=.642, p<.1; Figure 4, right pnel). Regionl left ventriculr mss correlted significntly with men cross-sectionl res of LMCA (r=.591, p<.1), plad (r=.756, p<.1), plcx (r=.733, p<.1), nd prca (r=.744, p<.1) (Figure 5). Age ws found to hve significnt negtive correltion with TCSA (r= -.531, p <.1; Figure 4, left pnel) nd with men cross-sectionl re of LMCA (r=-.453, p<.1), plad (r=-.47, p<.1), plcx (r=-.44, p<.1), nd prca (r=-.322, p<.5) (Figure 6). No significnt correltion ws found between cross-sectionl re of ech vessel nd totl coronry crosssectionl re with body weight, height, nd body surfce re. qutions predicting the cross-sectionl re of ech vessel nd the totl coronry cross-sectionl re from the regionl or totl left ventriculr mss, ge, nd body surfce re were sought using multivrite regression nlysis. Age nd regionl or totl left ventriculr mss were found to be significnt independent predictors of the cross-sectionl re for ech vessel nd of the totl coronry crosssectionl re (Tble 4). Body surfce re ws not significnt predictor of either vessel cross-sectionl re or totl coronry cross-sectionl re. Substntil informtion regrding norml coronry rtery dimensions in proximl coronry rtery segments cn be derived bsed on territory frction nd ge lone. Tble 5 provides the norml men dimeters of ech vessel by ge nd territory frction groupings. The rnges in prentheses re bsed on TABL 3. Coefficients nd Vlues for Comprison of Cross-sectionl Ares of Coronry Vessels With Potentil Determinnts of Artery Size Age Regionl left ventriculr msst Body weight Body height Body surfce re TCSA -.531t.642t LMCA -.453t.591t plad -.47t.756t plcx -.44t.733t prca -.322*.744t TCSA, totl coronry cross-sectionl re; LMCA, left min coronry rtery; plad, proximl left nterior descending rtery; plcx, proximl left circumflex rtery; prca, proximl right coronry rtery. *p<.5. tp<.1. *Totl left ventriculr mss ws used for TCSA becuse percent territory score corresponding to TCSA is 1%.

6 Leung et l Determinnts of Coronry Dimensions h% s I r-.531 p<o.1 o1 11 S = n C Cs n P 5 L%.4 - o A- _ = 3 ci _ 1 2. C) ~~~~ m og 12 % o1 _ ~~o' 2 o 1 _ 1 l X Age (Yers) Totl Left Ventriculr Mss (gm) FIGUR 4. Left pnel: Grph showing reltion between totl coronry cross-sectionl re nd ge. Right pnel: Grph showing reltion between totl coronry cross-sectionl re nd totl left ventriculr mss. Downloded from by on November 12, 218 men±2 SD. Regression equtions tht llow determintion of nticipted norml dimeter mesurements in proximl coronry rteries bsed on territory frction nd ge re included in Tble 5. This tble nd the regression equtions re pplicble to mle subjects with ngiogrphic mesurements mde fter nitroglycerin. Discussion Bckground Previous studies of norml humn coronry dimensions hve been performed primrily in postmortem herts.1-4 Although most of these studies obtined coronry mesurements under physiologiclly distending pressures, postmortem ltertions in smooth muscle distensibility might ffect ctul coronry cliber. In ddition, postmortem studies do not ccount for dynmic chnges in coronry blood flow. Therefore, necropsy exmintion my not ccurtely reflect ngiogrphic coronry dimensions mesured during distole. Moreover, the herts exmined in postmortem studies often hve preexisting crdic diseses such s left ventriculr hypertrophy, crdiomyopthy, vlvulr hert disese, nd congenitl hert disese tht could ffect coronry dimensions. For these resons, the pplicbility of pthologicl dt to vessels studied in vivo under norml distending pressure is dubious. Studies of norml coronry rtery size in vivo re few.5'6 Although these ngiogrphic studies mesured dimensions on coronry rteries tht ppered to be norml, most subjects hd significnt crdic lesions such s vlvulr hert disese, crdiomyopthy, nd left ventriculr hypertrophy tht my directly or indirectly ffect coronry dimensions. Furthermore, the ge rnge of ptients in these studies ws primrily centered in the middle-ge group, limiting the ssessment of ge-relted chnges in coronry dimensions. Vrition in coronry vsomotor tone mong different individuls ws not ccounted for in these studies tht were crried out in the 196s nd erly 197s. Becuse fctors including sex, coronry segment loction, vlvulr lesions, ventriculr hypertrophy, nd coronry vsomotor tone hve been shown to ffect vessel dimension,5,8,16,17 we tried to minimize these vritions in this study. We included only mle subjects, excluded ptients with ny crdic disese, nd used vsodiltor (nitroglycerin) to eliminte the effect of vritions in coronry vsomotor tone. Becuse vrition in ntomic distribution of coronry vessels might resonbly be expected to influence coronry dimensions, the regionl myocrdil territory nd left ventriculr mss supplied by the mesured rteries were quntitted. To encompss wide ge rnge in the present study (especilly subjects below ge 35 yers), we nlyzed coronry ngiogrms of herts from young mle donors erly fter trnsplnttion. This pproch rises the possibilities of confounding effects of crdic denervtion nd trnsplnt coronry rtery disese on coronry dimensions. However, the use of nitroglycerin in both trnsplnt nd nontrnsplnt subjects before ngiogrphy cuses mximl vsodilttion. This response is not likely to be ffected by denervtion or by bnormlities of endothelium derived relxing fctor (DRF) relese, reflecting the fct tht nitrtes hve direct effect on vsculr smooth muscle. The fct tht ngiogrphy ws obtined erly (men, 38 dys) fter trnsplnt surgery minimizes the possibility tht trnsplnt coronry rtery disese could ffect coronry lumen dimensions. Histopthologicl findings of subintiml fibrocellulr prolifertion in trnsplnt coronry vessels is not usully present until 3 months fter trnsplnttion, nd even then, the chnges re miniml.18 The lck of difference in coronry dimensions between trnsplnt herts nd ntive nontrnsplnted subjects in the yer ge group further suggests the vlidity of inclusion of donor-hert ngiogrms in this group. Coronry dimeter mesurements in this study were obtined from mesurements of single ngio-

7 23 Circultion Vol 84, No 6 December oc _ U) Reglonl LV Mss (gm) c cm - o.. 'M i= C) I.; 5 1 plad Regionl LV Mss (gm) 15 N J = 1 o.2 2 ;is C Downloded from by on November 12, 218 dh 5 h. J) plcx prca Regionl LV Mss (gin) Regionl LV Mss (gm) FIGUR 5. Grphs showing reltion between cross-sectionl re of the left min (LMCA), proximl left nterior descending (plad), proximl left circumflex (plcx), nd proximl right (prca) coronry rteries nd regionl left ventriculr (LV) mss. There is liner increse in vessel dimension for ech vessel with regionl left ventriculr mss. grphic projection of the segment being nlyzed. It is not often possible to obtin truly orthogonl projections of the proximl coronry rtery segments nlyzed in this study. In previous studies, 14-5% of coronry segments could not be dequtely imged in orthogonl projections Furthermore, coronry intrvsculr ultrsound studies of norml or nerly norml coronry rteries hve demonstrted circulr cross-sectionl profile so tht single dimeter mesurement ccurtely reflects the dimeter of the lumen from ll perspectives.22 Thus, dimeter mesurements from multiple projections should not lter the conclusions of this study. ffect of Regionl Myocrdil Territoty nd Left Ventriculr Mss Previous studies showed tht totl left ventriculr mss is n importnt determinnt of coronry dimensions in either norml or hypertrophied herts.7-1 However, there is no study to dte tht evlutes the reltion of regionl myocrdil territory or regionl left ventriculr mss with proximl coronry dimensions in vivo. Dt from previous studies suggested tht the proximl cross-sectionl re of coronry vessel correltes with the myocrdil volume within its territory.3,1 Rodriguez et l,3 by mesuring the volume of brium sulfte-geltin injected into postmortem coronry rteries, found tht there ws significnt liner reltion between the sums of the cross-sectionl res of the mjor coronry rteries (plad, plcx, nd prca) nd the cpcities of the coronry rteril tree. Koiw et l,1 by mesuring the regionl myocrdil volume in dogs with the use of the dynmic sptil reconstructor technique, lso found tht the cross-sectionl re of coronry rtery supplying volume of myocrdium ws relted to tht volume. Vieweg et 16 showed tht proximl coronry size is relted to "right, left, or mixed emphsis (dominnce)." In the present study, we used reproducible, semiquntittive territory scoring system to estimte the regionl myocrdil territory supplied by proximl rtery. The scoring system is bsed on the distinction between conduit nd terminl (i.e., nutrient) coronry vessels. Con-

8 Leung et l Determinnts of Coronry Dimensions 231 Cu 4) - s-i 2 o. g _UCh ) l * r = p <.1 o n S = 3.93 c] 1 n = U %o1[ o ] o 11 4& W g* Age (Yers) 8 ) - j X- C o. Ui U l Al l 9 I r=-.47 o pc<.1 s S = DqbJL o n=86 rp~ 1 [ 1 1 CP clo 11 ooo * Age (Yers) Downloded from by on November 12, 218 ) o _i Age (Yers) Age (Yers) FIGUR 6. Grphs showing reltion between cross-sectionl re of the left min (LMCA), proximl left nterior descending (plad), proximl left circumflex (plcx), nd proximl right (prca) coronry rteries nd ge. There is liner decrese in coronry cross-sectionl re with ge for ech vessel. duit coronry vessels serve s pthwy for blood flow to the terminl vessels, from which rterioles brnch into the myocrdium. The myocrdil territory score is bsed on the presence of terminl coronry vessels nd their reltive length, lthough to some extent spred of vessel brnches is considered.23,24 vlution of coronry territory score nd frction of totl left ventriculr myocrdium supplied by prticulr vessel, lthough bsed on specific rules, is subject to observer vribility. The coefficient of vrition ws 13-19% for territory score but only 11-13% for territory frction. One could develop computer-ssisted technique tht integrtes plnimetry or mnul trcing of coronry vessels on rdiogrphic imges cquired in severl orthogonl plnes to more precisely mke these mesurements. We chose n pproch tht lthough subjective nd thus prone to greter observer vribility is ccessible to the prcticing ngiogrpher. It is probble tht the reltion between coronry cross-sectionl re nd regionl left ventriculr mss would hve been even stronger if territory frction were more precisely N1 CD ) CL. ) C.) I I I I I o [ 1 1 ssessed. However, the strength of the observed correltions suggests dequcy of the current territory scoring system nd vlidity of the territory frction s determinnt of coronry vessel size. Seiler et l,25 in cnine study, lso showed tht the regionl myocrdil territory is proportionl to the summed rteril brnch lengths distl to ech point in the coronry rtery where lumen re ws mesured. This is consistent with our findings becuse the territory score used in this study is bsed on the sum of the reltive lengths of the distl brnches. We then derived the regionl left ventriculr mss from territory frctions nd echocrdiogrphiclly mesured totl left ventriculr mss. Our results show tht regionl left ventriculr mss is the strongest independent predictor of coronry cross-sectionl re. This level of correltion is comprble with previous postmortem nd cnine studies.3,1 These results suggest tht the effects of stenosis in conduit vessel on the totl left ventriculr myocrdium my be expressed s the product of mesure of stenosis severity multiplied by the reltive r p <.5 S n-87

9 232 Circultion Vol 84. No 6 December 1991 Downloded from by on November 12, 218 TABL 4. Multivrite Regression Anlysis of Totl or Regionl Left Ventriculr Mss, Age, nd Body Surfce Are s Determinnts of Coronry Vessel Dimensions Independent vribles Regionl left ventriculr Body surfce Vribles mss* Age re TCSA r.748 R2.56 p <.1 <.1* <.1 NS LMCA r.735 R 2.54 p <.1 <.1 <.1 NS plad r.82 R p <.1 <.1 <.1 NS plcx r.836 R p <.1 <.1 <.1 NS prca r.748 R2.56 p <.1 <.1 <.1 NS Multiple regression equtions for significnt vribles: 1) TCSA = (.115 totl LVM)+(-.188 ge) 2) LMCA men CSA = (.72 RLVM)+(-.17 ge) 3) plad men CSA =2.651+(.138 RLVM)+(-.62 ge) 4) plcx men CSA =7.992+(.11 RLVM)+(-.77 ge) 5) prca men CSA =8.899+(.187 RLVM)+(-.38 ge) TCSA, totl coronry cross-sectionl re; LMCA, left min coronry rtery; plad, proximl left nterior descending rtery; plcx, proximl left coronry rtery; prca, proximl right coronry rtery; LVM, left ventriculr mss; CSA, cross-sectionl re; RLVM, regionl left ventriculr mss. *Totl left ventriculr mss ws used for TCSA becuse percent territory score corresponding to TCSA is 1%. mount of totl left ventriculr myocrdium subtended by the stenosis. An lgorithm of this type my be pplied in the setting of multivessel disese. Furthermore, by compring the mesured dimeter with the theoreticl dimeter derived from the territory frction of coronry segment, diffuse coronry therosclerosis tht is not ngiogrphiclly pprent my be detected. ffects ofage nd Body Hbitus Published dt on the effects of ge on norml coronry dimensions yield inconsistent results.1-5,26,27 A slight tendency for dult coronry size to increse with ge hs been noted in three postmortem studies,',26,27 wheres no chnge in coronry size with ge hs been noted in three other postmortem studies2-4 nd in one ngiogrphic study.5 However, s previously noted, the relevnce of postmortem studies to coronry ngiogrphic mesurements in vivo is doubtful. An ngiogrphic study by McAlpin et 15 demonstrted tht those crdic lesions expected to substntilly increse myocrdil work nd thus coronry blood flow were ssocited with lrger coronry dimensions thn those of norml subjects. The uthors lso noted smller coronry dimeters in femle subjects, however, this difference ws entirely ccounted for by differences in body surfce re. In the current study, ll subjects were mles without crdic disese or hypertension; thus, the observed bsence of significnt reltion between body height, weight, nd surfce re to coronry dimeter ws nticipted. The results of this study show progressive decline in coronry dimensions with incresing ge tht is not explined by fctors such s myocrdil trophy. From the multivrite regression equtions, ge is significnt determinnt of ll proximl vessel crosssectionl res nd for totl coronry cross-sectionl re, lthough regionl myocrdil territory ws stronger predictor of vessel re. Rodriquez et l,3 in postmortem study mesuring the volume of injectte mss entering the coronry vessels under stndrd conditions, found tht there ws trend towrd lrger cpcity in younger compred with older sub-

10 Leung et l Determinnts of Coronry Dimensions 233 Downloded from by on November 12, 218 TABL 5. Men Dimeters nd Multiple Regression qutions of Coronry Arteries According to Age nd Vessel Territory Frction in the Study Popultion Men dimeter+sd (mm) Territory frction yers yers yers LMCA <7% SD ( ) ( ) ( ) 7-8% SD ( ) ( ) ( ) >8% 5.36± SD ( ) ( ) ( ) plad <35% 2.94± ± ±2 SD ( ) ( ) ( ) 35-45% 3.59± ±.5 3.8±.47 ±2 SD ( ) ( ) ( ) >45% SD ( ) ( ) ( ) plcx <2% 2.82± ± SD ( ) ( ) ( ) 2-3% 3.59± ± ± SD ( ) ( ) ( ) >3% ± ± SD ( ) ( ) ( ) prca <15% 2.84± ± ±2 SD ( ) ( ) ( ) 15-25% 3.73± ±2 SD ( ) ( ) ( ) >25% 4.26± ± ±.47 ±2 SD ( ) ( ) ( ) Multiple regression equtions: 1) LMCA men dimeter (mm) =3.488+(.24 territory frction)+(-.17 ge) (r=.549,p<.1) 2) plad men dimeter (mm) =2.719+(.35 territory frction)+(-.14 ge) (r=.558,p<.1) 3) plcx men dimeter (mm) =2.785+(.42 territory frction)+(-.2 ge) (r=.737,p<.1) 4) prca men dimeter (mm) =2.967+(.52 territory frction)+(-.12 ge) (r=.64,p<.1) LMCA, left min coronry rtery; plad, proximl left nterior descending rtery; plcx, proximl left circumflex rtery; prca, proximl right coronry rtery. jects, lthough the difference ws not sttisticlly significnt. In the postmortem study by Hutchins et l,2 coronry dimensions diminished significntly with ge in 57 crdiomyopthy ptients (ge, yers), lthough no overll effect of ge ws found in 33 norml ptients (ge, 6-79 yers). Possible Mechnisms for Age-Relted Chnge The exct mechnisms by which coronry dimensions decrese with ge is not certin. Possible explntions include 1) higher prevlence of concentric, ngiogrphiclly inpprent therosclerosis with incresing ge, 2) nontherosclerotic ge-relted subendothelil nd medil vessel wll thickening, 3) ttenuted coronry smooth muscle vsodiltory response to nitroglycerin in older subjects, 4) vessel size ltertions resulting from ge-relted decline in coronry flow demnds reflecting diminished physicl ctivity, nd 5) ge-relted chnge in myocrdil composition nd thus requirements for coronry blood flow. Age is well recognized fctor in coronry therosclerosis.28 Autopsy studies show tht coronry therosclerosis cn strt in childhood nd progress with dvncing ge The erliest lesion of therosclerosis, the ftty strek, is commonly present by 1-14 yers of ge. After ge 2 yers, ftty streks cn increse threefold with ppernce of dvnced lesions, fibrous plque, or therom tht my cuse loclized nd eccentric impingement on the coronry lumen nd thus become ngiogrphiclly pprent. It is evident from previous pthologicl studies nd more recent ngiogrphic studies tht concentric, reltively homogeneous therosclerosis my be present in vessels

11 Downloded from by on November 12, Circultion Vol 84, No 6 December 1991 tht pper ngiogrphiclly norml Although the use of different imging technology such s intrvsculr ultrsound my hve detected concentric, gerelted coronry therosclerosis, we believe tht by virtue of the stringent selection criteri, most of these ptients were truly disese free. Moreover, it is unlikely tht the 16% reduction in totl coronry cross-sectionl re in subjects from men ge yers nd the further 15% reduction from men ge yers could occur without development of some luminl irregulrity. Age-relted decline in nitroglycerin responsiveness is potentil fctor. However, nitroglycerin in ngiogrphiclly norml segments provokes 15-25% vsodilttion,35 the complete loss of which would be indequte to explin the mgnitude of ge-relted decline in vessel dimensions. Nontherosclerotic gerelted vessel wll chnges hve been documented in microscopic exmintion of coronry vessels of infnts nd children up to ge 2 yers.36 However, it is unlikely tht this "norml" developmentl chnge in the very young continues s n importnt fctor beyond this ge. Recently, the use of intrcoronry cetylcholine in subjects with ngiogrphiclly norml coronry rteries shows diminished DRF-medited coronry vsodilttion with ge.37 These findings suggest the presence of ngiogrphiclly inpprent endothelil bnormlities in most subjects studied beyond the ge of 3 yers.37 Although DRF-medited coronry vsodilttion decreses with ge, nitroglycerin responsiveness is mintined in these studies. In ddition, bnormlity in DRF-medited coronry dilttion lso occurs in trnsplnt ptients. Therefore, we used nitroglycerin before ngiogrphy in this study to induce mximl smooth-muscle vsodilttion nd to eliminte the possible effects of ltered DRF relese. Physicl ctivity hs been ssocited with increses in coronry dimensions,3839 prticulrly when ssessed fter nitroglycerin.4 Dt from the Frminghm Hert Study showed tht physicl ctivity declines with ge.41 In tht study, 24% of mle subjects ged yers prticipted in t lest 1 hour of conditioning ctivities (>31.5 kj/min) per week compred with only 3% of those ged 5 yers or older. This ge-relted decline in coronry flow demnds resulting from diminished physicl ctivity might ccount for the decrese in coronry vessel size. McAlpin et 15 speculted tht conditions tht ugment myocrdil oxygen requirements nd cuse myocrdil hypertrophy re ssocited with incresed size of epicrdil coronry rteries, rising the possibility tht the converse might lso occur. Recognizing the importnce of pthologicl conditions tht could ugment myocrdil work, ptients in this study were screened by both clinicl history nd exmintion nd by echocrdiogrphy (82% of subjects) to exclude myocrdil hypertrophy. In ddition, we found no difference in left ventriculr mss between the three ge groups. Previous studies hve lso shown tht left ventriculr mss usully remins unchnged or increses with ge Therefore, the decrese in coronry dimension with ging is probbly not medited through the effect of chnging left ventriculr mss. It is lso possible tht the composition of the myocrdium my chnge with ge. lderly herts my hve more interstitil tissue in reltion to myocytes nd, hence, less coronry flow demnd. Within this cohort of mle subjects with ngiogrphic mesurements obtined fter nitroglycerin dministrtion, there remins considerble subjectto-subject vribility in mesurements. Although, to some extent, this could reflect vribility in our ssessment of myocrdil territory frctions, it is probble tht genetic nd developmentl fctors contribute. Tble 5 provides rnge of mesurements tht cn be used s bsis for comprison. In ptients with visully pprent coronry disese, it is common to find portions of the coronry ntomy, prticulrly the left min nd other proximl rteries, tht pper concentriclly nd smoothly nrrowed but without discrete lesions.34 The results in Tble 5, lbeit limited to proximl segments nd mle subjects receiving nitroglycerin, provide n objective bsis for ssessing whether prticulr dimeter is within 95% probbility rnge. Adjustments for norml women, bsed on dt reported by McAlpin et l,5 suggest downwrd reduction in cross-sectionl re for women of 19% for the LMCA, 17% for the plad, 16% for the plcx, nd 12% for the prca. It is well estblished tht coronry dimensions re ffected by short-term physiologicl nd phrmcologicl interventions s well s by therosclerosis nd other vsculr diseses. The close reltion of epicrdil coronry vessel size to myocrdil oxygen demnds is supported not only by pst observtions in diseses tht increse myocrdil oxygen demnds (e.g., ortic stenosis nd systemic hypertension) but lso by our observtion in norml subjects of the close correltion between proximl coronry vessel size nd regionl left ventriculr mss. Presumbly, resting myocrdil oxygen demnds nd corresponding coronry blood flow re importnt determinnts of bsl coronry dimensions in humns. The ge-relted decline in epicrdil coronry dimensions rises the possibility tht reduction in either bsl coronry blood flow requirements or decline in the intermittent flow-medited stimulus provided by exercise provoction ccounts for ltered coronry epicrdil dimensions nd complince. Perhps short-durtion meditors of vsodilttion (e.g., DRF) hve longer-term effects tht lst beyond their immedite phrmcologiclly pprent vsculr response. The decline in coronry dimensions with ge hs multiple implictions. Clinicl trils using ngiogrphic end points my need to consider the ge of their subjects nd the confounding effects of phrmcologicl nd physiologicl interventions on vessel complince nd size of epicrdil coronry vessels

12 Downloded from by on November 12, 218 independent of ntitherosclerotic effects. It is lso possible tht reduction in epicrdil coronry crosssectionl re reltive to subtended myocrdium might contribute to diminished exercise cpcity of older individuls by incresing conduit vsculr resistnce nd thus decresing the trnsmyocrdil pressure grdient tht supports subendocrdil perfusion during exercise. Although multiple lterntive explntions for the decline in coronry dimensions with ge hve been discussed, most possibilities re not s persusive s the role of ge-relted decline in physicl ctivity. If periodic stimultion by exercise provokes increses in coronry blood flow tht, in turn, enhnces bsl coronry size nd/or complince, the converse is then likely; tht is, tht decline in physicl ctivity with ge diminishes coronry dimensions. This decline in coronry size my hve potentil dverse clinicl consequences in the setting of cute ischemi resulting from prtil vessel occlusion by either therom or thrombus. Acknowledgments We re indebted to Tommy C. Lee, MD; Sho- Zhou Go, MD; Anne Schwrzkopf, Voy Wiederhold, nd Brook Hollk for their substntil ssistnce in this project. References 1. hrlich W, de l Chpelle C, Cohn A: Antomicl ontogeny: A study of the coronry rteries. Am JAnt 1931;49: Hutchins GM, Bulkley BH, Miner MM, Boitnott JK: Correltion of ge nd hert weight with tortuosity nd cliber of norml humn coronry rteries. Am Hert J 1977;94: Rodriguez FL, Robbins SL: Cpcity of humn coronry rteries: A postmortem study. Circultion 1959;19: Wilens SL, Plir CM, Henderson DH: Size of the mjor epicrdil coronry rteries t necropsy: Reltion to ge, hert weight, nd myocrdil infrction. JAAA 1966;198: McAlpin RN, Abbsi AS, Grollmn JH, ber L: Humn coronry rtery size during life: A cinerteriogrphic study. Rdiology 1973;18: Vieweg WVR, Alpert JS, Hgn AD: Cliber nd distribution of norml coronry rteril ntomy. Cthet Crdiovsc Dign 1976;2: O'Keefe JH, Owen RM, Bove AA: Influence of left ventriculr mss on coronry rtery cross-sectionl re. Am J Crdiol 1987;59: Lewis BS, Gotsmn MS: Reltion between coronry rtery size nd left ventriculr wll mss. Br Hert J 1973;35: Pulsen S, Vetner M, Hgerup CM: Reltionship between hert weight nd the cross-sectionl re of the coronry osti. Act Pthol Microbiol Scnd 1975;83: Koiw Y, Bhn RC, Ritmn L: Regionl myocrdil volume perfused by the coronry rtery brnch: stimtion in vivo. Circultion 1986;74: Shn DJ, DeMri A, Kisslo J, Weymn A: The Committee on M-mode Stndrdiztion of the Americn Society of chocrdiogrphy: Recommendtions regrding quntittion in M-mode echocrdiogrphy: Results of survery of echocrdiogrphic mesurements. Circultion 1978;58: Devereux RB, Reichek N: chocrdiogrphic determintion of left ventriculr mss in mn: Antomic vlidtion of the method. 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13 236 Circultion Vol 84, No 6 December Ysue H, Mtsuym K, Mtsuym K, Okumur K, Morikmi Y, Ogw H: Responses of ngiogrphiclly norml humn coronry rteries to intrcoronry injection of cetylcholine by ge nd segment: Possible role of erly coronry therosclerosis. Circultion 199;81: Mnn VG, Spoerry A, Gry M, Jrshow D: Atherosclerosis in the Msi. Am J pidemiol 1972;95: Rose G, Prines RJ, Mitchell JRA: Myocrdil `infrction nd the intrinsic clibre of coronry rteries. Br Hert J 1967;29: Sims C, Aldermn L, Myll J, Bortz WJ, St Gor F, Hskell WL: Coronry size nd dilting cpcity of endurnce thletes (bstrct). Circultion 199;82(suppl LII):III Svge DD, Levy D, Dnnenberg AL, Grrison RJ, Cstelli WP: Assocition of echocrdiogrphic left ventriculr mss with body size, blood pressure nd physicl ctivity (The Frminghm Study). Am J Crdiol 199;65: Dnnenberg AL, Levy D, Grrison RJ: Impct of ge on echocrdiogrphic left ventriculr mss in helthy popultion (The Frminghm Study). Am J Crdiol 1989;64: Devereux RB, Luts M, Csle PN, Kligfield P, isenberg RR, Hmmen IW, Miller DH, Reis G, Aldermn MH, Lrgh JH: Stndrdiztion of M-mode echocrdiogrphic left ventriculr ntomic mesurements. J Am Coll Crdiol 1984;4: Grdin JM, Henry WL, Svge DD, Wre JH, Burn C, Borer JS: chocrdiogrphic mesurements in norml subjects: vlution of n dult popultion without cliniclly pprent hert disese. J Clin Ultrsound 1979;7: KY WORDS * rteriogrphy * crdic ctheteriztion e coronry rteries Downloded from by on November 12, 218