Prevalence and Significance of Residual Flow to the Infarct Zone During the Acute Phase of Myocardial Infarction

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1 lacc Vl. 5, N CLINICAL STUDIES Prevalence and Significance f Residual Flw t the Infarct Zne During the Acute Phase f Mycardial Infarctin HEINER BLANKE, MD, MARC COHEN, MD, FACC, KARL R, KARSCH, MD, RICHARD FAGERSTROM, PHD, K. PETER RENTROP, MD, FACC New Yrk, New Yrk and Gettingen, West Germany Residual 1Iw t the infarct ne was assessed by crnary angigraphy during the acute phase f mycardial infarctin in 13 patients. In 36 patients, the infarctrelated crnary artery was nt cmpletely bstructed, thereby prviding residual antergrade 1Iw t the infarct area (Grup I). Cmplete bstructin f the infarct vessel with residual 1Iw t the infarct ne by means f cllateral circulatin was bserved in 56 patients (Grup ). Cmplete bstructin f the infarct vessel withut residuaw was seen in 38 patients (Grup I). Ejectin fractin during the acute phase f infarctin was fund t be significantly higher in Grup I (55 ± 13%) than in either Grup (48 ± 13%) r Grup I (5 ± 1%) (p <.5). Grup patients had a lnger histry f angina pectris (14.2 ± 21.4 mnths) than did Grup I patients (.7 ± 3.1 mnths) (p <.1). Patients in Grup I and Grup were mre likely t be taking antianginal medicatin (56 and 54%, respectively) than were the patients in Grup I (16%) (p <.1). Thirty-seven patients in whm reperfusin techniques were nt emplyed had repeat angigraphy in the chrnic phase f infarctin, enabling assisement f spntaneus changes in left ventricular functin and crnary mrphlgy. Ejectin fractin (EF) did nt change significantly frm the acute t the chrnic stage in Grup I (.1EF = -1.3 ± 11.4%; n = 12) r Grup (.1EF = -1.4 ± 7.9%; n = 16); hwever, there was a significant decrease in Grup I (.1EF = -1.1 ± 7.5%; n = 9; p <.1). Tw findings characteried the patients with initial cmplete crnary bstructin whse ejectin fractin did nt decrease: cllateral 1Iw t the infarct area at angigraphy during the acute phase f infarctin in cnjunctin with spntaneus recanaliatin demnstrated at later repeat angigraphy. It is cncluded that the prevalence f residual 1Iw may be an imprtant cvariate in assessing the efficacy f interventins designed t limit infarct sie. (J Am Cli CardiI1985;5:827-3l) Crnary arterigraphy during the acute phase f mycardial infarctin can identify the presence and type f residual flw int the infarct ne (1-4). Residual flw can be present either in an antergrade fashin if the infarctrelated crnary vessel is incmpletely bstructed r in a retrgrade fashin by means f intercrnary cllateral channels. Thus, the infarct area can be characteried by three arterigraphic patterns: presence f antergrade flw, presence f retrgrade flw r cmplete avascularity. In the present study, the prevalence f these three patterns during the initial hurs f mycardial infarctin is assessed. In Frm the Divisin f Cardilgy, Department f Medicine, Munt Sinai Schl f Medicine and Munt Sinai Hspital, New Yrk, New Yrk and the Department f Medicine, University f Gettingen, Gettingen, West Germany. This study was supprted in part by the Snderfrschungsbereich 89 f the Deutsche Frschungsgemeinschaft, Gettingen, West Germany. Manuscript received September ; revised manuscript received Octber 3, 1984, accepted Nvember IS, Address fr reprints: K. Peter Rentrp, MD, Divisin f Cardilgy, Munt Sinai Hspital, One Gustave Levy Place, New Yrk, New Yrk by the American Cllege f Cardilgy additin, the three arterigraphic patterns are crrelated with clinical characteristics and acute left ventricular functin. Lastly, the different arterigraphic patterns are crrelated with sequential changes in left ventricular functin in a subset f patients in whm the natural histry f crnary disease was nt altered by attempted reperfusin. Methds Study patients. Between January 1977 and December 198, immediate cardiac catheteriatin and angigraphy were perfrmed in 158 patients presenting t the University f Gettingen Hspital with an admissin diagnsis f acute mycardial infarctin. The admissin diagnsis was based primarily n a histry f acute nset f chest pain f 3 minutes' duratin r lnger, which was suggestive f mycardial ischemia and nt relieved by sublingual nitrglycerin. Patients presenting 6 t 12 hurs after the nset f acute symptms were ffered catheteriatin nly if there was persistent chest pain suggestive f nging ischemia /85/$3.3

2 828 BLANKE ET AL. RESIDUAL FLOWTO INFARCf ZONE lacc Vl. 5, NO.4 April 1985: Patients with additinal nncrnary heart disease r incurable chrnic diseases were excluded frm immediate catheteriatin. Infrmed written cnsent was btained befre angigraphy. Ofthe J58 patients wh underwent catheteriatin during the acute stage f infarctin, 28 were excluded frm the study. In six patients, the diagnsis f acute mycardial infarctin was nt cnfirmed because the serum level f creatine kinase and its MB fractin failed t increase t at least twice the upper limit f nrmal. In eight patients, crnary arterigraphy was incmplete r the infarct-related artery culd nt be determined because f multiple ttal cclusins. In 14 patients, clinical and histrical data btained were nt cmpletefr the purpse f this study. Thus, the ttal study grup cnsisted f 13 patients with cmplete angigraphic and clinical data in whm the diagnsis f acute mycardial infarctin was cnfirmed by histry and serum enyme data. All patients except thse in cardigenic shck received intravenus nitrglycerin fr at least 72 hurs and heparin sulfate until they became ambulatry. Twenty-ne f the 13 patients were treated with intraartic balln cunterterpulsatin immediately after the baseline ventriculgraphic study and befre crnary angigraphy. These patients participated in a study which evaluated the effect f cunterpulsatin n infarct sie. Clinical data. The same bserver (H.B.) btained the medical histry and perfrmed the clinical examinatin at the time f admissin fr all patients. The fllwing variables were evaluated : histry f previus mycardial infarctin; time interval frm the first nset in life f angina pectris t the present infarctin; time interval frm nset f acute infarct symptms t emergency angigraphy; current use f antianginal medicatins including beta-receptr blcking agents, nitrates r calcium channel blcking drugs; age and sex. Just befre angigraphy was perfrmed during the acute phase f infarctin, each patient was assigned t a Kip functinal class. Angigraphic data. Biplane left ventriculgraphy and selective arterigraphy f bth crnary arteries were perfrmed in all patients as described previusly (5). The extent f crnary artery disease was cnsidered as the sum f all main epicardial branches with a 7% r greater narrwing in luminal diameter. The infarct-related artery and infarct ne were determined by crrelating arterigraphic findings with acute electrcardigraphic changes and the lcatin f wall mtin abnrmalities as assessed by cntrast ventriculgraphy. Cllateral flw t the infarct ne was determined t be present if tw angigraphers agreed that any prtin f the infarct-related artery was visualied via cllateral channels. Retrgrade fing f side branches that riginated distal frm the site f bstructin was accepted as evidence fcllateral flw, even if the epicardial segment f the infarct-related artery was nt visualied. Left ventricular ejectin fractin was calculated using the area-length methd (6). On the basis fthe angigraphic findings, three grups fpatients were defined. Grup I included patients whse infarct-related crnary artery was nt cmpletely bstructed, prviding antergrade flw t the infarct area. Grup cnsisted f patients with cmplete bstructin f the infarct-related artery and cllateral flw t the infarct area. Grup I included patients with an avascular infarct, that is, cmplete bstructin f the infarct-related artery and absence f cllateral flw. FUw-up angigraphy. Thirty-seven patients wh were studied befre the advent f reperfusin techniques returned fr repeat crnary arterigraphy and biplane left ventriculgraphy 89 ± 88 days after the initial angigram. Nne f these patients underwent crnary bypass surgery during the interval between the initial and fllw-up evaluatin. This subset was divided accrding t the acute arterigraphic patterns as defined fr the ttal study grup. Statistics. Three lgistic regressin analyses were cnducted, cmparing tw grups f patients at a time. Seven clinical variables and fur variable s determined at angigraphy were cnsidered. In a univariate analysis, each variable was evaluated fr its ability t discriminate between the tw grups at a prbability (p) value f less than.5. Subsequently a stepwise multivariate regressin analysis was perfrmed t determine a cmbinatin f independent variables that discriminated amng the grups. The examinatin f the differences in ejectin fractin change in the subset f patients with fllw-up angigraphy invlved ne-way analysis f variance and multiple cmparisns using Fisher's least significant difference technique. Results Baseline clinical and angigraphic characteristics (Table 1). Angigraphy in the acute phase revealed incmplete bstructin f the infarct-related artery in 36 patients (Grup I) ; in 2 f these patients cllateral channels t the infarct vessel were seen. Cmpletebstructin f the infarct-related artery and residual flw t the infarct area thrugh cllateral channels were fund in 56 patients (Grup ). The remaining 38 patients had an avascular infarct (Grup I). Intraartic balln cunterpul satin was in effect at the time f crnary arterigraphy in 3 Grup I patients, 13 Grup patients and 5 Grup I patients. The time interval frm the nset f angina pectris t infarctin was significantly lnger in Grup (14.2 ± 21.4 mnths) than in Grup I (.7 ± 3.1 mnths) (Fig. 1). Grup I patients als had a lnger histry f angina pectris than did Grup I patients; this difference was nt independently significant when antianginal medicatin was taken int accunt. Patients in bth Grups J and were significantly mre

3 lacc Vl. 5, N.4 BLANKE ET AL. 829 Table 1. Clinical and Angigraphic Characteristics f 13 Patients Ttal Occlusin Subttal Occlusin WithCll Withut Cll (n = 36) (n = 56) (n = 38) Age (yr) 56 ± 9 56 ± ± 1 Male (n. l%]) 32 (89%) 5 (89%) 33 (83%) Previus MJ 4(11%) 5 (9%) 2 (5%) Interval frm nset f 6.5 ± ± ± 3.1 AP t MI (m) Antianginal medicatins 2 (56%) 3 (54%) 6 (/6%) Interval frm nset f 8.2 ± ± ± 4. acute symptms t angi (hurs) Kip class I r 2 34 (94%) 51 (91%) 35 (92%) 3r4 2 (6%) 5 (9%) 3 (8%) LV systlic pressure (mm Hg) 126 ± ± ± 21 LVEDP (mm Hg) 16 ± 9 16 ± 8 16 ± 6 Infarct-related artery LAD 21 (58%) 34 (61%) 2 (53%) RCA 8 (22%) 16 (29%) 9 (24%) LCx 7 (/9%) 6 (11%) 9(24%) Extent f CAD 1 vessel 23 (64%) 32 (57%) 3 (79%) 2 vessel (31%) 16 (29%) 8 (21%) 3 vessel 2 (6%) 8 (/4%) EF (%) acute phase 55 ± ± 13 5 ± 1 EF (%) acute phase (subset)* 53 ± (n = 12) 51 ± 9 (n = 16) 47 ± 9 (n = 9) Delta EF (%)* 1.3± ± I ± 7.5 *Subset f patients with fllw-up angigraphy. Data are reprted as mean values ± standard deviatin. Angi = acute angigraphy; AP = angina pectris; CAD = crnary artery disease; Cil = cllateral vessels; EF = left ventricular ejectin fractin; Delta EF = the mean change in ejectin fractin frm the acute phase t the chrnic phase; LAD = left anterir descending crnary artery; LCx = left circumflex crnary artery; LVED? = left ventricular end-diastlic pressure; MI = mycardial infarctin; RCA = right crnary artery. likely t be treated with antianginal drugs (56 and 54%, respectively) than were patients in Grup I (16%) (Fig. 2). The time interval between the nset f acute symptms and emergency angigraphy was significantly lnger in Grup I (8,2 ± 7.5 hurs) and Grup (8.1 ± 6.6 hurs) than Figure 1. Duratin f chrnic angina pectris frm first nset in life t current infarctin fr the three grups f patients. Grup I = patients with subttal cclusin; Grup = patients with ttal cclusin but with cllateral flw; Grup I = patients with ttal cclusin and n cllateral flw. <[ Z l3 <[ 4 f-p<o.oh in Grup I (5. ± 4. hurs) (Fig. 3), In additin, Grup patients were mre likely t have multivessel crnary artery disease than were Grup I patients; hwever, this difference was nt independently significant when the interval frm first nset fangina t infarctin was cnsidered. Left ventricular ejectin fractin in the acute phase was signficantly higher in Grup I (55 ± 13%) than in either Grup (48 ± 13%) r Grup I (5 ± 1%) (Fig. 4). Figure 2. The percent f patients in each grup using antianginal medicatin (MEDS) at the time f admissin fr acute mycardial infarctin. u, 3 lil Q-E I- c: <[ a:: E 2 :::>- u 1 a:: ::I: u 6 (/) ZCl OUJ 5 (/) Z<[ 4 UJ j::- <[ Il. 3 <[ u..' OJ:: 2 * <[ 1 f---p<o. Ol-----i f-p<o.oh

4 83 BLANKE ET AL. lacc Vl. 5. N.4 'in 2 t; <t P<O.5--i Z f-p=o.oh 16 <t u.. 12 i= <t 8 a:: 4 UJ U <t I Figure 3. Interval frm the nsetf symptms f acute infarctin t angigraphy. There were n ther significant differences between Grups I and. Changes in ejectin fractin and mrphlgy f the infarct-related artery frm the acute t the chrnic stage. Fllw-up angigraphy in the chrnic stage f infarctin was perfrmed in 12 Grup I patients, 16 Grup patients and 9 Grup I patients. Ejectin fractin did nt change significantly frm the acute t the chrnic phase in either Grup I r Grup (Table 1, Fig. 5). Hwever, there was a significant decrease in ejectin fractin in Grup I ( ± 7.5%, P <.5). Repeat crnary angigraphy revealed patency f the initially cmpletely bstructed infarct vessel in 7 f 16 Grup patients and 4 f the 9 Grup I patients and prgressin t ttal cclusin in 2 f the 12 Grup I patients. Imprvement in left ventricular ejectin fractin was seen nly in thse Grup patients in whm spntaneus recanaliatin Figure 4. Left ventricular ejectinfractin (EF) in the acutephase f infarctin. 7 6!.. 5 u, 4 I- <l I-P<O.5-l f---p<o I <l 4 :: IJ.. Z 3 2 J 1 Acute SUBTOTAL n=12 TOTAL WITH COLLATERALS n=16 TOTAL WITHOUT COLLATERALS n=9 OL.- -L L.- -l Chrnic Figure 5. Left ventricular ejectin fractin in 37 patients during the acute and chrnic phases f infarctin fr the three grups f patients. --- refers t thse patients wh demnstrated spntaneus recanaliatin f the infarct-related vessel duringthe chrnic phase. had ccurred (Fig. 5). Patients with an avascular infarct as well as thse with cllateral vessels in whm the infarctrelated vessel did nt spntaneusly recanalie shwed a decrease in ejectin fractin (Fig. 5). Discussin Rle f crnary cllateral vessels. Previus studies (4,7) n the difference in duratin f angina pectris befre infarctin between patients with and withut cllateral flw yielded cntradictry results. In cntrast t the present study, Nhara et al. (4) fund n difference between patients with and withut cllateral flw. Their study emplyed acute in viv angigraphy; hwever, their sample sie was small. In agreement with ur findings, Fultn (7), wh crrelated clinical and autpsy data, bserved that patients with ttal cclusin and cllateral fing had a lnger histry f angina pectris than did patients withut cllateral fing. New nset f ischemic chest pain indicates that narrwing in a crnary artery has reached the critical degree at which there is interference with mycardial bld supply. A critical crnary artery narrwing is a pwerful stimulus fr the enlargement f cllateral channels (8). The time interval between the develpment f a critical stensis and thrmbtic cclusin appears t be shrter in thse patients withut cllateral flw than in patients with cllateral flw, the majrity f the frmer being characteried by a mre recent nset f anginal symptms fr which treatment has nt yet been initiated. These findings are cmpatible with Fultn's hypthesis that a minimal perid f time is necessary fr the enlargement f cllateral channels in human beings.

5 JACCVl. 5. N.4 BLANKE ET AL. 831 Althugh duratin f angina and prevalence f antianginal therapy befre infarctin are similar in patients wh have cmplete crnary bstructin with cllateral flw and patients with incmplete bstructin f the infarct-related artery, cllateral vessels were seen in nly tw patients f the latter grup. The pressure gradient acrss the cllateral cnduit is mst likely higher in patients with cmplete crnary bstructin than in thse with incmplete bstructin. Angigraphic studies during angiplasty in patients with a severe crnary lesin and lng-term angina have shwn that cllateral vessels ften becme immediately visible when antergrade flw is blcked cmpletely (9). The finding f a significantly shrter time interval between the nset f infarct pain and angigraphy in patients with an avascular infarct as cmpared with thse with residual flw culd be related t spntaneus early reperfusin. Alternatively, this difference may be explained by ur patient selectin criteria; patients presenting mre than 6 hurs after nset f infarctin were nt ffered catheteriatin in the acute phase unless the presence f ischemic viable mycardium was suggested by persistent chest pain. Our finding f a higher ejectin fractin during the acute phase f infarctin in patients with incmplete crnary bstructin as cmpared with thse with cmplete bstructin and cllateral flw suggests that antergrade flw thrugh a subttal lesin is larger than retrgrade flw thrugh cllateral channels, even if the subttal lesin is severe enugh t cause an acute infarctin. Preservatin f left ventricular functin and antergrade flw. Imprvement r preservatin f left ventricular functin during the time frm the acute t the chrnic phase f infarctin appears t depend n the preservatin r restratin f antergrade bld flw. All patients in whm the infarct-related vessel was cmpletely ccluded at initial and late angigraphy shwed a decrease in ejectin fractin. The grup f patients with subttal cclusin f the infarctrelated vessel at acute angigraphy did nt experience a significant decrease in left ventricular ejectin fractin. In thse patients with ttal cclusin in whm spntaneus recanaliatin ccurred, preservatin f functin seems t depend n an additinal factr: the presence f cllateral flw during the acute phase f infarctin. It is pssible that in this latter patient subset cllateral flw slwed the prgressin f mycardial necrsis frm the inner t uter layers f the ventricular wall, enabling spntaneus reperfusin t limit infarct sie in sme patients. Clinical implicatins. Our findings suggest that the availability f residual crnary flw t infarcting mycardium w influence the extent f damage. On the basis f several uncntrlled studies (2,3), it has been pstulated that the effectiveness f varius interventins designed t limit infarct sie may als be related t the availability f residual flw. In patients with an avascular infarct. intracrnary streptkinase infusin was assciated with imprvement in left ventricular functin nly if therapy cmmenced within 3 hurs after the nset f symptms (I). In patients with residual crnary flw, imprvement in functin was seen even when thrmblytic therapy was initiated later. In ther studies (1, ), intraartic balln cunterpulsatin and beta-receptr blckade were assciated with cntrl f ischemia, as suggested by clinical signs, nly in thse patients with residual crnary flw. The prevalence f the three angigraphic patterns described in the present study varies cnsiderably with that reprted in previus investigatins. Thus, incmplete bstructin f the infarct-related vessel was bserved in 5 (12) t 33% (13) f patients wh had early angigraphy. In the design f trials evaluating interventins t limit infarct sie, ne must cnsider that the early angigraphic pattern may be an imprtant cvariate influencing utcme. References I. Rentrp KP. Blanke H. Karsch KR. et al. Changes in left ventricular functin after intracrnary streptkinase infusin in clinically evlving mycardial infarctin. Am Heart J 1981;12: Rentrp P. Smith H. Painter L. Hlt J. Changes in left ventricular ejectin fractin after intracrnary thrmblytic therapy: results f the Registry f the Eurpean Sciety f Cardilgy. Circulatin 1983;68(suppl 1): Rgers WJ. Hd WP Jr. Mantle JA. et al. Return f left ventricular functin after reperfusin in patients with mycardial infarctin: imprtance f subttal stensis r intact cllaterals. Circulatin 1984;69: Nhara R. Kambara H. Murakami T. Kadta K. Tamaki S, Kawai C. Cllateral functin in early acute mycardial infarctin. Am J Cardil 1983;52: Rentrp P, Blanke H, Karsch KR. Kreuer H. Krnarmrphlgie und links-ventrikulaere Pumpfunktin im akuten Infarkstadium und ihre Aenderugen im chrnischen Stadium. Z Kardil 1979;68: Ddge HT, Sandler H. Baxley WA. Hawley RR. Usefulness and limitatins f radigraphic methds fr determining left ventricular vlumes. Am J Cardil 1966;18: Fultn WFM. The time factr in the enlargement f anastmses in crnary artery disease. Sctt Med J 1964;9: Khuri EM. Gregg DE, McGranahan GM Jr. Regressin and reappearance f crnary cllaterals, Am J Physil 1971;22: Rentrp P. Chen M, Phips R. Blanke H. Acute changes in cllateral fing during translurninal crnary angiplasty (abstr). Eur Heart J 1984;5(suppll): Leinbach RC, Gld HK. Harper RW, Buckley MJ, Austen WG. Early intraartic balln pumping fr anterir mycardial infarctin withut shck. Circulatin 1978;58: Gld HK. Leinbach RC. Harper RW. Usefulness f intravenus prpranll in predicting left anterir descending bld flw during anterir mycardial infarctin. Am J Cardil 1984;54: Mathey DG. Kuck KH. Tilsner V, Krebber HJ, Bleifeld W. Nnsurgical crnary artery recanaliatin in acute transmural mycardial infarctin. Circulatin 1981;63: Rentrp P. Feit F, Schneider R. Blanke H, Stecy p. and the Reperfusin Study Grup. Mt Sinai/New Yrk University Randmied Reperfusin Trial: pilt phase (abstr). J Am Cli Cardil 1984;3:525.

Time From Onset of Symptoms to Thrombolytic Therapy: A Major Determinant of Myocardial Salvage in Patients With Acute Transmural Infarction

Time From Onset of Symptoms to Thrombolytic Therapy: A Major Determinant of Myocardial Salvage in Patients With Acute Transmural Infarction 518 lacc Vl. 6. N.3 CLNCAL STUDES Time Frm Onset f Symptms t Thrmblytic Therapy: A Majr Determinant f Mycardial Salvage in Patients With Acute Transmural nfarctin DETLEF G. MATHEY, MO, FACC, FLORENCE H.