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Influence of Collateral Circulation on In-Hospital Death From Anterior Acute Myocardial Infarction ´ REZ-CASTELLANO, MD, EULOGIO J. GARCI´A, MD, MANUEL ABEYTUA, MD, NICASIO PE ´ A. SERRANO, MD, JAIME ELI´ZAGA, MD, JAVIER BOTAS, MD, JAVIER SORIANO, MD, JOSE ´ L. LO ´ PEZ-SENDO ´ N, MD, FACC, JUAN L. DELCA ´ N, MD JOSE Madrid, Spain

Objectives. Our purpose was to study whether the in-hospital prognosis of anterior acute myocardial infarction (AMI) is influenced by preexistent collateral circulation to the infarct-related artery. Background. Collateral circulation exerts beneficial influences on the clinical course after AMI, but demonstration of improved survival is lacking. Methods. We studied 238 consecutive patients with anterior AMI treated by primary angioplasty within the first 6 h of the onset of symptoms. Fifty-eight patients with basal Thrombolysis in Myocardial Infarction (TIMI) flow >1 in the infarct-related artery or with inadequate documentation of collateral circulation were excluded. Collateral channels to the infarct-related artery before angioplasty were angiographically assessed, establishing two groups: 115 patients (64%) without collateral vessels (group A) and 65 patients (36%) with collateral vessels (group B).

Results. There were no differences in baseline characteristics between groups A and B, except for the greater prevalence of previous angina in group B (15% vs. 34%, p 5 0.003). During the hospital stay, 26 patients (23%) in group A and 5 (8%) in group B died (p 5 0.01). Cardiogenic shock accounted for 74% of deaths. Cardiogenic shock developed in 30 patients (26%) in group A and in 4 (6%) in group B (p 5 0.001). The absence of collateral circulation appeared to be an independent predictor of in-hospital death (odds ratio 3.4, 95% confidence interval 1.2 to 9.6, p 5 0.02) and cardiogenic shock (odds ratio 5.6, 95% confidence interval 1.9 to 17, p 5 0.002). Conclusions. Preexistent collateral circulation decreases inhospital death from anterior AMI by reducing the incidence of cardiogenic shock. (J Am Coll Cardiol 1998;31:512– 8) ©1998 by the American College of Cardiology

In recent years, coronary collateral circulation in the setting of ischemic heart disease and particularly in myocardial infarction has been subjected to special interest. Some degree of collateral circulation is present at the onset of acute myocardial infarction (AMI) in nearly 40% of patients (1,2). Several studies have shown that the residual blood flow carried by collateral vessels at the time of AMI exerts some beneficial effects such as reduction in infarct size (3–5), improvement in residual ejection fraction and other indexes of pump function (6 – 8) and prevention of left ventricular aneurysm formation (9). However, a demonstration of whether collateral circulation improves prognosis after AMI is lacking (10,11). The purpose of our study was to determine whether the presence of collateral circulation to the infarct-related artery in the first hours of coronary occlusion decreases the in-hospital

mortality rate of patients with AMI. To assess angiographically the existence of collateral circulation early in AMI, when myocardial necrosis is taking place and theoretically the benefit of collateral circulation could be maximal, we selected those patients treated by primary percutaneous transluminal coronary angioplasty (PTCA). Because patients with nonanterior AMI had less frequently undergone primary PTCA in our institution, we selected for the present study only patients with anterior wall AMI to obtain a more homogeneous population.

From the Division of Interventional Cardiology, Department of Cardiology, “Gregorio Maran˜o´n” University General Hospital, Madrid, Spain. This work was presented in part at the XIXth Congress of the European Society of Cardiology, Stockholm, Sweden, August 1997 and was accepted for presentation at the 70th Annual Scientific Sessions of the American Heart Association, Orlando, Florida, November 1997. Manuscript received July 1, 1997; revised manuscript received October 23, 1997, accepted November 19, 1997. Address for correspondence: Dr. Nicasio Pe´rez-Castellano, Departamento de Cardiologı´a, Hospital General Universitario “Gregorio Maran˜o´n,” C/Doctor Esquerdo 46, 28007 Madrid, Spain. E-mail: [email protected]. ©1998 by the American College of Cardiology Published by Elsevier Science Inc.

Methods Study patients. We selected patients who fulfilled all the following criteria: 1) admission to the hospital because of suspected anterior wall AMI (continuous ischemic chest pain lasting .30 min and a minimum of 0.2 mV of ST segment elevation in two contiguous anterior precordial leads); 2) diagnostic coronary angiography showing complete occlusion of the left anterior descending coronary artery (LAD) (Thrombolysis in Myocardial Infarction [TIMI] flow grade 0 or 1); 3) treatment by primary PTCA within the first 6 h of the onset of symptoms; and 4) left and right coronary angiograms obtained before the attempted angioplasty of sufficient quality to assess the filling of the LAD and side branches by collateral circula0735-1097/98/$19.00 PII S0735-1097(97)00521-4

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Abbreviations and Acronyms AMI 5 acute myocardial infarction AV 5 atrioventricular CABG 5 coronary artery bypass graft surgery CK-MB 5 creatine kinase, MB fraction LAD 5 left anterior descending coronary artery PTCA 5 percutaneous transluminal coronary angioplasty TIMI 5 Thrombolysis in Myocardial Infarction (trial)

tion. Patients with AMI secondary to acute or subacute coronary occlusion after PTCA or coronary artery bypass graft surgery (CABG) and patients treated by PTCA after failed thrombolysis (rescue PTCA) were not considered. Coronary angiography and primary angioplasty. Patients received 300 mg of aspirin intravenously as soon as possible unless there was a known allergy. Coronary angiography and primary PTCA were performed in the first 6 h from the onset of symptoms of AMI. Left heart catheterization and left ventriculography were not performed at this time. Once the femoral artery was catheterized, 10,000 IU of heparin was administered with additional boluses of 3,000 IU if needed to achieve an activated clotting time of $350 s. Coronary arteriograms were obtained in at least two projections. Intracoronary nitroglycerin was not administered before diagnostic angiograms were obtained. Flow in the LAD was determined before and after primary PTCA and graded as described in the TIMI trial (12). The LAD occlusion was considered proximal if it was located before the origin of the first well developed septal branch, distal if it was located after the origin of the third diagonal branch and mid if located between these limits. Coronary stenoses were measured by an on-line automatic edge detection system (Phillips DCI). Angiographic images were recorded on 35-mm film at 12.5 frames/s. Primary PTCA was performed with conventional catheter balloon technique. Stents were used only for suboptimal balloon angioplasty result. The policy was to perform angioplasty only to the infarct-related artery, but in exceptional cases additional angioplasty to another vessel was performed because of compromised hemodynamic status. Intraaortic balloon pumping was used in patients with hemodynamic instability or established cardiogenic shock. The primary PTCA was considered successful when flow in the infarct-related artery at the end of the procedure was TIMI grade 2 or 3 and the residual stenosis was ,50%. Coronary collateral circulation. We analyzed the collateral circulation to the occluded LAD existent in the first 6 h of AMI before the angioplasty attempt. It was assessed in coronary cineangiograms by two experienced coronary angiographers who had no knowledge of patient data. We excluded from the present study patients whose angiograms were inadequate for assessing the collateral circulation to the LAD because the injection period was too short, filming of the LAD territory in contralateral injections was incomplete or right coronary angiograms were not obtained before angioplasty. Collateral

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circulation was graded by using a semiquantitative scale from 0 to 3 (collateral index) depending on the degree of angiographic opacification of the occluded LAD in the best injection (13): 0 5 no collateral circulation; 1 5 collateral filling of LAD side branches without visualization of any epicardial segment; 2 5 collateral partial filling of the epicardial segment, and 3 5 collateral filling of the complete epicardial segment. In case of noncoincidence, the angiographers reached a consensus. Groups. In the prospective design of this study we decided to classify the patients into two groups: group A, patients without angiographic collateral filling of the LAD or side branches (collateral index 0), and group B, patients with some angiographic collateral filling of the LAD or side branches (collateral index 1, 2 or 3). In-hospital clinical course. Adjunctive medical therapy followed the standards of the coronary care unit. The primary objective of this study was to examine in-hospital death. Secondary objectives were to examine the occurrence of reinfarction, malignant arrhythmias, mechanical complications and cardiogenic shock. Reinfarction was defined as the recurrence of ischemic chest pain of $30-min duration with ST segment elevation of $0.1 mV over the previous ST segment in two contiguous leads and an MB fraction of creatine kinase (CK-MB) profile consistent with the diagnosis. Malignant arrhythmias included sustained ventricular tachycardia, ventricular fibrillation or high degree atrioventricular (AV) block. Mechanical complications included free wall rupture, ventricular septal rupture and severe mitral regurgitation secondary to papillary muscle rupture. Cardiogenic shock was indicated by a systolic blood pressure ,90 mm Hg in association with signs of tissue hypoperfusion (cold extremities, cyanosis, oliguria or altered mental status) not derived from extramyocardial causes (hypovolemia, arrhythmias, tamponade, drugs). Statistical analysis. Continuous variables that did not follow a normal distribution according to the Shapiro-Wilk test such as age, CK-MB peak serum level and residual stenosis, are expressed as median and the 25th and 75th percentiles. Time followed a normal distribution and is expressed as mean 6SD. For comparisons of continuous variables between both groups the Student t test for unpaired observations was used. Unless otherwise specified, categoric variables are presented in the text and tables as number and percent of patients. We used the chi-square test to compare categoric variables between groups unless expected values were ,5, in which case we used the Fisher exact test. The association between collateral circulation as a four-grade variable and mortality was analyzed by using the Mantel-Haenszel test; collateral indexes 2 and 3 were combined because their expected values were ,5. Multivariate analyses for mortality and cardiogenic shock were performed by multiple logistic regression. Odds ratios were expressed together with 95% confidence intervals. All results were analyzed by using a two-sided significance level of 0.05, but all p values , 0.20 are reported. Data analyses were performed by using the statistical software JMP 3.0.1 from SAS Institute Inc, 1994, and SPSS 4.0 from SPSS Inc, 1990.

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Table 1. Descriptive Data and In-Hospital Course of the Initial 238 Patients Age (yr) Median (25th, 75th percentiles) Range Cardiogenic shock at admission Angiographic findings and primary angioplasty Baseline TIMI flow in LAD Grades 0 or 1 Grades 2 or 3* Multivessel disease Successful primary angioplasty† In-hospital clinical course Reinfarction Malignant arrhythmias‡ Mechanical complications§ Cardiogenic shock In-hospital death

65 (55, 71) 35–91 37 (16%)

205 (86%) 33 (14%) 114 (48%) 214 (90%) 10 (4%) 36 (15%) 8 (3%) 46 (19%) 39 (16%)

*Patients with a TIMI flow grade 2 or 3 excluded from the study. †TIMI flow grade $2 and residual stenosis ,50%. ‡Sustained ventricular tachycardia/ fibrillation or high degree atrioventricular block. §All mechanical complications were free wall ruptures. Data presented are number (%) of patients, unless otherwise indicated. LAD 5 left anterior descending coronary artery; TIMI 5 Thrombolysis in Myocardial Infarction trial.

Results Patients and study groups. From July 1991 to September 1996, 238 patients with suspected anterior wall AMI were treated in our institution by primary PTCA within the first 6 h from the onset of symptoms. One hundred twenty-seven of these patients were treated by primary PTCA because they were enrolled in investigative trials; the majority of them were randomly selected in a trial comparing PTCA with thrombolytic treatment. These protocols required informed written consent and were approved by the review committee of our institution. The remaining patients were selected to be treated by primary PTCA because they had contraindications to thrombolytic treatment, cardiogenic shock, a large infarction or other high risk characteristics. The descriptive data and clinical in-hospital course of this group are summarized in Table 1. For the present analysis, we selected 180 of these patients who fulfilled the criteria just described. The 58 patients who did not fulfill the criteria had left coronary angiograms showing a patent LAD (25 patients) with TIMI flow grade $2 (33 patients) or had angiograms inadequate for assessing the collateral circulation to the LAD, mostly because right coronary angiography was not performed before angioplasty. Of the 180 patients included, 115 patients (64%, group A) did not have angiographically visible collateral circulation to the LAD (collateral index 0). In the remaining 65 patients (36%, group B), we found some collateral filling of the LAD (collateral index 1 in 33 patients [18%], index 2 in 23 patients [13%] and index 3 in 9 patients [5%]). Baseline characteristics. The baseline clinical characteristics of groups A and B are summarized in Table 2. Significant differences between groups were not found in age, gender or

Table 2. Baseline Clinical Characteristics of Study Groups

Age (yr) Female gender Hypercholesterolemia Hypertension Cigarette smoking Diabetes mellitus Previous angina Previous MI Out of hospital cardiac arrest

Group A (n 5 115 [64%])

Group B (n 5 65 [36%])

p Value

64 (53, 71) 21 (18%) 28 (24%) 39 (34%) 68 (59%) 26 (23%) 17 (15%) 13 (11%) 8 (7%)

64 (57, 70) 12 (18%) 14 (22%) 29 (45%) 40 (62%) 13 (20%) 22 (34%) 13 (20%) 3 (5%)

NS NS NS 0.15 NS NS 0.003 0.11 NS

Data are presented as median (25th, 75th percentiles) or number (%) of patient group. Group A 5 patients with collateral index 0; Group B 5 patients with collateral index 1 to 3; MI 5 myocardial infarction.

prevalence of the main cardiovascular risk factors. However, group B had a greater prevalence of previous angina than did group A (22 patients [34%] vs. 17 [15%], p 5 0.003) and a tendency to a greater prevalence of previous myocardial infarction (13 patients [20%] vs. 13 [11%], p 5 0.11). Coronary angiography and primary angioplasty. The elapsed time between the onset of symptoms suggestive of AMI and the opening of the LAD was 195 6 86 min in group A and 211 6 90 min in group B (p 5 NS). The angiographic findings and the result of primary PTCA in both groups are presented in Table 3. There were no significant differences between groups in the number of diseased vessels, although in group A there was a tendency to present multivessel disease less frequently (51 patients [44%] vs. 36 [55%], p 5 0.15). The proximal segment of the LAD was less frequently occluded in group A than in group B (43 patients [37%] vs. 36 [55%], p 5 0.05). PTCA was considered successful in a similar proportion of patients from both groups. The proportion of patients who received stents during PTCA was also similar in both groups (22 patients [19%] in group A vs. 16 [25%] in group B, p 5 NS). An intraaortic balloon pump was implanted in 25 patients (22%) in group A and in 13 (20%) in group B (p 5 NS). In-hospital course and mortality rate. The clinical complications that occurred in both study groups are shown in Table 4. Of the 31 patients (17%) who died during the hospital stay, 26 (23%) were from group A and 5 (8%) from group B (p 5 0.01). A progressive decrease in the in-hospital mortality rate was observed with increasing grades of collateral circulation. The mortality risk in patients without collateral circulation was 2.5 times higher than in patients with collateral index 1 (p 5 0.06) and 3.6 times higher than in patients with collateral index 2 or 3 (p 5 0.03). This linear association was statistically significant by the Mantel-Haenszel test (p 5 0.01, Fig. 1). Other factors associated with in-hospital mortality by univariate analyses are presented in Table 5. The independent effect of collateral circulation on inhospital death was confirmed by a multiple logistic regression analysis. After adjustment for age, previous infarction, diabetes, multivessel disease and PTCA result, the absence of

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Table 3. Angiographic Findings and Primary Angioplasty Results Group A (n 5 115 [64%]) Diseased vessels 1-vessel disease 2-vessel disease 3-vessel disease LMCA Level of LAD occlusion Distal segment Mid-segment Proximal segment TIMI flow in LAD* Baseline Grade 0 Grade 1 After angioplasty Grade 0 Grade 1 Grade 2 Grade 3 Residual stenosis Successful primary angioplasty†

Group B (n 5 65 [36%])

p Value NS

64 (56%) 34 (30%) 14 (12%) 3 (3%)

29 (45%) 19 (29%) 14 (22%) 3 (5%)

5 (4%) 67 (58%) 43 (38%)

1 (2%) 28 (43%) 36 (55%)

0.05

NS NS 101 (88%) 14 (12%)

58 (89%) 7 (11%) NS

4 (4%) 9 (8%) 38 (33%) 64 (56%) 28% (15%, 35%) 102 (89%)

5 (8%) 3 (5%) 15 (23%) 42 (65%) 35% (22%, 40%) 57 (88%)

0.02 NS

*Patients with flow grades 2 and 3 were excluded from the study. †TIMI flow grade $2 in the infarct-related artery with residual stenosis ,50%. Data are presented as number (%) of patients or median (25th, 75th percentiles). LMCA 5 left main coronary artery; other abbreviations as in Table 1.

collateral circulation remained an independent predictor of in-hospital death (p 5 0.01). The final model, after excluding the variables that did not modify the independent weight of collateral circulation on in-hospital death, is shown in Table 6. Cardiogenic shock was the most frequent cause of mortality, accounting for 74% of deaths. Cardiogenic shock developed more often in patients from group A than in patients Table 4. In-Hospital Course Group A (n 5 115 [64%]) Peak CK-MB (U/liter) Reinfarction Malignant arrhythmias* All patients Patients with no or mild pump failure Mechanical complications† Cardiogenic shock All patients Before primary angioplasty After primary angioplasty Death

391 (233, 526) 5 (4%) 24 (21%) 6 (7%) of 85

Group B (n 5 65 [36%])

p Value

298 (166, 488) 2 (3%)

0.04 NS

6 (9%) 6 (10%) of 61

0.05 NS

5 (4%)

2 (3%)

NS

30 (26%) 24 (21%)

4 (6%) 2 (3%)

0.001 0.001

6 (5%)

2 (3%)

NS

26 (23%)

5 (8%)

0.01

*Sustained ventricular tachycardia/fibrillation or high degree atrioventricular block. †All mechanical complications were free wall ruptures proved at autopsy or operation. Data are presented as median (25th, 75th percentiles) or number (%) of patients. CK-MB 5 creatine kinase, MB fraction.

Figure 1. Linear association between collateral index (CI) and inhospital mortality rate (Mantel-Haenszel test, p 5 0.01). *Collateral indexes 2 and 3 were grouped because their expected values were ,5. Collateral circulation was index 2 in 23 patients and index 3 in 9 patients; 1 patient from each of these subgroups died.

from group B (30 patients [26%] vs. 4 [6%], p 5 0.001). The timing of shock seemed different in each group: In group A, 24 (80%) of the 30 patients who experienced cardiogenic shock were already in shock before PTCA, whereas in group B only 2 of 4 patients had shock before PTCA. Multiple logistic regression analysis proved that the absence of collateral circulation is also an independent determinant of cardiogenic shock (odds ratio 5.6, 95% confidence interval 1.9 to 17, p 5 0.002) after adjustment for age and previous infarction. This explains the higher in-hospital mortality rate of patients without collateral circulation.

Discussion Collateral circulation to the occluded LAD was identified by angiography within the first 6 h of symptom onset in 36% of patients with anterior AMI. This study demonstrates that in patients with anterior AMI, the presence of operating collateral vessels to the LAD in the initial hours reduces the in-hospital mortality rate by decreasing the occurrence of cardiogenic shock. Thus, the absence of collateral circulation to the infarct-related artery may be considered an adverse risk factor in the assessment of short-term prognosis after anterior AMI. Collateral assessment. It has been established (14 –17) that reperfusion can be achieved quickly and safely by emergency PTCA. Diagnostic angiography inherent in the primary PTCA procedure is a valuable opportunity for assessing coronary collateral circulation in the first hours of AMI. In recent years, alternative methods of evaluating coronary collateral circulation have been proposed (18 –21) on the basis that angiography lacks sufficient sensitivity. It is certain that angiography cannot detect collateral vessels ,100 mm in diameter and can miss some intramyocardial collateral vessels (9). However, it is also certain that all normal human hearts have, among the territories of the major coronary arteries, small anastomotic vessels

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Table 5. Factors Associated With In-Hospital Death (univariate analysis) Factor Present

Age* Female† Diabetes mellitus Cigarette smoking† Proximal LAD occlusion‡ Collateral circulation to LAD§ Multivessel disease Successful primary angioplasty\

Yes

No

OR (95% CI)

p Value

— 27% 36% 11% 24% 8% 25% 13%

— 15% 12% 26% 12% 23% 10% 48%

1.05 (1.01–1.09) 2.1 (0.8 –5.1) 4.1 (1.8 –9.4) 0.4 (0.2– 0.8) 2.4 (1.1–5.3) 0.3 (0.1– 0.7) 3.2 (1.4 –7.7) 0.2 (0.1– 0.5)

0.01 0.09 0.001 0.01 0.03 0.01 0.01 0.001

*OR (95% CI) per year of increase. Age (median; 25th, 75th percentiles) of survivors was 63 (53, 70) versus 69 (62, 73) years in nonsurvivors (p 5 0.01). †Association lost after adjustment for age. ‡Versus mid or distal occlusion. §Present if collateral index $1, absent if collateral index 5 0. \Thrombolysis in Myocardial Infarction flow grade $2 with residual stenosis ,50% at the end of the procedure. Data indicate mortality rate (%) of patients with the factor present (Yes) versus absent (No), the odds ratio (OR) with 95% confidence interval (CI) for death if the factor is present and the significance level (p value). The mortality rate was not different in patients with (19%) or without (17%) previous infarction. LAD 5 left anterior descending coronary artery.

that range up to 200 mm in diameter (22). Because collateral vessels that are too small to be visualized angiographically probably have no clinical impact, we believe that angiography offers sufficient sensitivity for clinical purposes. Collateral vessels exhibit vasomotor responses to different agents. For example, nitroglycerin enhances collateral flow by marked vasodilation (23), whereas, various substances generated by platelet aggregation and thrombus formation in the setting of AMI (e.g., serotonin, thromboxane A2) have been implicated in the vasoconstriction of small and collateral vessels of the area at risk (24). Because we did not inject intracoronary nitroglycerin before performing the diagnostic angiograms, the collateral circulation documented better reflects the spontaneous previous status, without pharmacologic enhancing. Previous coronary heart disease. In this study, patients with angiographically documented collateral vessels to the occluded LAD (group B) had a greater prevalence of previous angina. These findings are in accordance with previous works (25–29). Other studies (25,29) found a higher prevalence of myocardial infarction and multivessel disease in patients with collateral circulation. In our study, patients with collateral vessels only tended to have previous infarction and multivessel disease more frequently than did patients without collateral vessels (p 5 NS). The prevailing opinion is that patients with performed and matured collateral vessels probably have had a longer, although sometimes silent, course of ischemic disease Table 6. Multivariate Analysis for In-Hospital Death*

Age (OR/yr of increase) Previous infarction Collateral circulation absent†

OR (95% CI)

p Value

1.05 (1.01–1.09) 1.3 (0.4 –3.8) 3.4 (1.2–9.6)

0.01 NS 0.02

*Multiple logistic regression. †Collateral index 5 0. Abbreviations as in Table 5.

(25,26,28). The existence of a severe coronary stenosis, especially one with .90% diameter narrowing, or intermittent occlusions over a nonsignificant plaque, such as those in patients with vasospastic angina, can induce the development of collateral vessels from surrounding vascular beds that remain as potential conduits until a new total occlusion occurs (28). Nevertheless, high interindividual variability seems to exist for collateral development in response to ischemic stimuli (30). Mortality and complications. In our patients with anterior AMI treated by primary PTCA, the absence of collateral blood flow to the ischemic myocardium in the early hours of infarction was a strong independent predictor of cardiogenic shock and mortality. The benefit of having collateral circulation was striking, especially as the patients with collateral vessels at the time of AMI, our group B, had a greater prevalence of some high risk characteristics, such as occlusion of the LAD in the proximal segment, multivessel disease and previous infarction. The presence of only mild degrees of collateral circulation (Rentrop index 1) might already exert a protective effect. With respect to other complications, the proportions of reinfarction and free wall rupture were similar in groups A and B, although the number of these events was low. Malignant arrhythmias such as sustained ventricular tachycardia, ventricular fibrillation or high degree AV block were more frequent in patients without collateral vessels, although there were no differences between groups after patients with cardiogenic shock were excluded. Several studies (3–5) have demonstrated that collateral circulation at the time of AMI reduces infarct size, an effect that might explain, at least in part, how collateral vessels protect against cardiogenic shock and mortality. In this work, higher peak CK-MB levels were observed in patients without collateral circulation, but this finding has to be cautiously interpreted given the recognized limitations of CK-MB measurements in estimating infarct size (31–33), especially in patients with collateral circulation (34).

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When total arterial flow is reduced by coronary stenosis or occlusion, coronary vasodilator reserve is exceeded and flow to the ischemic region is distributed along a gradient that is inversely related to the gradient of intramyocardial pressure. Therefore, the small amounts of blood flow provided through the collateral route are distributed in a nonuniform pattern, being preferentially shunted to the subepicardial zone where intramyocardial pressure is lowest (35). In experimental models, nearly transmural infarcts develop in dogs with very little collateral flow, whereas nontransmural infarcts, with survival of myocardium in the subepicardial zone (36,37), develop in dogs with substantial collateral flow, which is always greatest in this zone. The lower incidence of cardiogenic shock in patients with collateral vessels could be explained, at least in part, by the preservation of an epicardial rim of viable myocardium when operating collateral vessels are present at the time of infarction. This phenomenon could ameliorate the systolic dysfunction and promote a partial functional recovery of the involved wall segment early after AMI. This mechanism could also explain the observation of others (9,38) of a low incidence of infarct expansion and aneurysm formation in patients with well developed collateral channels at the time of infarction. Limitations of the study. The population origin of the present study is a partly selected high risk group. Although the majority of patients were treated by primary PTCA in an unselected manner because of their participation in investigative trials, many patients in this study were selected to undergo primary PTCA because they had high risk characteristics, especially cardiogenic shock or extensive infarction. For this reason the rates of adverse events of the study population, particularly cardiogenic shock and death, are increased; consequently, the relative importance of collateral circulation in reducing cardiogenic shock and mortality might be less striking in unselected populations.

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