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CLINICAL RESEARCH: ACUTE MYOCARDIAL INFARCTION

Reduced collateral circulation to the infarct-related artery in elderly patients with acute myocardial infarction

Toshiya Kurotobi, MD, PhD^*, Hiroshi Sato, MD, PhD, FACC^,*, Kunihiro Kinjo, MD, PhD, Daisaku Nakatani, MD, Hiroya Mizuno, MD, Masahiko Shimizu, MD, Katsuji Imai, MD, PhD^*, Atsushi Hirayama, MD, PhD, FACC, Kazuhisa Kodama, MD, PhD, FACC, Masatsugu Hori, MD, PhD, FACC OACIS Group

^* Cardiovascular Division, Osaka Minami National Hospital, Kawachinagano, Japan
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
Cardiovascular Division, Osaka Police Hospital, Osaka, Japan

Manuscript received June 30, 2003; revised manuscript received October 21, 2003, accepted November 24, 2003.

^* Reprint requests and correspondence: Dr. Hiroshi Sato, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
satoz{at}medone.med.osaka-u.ac.jp

	Abstract

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OBJECTIVES: The purpose of this study was to investigate the hypothesis that circulation via collateral vessels to an infarct-related artery (IRA) is impaired with aging in patients with acute myocardial infarction (AMI).

BACKGROUND: Animal experiments have shown that advanced age blunts the development of new vessels in response to angiogenic cytokines.

METHODS: Of 3,573 consecutive patients with AMI, 1,934 patients who fulfilled the following criteria were enrolled in this study: 1) coronary angiograms were obtained within 72 h after the onset of AMI; and 2) IRA showed complete occlusion (Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 or 1). Collaterals to the IRA were angiographically evaluated using the Rentrop score. Rentrop scores 1 to 3 were defined as demonstrating significant collaterals.

RESULTS: The prevalence of collaterals decreased with age, from 47.9%, 45.8%, 43.4%, to 34.0% in patients <50 years, 50 to 59 years, 60 to 69 years, 70 years, respectively (p < 0.001). Advanced age was an independent factor predicting the absence of collateral circulation to the IRA. In contrast, time to catheterization, history of angina pectoris, and preinfarction angina were independent predictors for the presence of collaterals. Multivariate analysis showed that the absence of collaterals was an independent predictor of in-hospital mortality in elderly patients 70 years (odds ratio, 15.6; 95% confidence interval, 3.5 to 69.6), although this finding was not significant in patients <70 years.

CONCLUSIONS: Advanced age is associated with decreased angiographic presence of collaterals to the IRA in patients with AMI. This abnormality may contribute to the poor prognosis of elderly patients with AMI.

Abbreviations and Acronyms   AMI = acute myocardial infarction   CI = confidence interval   IRA = infarct-related artery   LCX = left circumflex coronary artery   MI = myocardial infarction   OACIS = Osaka Acute Coronary Insufficiency Study   OR = odds ratio   TIMI = Thrombolysis In Myocardial Infarction

Recently, in vivo animal experiments have shown that advanced age blunts angiogenesis and endothelial function, thus impairing the development of new collateral circulation (10). Furthermore, ischemic preconditioning (11,12) is impaired in elderly AMI patients, and vulnerability to myocardial ischemia is increased in the aged heart, which suggests that there is less tolerance against ischemia in the aging heart. If this is the case in the aging heart, the presence of collaterals to the IRA may play a critical role in elderly patients with AMI, and therefore would be a powerful independent predictor of in-hospital mortality rate. In this study, we examined whether advanced age impairs the development of collateral circulation to the IRA, and whether the absence of collateral circulation to the IRA is a determinant of poor in-hospital prognosis in elderly patients with AMI.

	Methods

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Patients.   The patients included in this study were selected from a total of 3,573 consecutive patients registered in the Osaka Acute Coronary Insufficiency Study (OACIS) from April 1998 to May 2002. A detailed description of this study has been published elsewhere (13–15). Briefly, all patients presenting within one week after the onset of AMI were prospectively registered, immediately after the diagnosis of AMI, defined by the presence of typical clinical symptoms, electrocardiographic findings, and release of cardiac enzymes. Patients who fulfilled the following criteria were selected as candidates for the present study: 1) coronary angiograms were obtained within 72 h after the onset of AMI; and 2) the IRA showed complete occlusion. Finally, a total of 1,934 patients met inclusion criteria and constituted the study population. This study was approved by the ethics review committee of each participating hospital.

Definitions.   Diabetes mellitus was defined as a fasting plasma glucose concentration 126 mg/dl or the use of antidiabetic therapy. Hypertension was defined as a history of a systolic blood pressure 140 mm Hg, a diastolic blood pressure 90 mm Hg, or the use of antihypertensive therapy. Hyperlipidemia was defined as a fasting total cholesterol concentration 220 mg/dl, a fasting triglyceride concentration 150 mg/dl, or the use of antihyperlipidemic therapy. Preinfarction angina was defined as the presence of typical chest pain within 72 h before the onset of AMI. A history of angina pectoris was defined as documented symptomatic coronary artery disease or typical chest pain occurring at least one month before AMI onset. Success of angioplasty was defined as achieving Thrombolysis In Myocardial Infarction (TIMI) flow grade 3.

Data collection and quality control.   Research cardiologists and specialized research nurses recorded data concerning sociodemographic variables, medical history, therapeutic procedures, and clinical events during the patient's stay in the hospital. Information was obtained by hospital medical records, by direct interview with the patient and his or her family, and by interviewing the treating physician. When written informed consent for entering the OACIS was obtained from patients, all in-hospital data were transmitted to a central data collection center located in the Department of Internal Medicine and Therapeutics at Osaka University Graduate School of Medicine for processing and analysis. Collaborating hospitals were encouraged to enter consecutive patients with AMI irrespective of treatment strategy and outcome. The OACIS included a university hospital, tertiary care centers, and smaller hospitals. Before initiation of this study, a research cardiologist and specialized research nurse at each site received a training manual that explained how to complete the case report form, defined each variable, and provided examples of correct responses. Double-key entry was used by the central data collection center to add each case report form to the database. Audits were performed electronically to detect out-of-range variables, inconsistencies, errors, and omissions. Queries were then telephoned to the local research cardiologists and specialized research nurses for resolution.

Coronary angiography and collateral evaluation.   We assessed the degree of collateral circulation to the IRA at the time of emergent catheterization. Three patients whose angiograms were inadequate for assessing the collateral circulation to the IRA were excluded from the present study. The degree of stenosis was scored according to the American Heart Association guidelines (16). Vessels with >75% stenosis were classified as having significant stenosis. The degree of perfusion of the IRA was determined according to the TIMI criteria, and total occlusion was defined as TIMI flow grade 0 or 1. Collateral circulation was graded by using a semiquantitative scale from 0 to 3, depending on the angiographic findings of the occluded artery using the best injection (17): 0 = no collateral circulation; 1 = collateral filling of side branches without visualization of any epicardial segments; 2 = collateral partially filling the epicardial segment; 3 = collateral completely filling the epicardial segment. Grades 1 to 3 were defined as the presence of collateral circulation to the IRA. Coronary angiograms were assessed in a blinded manner by two observers who reached a consensus in most cases. When there was disagreement, the difference was adjusted by a third independent doctor.

Statistical analysis.   Patients were arbitrarily divided into four age groups: <50 years, 50 to 59 years, 60 to 69 years, and 70 years. We compared the prevalence of collaterals among age groups using a chi-square test. Statistical comparisons of baseline, procedural and outcome variables between subgroups were performed using the chi-square statistic for categorical variables, and Student unpaired t test and analysis of variance for continuous variables. Age and time to catheterization are expressed as the mean ± SD. Univariate and multivariate logistic regression was used to assess the relationship between clinical background variables, angiographic findings and the presence of collateral circulation, and between clinical factors and in-hospital mortality. Variables incorporated into our analysis included characteristics previously identified as factors of well-known prognostic importance and coronary risk factors. These variables included Killip class 2, final TIMI flow grade 3, diabetes mellitus, number of diseased vessels, history of myocardial infarction (MI), age, absence of collaterals, hypertension, hyperlipidemia, and smoking. Odds ratios (OR) were expressed together with 95% confidence intervals (CI). Wald's chi-square value was determined for in-hospital mortality by multivariate analysis. Analyses of data were performed using statistical software (SPSS 10.0, SPSS Japan Inc., Tokyo, Japan). Results were considered significant at p < 0.05.

	Results

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Factors contributing to the prevalence of collateral vessels.   Baseline characteristics and the angiographic findings in patients with or without collaterals are summarized in Table 1. The patient population included 76.6% men and 23.4% women with a mean age of 64.0 years. The prevalence of collaterals was 41.5% in all of the enrolled patients. Compared with patients without collaterals, the mean age was significantly lower in patients with collaterals (62.7 ± 11.0 years vs. 65.0 ± 11.4 years; p < 0.001). The patients with collaterals had a greater prevalence of hyperlipidemia (44.3% vs. 39.0%; p = 0.03), history of angina pectoris (33.1% vs. 25.5%; p = 0.001), and preinfarction angina (53.1% vs. 45.6%; p = 0.002) than the patients without collaterals. Furthermore, the patients with collaterals had a smaller number of diseased vessels (1.27 vs. 1.36; p = 0.01), a lower prevalence of left circumflex infarction (8.2% vs. 15.9%; p < 0.001), and a longer time from the onset to catheterization (13.1 ± 16.5 h vs. 8.6 ± 11.7 h; p < 0.001) than the patients without collaterals. Significant differences between the groups were not observed for gender, smoking, hyperlipidemia, hypertension or diabetes mellitus, the use of primary angioplasty, and the successful restitution of TIMI flow grade 3. The prevalence of collaterals decreased with age, from 47.9%, 45.8%, 43.4%, to 34.0% in patients <50 years, 50 to 59 years, 60 to 69 years, and 70 years, respectively (p < 0.001) (Fig. 1). The ORs for the presence of collaterals to the IRA are summarized in Table 2. Based on univariate analysis, the presence of collaterals was significantly associated with age (OR, 0.98; 95% CI, 0.97 to 0.99), left circumflex coronary artery (LCX) infarction (OR, 0.42; 95% CI, 0.27 to 0.65), time to catheterization (OR, 1.02; 95% CI, 1.01 to 1.03), history of angina pectoris (OR, 1.41; 95% CI, 1.15 to 1.72), preinfarction angina (OR, 1.34; 95% CI, 1.12 to 1.62), number of diseased vessels (OR, 0.84; 95% CI, 0.74 to 0.96), and hyperlipidemia (OR, 1.23; 95% CI, 0.82 to 0.97). Based on multivariate analysis, age (OR, 0.98; 95% CI, 0.97 to 0.99), LCX infarction (OR, 0.47; 95% CI, 0.33 to 0.68), time to catheterization (OR, 1.02; 95% CI, 1.01 to 1.03), history of angina pectoris (OR, 1.49; 95% CI, 1.12 to 1.99), and preinfarction angina (OR, 1.35; 95% CI, 1.10 to 1.66) were independent contributing factors to the development of collaterals to the IRA.

View larger version (7K): [in this window] [in a new window]   Figure 1 The prevalence of collateral circulation to the infarct-related artery based on patient age. Prevalence of collaterals was significantly lower above 70 years of age.

View larger version (9K): [in this window] [in a new window]   Figure 2 The prevalence of pre-infarction angina pectoris (pre-AP) (a), presence of history of angina pectoris (AP) (b), and time from onset to catheterization (c) in patients below 70 and above 70 years of age. NS = not significant.

View larger version (10K): [in this window] [in a new window]   Figure 3 The prevalence of collaterals to the infarct-related artery in patients with pre-infarction angina (pre-AP) (a), history of angina pectoris (AP) (b), and early catheterization (6 h from the onset of acute myocardial infarction) (c) in patients below 70 or above 70 years of age.

	Discussion

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Factors contributing to circulation from collaterals.   Factors that may control the presence of collaterals after the onset of AMI have been demonstrated in previous clinical studies. The extent of collateral circulation is affected by the presence of multivessel disease (18), previous MI (19), preinfarction angina (7), history of angina pectoris (8), and time from onset to cardiac catheterization (20). Our results also show that preinfarction angina, history of angina pectoris, and time to cardiac catheterization are significantly associated with a higher prevalence of collateral circulation to the IRA (Tables 1 and 2). Moreover, our results show that the prevalence of collaterals is lower in patients above 70 years of age and that advanced age is an independent factor predicting the absence of collateral circulation to the IRA. Previous reports (3,7,20) have not determined the association between age and collaterals. This is probably because previous studies have been relatively small in scale, or because fewer elderly patients with AMI were enrolled due to the low rate of cardiac catheterization in this population. The prevalence of collaterals was significantly lower in patients above 70 years of age (Fig. 1); therefore, we compared the relation between these factors and the prevalence of collaterals to the IRA in patients below 70 years of age and in patients above 70 years of age. The prevalence of preinfarction angina, history of angina pectoris, and time from onset to catheterization were not different between the patients below 70 years of age and the patients above 70 years of age (Fig. 2). However, these factors were significantly associated with a higher prevalence of collaterals in patients below 70 years of age than in patients above 70 years of age (Fig. 3). The rate of increasing collaterals is associated with increasing time to catheterization both patients above and below 70 years of age. These findings seem to suggest that collateral formation to the IRA mediated by these factors is blunted in patients above 70 years of age compared with patients below 70 years of age. Collateral formation is a complex process involving mechanical factors and angiogenic factors, although it is mainly influenced by endothelial function. Endothelial cell function is compromised with increasing age (21,22). Therefore, age-dependent endothelial dysfunction may contribute to impaired collateral development in the setting of myocardial ischemia.

Effect of collateral circulation on in-hospital prognosis.   The presence of collateral circulation improves myocardial salvage (3–5) and prevents ventricular remodeling (6), thereby improving in-hospital prognosis independent of coronary reperfusion therapy (6,7,23–26). Because the aging heart might be expected to be less tolerant due to impaired biologic responses against myocardial ischemia, we compared the clinical effect of the presence of collateral circulation to the IRA in patients below and above 70 years of age. Killip class 2, final TIMI flow grade 3, the presence of diabetes mellitus, and the number of diseased vessels, but not the absence of collaterals, were independent contributing factors for in-hospital mortality in patients below 70 years of age (Table 3). However, the absence of collaterals was a strong independent contributing factor for in-hospital mortality in addition to Killip class 2 and final TIMI flow grade 3 (Table 4). Cardiogenic shock and life-threatening arrhythmias are more likely to be observed in elderly patients (27), and, as a result, elderly AMI patients have a poor short-term prognosis (28,29). Thus, age is a powerful independent predictor of in-hospital mortality (28). The present study demonstrates that the absence of collaterals to the IRA is a clinically important factor that predicts in-hospital mortality in elderly patients with AMI.

Study limitations.   The major limitation of this study is the patients' selection bias. The conclusions of this study are derived from patients with total coronary artery occlusion. Therefore, the significance of collateral circulation is limited to this group of patients. We should not extend our study results to broader populations of patients with AMI. The second limitation is related to the angiographic evaluation of coronary arteries. We evaluated the extent of collateral development using the semiquantitative Rentrop score. Some reports (30,31) suggest that coronary angiography lacks sufficient sensitivity to evaluate collateral formation. It is certain that angiography cannot detect collateral vessels <100 µm in diameter (6). Therefore, patients characterized as lacking collateral circulation might have small collaterals. The third limitation of this study is that the mechanisms responsible for poor collateral development in elderly patients with AMI were not clarified. Because the contributing factors for collateral development, prevalence of preinfarction angina, history of angina pectoris, time to catheterization were observed in similar frequencies in elderly patients compared with nonelderly patients, the potential for angiogenesis or reopening of pre-existing collateral channels may be impaired.

Conclusions.   Advanced age is an independent factor for the presence of collaterals to the IRA, and the absence of collateral circulation to the IRA is an independent risk factor for in-hospital mortality in elderly patients with AMI. Further clinical efforts to improve coronary circulation in elderly patients with AMI, either by coronary intervention or novel angiogenic treatments, are needed.

	APPENDIX

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For a list of persons and institutions who participated in OACIS, please see the July 7, 2004, issue of JACC at www.cardiosource.com/jacc.html.

	Acknowledgments

 
The authors thank Kumiko Miyoshi, Chizuru Hamaguchi, Hiroko Machida, Mariko Yoneda, Kana Sakatani, Nagisa Yoshioka, Miki Shinkura, Tomomi Miyai, Saeko Kakimoto, Rie Omoya, Tomoko Inoue, and Aki Yabuuchi for their excellent assistance with data collection.

	Footnotes

 
Supported by a Grant-in-Aid for Scientific Research (C)(2) (#15590743) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan, and by a research grant from Japan Arteriosclerosis Prevention Fund.

	References

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1. Schwartz H, Leiboff RH, Bren GB, et al. Temporal evolution of the human coronary collateral circulation after myocardial infarction. J Am Coll Cardiol. 1984;4:1088–1093[Abstract]
2. de Boer MJ, Reiber JH, Suryapranata H, van den Brand MJ, Hoorntje JC, Zijlstra F. Angiographic findings and catheterization laboratory events in patients with primary coronary angioplasty or streptokinase therapy for acute myocardial infarction. Eur Heart J. 1995;16:1347–1355[Abstract/Free Full Text]
3. Habib GB, Heibig J, Forman SA, et al. Influence of coronary collateral vessels on myocardial infarct size in humans: Results of phase i thrombolysis in myocardial infarction (timi) trial: the timi investigators. Circulation. 1991;83:739–746[Abstract/Free Full Text]
4. Hirai T, Fujita M, Yoshida N, Yamanishi K, Inoko M, Miwa K. Importance of ischemic preconditioning and collateral circulation for left ventricular functional recovery in patients with successful intracoronary thrombolysis for acute myocardial infarction. Am Heart J. 1993;126:827–831[CrossRef][Medline]
5. Christian TF, Schwartz RS, Gibbons RJ. Determinants of infarct size in reperfusion therapy for acute myocardial infarction. Circulation. 1992;86:81–90[Abstract/Free Full Text]
6. Hirai T, Fujita M, Nakajima H, et al. Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction. Circulation. 1989;79:791–796[Abstract/Free Full Text]
7. Perez-Castellano N, Garcia EJ, Abeytua M, et al. Influence of collateral circulation on in-hospital death from anterior acute myocardial infarction. J Am Coll Cardiol. 1998;31:512–518[Abstract/Free Full Text]
8. Nakagawa Y, Ito H, Kitakaze M, et al. Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: Retrospective clinical evidence of "preconditioning". J Am Coll Cardiol. 1995;25:1076–1083[Abstract]
9. Ito WD, Arras M, Winkler B, Scholz D, Schaper J, Schaper W. Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion. Circ Res. 1997;80:829–837[Abstract/Free Full Text]
10. Rivard A, Fabre JE, Silver M, et al. Age-dependent impairment of angiogenesis. Circulation. 1999;99:111–120[Abstract/Free Full Text]
11. Abete P, Ferrara N, Cacciatore F, et al. Angina-induced protection against myocardial infarction in adult and elderly patients: A loss of preconditioning mechanism in the aging heart? J Am Coll Cardiol. 1997;30:947–954[Abstract]
12. Abete P, Ferrara N, Cioppa A, et al. Preconditioning does not prevent postischemic dysfunction in aging heart. J Am Coll Cardiol. 1996;27:1777–1786[Abstract]
13. Kinjo K, Sato H, Sato H, et al. Circadian variation of the onset of acute myocardial infarction in the Osaka area, 1998 to 1999: Characterization of morning and nighttime peaks. Jpn Circ J. 2001;65:617–620[CrossRef][Medline]
14. Ohnishi Y, Tanaka T, Yamada R, et al. Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population. Hum Genet. 2000;106:288–292[CrossRef][Medline]
15. Ozaki K, Ohnishi Y, Iida A, et al. Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet. 2002;11:11[Medline]
16. Austen WG, Edwards JE, Frye RL, et al. A reporting system on patients evaluated for coronary artery disease: Report of the ad hoc committee for grading of coronary artery disease, council on cardiovascular surgery, american heart association. Circulation. 1975;51:5–40[Medline]
17. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol. 1985;5:587–592[Abstract]
18. Vyssoulis G, Kyriakidis M, Karpanou E, et al. A prospective angiographic study of the coronary collateral circulation in coronary arterial disease. Int J Cardiol. 1990;27:187–191[CrossRef][Medline]
19. Hansen JF. Coronary collateral circulation: Clinical significance and influence on survival in patients with coronary artery occlusion. Am Heart J. 1989;117:290–295[CrossRef][Medline]
20. Rentrop KP, Feit F, Sherman W, Thornton JC. Serial angiographic assessment of coronary artery obstruction and collateral flow in acute myocardial infarction: Report from the second mount sinai-new york university reperfusion trial. Circulation. 1989;80:1166–1175[Abstract/Free Full Text]
21. Tschudi MR, Barton M, Bersinger NA, et al. Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery. J Clin Invest. 1996;98:899–905[Medline]
22. Gerhard M, Roddy MA, Creager SJ, Creager MA. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension. 1996;27:849–853[Abstract/Free Full Text]
23. Rentrop KP, Feit F, Sherman W, et al. Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: Primary end point findings of the second mount sinai-new york university reperfusion trial. J Am Coll Cardiol. 1989;14:58–64[Abstract]
24. Hirayama A, Adachi T, Asada S, et al. Late reperfusion for acute myocardial infarction limits the dilatation of left ventricle without the reduction of infarct size. Circulation. 1993;88:2565–2574[Abstract/Free Full Text]
25. Nohara R, Kambara H, Murakami T, Kadota K, Tamaki S, Kawai C. Collateral function in early acute myocardial infarction. Am J Cardiol. 1983;52:955–959[CrossRef][Medline]
26. Forman MB, Collins HW, Kopelman HA, et al. Determinants of left ventricular aneurysm formation after anterior myocardial infarction: A clinical and angiographic study. J Am Coll Cardiol. 1986;8:1256–1262[Abstract]
27. Hands ME, Rutherford JD, Muller JE, et al. The in-hospital development of cardiogenic shock after myocardial infarction: Incidence, predictors of occurrence, outcome and prognostic factors: the milis study group. J Am Coll Cardiol. 1989;14:40–48[Abstract]
28. Maggioni AP, Maseri A, Fresco C, et al. Age-related increase in mortality among patients with first myocardial infarctions treated with thrombolysis: the Investigators of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2). N Engl J Med. 1993;329:1442–1448[Abstract/Free Full Text]
29. Goldberg RJ, Gore JM, Gurwitz JH, et al. The impact of age on the incidence and prognosis of initial acute myocardial infarction: The worcester heart attack study. Am Heart J. 1989;117:543–549[CrossRef][Medline]
30. Sabia PJ, Powers ER, Jayaweera AR, Ragosta M, Kaul S. Functional significance of collateral blood flow in patients with recent acute myocardial infarction: A study using myocardial contrast echocardiography. Circulation. 1992;85:2080–2089[Abstract/Free Full Text]
31. Piek JJ, Koolen JJ, Metting van Rijn AC, et al. Spectral analysis of flow velocity in the contralateral artery during coronary angioplasty: A new method for assessing collateral flow. J Am Coll Cardiol. 1993;21:1574–1582[Abstract]

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