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Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 +/- 0.84 vs. 4.77 +/- 1.71 mm2, respectively; P < 0.001). In the porcine coronary model, site-specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments., (Copyright 2005 Wiley-Liss, Inc.)

Background: Smooth muscle cell (SMC) hyperplasia is an important mechanism of restenosis after coronary angioplasty and the primary mechanism of restenosis within coronary stents. Ethanol has been shown to reduce the response of SMCs to local growth stimulants in vitro. This study was carried out to determine whether local delivery of ethanol solution could reduce intimal hyperplasia induced by balloon injury., Methods and Results: Three groups of juvenile domestic pigs underwent oversized balloon dilation injury of the left anterior descending and left circumflex coronary arteries. Immediately after the balloon injury, one of the arteries was randomized to local delivery of 15% ethanol with a local delivery balloon catheter, and the other received no further treatment. Histological and morphometric studies were carried out at 2 weeks in group 1 (n=16) and at 4 weeks in group 2 (n=10). In the third group (n=15), animals were killed at days 4, 8, and 14 after balloon injury, and coronary artery segments were studied by immunohistochemical staining against proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU). Histological injury scores were not different between the ethanol-treated and untreated arterial segments in either group 1 or 2. The neointimal areas were significantly smaller in the ethanol-treated arterial segments than in the untreated segments (0.25+/-0.08 versus 0.57+/-0.08 mm2, P=.004, at 2 weeks; 0.33+/-0.05 versus 0.54+/-0.07 mm2, P=.03, at 4 weeks). SMC proliferative activity was significantly lower in ethanol-treated arteries than in untreated arteries at 4 and 8 days after injury by BrdU and PCNA staining., Conclusions: Local delivery of 15% ethanol solution to pig coronary arteries significantly decreased the SMC proliferative activity and neointimal formation induced by balloon dilation injury.

Intravascular ultrasound guidance has been suggested as a prerequisite before managing patients receiving slotted tubular stents without anticoagulation. The purpose of this prospective observational study was to determine if patients receiving this stent can be similarly managed following angiographic guided stent deployment without intravascular ultrasound assistance. A total of 137 patients receiving slotted tubular stents were selected to receive a protocol of aspirin 325 mg and ticlopidine 250 mg for 30 days following the satisfaction of certain angiographic criteria. These criteria were: adequate coverage of intimal dissections, absence of residual filling defects, and normal (TIMI III) flow in the stented vessel at the end of the procedure. The stenting procedure was planned in 68% of patients and unplanned in 32% of patients. During the 30 day clinical follow period there were no stent thrombosis events, no Q-wave myocardial infarctions, and no deaths. Non-Q-wave myocardial infarction occurred in 3 patients (2.2%), hemorrhage requiring blood transfusion in 3 patients (2.2%), and 1 patient (0.7%) developed a pseudo-aneurysm of the cannulated femoral artery. These data indicate that patients receiving slotted tubular stents with optimal angiographic results can be safely managed with the combination of aspirin and ticlopidine without anticoagulation or the need for intravascular ultrasound guidance.

Background: The proposed mechanisms of restenosis after coronary angioplasty include neointima formation, vessel wall remodeling and mural thrombus. Poloxamer 188 does not inhibit coagulation factors, but was shown to reduce mural thrombus formation in pig coronary arteries after intracoronary stenting in an acute study. This study was performed to examine whether this agent may reduce neointima formation., Methods: Thirty domestic juvenile pigs of weight 20-30 kg were anesthetized. A left angiogram was performed via a femoral artery. Proximal left anterior descending and circumflex arteries were dilated three times with a 20-30% oversized coronary angioplasty balloon catheter. Fifteen animals were allocated randomly to receive intravenous infusions of poloxamer 188, starting 30 min before angioplasty and continuing for 24 h. The remaining 15 received intravenous 0.45% saline and served as controls. The animals were killed 2 weeks after the angioplasty. Histologic studies of the arteries were performed. The severity of the injury and the amount of thrombus material incorporated in the neointima were assessed by semiquantitative methods., Results: There was no significant difference between injury scores in the two groups. Thrombus material in the neointima in the treatment group was significantly less than that in those of the control group (thrombus areas 0.013 +/- 0.004 compared with 0.029 +/- 0.006 mm2, P < 0.02), but there were no significant differences between the neointimal (0.60 +/- 0.08 and 0.60 +/- 0.13 mm2) and luminal (2.51 +/- 0.21 and 2.44 +/- 0.26 mm2) areas in treatment and control groups., Conclusion: Continuous 24 h intravenous infusion of poloxamer 188 after balloon injury in pig coronary arteries may reduce mural thrombus formation significantly, but did not reduce neointima formation.

Prosthetic intracoronary stenting has become an important adjunct to balloon angioplasty in the percutaneous treatment of coronary artery disease. However, there are few reports of the long-term histologic consequences of stenting in the world literature. We report the arteriographic, histologic, and ultrastructural examination of a flexible tantalum wire coil stent implanted in the coronary artery of a dog for 7 years. The vessel was arteriographically patent without evidence of either stenosis or ectasia. The stent had been incorporated into the arterial wall, and was covered with a neointima of approximately 100 microns maximum thickness. There was necrosis of the tunica media adjacent to the stent but the inflammatory response was restricted to occasional macrophages in the neointima of the immediate vicinity of the stent wire. The endothelial cell layer was normal in its morphologic appearance. In summary, the flexible tantalum wire coil stent was well tolerated by the host blood vessel and demonstrated acceptable biocompatibility for the 7-year duration of its implantation in the normal dog coronary artery.

Background: Although the development of thrombus or dissection during percutaneous transluminal coronary angioplasty (PTCA) increases the risk of abrupt vessel closure, the magnitude of the effect is difficult to define., Objective: The aim of the study was to determine prospectively the effect of the development of thrombus or dissection on PTCA procedural outcome., Methods: Data from 591 consecutive angioplasty procedures involving 756 lesions at 9 clinical centers were included in a prospective registry with a core angiographic laboratory., Results: Clinical success (defined as < 50% stenosis of all target lesions assessed in a core angiographic laboratory, with no major complications of death, Q wave or non-Q wave myocardial infarction or emergency CABG) was achieved in 497 patients (84%). Major complications occurred in 45 (7.6%). Abrupt vessel closure, including both established closure (TIMI grade 0 or I flow) and impending closure (> 50% stenosis, TIMI grade 0-2 flow, plus use of additional interventions) occurred in 65 patients (11%). Angiographically visible dissections developed in 40% of lesions; more severe grades of dissection were associated with reduced success rates, and increased incidence of and abrupt vessel closure and major complication. Angiographic evidence of thrombus (filling defects) developed in 12.3% of lesions; the presence of thrombus was associated with significantly lower procedural success (61% vs. 86%) and significantly higher rates of abrupt vessel closure (28% vs 7%) and major complications (24% vs. 6%). With multivariable analysis, thrombus was identified as an independent predictor of procedural success, abrupt vessel closure, and major complications., Conclusions: The development of severe dissections or thrombus following PTCA is associated with significantly lower procedural success rates and higher rates of abrupt vessel closure and major complications. Patients who develop severe dissection or thrombus may be appropriate candidates for more aggressive forms of therapy.

BACKGROUND. Acute closure remains a significant limitation of percutaneous transluminal coronary angioplasty (PTCA) and underlies the majority of ischemic complications. This study details the clinical and angiographic characteristics of a series of patients receiving an intracoronary stent device to manage acute and threatened closure and presents the early clinical results. METHODS AND RESULTS. From October 1989 through June 1991, 115 patients undergoing PTCA received intracoronary stents to treat acute or threatened closure in 119 vessels. Sixty-three percent had multivessel coronary disease, 33 (29%) had undergone prior coronary artery bypass grafting (CABG), and 52 (45%) had had previous PTCA. Using the American College of Cardiology/American Heart Association (ACC/AHA) classification, 15% of lesions were class A, 55% were class B, and 30% were class C. Eight patients were referred with severe coronary dissection and unstable angina after PTCA at other institutions. Acute closure was defined as occlusion of the vessel with TIMI (Thrombolysis in Myocardial Infarction) 0 or 1 flow immediately before stent placement. Threatened closure required two or more of the following criteria: 1) a residual stenosis greater than 50%, 2) TIMI grade 2 flow, 3) angiographic dissection comprising extraluminal dye extravasation and/or a length of greater than 15 mm, 4) evidence of clinical ischemia (either typical angina or ECG changes). Twelve vessels (10%) met the criteria for acute closure, and 87 vessels (73%) satisfied the criteria for threatened closure. Twenty vessels (17%) failed to meet two criteria. Stenting produced optimal angiographic results in 111 vessels (93%), with mean diameter stenosis (+/- 1 SD) reduced from 83 +/- 12% before to 18 +/- 29% after stenting. Overall, in-hospital mortality was 1.7% and CABG was required in 4.2%; Q wave myocardial infarction (MI) occurred in 7% and non-Q wave MI in 9%. Stent thrombosis occurred in nine patients (7.6%). For the 108 patients who presented to the catheterization laboratory without evolving MI, Q wave MI occurred in 4% and non-Q wave MI occurred in 7%. Angiographic follow-up has been performed in 81 eligible patients (76%), and 34 patients (41%) had a lesion of greater than or equal to 50%. CONCLUSIONS. This stent may be a useful adjunct to balloon dilatation in acute or threatened closure. Randomized studies comparing this stent with alternative technologies are required.

The morphologic changes in atherosclerotic coronary arteries and saphenous vein bypass grafts after placement of a balloon-expandable flexible coil stent (Cook) are described. In each case, the vessels were patent despite morphologic evidence of injury and dissection in the vessel wall. The stented region was reendothelialized and the tissue overlying the stent wires consisted primarily of smooth muscle cells. There was minimal inflammatory reaction to the stent wires. These findings suggest that the balloon-expandable flexible coil stent can effectively maintain vessel patency even in the setting of postangioplasty lumen disruption. In addition, the vessels tolerate the metal prosthesis with little evidence of tissue inflammatory reaction.

Coronary aneurysms are rare after conventional angioplasty and have not been reported after coronary stenting. Coronary artery stent sites were examined by follow-up angiography at a median of 4 months in 29 patients who received the Cook stent (Gianturco-Roubin) for acute coronary closure. Nineteen patients were treated with glucocorticoids administered intravenously or orally, or both, with or without colchicine and results were compared with those in 10 patients who were treated with neither agent. Standard therapy for all patients included routine administration of aspirin and heparin before and warfarin sodium (Coumadin) and aspirin after stent placement. Most patients also received dipyridamole and lovastatin during the follow-up period. Compliance with medications was confirmed by telephone conversation with each patient. Six (32%) of the 19 stented arteries showed evidence of coronary artery aneurysm, defined as expansion of the lumen outside the margins of the stent. None of the patients in the control group (who did not receive steroids or colchicine) developed aneurysm. This pattern of altered vascular healing in stented coronary segments appears to be due to the addition of multiple anti-inflammatory drugs rather than to stent presence alone. This observation demonstrates the possibility of medical impairment of normal vascular remodeling after acute injury and stent placement, which may be of benefit in designing future trials on restenosis.

Intracoronary stents may potentially alleviate some of the problems associated with coronary angioplasty. Since the anatomy and physiology of swine coronary arteries closely resemble those of humans, the response to implantation of the Glanturco-Roubin, balloon-expandable, flexible stent was studied in this model. Additionally, the effect of aspirin, 1 mg/kg/day orally, on this response was evaluated. Eighteen Hanford minature swine underwent stenting of the left anterior descending coronary artery. Two died within 24 hours of stent implantation. The 16 survivors were put to death at 4 (n = 4), 11 (n = 4), 28 (n = 4), 56 (n = 3), and 180 (n = 1) days. Angiographically, reduction of stent lumen diameter of 0.1 to 1.3 mm was observed and was maximum at 11 days, with gradual improvement at subsequent time periods. Scanning electron microscopy, transmission electron microscopy, and light microscopy showed early disruption of subjacent endothelium, and adherence of platelets to exposed subendothelium and stent wires. Microthrombi were readily apparent. At 11 days, intimal thickening, made up predominantly of smooth muscle cells with abundant extracellular matrix, was observed and covered the stent wires. At 28 days, regression of intimal thickening was apparent and a confluent endothelium with flow-directed orientation was seen. At 56 and 180 days, the luminal surface was smooth; intimal thickening averaged 525 microns over the stent wires and 55 microns away from the wires. Findings in aspirin-treated animals were similar to results in those that did not receive aspirin. Thus in this swine model, stent implantation results in a time-dependent and self-limited vascular response.

Early thrombosis has complicated human stent implantation in several trials. To determine the best anticoagulation/antiplatelet therapy to maintain stent patency after percutaneous transluminal coronary angioplasty, we implanted the flexible balloon-expandable coil stent into the left anterior descending coronary artery of 28 atherosclerotic 8-month-old Hanford miniature swine. Animals were randomly assigned to one of three treatment groups: group A, aspirin (1 mg/kg/day) and dipyridamole (1 mg/kg three times a day); group B, aspirin and dipyridamole (same doses) plus Coumadin (dose required to prolong prothrombin time 1.3-1.5-fold that of normal); and group C, control. Adjuvant therapy was begun 3 days before stenting. Two pigs (one from group A and one from group B) died during implantation, both without thrombosis. Twenty-six animals survived until follow-up angiography and sacrifice at 1 month. No occlusive thrombosis of the stent occurred in survivors. Reduction of the stent lumen diameter was observed in every case at follow-up. Percent lumen reduction was 19% in group A, 26% in group B, and 24% in group C. Marked smooth muscle cell hyperplasia was seen by light and transmission electron microscopy at stent struts. Scanning electron microscopy of the luminal surface showed a variable morphology consisting of normal endothelium, adherent leukocytes, stellate periluminal cells, and occasional fibrin strands and red blood cells. Luminal narrowing was not affected by anticoagulation therapy, antiplatelet drugs, cholesterol level, or stent sizing. We conclude that occlusive thrombosis does not complicate stent implantation in this model but that substantial luminal narrowing due in part to smooth muscle hyperplasia does occur. The significance of luminal narrowing at the stent site requires further study.

Intimal tear or dissection is an important descriptor of ischemic complications after coronary angioplasty, but only the minority of patients will develop an acute ischemic event. To identify additional factors that may predict the development of an ischemic event when arterial disruption occurs during otherwise uncomplicated angioplasty, the records of 1,346 patients prospectively identified as having tear or dissection without immediate vessel closure were examined. Ischemic complications, defined as ischemic chest pain, myocardial infarction, the need for coronary bypass surgery, or death, occurred in 120 patients (9%). Significant multivariate correlates of an ischemic complication were the presence of unstable angina or a totally occluded vessel before angioplasty and diameter stenosis of greater than 30% after angioplasty. Detailed geometric and videodensitometric analysis of the postdilatation angiograms of a subset of 96 consecutive patients was carried out. Ischemic complications occurred in 11 patients (11%). Multivariate analysis revealed that the independent correlates of complications, in decreasing order of importance, were the length of the tear or dissection (p = 0.001), diameter stenosis after angioplasty (p = 0.001), cross-sectional area after dilatation measured by videodensitometric methods (p = 0.013), and the presence of extraluminal contrast (p = 0.044). When tear or dissection occurs during otherwise uncomplicated coronary angioplasty, patients at risk of developing delayed ischemic complications can be identified and may benefit from measures designed to minimize this risk. By controlling for the geometric or mechanical factors that result in tear or dissection, it has been possible to identify factors not previously thought associated with ischemic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Restenosis after successful PTCA remains a major problem limiting the efficacy of the procedure. The pathophysiologic mechanism of restenosis has been enigmatic so far, but accumulated evidence strongly suggests that intimal hyperplasia is the major mechanism. Based on current understanding of the process of intimal hyperplasia, one unifying concept may be that there are at least two major local biologic determinants influencing this process, lesion characteristics and regional flow dynamics. Lesion characteristics include the plaque structure and the quantity of smooth muscle. These may provide the anatomic substrate that determines the extent of injury and the degree of smooth muscle cell proliferation. The amount of smooth muscle cells in the stenotic lesion activated by injury to undergo proliferation may determine the eventual bulk of the restenotic lesion. In addition, low wall shear stress could promote intimal hyperplasia and cause structural change of vessels to decrease the lumen, whereas high wall shear stress exerts the opposite effects. Intimal hyperplasia after balloon injury is a complex process involving platelets, growth factors, endothelial cells, smooth muscle cells, mechanical injury, wall shear stress, and probably other unknown factors. Platelets not only contribute growth factors such as PDGF but also cause organized thrombus. Different growth factors may be involved in initiating smooth muscle cell proliferation and may come from many different sources, including smooth muscle cells, endothelial cells, and macrophages. Intact confluent endothelial cells may produce heparin sulfates and inhibit intimal proliferation; however, regenerating endothelial cells may have the opposite effect. Thus, the proliferative potential of smooth muscle cells, endothelial recovery, extent of injury, wall shear stress, and other unknown factors may all influence this process. Based on these concepts concerning the biology of restenosis, some research directions concerning potential forms of therapy are proposed.

Seventeen postangioplasty cases were morphologically studied at postmortem. Four of the eleven, early and intermediate cases (few hours to 1 month from angioplasty to death), revealed intraluminal thrombi, although in only two cases were those thrombi occlusive. Almost all of the nine early cases (eight of nine) exhibited intimal disruptions. Except for two of these cases in which circumferential and/or longitudinal dissections were present, the remainder of the intimal cracks were superficial and of limited extent. Limited dissection between intima and media is not considered a serious or detrimental local event. The early cases showed an aneurysmal dilatation of the plaque-free segment of the arterial wall in eccentric plaques. This finding was interpreted as the result of uneven distribution of the dilating force (circumferential stress) on the aterial wall. Late cases (survival over 1 month) revealed characteristic medial and intimal lesions indicative of the initial dilatation injury. It is hypothesized that intrinsic arterial wall changes (medial disruption) at the plaque-free segment and the resulting altered arterial geometry at the site of dilatation have a significant hemodynamic effect on the vascular conduit and may enhance and sustain the myoproliferative intimal response.

To determine the importance of predilatation stenosis morphology on the risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA), 500 procedures were randomly chosen for analysis from 3,839 consecutive successful PTCA procedures. Angiographic follow-up was available for 308 patients (62%) at a mean of 7.3 +/- 3.4 months after PTCA. One dilated site was randomly chosen per procedure. One hundred and one sites had documented restenosis (greater than or equal to 50% mean diameter stenosis from multiple projections) by quantitative angiography (33% of all sites restudied and 20% of all sites dilated). Twenty-eight morphologic variables and 20 other angiographic, clinical and procedural variables were analyzed by an observer blinded to clinical outcome. Univariate analysis found post-PTCA percent stenosis greater than 30% (p = 0.005), bend point location (p = 0.01), post-PTCA gradient greater than 15 mm Hg (p = 0.02), angina class III to IV (p = 0.03), age (p = 0.04) and the absence of dissection (p = 0.04) to predict restenosis. Multivariate analysis found only 2 significant (p less than 0.05) independent predictors of restenosis: post-PTCA percent stenosis greater than 30% and bend point location. Restenosis occurred in 41% of lesions located at an end-diastolic vessel angle greater than or equal to 45 degrees compared with 28% in lesions on lesser bends. Thus, only 1 predilatation morphologic characteristic, stenosis location at a bend point, was an important independent predictor of restenosis, and should be considered when assessing patients for PTCA.

The transstenotic pressure gradient recorded during coronary angioplasty (PTCA) reflects the dynamic relationship that exists between coronary blood flow and the effective cross-sectional area of the arterial lumen. An apparent relationship between the dynamic behavior of the pressure gradient and subsequent acute vessel closure was observed in our catheterization laboratory. We therefore examined the usefulness of the pressure gradient trend in predicting acute complications after 463 attempted PTCA procedures. Two pressure gradient trend patterns were identified: (1) a rising trend pattern identified by an increasing pressure gradient in the interval after deflation of the angioplasty, and (2) a stable trend pattern identified by a constant or decreasing pressure gradient. The incidence of acute vessel closure (17% vs 4%, p = .0001), emergency CABG (5.6% versus 1%, p less than .05), and myocardial infarction (13% versus 2%, p less than .0001) after the PTCA procedure was significantly higher among patients with rising trend patterns when compared with patients with stable trend patterns. Multivariate analysis identified independent predictors for an acute closure event as rising trend pattern (p less than .001), post-PTCA gradient (p less than .05), and post-PTCA percent diameter stenosis (p less than .02). Independent predictors for emergency coronary artery bypass grafting and myocardial infarction were post-PTCA gradient (p less than .001) and a rising trend pattern (odds ratio = 2.91, p less than .001), respectively. The dynamic behavior of the gradient trend provides additional useful information about the results of dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Smooth muscle cell proliferation induced by intimal denudation similar to that produced by coronary angioplasty has been decreased by early and brief heparin administration in animal models. Heparin might also decrease the incidence of thrombus-induced postdenudation arterial obstruction, albiet at risk of bleeding. To evaluate the risks and benefits of heparin after coronary angioplasty, 416 patients (469 vessel sites) with successful coronary angioplasty without large dissection were randomized to heparin (titrated to partial thromboplastin time 1.5 to 2.5 times normal) or dextrose administered for 18 to 24 hours. Patients also had received heparin during angioplasty (usually 10,000 to 15,000 units), and they received aspirin for a period of 6 months. Heparin and dextrose groups were not different in the percentage of patients with male sex (74% in the heparin group and 75% in the dextrose group, p = NS), postangioplasty tear or dissection (30% in the heparin group and 30% in the dextrose group, p = NS), or postangioplasty percent stenosis greater than 35% (31% in the heparin group and 30% in the dextrose group, p = NS). Partial thromboplastin time during treatment in the heparin group was 56 +/- 22 seconds and in the dextrose group 27 +/- 9 seconds (p less than 0.001). Late angiographic follow-up (180 +/- 81 days) was achieved in 58.4% in the heparin group and 64.5% in the control group. Of patients with late angiographic follow-up, 41.2% and 36.7% randomized to heparin and dextrose, respectively, had documented restenosis (greater than or equal to 50% diameter stenosis at one or more the sites dilated) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Eighty-six consecutive hospital survivors (aged less than or equal to 60 years) of a first non-Q-wave acute myocardial infarction (MI) were followed up prospectively. Coronary arteriography was performed a median of 2 weeks after MI. The size of the MI was small (as judged by a mean peak creatine kinase level of 906 IU/liter); 90% were in Killip class I, and the mean left ventricular ejection fraction was 60 +/- 11% (+/- standard deviation). Forty-nine patients had 1 vessel significantly narrowed by disease (greater than or equal to 70% luminal diameter reduction), 19 had 2-vessel, 2 had 3-vessel, 3 had left main (greater than or equal to 50% luminal diameter reduction), and 13 minimal or no coronary artery disease (CAD). Complete occlusion of the MI-related vessel was present in 33 patients. All 33 and an additional 5 patients had collateral vessels to the MI area. During a mean follow-up of 25 months, 1 cardiac death and 4 recurrent infarcts (3 with non-Q-wave MI) occurred. Angina occurred in 53 patients (62%) and responded medically in all but 7 who underwent coronary artery surgery. Angina after MI occurred frequently in patients with severe proximal left anterior descending CAD (greater than or equal to 90%), and in those with CAD (greater than or equal to 50%) in a vessel supplying collaterals to the infarct area. Because angina can be managed medically in most patients and the outcome is good, routine coronary angiography is not indicated in asymptomatic survivors less than or equal to 60 years of a first non-Q-wave MI.