A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study.

Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with clopidogrel is associated with increased ischemic complications after percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic strategy among patients undergoing PCI for ST-elevation myocardial infarction (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to a strategy of prasugrel 10 mg daily or an augmented dosing strategy of clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was the proportion of at-risk carriers exhibiting high on-treatment platelet reactivity (HPR), a marker associated with increased adverse cardiovascular events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of at least one at-risk variant. Treatment with prasugrel significantly reduced HPR compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs 24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point-of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8) and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9) for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24-34.92; P=0.03). We confirmed that concurrent identification of three separate genetic variants in patients with STEMI receiving PCI is feasible at the bedside. Among carriers of at-risk genotypes, treatment with prasugrel was superior to an augmented dosing strategy of clopidogrel in reducing HPR.

A novel approach to safe redo-sternotomy in a patient with aortocutaneous fistula from an infected ascending aorta graft.

This case describes a novel approach to a safe redo-sternotomy in a patient presenting with an aortocutaneous fistula from a previous infected ascending aorta graft.

Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease.

BACKGROUND: Standard perfusion imaging may underestimate the extent of disease in 3-vessel coronary atherosclerosis. This study determined whether positron emission tomography quantification of perfusion reserve by use of rubidium 82 net retention defined a greater extent of disease than the standard approach in patients with 3-vessel disease. METHODS AND RESULTS: Rb-82 net retention was quantified as an estimation of absolute perfusion at rest and with dipyridamole stress by use of dynamic positron emission tomography imaging. The percent of abnormal myocardial sectors, as compared with a normal database, for a standard and quantification approach was determined. Twenty-three patients were evaluated. Defect sizes were larger in patients with 3-vessel disease (n = 13) by use of quantification methods: 44% +/- 18% of the myocardial sectors were abnormal by use of the standard approach versus 69% +/- 24% of sectors when measured by quantification of the stress-rest perfusion difference (P =.008). In patients with single-vessel disease (n = 10), defect sizes were smaller with quantification methods. CONCLUSIONS: Quantification of Rb-82 net retention to measure the stress-rest perfusion difference in the myocardium defined a greater extent of disease than the standard approach in this group of patients with triple-vessel disease. More accurate measurement of the extent of coronary artery disease could facilitate better risk stratification and identify more high-risk patients in whom aggressive intervention is required.

Acute outcome with the flexicut directional coronary atherectomy catheter for the treatment of coronary in-stent restenosis.

In-stent restenosis (ISR) is a growing problem that is without a practical, efficacious treatment strategy. The purpose of this study was to determine the acute outcome of 17 patients with coronary ISR who were treated with the new 8 French (Fr), guide-catheter compatible Flexicut directional atherectomy catheter (Guidant Corporation, Santa Clara, California). Failure to deliver the device occurred in 2/17 ISR lesions. The remaining 15 ISR lesions were successfully debulked (e.g., minimum lumen diameter pre-procedure: 0.30 +/- 0.16 mm; post-atherectomy plus adjuvant therapy: 2.16 +/- 0.57 mm). Of note, the reference vessel diameter was only 2.62 +/- 0.63 mm. In 11/15 tissue specimens, macroscopic or microscopic particles consistent with stent material were found. There was an absence of acute closure or elevations of creatinine phosphokinase levels. Apart from 1 patient who developed recurrent restenosis, all other patients demonstrated either clinical improvement or lack of restenosis during early clinical follow-up (mean, 5 months). We conclude that use of the Flexicut catheter provides satisfactory debulking and early clinical outcomes in patients with ISR. Long-term follow-up of these and additional patients will be helpful in determining the efficacy of the Flexicut atherectomy catheter for the treatment of ISR.

Predictors of improvement in left ventricular function after percutaneous revascularization of occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA).

BACKGROUND: The Total Occlusion Study of Canada (TOSCA) is a multicenter, randomized trial evaluating the effect of stenting with > =1 heparin-coated stent on long-term patency after percutaneous coronary intervention by balloon angioplasty of occluded coronary arteries. The purpose of the current study was to compare the effect of stenting and balloon angioplasty on global left ventricular ejection fraction (LVEF) and regional wall motion and to examine what clinical and angiographic factors may have an effect on left ventricular function in this setting. METHODS AND RESULTS: Analysis at the core angiographic laboratory of paired baseline and follow-up left ventricular angiograms, as well as target vessel patency, was possible in 244 of 410 cases. An improvement in LVEF was observed in the entire group (59.4% +/- 11% to 61.0% +/- 11%, P =.003). The LVEF change was +1.84 +/- 7.54 in the stent group (P =.009) and 1.28 +/- 8.16 in the percutaneous transluminal coronary angioplasty group (P =.085). There was no significant intergroup difference. Patients with duration of occlusion < or =6 weeks had an improvement in LVEF (+2.98 +/- 8.68, P =.0006), whereas those with an occlusion duration of > 6 weeks had no improvement (+0.48 +/- 7.01, P not significant). Multivariate analysis revealed baseline LVEF <60%, duration of occlusion < or =6 weeks, and Canadian Cardiology Society angina class I or II to be independent predictors of improvement in LVEF. CONCLUSIONS: The restoration of coronary patency of nonacute occluded coronary arteries is associated with a small but significant improvement in regional and global left ventricular function, especially in patients with recent occlusions and depressed left ventricular function. In spite of significant effect on long-term patency, stenting of nonacute coronary occlusions does not result in significantly better left ventricular function compared with balloon angioplasty in this setting.

Pharmacodynamics and pharmacokinetics of eptifibatide in patients with acute coronary syndromes: prospective analysis from PURSUIT.

BACKGROUND: Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS. METHODS AND RESULTS: Patients were randomly assigned to an intravenous bolus (180 microgram/kg) and 72-hour infusion of eptifibatide (2.0 microgram/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L-arginine chloromethylketone anticoagulants. Although eptifibatide produced profound, prolonged inhibition of platelet aggregation during therapy, aggregation appeared to recover partially by 4 hours after the bolus. The aggregation response was greater with thrombin receptor agonist peptide versus ADP stimulation; inhibition of platelet aggregation was greater in blood samples anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly with receptor occupancy but not with inhibition of platelet aggregation. CONCLUSIONS: A bolus and infusion of eptifibatide inhibits platelet aggregation profoundly in patients with ACS and is followed by brief, partial recovery. These results enhance our understanding of the relation between pharmacodynamic and clinical effects of eptifibatide in such patients and may have important implications for its use in percutaneous interventions.

Percutaneous removal of pulmonary artery emboli with Hydrolyser catheter in pigs.

OBJECTIVE: To evaluate the efficacy and safety of the Hydrolyser catheter for percutaneous treatment of massive pulmonary embolism in pigs. MATERIALS AND METHODS: Twelve pigs, each weighing between 55 kg and 89 kg, were used. Radioopaque 9 cm x 0.8 cm and 4.5 cm x 0.8 cm clots, produced by mixing pig blood with iodinated contrast agent in vacutainers, were injected via the jugular vein until central pulmonary embolism (main and proximal lobar arteries) was obtained with significant systemic and pulmonary hemodynamic modifications. From a femoral approach, the 7-French Hydrolyser thrombectomy catheter was run over a 0.025-inch (0.64-mm) guide wire to remove the pulmonary emboli. Hemodynamic, gasometric and angiographic monitoring was performed before and after treatment. The procedure's safety and completeness of emboli removal was assessed by cardiopulmonary autopsy. RESULTS: Three of the 12 pigs died during embolization. Thrombectomy was therefore performed in 9, and central emboli could be obtained in 7 of the 9. The Hydrolyser could be manipulated only in central pulmonary arteries and could aspirate only central emboli in 5 of the 7 pigs that had them. Despite minimal angiographic improvement seen in these 5, there was no significant hemodynamic and gasometric improvement after treatment. The procedure induced an increase in free hemoglobin blood levels. Autopsies revealed an average of 2 endothelial injuries per pig (mainly adherent endocardial thrombi) in both nontreated (n = 3) and Hydrolyser-treated (n = 9) groups. CONCLUSION: The Hydrolyser thrombectomy catheter can be promptly positioned and easily steered in central pulmonary arteries. It can be used to partially remove central emboli, but not peripheral pulmonary emboli. Most of the injuries observed may not have been strictly related to Hydrolyser use. The pig might not be a suitable animal model for treatment of massive pulmonary embolism.

Stenting versus thrombolysis in acute myocardial infarction trial (STAT).

OBJECTIVES: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Outcome of acute ST-segment elevation myocardial infarction in patients with prior coronary artery bypass surgery receiving thrombolytic therapy.

BACKGROUND: Patients with prior coronary bypass surgery with acute ST-segment elevation myocardial infarction (MI) pose an increasingly common clinical problem. We assessed the characteristics and outcomes of such patients undergoing thrombolysis for acute MI. METHODS AND RESULTS: We compared the characteristics and outcomes of patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had prior bypass (n = 1784, 4% of the population) with those without prior coronary artery bypass grafting (CABG), all of whom were randomized to receive one of four thrombolytic strategies. Patients with prior bypass were older with significantly more prior MI and angina. Overall, 30-day mortality was significantly higher in patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these patients also had significantly more pulmonary edema, sustained hypotension, or cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated alteplase over the streptokinase monotherapies. In the 62% of patients with prior CABG who underwent coronary angiography, the infarct-related vessel was a native coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001). CONCLUSIONS: The 30-day mortality in patients with prior CABG was significantly higher than that for patients without prior CABG. As in the overall trial, these patients derived an incremental survival benefit from treatment with accelerated alteplase, but mortality remained high (16.7%) at 1 year. These results are at least partially explained by the higher baseline risk of these patients and by the lower rate of patency of the infarct-related artery.

Endoglin is overexpressed after arterial injury and is required for transforming growth factor-beta-induced inhibition of smooth muscle cell migration.

Endoglin is a homodimeric membrane glycoprotein primarily expressed on endothelial cells. In association with transforming growth factor (TGF)-ss receptors I and II, it can bind TGF-beta1 and -beta3 and form a functional receptor complex. There is increasing evidence that endoglin can modulate the cellular response to TGF-beta, a factor implicated in vascular lesion formation in human and experimental models. The purpose of this study was to analyze the expression of endoglin in normal and balloon-injured porcine coronary arteries and in normal and atherosclerotic human coronary arteries and to determine its ability to mediate the effects of TGF-beta on the migration of vascular smooth muscle cells (SMCs). In normal porcine coronary arteries, endoglin was of low abundance and was found primarily on endothelial cells and adventitial fibroblasts, as well as on a minority of medial SMCs. On days 3, 7, and 14 after angioplasty, endoglin was present not only on endothelial cells but also on adventitial myofibroblasts and medial SMCs of porcine coronary arteries. By day 28, few or no cells expressed endoglin. In situ hybridization revealed that endoglin mRNA expression appeared to be highest in endothelial cells on days 3, 7, and 14 days after injury and absent thereafter. With a second balloon injury, a similar pattern of endoglin protein and mRNA expression was observed. In human vascular tissue, endoglin immunolabeling was higher in endarterectomy specimens removed from diseased coronary arteries than in normal internal mammary arteries. In vitro, antisense oligonucleotides to endoglin decreased its expression and antagonized the TGF-beta-mediated inhibition of human and porcine SMC migration. In summary, upregulation of endoglin occurs during arterial repair and in established atherosclerotic plaques and may be required for modulation of SMC migration by TGF-beta.

Infusion of an antialpha4 integrin antibody is associated with less neoadventitial formation after balloon injury of porcine coronary arteries.

BACKGROUND: The alpha4beta1 (or very late antigen-4 [VLA-4]) integrin is thought to play a role in inflammatory processes, mediating mononuclear leukocyte infiltration. The adventitial response to balloon injury is an important determinant of neointimal formation and arterial remodelling. OBJECTIVES: To determine whether the monoclonal antibody hHP1/2 directed against the human alpha4-integrin subunit decreases neoadventitial formation and subsequent luminal narrowing following balloon injury. DESIGN: Randomized, double-blind, placebo controlled study. SETTING: Tertiary care, Canadian university hospital vascular biology laboratory. ANIMALS AND METHODS: In 16 pigs, two coronary arteries were injured with an oversized balloon, while a third coronary artery was designated as an uninjured control vessel. One hour before balloon injury, 5 mg/kg of hHP1/2 was administered to eight animals, while another eight animals received an infusion of a saline placebo. Animals were killed three and 14 days following balloon injury. MAIN RESULTS: Administration of hHP1/2 resulted in an immediate decrease in circulating monocyte and lymphocyte counts. These parameters returned to normal within three days. There was a decrease in neoadventitial formation 14 days after arterial injury in pigs treated with hHP1/2 compared with controls (2.26+/-0.77 versus 3.42+/-1.01 mm, respectively, P=0.04). There was a loss of lumen area between days 3 (4.33+/-1.09 mm2) and 14 (3.09+/-0.38 mm2, P=0.02) after balloon injury in pigs treated with saline, but not in the pigs treated with hHP1/2. CONCLUSIONS: Administration of an antibody to the alpha4-integrin subunit is associated with less neoadventitial formation and less lumenal narrowing after balloon injury. This novel therapy may play an important role in modulating arterial remodelling and thereby may reduce restenosis following percutaneous coronary interventions in humans.

Enhanced efficacy of eptifibatide administration in patients with acute coronary syndrome requiring in-hospital coronary artery bypass grafting. PURSUIT Investigators.

BACKGROUND: Patients with a recent episode of non-ST-segment elevation acute coronary syndrome before CABG have higher rates of operative morbidity and mortality than patients with stable coronary syndromes. The efficacy of administering eptifibatide to these patients undergoing in-hospital CABG is unknown. METHODS AND RESULTS: The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomized 10 948 patients to receive either eptifibatide or placebo. There were 1558 study participants who underwent in-hospital CABG: 692 received placebo, and 866 received eptifibatide. The main substudy analysis end point was death or myocardial infarction (MI) rates at the 6-month follow-up. The 30-day death or MI rates were 30. 8% and 26.1% for the placebo and eptifibatide groups, respectively (P:=0.041). The benefit of eptifibatide administration persisted through 6-months of follow-up (32.7% versus 27.6% for placebo versus eptifibatide, respectively; P:=0.029). There was a greater reduction in the 6-month death or MI rate for patients who received eptifibatide within 72 hours of CABG (33.6% versus 23.8%; P:=0.002) compared with the >72-hour group (31.6% versus 32%; P:=1.0). The incidence of major bleeding was 56.6% for placebo-treated patients versus 58.2% for eptifibatide-treated patients (P:=0.7). CONCLUSIONS: Eptifibatide administration in patients undergoing in-hospital CABG with a recent episode of a non-ST-segment elevation acute coronary syndrome results in a significant reduction in death or MI that is evident at 7 days and persists through the 6-month follow-up without a significant increase in perioperative bleeding rates.

Stenting of an unprotected left main coronary artery stenosis in a cardiac transplant patient.

Cardiac allograft vasculopathy is the leading cause of death in cardiac transplant patients who survive the first year. Retransplantation is limited by shortage of donors and reduced survival rates compared with the initial transplant. Recent reports of successful stenting in these patients may offer some hope, although randomized trials are lacking. Successful stenting of an 'unprotected' left main coronary artery stenosis under cardiopulmonary support is presented in a cardiac transplant patient. A 16-month follow-up angiogram demonstrated a patent stent without restenosis and no interim clinical events.

Establishing an approach for patients with recent coronary occlusion: identification of viable myocardium.

BACKGROUND: Revascularization of occluded coronary arteries after myocardial infarction (MI) may restore flow to viable myocardium and improve ventricular function. The aim of this pilot study was to determine the potential utility of thallium-201 viability imaging for the prediction of recovery of regional ventricular function in patients undergoing revascularization of total or subtotal occlusion of infarct-related arteries (TIMI 0-2 flow) during the convalescent period after MI. METHODS: Twenty-three patients were identified < 6 weeks after MI and underwent Tl-201 viability imaging (rest imaging, n = 16; stress/reinjection imaging, n = 7) and radionuclide angiography. Patients were revascularized with percutaneous transluminal coronary artery in 10, stent in 10, and bypass in 3. Follow-up radionuclide angiography at 3 months was used to assess recovery of regional wall motion. RESULTS: Among 41 abnormal wall motion segments in the infarct territories, the sensitivity, specificity, and accuracy for Tl-201 imaging in the prediction of recovery of regional function were 89% (25/28), 54% (7/13), and 78% (32/41), respectively. When 8 segments supplied by vessels with restenosis to >70% were excluded, specificity improved to 70%. Wall motion scores improved in those with adequate revascularization (1.6+/-1.4 vs 2.7+/-1.6; P < .001) but not in those with restenosis or occlusion (1.8+/-1.0 vs 2.0+/-1.6; P = NS). CONCLUSIONS: In patients with an occluded artery after MI, Tl-201 viability imaging can detect recoverable myocardium with reasonable accuracy and may help select which patients will most benefit from revascularization.

Time course and importance of neoadventitial formation in arterial remodeling following balloon angioplasty of porcine coronary arteries.

OBJECTIVES: Arterial remodeling has been suggested as the predominant factor in restenosis. However, the time course and morphometric factors that determine whether remodeling occurs remain unclear. We hypothesized that arterial remodeling does not occur in all arteries following balloon injury and is dependent on neoadventitial formation. METHODS: Using single (SI) and double (DI) balloon injury of Yorkshire porcine coronary arteries we examined changes in morphometry 3, 7, 14, 28 days following balloon injury. RESULTS: In both SI and DI arteries, the neoadventitia (NAD) area expanded by day 3 and was the first compartment to increase following injury. In SI arteries lumen area (LA) decreased between day 3 and 14 while in DI arteries, there was significantly less loss in LA. In SI arteries, contracture of the area circumscribed by the external elastic lamina (EEL), which occurred predominantly between day 7 and 14, accounted for 67% of the loss of LA. CONCLUSIONS: Accumulation of NAD appears to be the earliest change in the vessel wall following balloon injury of normal or previously injured arteries and precedes the growth of the I + M (intima and media). The predominant mechanism for lumenal narrowing following single balloon injury of a normal artery is remodeling. In contrast, remodeling does not occur in DI arteries, possibly due to differences in the degree of adventitial fibrosis of normal and injured arteries.

Predictors of long-term outcome after stent implantation in a saphenous vein graft.

Stenting of saphenous vein graft (SVG) lesions is associated with significant clinical events at late follow-up. We sought to determine predictors of clinical outcome after this procedure. One hundred twenty-eight balloon-expandable stents were implanted in the SVGs of 106 patients. Baseline clinical and angiographic characteristics were analyzed. All grafts, including those not stented, were scored for extent of disease involving the luminal surface of the graft, and for the presence of low profile lesions (< 50% graft stenosis) and/or high profile lesions (> or = 50% graft stenosis). The in-hospital success rate was 98.1%. Before discharge, no patient died, required bypass surgery, or had repeat angioplasty of the same graft. Follow-up was obtained on all the patients. At a median of 18 months, 15% had died, 17% had experienced myocardial infarction, 20% had required repeat bypass surgery, and 37% needed repeat angioplasty to either the same site or a different lesion. Event-free survival was recorded in only 44% of the patients. The cumulative Kaplan-Meier survival at 2.4 years was 78.7%. Using the Cox proportional hazards model, predictors of survival were the absence of a high profile lesion in any nonstented patent graft (p = 0.004), and the use of lipid-lowering agents at follow-up (p = 0.01). Stenting SVG lesions can be performed with a high degree of procedural success, but at long-term follow-up there is a high rate of cardiac events. The absence of a high profile lesion in any nonstented patent graft is the strongest predictor of survival.

Adventitial angiogenesis early after coronary angioplasty : correlation with arterial remodeling.

The spatial correlation between arterial wall microvessels and the accumulation of atherosclerotic plaque is well documented. The role of these microvessels in the development of primary and restenotic lesions is not known. To investigate the effect of interventional procedures on arterial wall microvessels, we studied the adventitial microvascularity of porcine coronary arteries subjected to angioplasty. Twenty-two juvenile domestic swine were subjected to single or repeated (double) balloon angioplasty of the coronary arteries, with the interval between the first and second injury being 14 days. The number, density, and size of adventitial microvessels were measured 1 hour as well as 3, 7, 14, and 28 days after injury. One hour after single balloon injury, there were very few intact adventitial microvessels. Adventitial microvessel number, microvessel area density, and microvessel size were maximal 3 days after single (SI) and double (DI) injury but subsequently underwent progressive regression. Adventitial endothelial cell replication, as assessed by the incorporation of bromodeoxyuridine, was very low for the majority of arteries. Maximal endothelial cell replication indices were observed 3 days after SI and DI (eg, 12.0+/-3.3%). Early after SI the central arterial lumen area transiently increased, then renarrowed. The lumen area did not change after DI. Arterial remodeling occurred, as the accumulation of intimal and medial mass was correlated with expansion of the external elastic lamina. Adventitial microvessel area density was correlated with central arterial luminal area (R=0.34, P=0.04). The adventitial microvessel area density and the microvessel size index were greater late after DI compared with SI. These data indicate that adventitial angiogenesis occurs within 3 days after balloon injury and that regression of adventitial microvessels after SI corresponds with arterial narrowing. Changes in the adventitial microvasculature may be a component of arterial remodeling after balloon angioplasty.

Coronary stenting in unstable angina: early and late clinical outcomes.

OBJECTIVE: To examine the procedural and long term success of coronary stenting in patients presenting with unstable angina and the effect of warfarin on the clinical outcome of these high risk patients. DESIGN: A nonrandomized, retrospective analysis of patients presenting with unstable angina. SETTING: A tertiary care, Canadian university-affiliated teaching hospital. PATIENTS: Of 1250 patients who underwent percutaneous transluminal coronary angioplasty between January 1994 and June 1995, 365 underwent coronary stenting. The study population consisted of the 156 patients presenting with unstable angina who underwent coronary stenting. Patients with Canadian Cardiovascular Society class IV and postinfarction angina were included. INTERVENTIONS: Stent delivery by standard techniques to the target lesion was successful in all patients. At discharge, 88 patients were prescribed warfarin, ticlopidine and acetylsalicylic acid (ASA); the remaining 68 patients received only ticlopidine and ASA. Late clinical outcomes were assessed by telephone interview. RESULTS: The overall procedural success rate was 96%. One patient died in hospital (0.6%). Other events were abrupt closure (1.9%), myocardial infarction (1.9%) and urgent bypass surgery (1.9%). During follow-up, target vessel reintervention was needed in 19.6% of patients. Early and late clinical outcomes did not differ significantly between anticoagulated patients and those treated with antiplatelet agents alone, but anticoagulated patients had a significantly longer hospital stay. CONCLUSIONS: Coronary stenting in patients with unstable angina was associated with excellent procedural success and favourable late clinical outcomes. Warfarin added no apparent additional clinical benefit to antiplatelet agents in this high risk population.

Late clinical and angiographic follow-up after stenting in evolving and recent myocardial infarction.

OBJECTIVES: This study sought to assess the late clinical and angiographic outcomes of patients who received stents within the first week of acute myocardial infarction (AMI). BACKGROUND: Recent studies have demonstrated that stenting of the infarct-related artery is a useful adjunct to balloon angioplasty in patients with AMI. However, there are limited data on the late clinical and angiographic outcomes of these patients. METHODS: Between January 1994 and September 1995, 32 patients at our institution underwent stenting of the infarct-related artery within 1 week of AMI: 13 within 14 hours (evolving group) and 19 between days 2 and 7 (recent AMI group). Late clinical follow-up was obtained on all survivors. Quantitative angiographic measurements were recorded on the stented segments before stenting, immediately after stenting, and on the follow-up angiograms. RESULTS: At 13.1+/-6.4 months from the time of stenting, three patients died and three required repeat angioplasty, but no patient had reinfarction or required bypass surgery. At follow-up 26 (81%) of 32 patients remained free of major cardiac events; of these, 24 (92%) were free of angina. Repeat angiography performed at 10.8+/-7.5 months in 26 (87%) of 30 discharged patients showed that all infarct-related arteries were patent and the restenosis rate was low: 22% in the 13 patients with evolving AMI (<14 hours) and 12% in the 19 patients with recent AMI (days 2 through 7). CONCLUSION: In this study stenting of the infarct-related artery in patients with evolving and recent AMI was associated with a favorable late clinical outcome. Patency of the infarct-related artery was well maintained, and the restenosis rate was low.