Stenting after optimal lesion debulking (sold) registry. Angiographic and clinical outcome

BACKGROUND: Coronary stenting has reduced restenosis in focal de novo lesions, but its impact has been less pronounced in complex lesion subsets. Preliminary data suggest a role for plaque burden in promoting intimal hyperplasia after stent implantation. The aim of this study was to test the hypothesis that plaque removal with directional atherectomy before stent implantation may lower the intensity of late neointimal hyperplasia, reducing the incidence of in-stent restenosis. METHODS AND RESULTS: Seventy-one patients with 90 lesions underwent directional atherectomy before coronary stenting. Intravascular ultrasound-guided stenting was performed in 73 lesions (81%). Clinical success was achieved in 96% of patients. Procedural complications were as follows: emergency bypass surgery in 1 patient (1.4%), who died 2 weeks later; Q-wave myocardial infarction in 2 patients (2.8%); and non-Q-wave myocardial infarction in 8 patients (11.3%). None of the patients had stent thrombosis at follow-up. Angiographic follow-up was performed in 89% of eligible patients at 5.7+/-1.7 months. Loss index was 0.33 (95% CI, 0.26 to 0.40), and angiographic restenosis was 11% (95% CI, 5% to 20%). Clinical follow-up was performed in all patients at 18+/-3 months. Target lesion revascularization was 7% (95% CI, 3% to 14%). CONCLUSIONS: Directional atherectomy followed by coronary stenting could be performed with good clinical success rate. Also, these data point to a possible reduction in angiographic restenosis and a significant reduction in the need for repeated coronary interventions. Therefore, a randomized clinical trial seems appropriate to test the validity of this approach.     

Angina pectoris caused by coronary microvascular spasm

BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.     

Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm

BACKGROUND: Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS: G?ttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). CONCLUSIONS: These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.     

Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis. Increased gene expression in the intima of injured carotid arteries and human restenotic coronary lesions

Proliferation of vascular smooth muscle cells (VSMCs) is considered to be one key event underlying the pathophysiology of restenosis after angioplasty. The parathyroid hormone-related peptide (PTHrP) and its receptor, a local autocrine and paracrine regulator of cellular growth in a variety of normal cell types, have been reported in the vicinity of VSMCs. To investigate how PTHrP might be involved in the process of neointimal formation after balloon angioplasty, we examined PTHrP expression in balloon-denuded rat carotid arteries and human coronary arteries that had been retrieved by directional atherectomy. In rat carotid arteries, the RNase protection assay and in situ hybridization demonstrated that PTHrP mRNA expression increased fourfold to sixfold 1 to 7 days after denudation and continued for 28 days, coincident with downregulation of PTH/PTHrP receptor mRNA expression. In situ hybridization and immunohistochemistry revealed that PTHrP expression in balloon-denuded carotid arteries was mainly localized to the neointima. To confirm the involvement of the PTHrP in human coronary artery restenotic lesions, immunohistochemical analysis of human coronary atherectomy specimens (23 primary and 10 restenotic lesions) was then performed. The number of intimal cells that expressed PTHrP protein was significantly higher in restenotic (407 +/- 53 cells/mm2; range, 143 to 739) than in stable angina (50 +/- 12 cells/mm2; range, 18 to 132; P<.05) or unstable angina (129 +/- 16 cells/mm2; range, 21 to 232; P<.05) specimens. These data demonstrate that PTHrP gene expression in VSMCs markedly increases during neointimal formation, supporting the hypothesis that PTHrP may play an important role in vascular stenosis as a regulator of VSMC proliferation.     

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome;16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.     

Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis

BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty is the major limitation of the long-term success of this procedure. The process of restenosis is similar to an accelerated form of atherosclerosis. Thus, therapeutic interventions that limit the progression and initiation of atherosclerosis may be beneficial in the treatment of restenosis. One such intervention is the antioxidant drug probucol, which has demonstrated benefit in animal models of atherosclerosis. METHODS AND RESULTS: Twenty-six female domestic swine were divided into three study groups (control, n = 9; low-dose probucol, n = 9; high-dose probucol, n = 8) before oversized balloon injury of the left anterior descending and left circumflex coronary arteries. Probucol (1 g/d, low-dose group; 2 g/d, high-dose group) was administered 2 days before balloon injury and was continued until the swine were killed 2 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area (square millimeters), maximal intimal thickness (millimeters), and residual lumen (ratio of luminal to intimal plus luminal area). Treatment with high-dose probucol significantly reduced neointimal formation compared with control animals (decreases of 36% in intimal area, P = .007; 20% in maximal intimal thickness, P = NS; and an increase of 15% in residual lumen, P = .02). CONCLUSIONS: The major finding of this study is that the antioxidant drug probucol reduces neointimal formation after oversized balloon injury in a swine model of restenosis. This suggests that active oxygen species may play a role in restenosis.     

Swine model of coronary restenosis: effect of a second injury

Looking for a coronary artery restenosis model closer to human pathology, a protocol of balloon injury/reinjury (plaque of dilatation) in swine coronary artery was designed. Pig coronary arteries (n = 24) were dilated for this study: 12, group 1, once (sacrifice at 10.0 +/- 2.2 weeks); 6, group 2, twice at 2-wk intervals (sacrifice at 5.2 +/- 0.2 wk); 6, group 3, twice at 4-wk intervals (sacrifice at 9.3 +/- 1.9 wk). A single overdilatation resulted in an eccentric neointimal hyperplasia representing half of the wall area (group 1, 45.6 +/- 5.1%). In animals (groups 2 and 3) subjected to redilatation, fracture length, ratio of fracture length to internal elastic lamina (IEL) circumference, and neointimal hyperplasia response were similar to those observed in group 1. In group 3, the shape of the lesion appeared more concentric and the fracture of the IEL more fragmented than in group 1. Although this model of injury/reinjury did not lead to more severe intimal hyperplasia, performing a second angioplasty at the same site did lead to a more concentric intimal response, related to multiple fractures of the IEL.     

Intravascular ultrasound in determining the end point of percutaneous transluminal coronary angioplasty

Intravascular ultrasound (IVUS) imaging was used to measure internal luminal area immediately after percutaneous transluminal coronary angioplasty (PTCA) in 83 patients (59 males, 24 females, mean age 63 +/- 12 years) with angina pectoris to determine the need for additional intervention. The effectiveness of these interventions to prevent restenosis was also studied. Thirty-five patients (42%) with insufficient dilatation revealed an internal luminal area less than 5 mm2 or luminal stenosis greater than 60% as evaluated by IVUS imaging following the procedure. The luminal area increased from 4.5 +/- 1.1 to 7.9 +/- 2.8 mm2 and the percentage luminal stenosis improved from 66 +/- 9% to 54 +/- 9% in patients who underwent further dilatation with a larger size balloon, longer dilatation time, directional coronary atherectomy, or stenting. The insufficient dilatation group exhibited hard plaque and calcification more frequently than in the other group (48 patients, 58%) in whom sufficient dilatation of the target lesion was achieved. The incidence of restenosis in the sufficient dilatation group was 25%, compared to 33% of the patients receiving additional treatment after IVUS imaging and 42% in the 192 patients who underwent PTCA without IVUS imaging. IVUS imaging is a useful method for evaluation of complex luminal morphology to decrease the incidence of restenosis and for determination of the end point and the extent of dilatation required.     

Histopathologic features in atherectomy samples obtained from patient with unstable angina, stable angina and restenosis. Directional Atherectomy Lombardi Group

BACKGROUND: The present study was aimed at investigating the pathologic features of directional coronary atherectomy (DCA) samples obtained from 194 patients (14 females) with stable (n = 68) and unstable (n = 95) angina, and with restenosis (n = 27). METHODS: DCA samples were obtained from culprit lesions, using the Simpson technique. Unstable angina was classified according to E. Braunwald criteria. Stable angina was grouped according to the presence or absence of a prior myocardial infarction (MI). DCA samples were fixed, processed, serially cut and stained with hematoxilin-eosin and with Movat pentachrome stain. RESULTS: The major pathologic findings were thrombosis, inflammation of the superficial plaque layers, and neointimal hyperplasia which often coexisted within a same sample. Their frequencies, in that order, were distributed in the differing groups of patients as follows: 21% (n = 9), 29.2% (n = 12) and 51% (n = 21) of the 41 cases with stable angina without prior MI. 40.7% (n = 11), 40.7% (n = 11), and 51.8% (n = 14) of the 27 cases with stable angina with prior MI. 25% (n = 4), 56.2% (n = 9) and 68.7% (n = 11), of the 16 cases with BI unstable angina. 35.3% (n = 14), 55.8% (n = 19) and 44% (n = 15), of the 34 cases with BII unstable angina. 44.4% (n = 4), 33.3% (n = 3) and 33.3% (n = 3), of the 9 cases with BIII unstable angina. 48.2% (n = 14), 48.2% (n = 14) and 51.8% (n = 15), of the 29 cases with CII unstable angina at 35.8 days after MI. 60% (n = 3), 60% (n = 3) and 40% (n = 2), of the 5 cases with CIII unstable angina at 8.3 days after MI. 26% (n = 7), 48% (n = 13) and 85.1% (n = 23), of the 27 cases with restenosis. According to above observation, the frequency of coronary thrombosis increases with the increase of the severity of myocardial ischemia. However, thrombosis is not found in most unstable angina without prior MI (63% of BI-II-III unstable angina cases do not have thrombus). In addition, thrombus is not a specific finding of unstable angina, given its occurrence, although in a much lower percentage of cases, in stable angina and in restenosis. CONCLUSIONS: Present data show that different ischemic and plaque lesions. This observation questions on the pathogenetic role of thrombus in unstable angina and calls for further investigations on inflammation and neointimal hyperplasia, as well as on the the reciprocal relation between these findings which are often combined within a same lesion.     

Increased apoptosis and necrosis of coronary plaques in unstable angina

In acute coronary syndromes, arteriosclerotic plaques are characterized by inflammation and decreased smooth muscle cell density. The underlying pathogenic processes remain unclear. Among others, increased programmed cell death (apoptosis) is postulated. Coronary atherectomy specimens from 26 patients with unstable angina (group 1) and from 24 patients with stable angina (group 2) were examined, using immunohistochemistry (TUNEL test to detect fragmented DNA) and transmission electron microscopy. The objectives of the present study were to evaluate plaque group differences in the cellular composition, to detect and quantify cell death, and to differentiate between apoptosis and necrosis. Group 1 lesions contained more macrophages and lymphocytes as well as significantly (p = 0.01) less smooth muscle cells compared with group 2 lesions, whereas both revealed a comparable cell density. All plaques showed signals for fragmented DNA. TUNEL-positive cells were seen more frequently in lesions with unstable angina (p = 0.04). Ultrastructural analysis revealed signs of programmed cell death, such as nuclear alterations, cellular condensation due to lost adhesion, and apoptotic bodies. Importantly, group I lesions comprised significantly more apoptotic SMCs and apoptotic macrophages compared with group 2 lesions (28% vs. 16%; p = 0.02). Also, cellular necroses were found to be increased in lesions with unstable angina (18% vs. 8%; p = 0.02). The density of macrophages showed a positive correlation to the incidence of cellular necroses in group 1 lesions (r = 0.44; p = 0.02), but not in group 2 lesions. In both plaque groups, this determinant was independent from cellular apoptosis, also at high levels as found with unstable angina. The present study on coronary atherectomy specimens with unstable angina reveals intimal macrophage infiltration and the density of apoptotic as well as necrotic intimal cells to be increased, whereas the content of intact SMCs was reduced. Increased, macrophage-independent apoptosis strongly points to the presence of one or several pro-apoptotic intimal factor(s) predisposing to plaque rupture. Implications of our findings may be directed to identify this (these) factor(s) and to modulate endogenous apoptotic activity with the ultimate goal to raise regional smooth muscle cell density.     

Action of intracoronary nitroglycerin in refractory coronary artery spasm

Coronary artery spasm usually responds to sublingual nitroglycerin. This report describes four patients with variant angina and one patient with rest angina who had coronary spasm that was refractory to sublingual or i.v. nitroglycerin. In four patients, spasm occurred spontaneous and in one patient after 0.05 mg of ergonovine. In each case, 25-100 micrograms of intracoronary nitroglycerin promptly (30-45 seconds) resulted in reopacification of the vessel involved in spasm and resolution of evidence for ischemia. Thus, intracoronary nitroglycerin can reverse coronary artery spasm that does not respond to systemic nitroglycerin administration.     

Restenosis and arterial remodelling after coronary angioplasty

Restenosis after coronary angioplasty (PTCA) is a complex process and is still the major problem, despite improvements in equipment and technique. Thrombus formation and intimal hyperplasia have been considered to be the main causes of the development of restenosis after primary successful angioplasty. As yet, pharmacological trials to prevent restenosis have failed to prevent it, despite the fact that the therapy has been aimed at reducing thrombus formation and intimal hyperplasia. Several new angioplasty devices have been developed. Series of observations and a few controlled trials have demonstrated restenosis rates similar to those obtained with conventional balloon angioplasty, except in the case of stent implantation, which appears to be promising. Intravascular ultrasound studies have provided new insight and a more complete understanding of the process leading to restenosis. Vascular remodeling is now considered as an important pathogenetic factor. It consists of a change in the cross-sectional vessel area and may involve an actual constriction of the artery. This may lead to lumen-narrowing and finally restenosis with minimal neointimal formation. In this review we summarise the literature on the restenosis process and the current status of the clinical trials aimed at preventing restenosis.     

ST elevation during ergometric test: correlation with coronary angiography

BACKGROUND: ST elevation during ergometric stress test (EST) is relatively rare. Its prevalence depends upon the tested population but occurs more frequently in patients who have had myocardial infarction or variant angina. This phenomenon is very rare in patients with typical exertional angina and its pathogenesis is still unclear. MATERIAL AND METHODS: We studied a group of 75 consecutive patients with exertional angina who underwent EST and coronary angiography. A symptom limited EST was performed in the upright position on a cycloergometer with load increases of 25 watts every 3 minutes and 12 leads were monitored during all test. Coronary angiography was performed according to Judkins technique. From these patients, according to Froelicher's criteria, a group of 49 patients (age 32-68, mean 51.6 years), without myocardial infarction and/or left ventricular asynergy, was selected. RESULTS: All patients had a coronary artery disease (16 patients with 3 vessels, 11 patients with 2 vessels and 22 patients with 1 vessel disease). The EST was positive for ST depression in 31 patients (63.3%) and for ST elevation in 5 patients (10.1%), while 13 patients (26.6%) had a non diagnostic EST. The ST elevation occurs in V1-V2 and it was associated in all cases with a stenosis in the left anterior descending (LAD) artery. Therefore we divided the 19 patients with LAD stenosis into two subgroups: subgroups A (9 patients, mean age 49.6 years) with LAD stenosis > or = 90% and subgroups B with LAD stenosis between 70% and 90%. ST elevation occurs in 5 patients (55.5%) of subgroup A and in no patient of the subgroup B. Moreover, in the subgroup A ST elevation seems to be related to the anatomic localization of the stenosis: in fact it appears in 83.3% of patients with LAD stenosis located before the onset of the first diagonal branch. CONCLUSIONS: From these data it can be desumed that ST elevation in V1-V2 that occurs in patients with exertional angina and without myocardial infarction or variant angina is strongly predictive of a very important LAD stenosis.     

Insulin resistance associated with compensatory hyperinsulinemia as an independent risk factor for vasospastic angina

BACKGROUND: It is generally believed that coronary artery spasm plays an important role in the progression of obstructive coronary artery disease. Since insulin resistance together with hyperinsulinemia plays an important role in the pathogenesis of coronary atherosclerosis, we investigated the association of hyperinsulinemia and insulin resistance with vasospastic angina (VAP). METHODS AND RESULTS: The study population consisted of 60 patients with VAP and 42 control subjects (62 subjects with normal glucose tolerance and 40 with impaired glucose tolerance). Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method for nondiabetic, normotensive, nonobese subjects (16 control subjects, 16 obstructive coronary artery disease patients, and 16 VAP patients). Compared with the control group, the 2-hour insulin area (area under the plasma insulin concentration-time curve) during a 75-g oral glucose tolerance test was significantly higher in both VAP groups with normal and impaired glucose tolerance. A high frequency of vasospastic angina was observed in subjects with clustered risk factors for insulin resistance syndrome, suggesting a close association of VAP with this syndrome. In stepwise discriminant analysis, the 2-hour insulin area was significantly associated with VAP independent of other risk factors. SSPG level in VAP was about twofold over control, indicating the presence of insulin resistance in patients with VAP. However, no differences were found between patients with VAP and obstructive coronary artery disease with respect to mean SSPG level. CONCLUSIONS: SSPG level was significantly elevated in patients with VAP and obstructive coronary artery disease compared with control subjects. This indicates that hyperinsulinemia is secondary to insulin resistance, both of which are thought to play important roles as risk factors for VAP in the early atheromatous lesion and in the future development of occlusive lesions when chronically present.     

Tissue-factor antigen and activity in human coronary atherosclerotic plaques

BACKGROUND: Coronary atherosclerotic-plaque thrombosis is a key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque rupture or fissuring frequently occurs in atherosclerosis, only a small proportion of ruptured plaques develop thromboses. METHODS: Tissue-factor antigen and activity were measured in atherectomy samples from 50 consecutive patients with coronary artery disease (stable angina n = 19, unstable angina n = 24, and myocardial infarction n = 7). FINDINGS: Median tissue-factor antigen and activity concentrations were significantly higher in plaques from patients with unstable angina and myocardial infarction than in those from patients with stable angina (antigen: 66.1 pg/mg [interquartile range 43.8-82.5] vs 32.4 pg/mg [9.8-43.4], p = 0.0001; activity: 0.22 mU/mg [0.17-0.41] vs 0.13 mU/mg [0.05-0.16], p = 0.0004). INTERPRETATION: Tissue-factor, an initiator of the coagulation cascade, may account for the different thrombotic responses to the rupture of human coronary atherosclerotic plaques.     

Impact of diabetes mellitus on percutaneous revascularization (CAVEAT-I). CAVEAT-I Investigators. Coronary Angioplasty Versus Excisional Atherectomy Trial

We examined the relation between diabetes mellitus and outcomes in patients undergoing percutaneous coronary revascularization in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I), a randomized trial comparing treatment with either percutaneous transluminal coronary angioplasty or directional atherectomy for de novo lesions in native coronary arteries. Acute success and complication rates, 6-month angiographic restenosis rates, and 1-year clinical outcomes were compared between diabetic and nondiabetic patients undergoing each procedure. Acute success rates between diabetic (n = 191) and nondiabetic (n = 821) patients were similar for both revascularization techniques. Except for the need for dialysis, complication rates were also similar. Six months after atherectomy, diabetic patients had significantly more angiographic restenosis than nondiabetics (59.7% vs 47.4%) and significantly smaller minimum luminal diameters (1.20 vs 1.40 mm). Diabetics undergoing atherectomy required more frequent bypass surgery (12.8% vs 8.5%) and more repeat percutaneous revascularizations (36.5% vs 28.1%) than nondiabetics undergoing atherectomy. Restenosis rates, minimum luminal diameters and repeat revascularizations between diabetics and nondiabetics undergoing angioplasty were similar. The higher restenosis and repeat revascularization rates and the smaller minimum luminal diameter at follow-up in diabetic patients suggest that atherectomy may provide only modest benefit for these patients. The increased restenosis rate in diabetics undergoing atherectomy (but not angioplasty) requires further evaluation.     

Myocardial perfusion scintigraphy to evaluate patients after coronary stent implantation

Coronary stent implantation is an increasingly accepted revascularization method. The 20%-30% restenosis rate during the first 6 mo requires a close follow-up of the patients. Since there is very little data available defining the role of perfusion scintigraphy in the management of this population, the aim of this study was to assess the diagnostic performance of stress myocardial perfusion imaging for detecting restenosis in patients after coronary stent implantation. METHODS: In 82 patients, 93 rest or stress SPECT studies were performed using 201Tl and 99mTc-hexakis-2-methoxyisobutyl isonitrile to evaluate 99 vascular territories with implanted coronary stents. The average interval between the stent implantation and the scintigraphic study was 210.5 +/- 129.6 days. The scintiscans were visually evaluated. A stress-induced perfusion defect with reversibility at rest was used as the criterion for stent restenosis. RESULTS: Coronary angiography revealed a stenosis of > 50% diameter in the region of the stent in 19 arteries, while in 80 arteries there was no evidence of restenosis angiographically. With perfusion scintigraphy, 15/19 vascular territories with restenosed stents showed stress-induced perfusion abnormalities (sensitivity = 79%), while 62/80 territories without restenosis did not (specificity = 78%). In territories without a myocardial infarction (n = 48), sensitivity and specificity values were 8/8 (100%) and 36/44 (82%), and in territories with a myocardial infarction (n = 47) 7/11 (64%) and 26/36 (72%), respectively. Side branch stenosis was fairly frequent in patients without stent restenosis but with a reversible perfusion pattern on their scintiscan (8/18); however, these stenoses were induced infrequently by the stents (3 cases). CONCLUSION: Using the criterion of defect reversibility, stress perfusion SPECT can accurately detect restenoses of coronary artery stents. This method is most accurate for evaluating patients without a previous myocardial infarction in the stented vascular territory.     

Selective ET(A) receptor antagonism reduces neointimal hyperplasia in a porcine coronary stent model

BACKGROUND: As endothelin binds to ET(A) receptors, it stimulates vascular smooth muscle cell proliferation and may thus be pivotally involved in the pathogenesis of restenosis. This study assessed the ability of a potent and selective ET(A) antagonist to reduce neointimal hyperplasia in a porcine coronary artery stented injury model. METHODS AND RESULTS: Fifty-five pigs were randomized to receive placebo or the oral ET(A)-selective antagonist ABT147627 twice daily for 28 days in one of three doses: 0.75 mg/kg (low), 3.75 mg/kg (mid), and 10.0 mg/kg (high). Each underwent oversized stent deployment in two randomly assigned major epicardial coronary arteries. Three animals (5.5%) died as a consequence of stent thrombosis within 24 hours of the procedure. The remaining 52 animals (13 pigs per group) survived without complication until predetermined euthanasia at 28 days. In the placebo group, mean injury score was 1.73+/-0.80, with a mean neointimal response of 0.45+/-0.24 mm. By comparison, the low-dose group had a similar mean injury score of 1.79+/-0.75 with reduced neointimal response, 0.36+/-0.22 mm (P<0.01). Mean injury score in the mid-dose animals was significantly greater than in the placebo group (1.94+/-0.92; P<0.05). The neointimal hyperplasia associated with this injury was less than with placebo, although the difference did not reach statistical significance (0.40+/-0.25 mm; P=0.05). In the high-dose pigs, mean injury score was also significantly greater than in the placebo arm (1.93+/-0.73; P<0.05). Despite this, neointimal response was also significantly less (0.37+/-0.37 mm; P<0.01). CONCLUSIONS: Oral, selective ET(A) receptor antagonism significantly reduced neointimal hyperplasia forming over porcine coronary stented injuries in the first 28 days. This strategy may have clinical potential for the limitation and treatment of coronary restenosis after percutaneous revascularization.     

Myocardial infarction as a complication of new interventional devices

Percutaneous transluminal coronary balloon angioplasty has been associated with acute myocardial infarction (MI) as a complication of the procedure. Abrupt closure, distal coronary embolization, intimal dissection, coronary spasm, and acute thrombosis are the principal etiologies. New interventional devices (stent, laser, and atherectomy catheters) have been introduced as alternatives or adjuncts to balloon angioplasty. With use of the New Approaches to Coronary Intervention Registry, the incidence, predictors, and outcome of MI as a complication of using these devices as the primary mode of intervention were studied. There were 3,265 patients from 39 participating centers in the cohort treated with new devices. MI was reported as an in-hospital complication of using new devices in 154 patients (4.7%), including Q-wave MI in 36 patients (1.1%), and non-Q-wave MI in 119 patients (3.6%). MI rates were not significantly different among all patients with devices in the cohort treated with atherectomy (directional, extractional, rotational), laser (AIS, Spectranetics) or the Palmaz-Schatz stent. Multivariate logistic regression showed that post-procedure MI was associated with multivessel disease, high surgical risk, postinfarction angina, and presence of a thrombus prior to the procedure. Prior percutaneous transluminal coronary angioplasty was inversely related to the incidence of MI. When a specific cause of MI could be detected, the main etiologies were: coronary embolus 16.9%, and abrupt closure 27.3%. Other major in-hospital complications were higher in the MI group than the non-MI group: death 7.8% versus 0.8% (p <0.001), and bypass surgery 13.6% versus 1.7% (p <0.001). At 1 year, mortality rates remain higher at 12.9% in the MI group versus 4.9% in the non-MI group (p <0.01). Despite different indications for the use of new devices, they were not predictors for MI with the exception of the rotablator. The incidence of MI (1.1% Q-wave, 3.6% non-Q-wave) was comparable to previously reported rates for balloon angioplasty. The occurrence of MI is associated with an increase in other in-hospital complications and a doubling of 1-year mortality.     

New insights for dinucleotide backbone binding in conserved C5''-H . . . O hydrogen bonds

OBJECTIVE: Although a number of pharmacologic agents have been shown to reduce intimal hyperplasia in animal models of restenosis, to date no systemic agent has conclusively been shown to be effective in humans. Recently, considerable attention has been directed towards endothelin (ET), a potent vasoconstrictor and a powerful mitogen for vascular smooth muscle cells, as a mediator of intimal hyperplasia. Endothelin-1 has been shown to be mitogenic for human saphenous vein smooth muscle cells, and expression also is elevated in human vein graft stenosis. The aim of this study was the investigation of whether ET receptor antagonists can attenuate neointima formation in a laboratory model of vein graft intimal hyperplasia and the determination of whether the effects are mediated by a specific ET receptor subtype. METHODS: We used an organ culture of human saphenous vein, a well-validated model of vein graft intimal hyperplasia. Paired segments of human long saphenous vein were cultured with and without the following antagonists: bosentan, a nonselective ET receptor antagonist; BQ 123, a specific endothelin-A antagonist; or BQ 788, a specific endothelin-B (ETB) antagonist. After 14 days in the culture, the segments were fixed and processed and the sections were immunostained to facilitate the measurements of neointimal thickness with a computerized image analysis system. RESULTS: The nonselective antagonist bosentan and the ETB selective antagonist BQ 788 significantly reduced neointima formation by 70% (P = .001) and 50% (P = .03), respectively, but the ETA antagonist BQ 123 had no significant effect on the reduction of neointima formation (P = 1.0). CONCLUSION: The results of this study imply an important role for ET as a mediator of human vein graft intimal hyperplasia and imply further that a specific ETB antagonist may have a therapeutic potential for the prevention of vein graft stenosis.