Lp-PLA2- a novel risk factor for high-risk coronary and carotid artery disease.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is at the crossroads of lipid metabolism and the inflammatory response. It is produced by inflammatory cells, bound to LDL and other lipoproteins, and once in the arterial wall facilitates hydrolysis of phospholipids. Elevated serum levels of Lp-PLA2 have been associated with increased cardiovascular risk in healthy populations and in patients with known vascular disease. Here, we review the role of Lp-PLA2 in the development of atherosclerosis and progression to unstable disease, the utility of Lp-PLA2 as a risk predictor for coronary and carotid events and the potential clinical benefit of pharmacologic inhibition of Lp-PLA2.

First-In-Man application of a miniature self-contained intracoronary magnetic resonance probe. A multi-centre safety and feasibility trial.

AIMS: To assess safety and feasibility of intracoronary Magnetic Resonance (MR) Spectroscopy in living patients, using a self-contained MR catheter. METHODS AND RESULTS: Prospective, multi-centre study in patients with stable or unstable angina that were scheduled for percutaneous coronary diagnostic or therapeutic catheterization. We assessed the feasibility of an intravascular MR catheter, capable of analysing the arterial wall without external magnets or coils, by differentiating lipid rich, intermediate and fibrotic areas of the atherosclerotic plaque on the basis of differential water diffusion.Twenty-nine patients were included at 4 centres. The intracoronary MR-spectroscopy procedure was well tolerated; no MACE and no device related serious adverse event was observed. The MR catheter was successfully advanced into the lesion in 28 patients. Introduction of the MR catheter was not possible in one patient with a tortuous proximal right coronary artery. MR data were obtained in 22 patients. According to the predominant MR pattern, lesions were classified as fibrous plaque in 4 patients, as intermediate plaque in 4 patients and as lipid-rich plaque in 8 patients. Six patients were excluded from analysis because artifacts impeded the quality of the MR signal. Plaque type did not show a correlation with angina status (p=0.552; all groups) or angiographic parameters, such as minimal lumen diameter and diameter stenosis. CONCLUSIONS: This prospective, multi-centre study demonstrates for the first time that coronary artery assessment of potentially vulnerable, non-flow limiting lesions using a dedicated intravascular MR catheter, free of external magnets or coils, is feasible in clinical practice. Assessment of the coronary wall may provide important data regarding the composition of the atherosclerotic lesion, which then could contribute to predicting the likelihood of eventual rupture and clinical instability.

Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population.

Intimal hyperplasia within the body of the stent is the primary mechanism for in-stent restenosis; however, stent edge restenosis has been described after brachytherapy. Our current understanding about the magnitude of in vivo intimal hyperplasia and edge restenosis is limited to data obtained primarily from select, symptomatic patients requiring repeat angiography. The purpose of this study was to determine the extent and distribution of intimal hyperplasia both within the stent and along the stent edge in relatively nonselect, asymptomatic patients scheduled for 6-month intravascular ultrasound (IVUS) as part of a multicenter trial: Heparin Infusion Prior to Stenting. Planar IVUS measurements 1 mm apart were obtained throughout the stent and over a length of 10 mm proximal and distal to the stent at index and follow-up. Of the 179 patients enrolled, 140 returned for repeat angiography and IVUS at 6.4 +/- 1.9 months and had IVUS images adequate for analysis. Patients had 1.2 +/- 0.6 Palmaz-Schatz stents per vessel. There was a wide individual variation of intimal hyperplasia distribution within the stent and no mean predilection for any location. At 6 months, intimal hyperplasia occupied 29.3 +/- 16.2% of the stent volume on average. Lumen loss within 2 mm of the stent edge was due primarily to intimal proliferation. Beyond 2 mm, negative remodeling contributed more to lumen loss. Gender, age, vessel location, index plaque burden, hypercholesterolemia, diabetes, and tobacco did not predict luminal narrowing at the stent edges, but diabetes, unstable angina at presentation, and lesion length were predictive of in-stent intimal hyperplasia. In a non-radiation stent population, 29% of the stent volume is filled with intimal hyperplasia at 6 months. Lumen loss at the stent edge is due primarily to intimal proliferation.

Local delivery of a hydrophobic heparin reduces neointimal hyperplasia after balloon injury in rat carotid but not pig coronary arteries.

BACKGROUND: Intimal hyperplasia following percutaneous interventional vascular procedures is a major cause of restenosis. Although heparin inhibits intimal hyperplasia, it has not proven clinically useful in part due to an inadequate duration of intramural drug residence. This study was designed to evaluate the efficacy of local delivery of hydrophobic heparin (PTIR-RS-1), exhibiting increased intramural binding, on neointimal hyperplasia after angioplasty injury. METHODS AND RESULTS: PTIR-RS-1 was delivered locally into rat carotid arteries at three doses: 0.1 mM (440 IU), 0.3 mM (1320 IU), or 1.0 mM (4400 IU). Animals were killed at 14 days. In the pig, the doses tested were the low dose in the rat and a high dose 1 log higher. Animals were killed 28 days later. Morphometric analysis was performed to evaluate the intima: media ratio in rats and the normalized neointimal area in pigs. In rats a significant reduction in neointimal to medial area ratio from 0.73 +/- 0.15 for control vs 0.80 +/- 0.27 for sodium heparin (P = NS) and 0.15 +/- 0.07 for the 0.1 mM PTIR-RS-1 dose (P < 0.008). In pigs, PTIR-RS-1 the high dose reduced the normalized neointimal area by 16%, a difference that was not statistically significant. CONCLUSIONS: Increased hydrophobicity of heparin reduced neointimal area following balloon overstretch injury in the rat carotid but not the pig coronary artery model. This study attests to the importance of performing studies evaluating the pharmacologic effect of local delivery of a medication in at least two animal models of restenosis.

Gene delivery from a DNA controlled-release stent in porcine coronary arteries.

Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.

Prospective study correlating fibrinopeptide A, troponin I, myoglobin, and myosin light chain levels with early and late ischemic events in consecutive patients presenting to the emergency department with chest pain.

BACKGROUND: Although thrombus formation plays a major role in acute coronary syndromes, few studies have evaluated a thrombus marker in risk stratification of patients with chest pain. Furthermore, the relation between markers that reflect myocardial injury and thrombus formation that may predict events in a heterogeneous patient population is unknown. This study correlated markers of thrombus and myocardial injury with early and late ischemic events in consecutive patients with chest pain. METHODS AND RESULTS: Serum troponin I (TnI), myoglobin, and myosin light chain levels were obtained from 247 patients and urinary fibrinopeptide A (FPA) from 178 of the 247. By multivariate analysis, patients with an elevated FPA level were 4.82 times more likely to die or have myocardial infarction, unstable angina, and coronary revascularization at 1 week (P=0.002, 95% CI 1.78, 13.03), whereas those with an elevated TnI (>0.2 ng/mL) were 9.41 times more likely (P<0.001, 95% CI 2.84, 31.17). At 6 months (excluding the index event), an elevated FPA level was an independent predictor of events, with an odds ratio of 9.57 (P<0.001, C1 3.29, 27.8), and was the only marker to predict a shorter event-free survival (P<0.001). The other markers did not independently correlate with cardiac events, although MLC incrementally increased early predictive accuracy in combination with the FPA and TnI. CONCLUSIONS: Elevated FPA and TnI correlated with cardiac events during the initial week in patients presenting to the Emergency Department with chest pain. FPA predicted adverse events and a shorter event-free survival at 6 months.

Combination therapy with clopidogrel and aspirin after coronary stenting.

Combination antiplatelet therapy using aspirin and ticlopidine has been the standard of care for prevention of subacute thrombosis following coronary stent implantation. However, the use of ticlopidine is associated with a significant risk of adverse hematologic side effects. Clopidogrel is an inhibitor of ADP-induced platelet aggregation that has a better safety profile than ticlopidine. We examined the 30-day clinical outcome following coronary stent implantation in 253 consecutive patients treated with clopidogrel and aspirin. Follow-up was achieved in 99% of patients and four adverse events were documented. Two patients had angiographically confirmed subacute stent thrombosis (0.8%), and both of these patients underwent successful repeat angioplasty at the stent site. There were two patient deaths during follow-up (0. 8%). One was sudden within 1 week of stent placement and the other occurred in a patient with multisystem organ failure after an extensive myocardial infarction that antedated the stent procedure, with no clinical evidence for stent thrombosis. The combined frequency of subacute stent thrombosis and death was 1.6%. This is comparable to prior studies using the combination of ticlopidine and aspirin following stenting. Therefore, clopidogrel in combination with aspirin appears to be a safe and effective therapy in the prevention of subacute thrombosis following coronary stent implantation.

Predictors of clinical outcome following percutaneous intervention for in-stent restenosis.

Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (

Heparin infusion prior to stenting (HIPS) trial: final results of a prospective, randomized, controlled trial evaluating the effects of local vascular delivery on intimal hyperplasia.

BACKGROUND: Local delivery of pharmacologic agents or genes at the site of angioplasty is a promising approach to reduce restenosis. However, there are unresolved questions concerning the safety and feasibility of local vascular delivery in clinical practice as well as the efficacy of delivered drug. To this end, the safety, feasibility, and efficacy of local delivery of heparin were evaluated in the Heparin Infusion Prior to Stenting (HIPS) trial. METHODS AND RESULTS: A total of 179 patients were enrolled in this multicenter, randomized, prospective, core laboratory-evaluated trial. Patients were randomly assigned to 5000 U heparin either administered to the coronary artery lumen or infused into the arterial wall immediately after angioplasty and before stent placement. End points included procedural events and clinical, angiographic, and intravascular ultrasound events at 6 months. Patient groups were evenly matched. There was no difference in the incidence of arterial injury, defined as an increase in arterial dissection, acute closure, or decrease in Thrombolysis In Myocardial Infarction grade blood flow in the group receiving local delivery. At follow-up there was no difference in the major adverse event rate between intraluminal (22.7%) and local groups (24.7%). There was no difference between intraluminal and local therapy in the angiographic in-stent restenosis rate (12.5%, 12.7%) or the in-stent volumetric analysis by intravascular ultrasound (IVUS) (37.19 +/- 20. 86 mm(3) vs 43.79 +/- 25.52 mm(3)). CONCLUSIONS: Local delivery of 5000 U heparin into the arterial wall before stent implantation is safe and feasible. There was not a favorable effect of locally delivered heparin on clinical, angiographic, or IVUS end points of restenosis. The use of IVUS to measure volume of intimal hyperplasia in a multicenter, core laboratory-controlled trial is feasible.

Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans.

OBJECTIVES: This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty. BACKGROUND: Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models. METHODS: In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon. RESULTS: The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 +/- 0.44 vs. 1.49 +/- 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables. CONCLUSIONS: Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis.

Increased thrombin activity correlates with increased ischemic event rate after percutaneous transluminal coronary angioplasty: lack of efficacy of locally delivered urokinase.

BACKGROUND: Angiographic thrombus is associated with increased coronary occlusion and restenosis rates after angioplasty. Administration of intracoronary urokinase decreases the incidence of thrombus but is associated with an increased periprocedural event rate, including stroke and myocardial infarction. An alternative approach is to deliver the agent directly into the arterial wall, thereby reducing the thrombotic substrate in the absence of a systemic effect of the delivered agent. OBJECTIVE: This randomized, double-blind, prospective study correlated intracardiac fibrinopeptide A levels with the ischemic events after angioplasty and evaluated whether locally administered urokinase could reduce the event rate. METHODS: Fifty-four patients with acute coronary syndromes were randomly assigned to local delivery of urokinase or saline. Levels of fibrinopeptide A, a marker of thrombin activity, were obtained before and after administration of heparin, after 2 balloon inflations, and at the end of the procedure in 43 patients and were correlated with ischemic events within the 6-month follow-up period (death, myocardial infarction, or recurrent ischemia). RESULTS: Multivariant analysis revealed that an elevated fibrinopeptide A level before angioplasty significantly correlated with an increased likelihood of an adverse event over the 6-month clinical follow-up. A postangioplasty reduction in the fibrinopeptide A level was noted in control patients (P <.001), but not after local urokinase administration, and the final fibrinopeptide A level was higher in the urokinase group (P =.02). Urokinase had no effect on the procedural results. On follow-up more patients receiving urokinase (13 of 27) had ischemic events than did control patients (6 of 25, P =.04). Most events were recurrent ischemia caused by restenosis. CONCLUSIONS: Heparin-resistant thrombin activity, as evidenced by an increased fibrinopeptide A level correlates with ischemic events on long-term follow-up. Local delivery of urokinase increased the event rate.

Case study: analysis of an acute anterior-lateral myocardial infarction in a 16-year-old patient with familial hypercholesterolemia.

This article presents a case study of a 16-year-old male patient with a significant family history for hypercholesterolemia and coronary artery disease, who suffered an anterior lateral myocardial infarction. On admission, his electrocardiograms revealed the classic pattern of an anterior lateral acute myocardial infarction plus a left anterior hemiblock. His cholesterol level was 750 mg/dL, and his low-density lipoprotein was 650 mg/dL. He underwent a cardiac catheterization that revealed an occluded left anterior descending artery requiring a percutaneous transluminal angioplasty and three coronary stents. The 12-lead electrocardiograms on admission and before discharge are analyzed. This article discusses the electrocardiogram characteristics of anterior lateral wall myocardial infarction coupled with a left anterior hemiblock.

Clinical utility of troponin T levels and echocardiography in the emergency department.

We investigated the clinical utility of cardiac troponin T (TnT) and echocardiography in the emergency department to predict subsequent in-hospital diagnosis and adverse cardiac events. TnT is a cardiac-specific protein released during cell injury such as that following acute myocardial inFarction (MI). Unlike creatine kinase-MB isoenzymes, TnT is increased in a subset of patients with unstable angina, and these may be at higher risk for subsequent cardiac events. Echocardiography is a useful noninvasive imaging technique for the assessment of ischemic heart disease in acute care settings because of its mobility and rapid results. Serial TnT determinations and echocardiographic images were prospectively evaluated in 100 patients with chest discomfort and admitted to the hospital. Serum was obtained for CKMB and TnT on presentation to the emergency department and 4, 8, 16 and 24 hours later. TnT was considered increased when at values greater than 0.1 microg/L. Echocardiograms were recorded on videotape in the emergency department and images reviewed in a blinded fashion for wall-motion abnormalities. When available, current echocardiographic results were compared with previous results to determine whether a new wall-motion abnormality was present. Of the 100 patients (57 men, 43 women), TnT was increased in 21 of 21 with acute MI and 15 of 41 with unstable angina. One of the 38 patients with stable angina had an increased TnT value and died 5 months later of a noncardiac cause. Ninety percent of patients who sustained acute MI had a TnT increase detected within 4 hours of presentation. Fifteen of 18 patients with acute MI and 9 of 37 patients with unstable angina had a new wall-motion abnormality on echocardiography. The combination of TnT levels with echocardiography yielded a positive predictive value of 84% and a negative predictive value of 90% for adverse cardiac events in the follow-up population, which was more accurate than either test analyzed separately. TnT and echocardiography are useful tests in emergency department triage of unstable coronary syndromes. Both tests are predictive of discharge diagnosis and follow-up events. However, the combined utility of TnT levels and echocardiographic imaging is a more powerful predictor of adverse cardiac events than isolated results.

Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries.

Vascular restenosis involves contraction, proliferation, and remodeling of the arterial wall in response to overstretch injury. Mitogen-activated protein kinases (MAPKs) are implicated in both contraction and proliferation of vascular smooth muscle (VSM), and studies of porcine carotid arterial muscle strips have shown that mechanical stretch leads to the activation of the extracellular signal-regulated kinase (ERK) family of MAPKs in vivo. We, therefore, analyzed the acute effect of mechanical overstretch injury on ERK-MAPK (herein referred to simply as MAPK) activity in porcine coronary and carotid arteries in vivo. Balloon angioplasty catheters were inflated to 6 atm three times over 5 minutes at a balloon-artery ratio of 1.2:1 in either porcine coronary or carotid arteries. The arteries were snap-frozen after angioplasty, and MAPK activity was measured. Angioplasty of the left anterior descending (LAD, n = 5), left circumflex (LCx, n = 5), and carotid (n = 5) arteries effected an increase in MAPK activity compared with the activity in uninstrumented right coronary arteries (RCAs) or carotid arteries from the same animals used for controls. Balloon angioplasty of carotid arteries led to an increase in MAPK activity that was 7.7-fold over the activity in control arteries and comparable to the activity in stretched carotid arterial muscle strips in vivo. The increase in coronary artery kinase activity on angioplasty was variable from animal to animal. The increase in MAPK activity over that in control arteries ranged from 4.5- to 31.7-fold (mean +/- SEM, 10.7 +/- 5.3) in the LAD and 1.8- to 31.3-fold (mean +/- SEM, 9.7 +/- 5.7) in the LCx. There were no apparent inherent differences in the levels of MAPK activity in the three different types of coronary arteries (RCA, LAD, and LCx) without instrumentation. MAPK activation occurs rapidly during angioplasty, suggesting that this kinase may play an early role in initiating the injury response in both porcine coronary and carotid arteries. MAPKs may be key enzymes targeted to treat or prevent restenosis.

Measurement of coronary artery calcium with dual-slice helical CT compared with coronary angiography: evaluation of CT scoring methods, interobserver variations, and reproducibility.

OBJECTIVE: This study was performed to evaluate new scoring methods for quantitating coronary artery calcifications with helical CT and to compare the results with those of quantitative coronary angiography in patients with suspected coronary artery disease. SUBJECTS AND METHODS: Unenhanced dual-slice helical CT and coronary angiography were performed within 24 hr of each other in 101 patients with symptoms of coronary artery disease. Coronary artery calcifications with a density above 90 H were identified on each slice and, with the same regions of interest, quantitative scoring was performed at thresholds of 90 H (new) 130 H (old). Two mathematical algorithms (one new and one old) were evaluated for both thresholds (yielding four scoring systems). By CT imaging, we defined disease as a score of greater than zero. By angiography, we defined disease as a 50% or greater reduction in the luminal diameter of any major vessel. Interobserver variations in calcification scoring were evaluated. Seventeen of our patients. also underwent a second, consecutive CT scan to determine reproducibility. RESULTS: With the new threshold and the new algorithm, the sensitivity, specificity, and accuracy of helical CT in predicting disease were 88%, 52%, and 76%, respectively. We found a moderate positive association between the total CT calcification score and the number of stenotic coronary arteries at angiography (Pearson's correlation coefficient, .43; p = .05 [analysis of variance]). The accuracy and the area under the receiver operating characteristic curve were higher with the new threshold and the new algorithm. Interobserver agreement in calcification scoring was high (intraclass correlation coefficient, .99 [n = 85]), as was reproducibility (intraclass correlation coefficient, .94 [n = 17]). Reproducibility was higher when scoring was based on the new threshold and the new algorithm. CONCLUSION: The quantity of coronary artery calcifications as measured by helical CT correlated positively with obstructive coronary artery disease as measured by angiography. Interobserver agreement and reproducibility were excellent. A new scoring method showed promise.

Vascular repair mechanisms after directional atherectomy or percutaneous transluminal coronary angioplasty in atherosclerotic rabbit iliac arteries.

Although directional atherectomy (DA) reduces the plaque burden, successful revascularization is not associated with a reduced restenosis rate when compared with percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study was to compare and contrast the vascular response to DA-induced and PTCA-induced injury. Six to 8 weeks after induction of atherosclerosis, PTCA (n = 34) was performed in one iliac artery and DA in the other (n = 30). Arteries were obtained at 6 time points: 1, 3, 5, 7, 14, and 28 days. Eleven arteries that did not undergo an intervention acted as controls. Radiograms obtained before and after intervention and at euthanization were compared. Morphometric, histologic, and immunohistochemical analyses were performed. Both PTCA and DA resulted in an immediate increase in luminal diameter that subsequently decreased over the ensuing month. PTCA caused deep dissection (7 of 8 arteries), often extending to the adventitia, whereas stand alone DA resulted in deep cleft formation (4 of 5). Of the 30 arteries that underwent DA, 4 exhibited an increase in luminal diameter in the absence of tissue retrieval. Thrombus was observed in both the dissection planes and the clefts within the first 7 days, and cellular ingrowth was appreciated at 5 to 7 days. By 7 days the artery was repaired, and the histologic appearance of the arteries that had undergone PTCA could not be differentiated from the arteries that had undergone DA. Increased intimal and medial collagen and elastin was noted at 14 and 28 days. An increase in the area bordered by the external elastic lamina was observed in both groups. Although successful DA results in tissue removal and the production of a deep tissue cleft and PTCA causes a dissection, both produce a condition in which the arterial injury exposes the arterial media to blood, causing thrombus formation and inflammation with subsequent cellular accumulation into the thrombotic framework.

Exercise echocardiography, angiography, and intracoronary ultrasound after cardiac transplantation.

Fifty-one consecutive patients underwent exercise echocardiography, angiography, and intracoronary ultrasound (ICUS) 2.5 years (range from 1 to 6) after cardiac transplantation. The average age of the donor was 29 years (range 13 to 50), and the average age of the recipient was 49 +/- 12 years. In total, 78 studies were performed, as 25 patients had >1 annual evaluation and 2 patients had 3 consecutive annual evaluations. Of the 78 angiographic studies, 40 (26 patients) had evidence of coronary artery disease, defined as a focal stenosis (>20%, n=4) or luminal irregularities (n=36). However, by ICUS all 51 patients had intimal thickening at some point, with 34 patients possessing diffuse disease and 17 focal intimal thickening only. Of the 25 serial studies, 12 progressed by at least 1 Stanford class. The sensitivity of angiography for determination of class III to IV intimal thickening was 64% and the specificity was 76%. On exercise echocardiography, 6 examinations revealed resting wall motions abnormalities, whereas 6 had inducible wall motion abnormalities with exercise. The sensitivity of exercise echocardiography to determine class III to IV intimal thickening was 15%, and the specificity was 85%. In conclusion, exercise echocardiography is an insensitive method for predicting transplant-mediated coronary artery disease, whereas luminal irregularities on angiography may predict the presence of Stanford grade III to IV intimal thickening.

Microparticle deposition in periarterial microvasculature and intramural dissections after porous balloon delivery into atherosclerotic vessels: quantitation and localization by confocal scanning laser microscopy.

Local delivery of pharmacologic or genetic agents with a porous balloon catheter offers a potential therapeutic approach to reducing restenosis and atherosclerosis and minimizing undesirable systemic toxicity. However, the delivery efficiency and intramural retention of liquid agents is low. The local intramural delivery and prolonged retention of 5 microns microparticles (MP) has been described previously. The current study was designed to evaluate the distribution of locally delivered MPs and to determine the effects of MP size and infusion pressure on intramural delivery efficiency. A 1% suspension of fluorescent, latex MPs (1 or 4.5 microns in diameter) was infused at either 3 or 6 atm into atherosclerotic rabbit femoral arteries (n = 32) immediately after angioplasty. Four groups of arteries were evaluated: 1) 1 micron MPs infused at 3 atm; 2) 1 micron MPs at 6 atm; 3) 4.5 microns MPs at 3 atm; and 4) 4.5 microns MP at 6 atm. The location of MPs was evaluated by fluorescent and light microscopy and confocal laser scanning microscopy. The tissue was dissolved and the delivered MPs quantified. All groups manifested numerous MPs within the vasa vasorum and periadventitial microvasculature, with a substantially lesser number within the neointimal and medial layers. The intramural deposition of the MPs was associated with dissection within the intima or media caused by the antecedent angioplasty or local delivery, indicating that an intact vessel wall is an anatomic barrier to MP delivery. The median values of fractional intramural delivery, defined as the percentage of infused MPs retained within the arterial wall, were 0.059%, 0.071%, 0.047%, and 0.062% for the groups 1 through 4, respectively (p not significant [NS]). The values of intramural particle concentration, expressed as the total number of MPs per weight of arterial tissue, were 55, 65, 1.5, and 1.2 x 10(4) MPs/mg for groups 1 through 4, respectively (p < 0.001 for 1 micron vs 4.5 microns MPs). Although more 1 microM MPs were delivered than 4.5 microns MPs, the fractional intramural delivery was unaffected by particle size or infusion pressure. The local delivery of MPs at atherosclerotic sites after angioplasty is characterized by fractional intramural delivery values similar to values of nonparticulate agents, with few MPs deposited into intima or media in the absence of a dissection caused by the antecedent angioplasty or the delivery procedure itself.

Transthoracic echocardiographic detection of coronary atherosclerosis.

Coronary atherosclerosis is a pathologic process that produces thickening of the walls of the coronary arteries to the point that flow through those vessels may be impaired. This study attempts to use transthoracic echocardiography to detect coronary atherosclerosis. Eighty-nine patients undergoing coronary angiography were examined with a broad-band ultrasonic transducer with a frequency between 3 and 5 MHz. A modified short axis examination was utilized to identify left main and proximal left anterior descending arteries. The examination was recorded digitally and displayed in a 32-cell, quad screen cine loop. Fifty-six of the 89 patients (63%) had obstructive coronary artery disease (CAD) (i.e, at least 1 vessel with 50% obstruction). There were 14 patients with CAD but no vessel had > or = 50% obstruction. Nineteen patients (21%) had angiographically normal arteries. The coronary echograms were judged qualitatively for brightness, uniformity, and persistence (defined as the ability to see segments of the artery walls in more frames than other segments). The length of the coronary artery visualized, the width of the left main coronary artery, and the width of the thickest segment of the coronary artery walls were quantitatively measured. More than 2 cm of the left coronary artery was seen in almost all patients. Segmental changes were noted in 52 of the 56 patients with obstructive CAD, 12 of the 14 patients with nonobstructive CAD, and 3 of the 19 patients with normal arteries. Persistence greatly enhanced the ability to judge the segmental changes. Forty-six patients with obstructive disease had wall thickness > or = 1.5 mm. Only 6 patients with nonobstructive coronary arteries had this wall thickness, and only 1 normal subject had thick walls. The ultrasonic findings were useful in predicting the presence or absence of coronary atherosclerosis to varying degrees of sensitivity and specificity based on the segmental findings and wall thickness measurements. The results of this study indicate that a transthoracic ultrasonic examination of the proximal left coronary artery could be a clinically valuable tool in the qualitative identification of coronary atherosclerosis.