High soluble Fas and soluble Fas Ligand serum levels before stent implantation are protective against restenosis.

Percutaneous coronary intervention (PCI) represents the most important treatment of coronary artery stenosis today. But instent restenosis (ISR) is a limitation for the outcome. Fas and Fas Ligand have been implicated in apoptosis and vessel wall inflammation. Their role in ISR is not known so far. In this prospective study we studied 137 patients with stable coronary artery disease who underwent elective PCI. Blood samples were taken directly before and 24 hours after PCI. Soluble (s)Fas and sFas Ligand serum levels were measured by ELISA. Restenosis was evaluated six to eight months later either by coronary angiography or by exercise testing. During the follow-up period, 18 patients (13%) developed ISR. At baseline, patients with ISR had significantly lower median sFas, as well as sFas Ligand levels compared to patients without ISR (sFAS: ISR 492 pg/ml, no ISR 967 pg/ml, p=0.014; sFAS Ligand: ISR: 26 pg/ml, no ISR: 42 pg/ml, p=0.001). After PCI median sFas levels significantly decreased in patients with ISR compared to patients without ISR [ISR: -152 pg/ml (IQR -36 to -227), no ISR: -38 pg/ml (IQR -173 to +150 pg/ml), p=0.03]. sFas Ligand levels after PCI significantly increased in ISR patients compared to patients without ISR [ISR: 14 pg/ml (IQR -3 to +26 pg/ml), no ISR -6 pg/ml (IQR -22 to +21 pg/ml), p=0.014]. In conclusion, sFas and sFas Ligand seem to be associated with the development of ISR. Determination of serum levels before and after PCI might help identifying patients at higher risk of ISR.

Tracking the migration of cardially delivered therapeutic stem cells in vivo: state of the art.

Cell-based therapy is a promising, novel therapeutic strategy for cardiovascular disease. The rapid transition of this approach from the benchside to clinical trials has left a gap in the understanding of the mechanisms of cell therapy. Monitoring of cell homing and the fate of cardially delivered stem cells is fundamental for clarification of the myocardial regenerative process. Noninvasive imaging techniques allow an in vivo evaluation of the survival, migration and differentiation of implanted stem cells over time, and by this means, can help to answer unresolved questions. The most promising in vivo tracking methods involve the direct, nonspecific labeling of cells including MRI, radionuclide imaging and the use of reporter-gene imaging. This review summarizes the most important results of animal and human studies in which the fate and biodistribution of cardially delivered stem cells are assessed through different in vivo tracking methods.

Plasminogen activator inhibitor-1 predicts coronary in-stent restenosis of drug-eluting stents.

BACKGROUND: We tested the hypothesis that plasma levels of plasminogen activator inhibitor-1 (PAI-1) are influenced by percutaneous coronary intervention (PCI) with the implantation of drug eluting stents (DES) and are able to predict the occurrence of in-stent restenosis (ISR). METHODS AND RESULTS: PAI-1 active antigen plasma levels were determined in 75 patients before and 24 h after PCI with DES implantation. Patients with ISR after six to eight months (16%) showed significantly lower PAI-1 plasma levels before PCI (ISR, 11.7 +/- 8.1 ng mL(-1); non-ISR, 22.8 +/- 18.8 ng mL(-1); P <0.05). PAI-1 levels in the lowest tertile were associated with a 9.5-fold increased risk of ISR, independent of clinical risk factors, angiographic or procedural characteristics, compared to the highest tertile (P < 0.05). The induced change of PAI-1 active antigen 24 h after PCI was significantly higher in patients with ISR (ISR, +5.6 +/- 8.0 ng mL(-1); non-ISR, -3.2 +/- 12.1 ng mL(-1); P < 0.05) with positive correlation to late lumen loss (r = 0.30; P < 0.05). CONCLUSIONS: ISR after DES implantation is significantly related to plasma levels of PAI-1 active antigen before and after PCI. If confirmed by larger multicenter studies, the determination of PAI-1 plasma levels might be clinically helpful in the identification of patients at high risk of developing of ISR, even after DES implantation.

First in-human randomized comparison of an anodized niobium stent versus a standard stainless steel stent--an intravascular ultrasound and angiographic two-center study: the VELA study.

OBJECTIVES: The purpose of this study was to test the hypothesis that a niobium stent might lower the restenosis rate in de novo coronary lesions as compared to a bare metal stent. BACKGROUND: Recent data have suggested that inflammatory and allergic reactions to certain compounds in metal stents may play a role in the onset of restenosis. Thus, niobium as an inert material might be beneficial in lowering the rate of restenosis. METHODS: In this single blind, two-center prospective trial patients were randomized into two groups; the first group (n=32) received a niobium stent (VELA STF), the second group (n=33) a bare metal stent (Antares STF). Clinical follow-up was performed at 1 and 6 months, angiographic and intravascular ultrasound analyses were performed at the 6-month follow-up. RESULTS: All stents were successfully deployed. There was one stent thrombosis in each group. There were no significant differences concerning minimal lumen diameter, percent stenosis, and late lumen loss as assessed by intravascular ultrasound (IVUS) at the 6- month follow-up. At 30 days and at 6 months, there were no differences observed between the two groups regarding the rate of major cardiac adverse events. Immediately after stent implantation minimal lumen diameter was significantly larger (p=0.01) and residual percent stenosis significantly lower (p=0.01) in the niobium stent group. CONCLUSION: The use of a niobium stent showed comparable results with other non-drug-eluting stents; however the inert qualities of this first generation niobium stent did not translate into a mid- or long-term benefit.

Quantification of dose perturbation by plaque in vascular brachytherapy.

BACKGROUND: Dose prescription and reporting in vascular brachytherapy (VBT) is based on the assumption that the vessel wall is water equivalent, which does not consider a possible dose perturbation by plaque. As the extent of this perturbation is unknown, we aimed to quantify dose attenuation by atherosclerotic plaque for beta- and gamma-radiation. MATERIAL AND METHODS: The dose delivered from Strontium-90/Yttrium-90 ((90)Sr/Y) and Iridium-192 ((192)Ir) sources with and without human peripheral arteries ((90)Sr/Y: n = 38, (192)Ir: n = 7) surrounding the respective delivery catheter was determined with radiochromic films. Plaque and vessel wall thickness were measured using light microscopy. From the ratio-attenuated doseunattenuated dose (dose perturbation factor: DPF) we determined averaged attenuation coefficients for atherosclerotic plaque (micro(P)) and the residual part of the vessel wall (micro(W)) by regression analysis based on the function DPF = exp(-micro(P) * plaque thickness -micro(W) * residual wall thickness). RESULTS: Attenuation in case of (192)Ir was less than the measurement uncertainties. For beta-radiation correlation was found by discrimination between calcified and noncalcified plaque. Classifying noncalcified plaque as normal arterial tissue, the regression coefficient was r = 0.845 at micro(P)= 0.5356 mm(-1) and micro(W) = 0.0663 mm(-1). CONCLUSIONS: Vascular brachytherapy with beta radiation in calcified arteries results in significant dose attenuation within the vessel wall, which can be calculated on knowing the vascular morphometry. Thus, plaque thickness should be taken into account in treatment planning and retrospective analyses.

Predictive value of plasma plasminogen activator inhibitor-1 for coronary restenosis: dependence on stent implantation and antithrombotic medication.

BACKGROUND: The plasmin activation system is involved in the development of restenosis after percutaneous coronary interventions (PCI). Conflicting data exist concerning the role of plasminogen activator inhibitor-1 (PAI-1) and its predictive value for restenosis. OBJECTIVES: To evaluate the fibrinolytic response to injury after PCI with or without stent implantation on different antithrombotic medications and its relation to late restenosis. PATIENTS AND METHODS: Eighty consecutive patients with successful PCI without (balloon only; n = 37) or with stent implantation (stent; n = 43) on different antithrombotic regimes (balloon only, aspirin; stent, aspirin/coumadin/dipyridamole vs. aspirin/ticlopidine). Blood samples were taken at baseline and up to 7 days after PCI and PAI-1 active antigen and tissue plasminogen activator (t-PA) antigen were determined. Restenosis was angiographically determined after 6 months. RESULTS: PCI increased both t-PA and PAI-1 levels (P < 0.001), with a significant prolonged and pronounced increase in stent vs. balloon-only patients (P < 0.05). Restenosis (stent 26%; balloon 38%) was significantly correlated to an attenuated PAI-1 increase after 24 h in the ticlopidine group (P = 0.007; restenosis, relative Delta PAI-1 + 50 +/- 28%; non-restenosis, + 139 +/- 50%), but not in the coumadin group. In the balloon-only group late restenosis (ISR) was associated with a trend for an augmented PAI-1 increase after 24 h. CONCLUSIONS: Coronary stent implantation significantly increases t-PA and PAI-1 plasma levels up to 1 week compared with balloon angioplasty alone. ISR in ticlopidine-treated patients was associated with an attenuated early PAI-1 active antigen increase. A less than 50% increase 24 h after stent implantation under ticlopidine treatment may identify patients at risk for the development of ISR.

Assessment of the safety and efficacy of the novel tetrapeptide ITF-1697 on infarct size after primary PTCA in acute myocardial infarction: a randomised, placebo-controlled pilot trial.

OBJECTIVE AND DESIGN: ITF-1697 is a chemically modified LYS-Pro tetrapeptide that corresponds to sequence 113-116 of C-reactive protein. Previous studies have demonstrated significant anti-ischaemic and antithrombotic activity of this tetrapeptide. The aim of this prospective, randomised, double-blind study in patients with acute myocardial infarction undergoing coronary revascularisation was to investigate the safety and efficacy of prolonged intravenous (i.v.) infusion of ITF-1697 at different doses on reduction of infarct size, as assessed by radionuclide imaging. PATIENTS AND METHODS: Injection of technetium-99m (Tc99m) was followed by injection of ITF-1697 or placebo bolus and 24-hour infusion in patients with acute myocardial infarction. Percutaneous transluminal coronary angioplasty (PTCA) was performed and succeeded by radionuclide imaging. A second Tc99m injection and radionuclide imaging was performed 7 days after the PTCA or at hospital discharge. The primary efficacy variable was set as the ratio between the myocardial salvage (size of the initial perfusion defect minus the final size of the infarct) and the initial area at risk (myocardial salvage index). Twenty-three patients were included in the study protocol, of whom nine were randomised to the ITF-1967 dose 1 group (loading dose 55 microg/kg i.v., infusion 0.5 microg/kg/min for 24 hours), a further nine to the ITF-1697 dose 2 group (loading dose 110 microg/kg i.v., infusion 1.0 microg/kg/min for 24 hours), and the remaining five to the placebo group. RESULTS: The defined safety variables (adverse events, laboratory parameters, vital signs and clinical outcome) exhibited no relationship to the application of ITF-1697. Comparison of myocardial salvage index revealed no statistical difference within the three groups (p = 0.65). Hypothesis testing on the myocardial salvage as well as the empirical and bias-correct confidence intervals (CIs) revealed significant differences between the ITF-1697 dose 2 group and the placebo group (95% CI 2.75, 18.07). CONCLUSION: The application of the tetrapeptide ITF-1697 during acute myocardial infarction to reduce infarct size was found to be feasible and safe in this pilot trial.

Percutaneous interventions in radiation-associated coronary in-stent restenosis.

This study was performed to evaluate the outcome of percutaneous revascularization in "edge restenoses" developing after radioactive stent implantation in de novo and in-stent lesions. Twenty-one consecutive patients undergoing target lesion revascularization (TLR) at any follow-up after phosphorus-32 radioactive stent implantation were included in this study. We assessed the incidence of death, myocardial infarction, repeated TLR and recurrent angina over the following 18 months. After 6 months, TLR rate was 28.6%, and no stent thromboses, deaths or Q-wave myocardial infarctions occurred. Among the patients with TLR there were significantly more subjects who had received a radioactive stent in a previous in-stent restenosis (66.7% vs. 0% in patients without second restenosis; P <0.001), or who had received two radioactive stents (83.3% vs. 33.3%; P = 0.038). After 18 months, TLR rate was 33.3%, and two patients (9.5%) had died. Restenosis after intravascular radiotherapy can be safely treated by percutaneous interventional techniques, yielding an acceptable clinical result within 18 months.

Combined use of retrograde myocardial and distal coronary protection for last vessel intervention in an aortocoronary vein graft.

Feasibility, safety, and clinical efficacy of the combined application of the PercuSurge system and the Myoprotect SSR device was demonstrated in a patient with high-risk anatomy undergoing saphenous vein graft intervention. This combined approach of coronary and myocardial protection may be considered in high-risk aortocoronary vein graft interventions.

An iatrogenic coronary arteriovenous fistula causing a steal phenomenon: an intracoronary Doppler study.

We present the case of a 67-year-old man in whom a guidewire broke at rotablation of the right coronary artery, creating an iatrogenic aneurysmal arteriovenous fistula to the coronary sinus. Successful Doppler wire-guided fistula occlusion by percutaneous coil embolization lead to normalization of coronary blood flow and relief of the patient's symptoms. Myocardial ischemia in this patient may have been due to a steal phenomenon caused by coronary artery fistulae, as suggested by blood flow velocity data obtained before and after fistula occlusion.

Online myocardial viability assessment in the catheterization laboratory via NOGA electroanatomic mapping: Quantitative comparison with thallium-201 uptake.

BACKGROUND: The aim of this prospective study was to investigate the concordance between quantitative resting (201)Tl uptake as an established myocardial viability index and the electrical activity of the heart, determined by NOGA nonfluoroscopic electroanatomic mapping. METHODS AND RESULTS: The myocardial resting and late resting thallium uptakes of 384 myocardial segments from 32 patients (27 males aged 65+/-8 years) with previous myocardial infarction and chronic stable angina were compared with unipolar voltage potentials and local shortening of the left ventricle as assessed by electroanatomic mapping. The quantitative thallium uptake data were analyzed by polar map analysis by division into 12 comparable myocardial segments, as represented in electroanatomic mapping images. Unipolar voltage potentials exhibited a significant logarithmic correlation with both resting and late resting thallium uptake (attenuation corrected: r=0.660 and r=0.744; non-attenuation corrected: r=0.623 and r=0.721). Receiver operator characteristic analyses revealed unipolar voltage cutoff points of 12.0 mV (predictive accuracy 0.853, P< 0.001; sensitivity/specificity 81%) for normal myocardium and 6.4 mV (predictive accuracy 0.901, P< 0.001; sensitivity/specificity 82%) for nonviable myocardium assessed by attenuation-corrected (201)Tl late resting images and of 12.7 mV (predictive accuracy 0.822, P<0.001; sensitivity/specificity 75%) and 6.5 mV (predictive accuracy 0.808, P<0.001; sensitivity/specificity 73%) for non-attenuation-corrected late resting (201)Tl images. CONCLUSIONS: These results indicate that the unipolar voltage potentials obtained by electroanatomic mapping correlate well with standard quantitative late resting (201)Tl imaging for the evaluation of myocardial viability; thus, NOGA endocardial mapping provides useful "online" data at the time of catheterization, especially when information from other methods for viability assessment is unavailable.

Fatal late coronary thrombosis after implantation of a radioactive stent: postmortem angiographic and histologic findings--case report.

Postmortem angiography and histologic analysis of a fatal coronary thrombosis 4 months after implantation of a radioactive stent are described. Histologic findings suggested incomplete re-endothelialization in the segment with the stent. Ionizing radiation may delay re-endothelialization after revascularization, thus maintaining the thrombogenicity of the irradiated vessel segment. Thus, prolonged antiplatelet therapy should be considered after intravascular radiation therapy.

Adaptive remodeling of the infarct-related artery is associated with recurrent ischemic events after thrombolysis in acute myocardial infarction.

BACKGROUND: Recurrent ischemic events occur during the hospital stay of 7-32% of patients after successful thrombolytic treatment of acute myocardial infarction (AMI). OBJECTIVE: To define the association between postinfarction angina pectoris and the clinical, angiographic, and intravascular ultrasound (IVUS) parameters of the infarct-related artery for consecutive prospectively included patients. METHODS: Clinical, qualitative, and quantitative angiographic and IVUS data for 64 patients (56 men, aged 53+/-12 years) with thrombolysis of AMI were analyzed. All patients underwent coronary angiography and pre-interventional IVUS measurement electively within 1 month of AMI or at the time of the occurrence of postinfarction angina pectoris. Classification as adaptive or constrictive remodeling was according to whether the cross-sectional area of a vessel was larger or smaller than that of the proximal or distal reference segment. RESULTS: Nineteen of the 64 patients (29.7%) suffered from recurrence of ischemic events (group 1), whereas 45 patients (60.3%, group 2) remained free from symptoms. In univariate analyses, multivessel disease (42 versus 24%, P= 0.0236) and adaptive remodeling (63 versus 24%, P= 0.0032) were found to occur more commonly among patients in group 1. The patients in group 1 exhibited larger total vessel cross-sectional areas than did the patients in group 2 (17.5+/-4.2 versus 14.9+/-6.1 mm2, P = 0.0556). In multivariate regression analysis, adaptive remodeling proved to be a significant predictor (P = 0.0145) of the recurrence of ischemic events after thrombolysis of AMI. CONCLUSIONS: Adaptive remodeling of the infarct-related artery is associated with early postinfarction angina pectoris after thrombolysis of AMI.

Dose-volume histograms based on serial intravascular ultrasound: a calculation model for radioactive stents.

BACKGROUND AND PURPOSE: Radioactive stents are under investigation for reduction of coronary restenosis. However, the actual dose delivered to specific parts of the coronary artery wall based on the individual vessel anatomy has not been determined so far. Dose-volume histograms (DVHs) permit an estimation of the actual dose absorbed by the target volume. We present a method to calculate DVHs based on intravascular ultrasound (IVUS) measurements to determine the dose distribution within the vessel wall. MATERIALS AND METHODS: Ten patients were studied by intravascular ultrasound after radioactive stenting (BX Stent, P-32, 15-mm length) to obtain tomographic cross-sections of the treated segments. We developed a computer algorithm using the actual dose distribution of the stent to calculate differential and cumulative DVHs. The minimal target dose, the mean target dose, the minimal doses delivered to 10 and 90% of the adventitia (DV10, DV90), and the percentage of volume receiving a reference dose at 0.5 mm from the stent surface cumulated over 28 days were derived from the DVH plots. Results were expressed as mean+/-SD. RESULTS: The mean activity of the stents was 438+/-140 kBq at implantation. The mean reference dose was 111+/-35 Gy, whereas the calculated mean target dose within the adventitia along the stent was 68+/-20 Gy. On average, DV90 and DV10 were 33+/-9 Gy and 117+/-41 Gy, respectively. Expanding the target volume to include 2.5-mm-long segments at the proximal and distal ends of the stent, the calculated mean target dose decreased to 55+/-17 Gy, and DV 90 and DV 10 were 6.4+/-2.4 Gy and 107+/-36 Gy, respectively. CONCLUSIONS: The assessment of DVHs seems in principle to be a valuable tool for both prospective and retrospective analysis of dose-distribution of radioactive stents. It may provide the basis to adapt treatment planning in coronary brachytherapy to the common standards of radiotherapy.

Directional coronary atherectomy: the Vienna experience.

BACKGROUND: Several multicenter trials have shown excellent results for directional coronary atherectomy (DCA) in a selected patient cohort. To prove the applicability of this method in daily clinical routine and a nonselected patient cohort, we analyzed 46 consecutive cases performed at our catheterization lab. METHODS: DCA was performed as a routine procedure in 45 suitable patients. Balloon dilatation or stent implantation postprocedure was accomplished only in case of unsatisfactory results. Quantitative coronary angiography was achieved pre- and postprocedure as well as at 6-month follow-up. RESULTS: Optimal atherectomy < 20% residual stenosis was reached in 24 (52%) of 46 target lesions and a residual stenosis < 50% in 46 (100%) lesions. Procedure-related complications occurred in three (6%) patients (one major complication, death, < 24 hours, 2%; two minor complications, pseudoaneurysm, 4%). The 6-month angiographic follow-up revealed a binary restenosis rate of 29% (n = 11). Ten out of 11 restenotic lesions required revascularization. When patients were stratified in two groups according to their preprocedural minimal lumen diameter (MLD), this parameter proved to be a very strong predictor of outcome. The percentage of restenosis was significantly higher in patients with an MLD > 1.60 mm compared to patients with a smaller MLD (54% vs 19.3%; P < 0.0001). Reference vessel diameter preprocedure did not differ significantly. CONCLUSIONS: Our study demonstrated that DCA is a suitable technique for the daily clinical routine, as the rates of complications and restenosis were similar to that in a highly selective patient cohort. Additionally, our study showed that patient selection should include preprocedural analysis of MLD in order to achieve optimal results. Therefore, atherectomy yielded comparable results to other conventional techniques and may be used instead of or in combination with them.

Successful emergency percutaneous cardiopulmonary support during coronary intervention in an 80-year old patient.

In an 80-year old patient with acute coronary syndrome emergency institution of stand-by percutaneous cardiopulmonary support (PCPS; Bio-Medicus; Medtronic Inc, Minneapolis MN) for hemodynamic collapse in the cardiac catheterization laboratory resulted in successful hemodynamic stabilization and enabled safe performance of a complex coronary intervention. Weaning from PCPS was effectuated after 4 hours total extracorporal circulation time. Despite development of a systemic inflammatory response syndrome and prolonged weaning from mechanical ventilation the patient could be discharged from the intensive care unit after 14 days and eventually from hospital another 28 days later with favorable outcome. Although an increased complication rate with prolonged rehabilitation has to be taken into account percutaneous cardiopulmonary support may constitute a live-saving option even in selected elderly patients.

Pre-existing arterial remodeling is associated with in-hospital and late adverse cardiac events after coronary interventions in patients with stable angina pectoris.

OBJECTIVES: The goal of this study was to investigate the association between the atherosclerotic arterial remodeling and the incidence of cardiac events after coronary interventions in patients with stable angina. BACKGROUND: The local mode of de novo atherosclerotic remodeling is associated with plaque vulnerability and clinical symptoms. It may, therefore, reflect plaque morphology influencing the long-term outcome after coronary interventions. METHODS: Quantitative angiography and intravascular ultrasound were obtained in 244 patients with stable angina before and after single-vessel revascularization. On the basis of the lesion and the reference segment vessel size, patients were categorized into three groups (adaptive [AR], constrictive [CR] and intermediate [IR] remodeling). The lesion was analyzed for lumen, total vessel and plaque areas. Clinical follow-up was obtained at a mean period of 7.7+/-3.7 months. RESULTS: Patients with CR had a higher rate of in-hospital complications (10.9% vs. 2.9% and 2.7% in group CR vs. AR and IR, p = 0.035). In contrast, patients with AR had the highest rate of major adverse cardiac events (MACE) (44.3% vs. 25.5% in IR and 28.1% in CR, p = 0.024) with a predominance of revascularization at follow-up. Both target lesion restenosis (p = 0.036) and nontarget lesion de novo stenosis (p = 0.007) occurred more frequently in this group. Adaptive remodeling was a significant predictor of MACE in multivariate analysis. CONCLUSIONS: Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.

Plasma levels of C-reactive protein after coronary stent implantation.

AIMS: This study was designed to investigate the role of inflammation on the occurrence of angiographic restenosis 6 months after coronary stent implantation and the influence of different kinds of antithrombotic and antiplatelet strategies on inflammation. METHODS AND RESULTS: In an open randomized trial, 40 consecutive patients were treated with aspirin (100 mg. day(-1)) and either ticlopidine (2x250 mg. day(-1)) (n=17), or phenprocoumon (INR 2.0-3.0) and dipyridamole (3x160 mg. day(-1)) (n=23) after successful elective coronary stent implantation. Plasma levels of C-reactive protein were determined one day before stent implantation and serially thereafter twice daily up to 120 h. C-reactive protein plasma levels increased significantly (P<0.0001) after stent implantation. Phenprocoumon and dipyridamole or ticlopidine had no effect on C-reactive protein plasma levels (P=0.51) or the occurrence of angiographic restenosis (P=0.48). C-reactive protein plasma levels were significantly higher in patients with lesion type C compared to types A or B (P=0.035), respectively. C-reactive protein plasma levels were significantly higher and mean shoulder levels occurred 48 h later in patients with restenosis compared to patients without restenosis after 6 months (P=0.038). CONCLUSIONS: Elevated C-reactive protein plasma levels still persisting 96 h after stent implantation might reflect a prolonged inflammatory reaction to coronary stent implantation which might causally be involved in pathophysiological mechanisms leading to restenosis.