Randomized Trial of Primary PCI with or without RoutineManual Thrombectomy

During primary percutaneous coronary intervention (PCI), manual thrombectomymay reduce distal embolization and thus improve microvascular perfusion. Smalltrials have suggested that thrombectomy improves surrogate and clinical outcomes,but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction(STEMI) undergoing primary PCI to a strategy of routine upfront manualthrombectomy versus PCI alone. The primary outcome was a composite of deathfrom cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, orNew York Heart Association (NYHA) class IV heart failure within 180 days. The keysafety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomygroup versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in thethrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). Therates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone;hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plusstent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio,1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurredin 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%)in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy,as compared with PCI alone, did not reduce the risk of cardiovasculardeath, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heartfailure within 180 days but was associated with an increased rate of stroke within30 days. (Funded by Medtronic and the Canadian Institutes of Health Research;TOTAL ClinicalTrials.gov number, NCT01149044.

A method for matching the refractive index and kinematic viscosity of a blood analog for flow visualization in hydraulic cardiovascular models.

In this work, we propose a simple method to simultaneously match the refractive index and kinematic viscosity of a circulating blood analog in hydraulic models for optical flow measurement techniques (PIV, PMFV, LDA, and LIF). The method is based on the determination of the volumetric proportions and temperature at which two transparent miscible liquids should be mixed to reproduce the targeted fluid characteristics. The temperature dependence models are a linear relation for the refractive index and an Arrhenius relation for the dynamic viscosity of each liquid. Then the dynamic viscosity of the mixture is represented with a Grunberg-Nissan model of type 1. Experimental tests for acrylic and blood viscosity were found to be in very good agreement with the targeted values (measured refractive index of 1.486 and kinematic viscosity of 3.454 milli-m2/s with targeted values of 1.47 and 3.300 milli-m2/s).

Late (> 48 hr) myocardial infarction after PTCA: clinical and angiographic characteristics of infarction related or not to the angioplasty site.

Since late myocardial infarctions after percutaneous coronary interventions have not been well characterized, we intended to evaluate the characteristics of myocardial infarctions occurring > 48 hr after balloon angioplasty of native coronary arteries or saphenous vein grafts. The Montreal Heart Institute database (1985-1996) was interrogated for all patients readmitted with a diagnosis of MI more than 48 hr after successful percutaneous transluminal coronary angioplasty (PTCA). We compared the clinical, procedural, and angiographic variables between MIs related or not to the index PTCA site. One hundred and ninety-three patients presented with late myocardial infarction (MI) following balloon angioplasty. The median time elapsed between PTCA and MI was 55 days compared to 968 days when MI was unrelated to the PTCA site. MIs related to the PTCA site were more likely non-Q-wave (76% vs. 35%, P = 0.0001) with less marked CK-MB rise. Angiography showed less complex lesions (63% vs. 90%, P = 0.001) and better thrombolysis in myocardial infarction (TIMI) grade flow (TIMI II to III, 66% vs. 56%, P = 0.01) when the culprit lesion was at the PTCA site. Independent predictors of MI at the PTCA site were vein graft dilation, female sex, and residual stenosis post-PTCA. Myocardial infarctions occurring late after PTCA have a distinct time course and present specific characteristics according to their relationship or not to the previously dilated site.

A novel realistic three-layer phantom for intravascular ultrasound imaging.

Intravascular ultrasound (IVUS) is an imaging modality that experienced a tremendous development over the last 20 years. Phantoms for IVUS are rare and poorly documented. The aim of this paper is to propose an original IVUS phantom that has geometries and specular textures closer to those of coronary arteries than conventional tube-like phantoms. The proposed phantom has a three-layer aspect, reproducing the intima, media and adventitia that compose the arterial wall. It is made of an agar-based compound, with water, glycerol and cellulose particles. Fourteen phantoms were quantified using IVUS. Six phantoms were evaluated by both photomacroscopy and IVUS. There was an excellent correlation between phantom dimensions evaluated by photomacroscopy and the nominal values (mold dimensions). The IVUS quantification of the phantom was closely correlated to the measurements obtained by photomacroscopy. These results demonstrate that a multilayer phantom, with known and reproducible dimensions and with realistic geometric and echographic properties has been developed.

In vitro response of human and porcine vascular cells exposed to high dose-rate gamma-irradiation.

AIM: The objective of this study was to compare the in vitro response of human and pig endothelial cells, smooth muscle cells and fibroblasts exposed to conventional high dose-rate gamma-irradiation. MATERIALS AND METHODS: Clonogenic cell survival and growth responses were obtained after irradiation of plateau-phase cells with a 60Co source at a dose-rate of 1.5 Gy/min. DNA single-strand breaks were also evaluated using an alkaline filter elution technique. RESULTS: Overall, both the pig and human cell lines showed a similar response to conventional high dose-rate irradiation. Using clonogenic assays, the human aortic smooth muscle cell line was more sensitive than the fibroblast and endothelial cell lines, whereas the pig endothelial cell line was more sensitive than smooth muscle cells and fibroblasts. Shortly after irradiation (10 days) there was a temporary growth arrest, which was similar for endothelial, smooth muscle cells and fibroblasts with doses above 6 Gy. There was also a non-linear, dose-dependent growth delay up to 4 weeks after irradiation. This effect was also consistent between the different cell lines. Using alkaline filter elution, there was no significant difference in relative elution between endothelial cells, smooth muscle cells and fibroblasts, indicating similar DNA damage among the different cell lines. CONCLUSION: The in vitro response of human and pig endothelial cells, smooth muscle cells and fibroblasts exposed to high dose-rate irradiation appeared similar. The pig model seems well suited to evaluate the short- and long-term effects of ionizing radiation in the prevention of restenosis after vessel injury.

The effects of intracoronary brachytherapy on the natural history of postangioplasty dissections.

OBJECTIVES: The aim of this study was to determine the natural history of postangioplasty intravascular ultrasound (IVUS)-detected dissections and to assess the influence of intracoronary beta-radiation on dissection resolution. BACKGROUND: Intracoronary radiotherapy is considered to impair exaggerated vessel healing. Conversely, excessive healing impairment may increase the risk of complications due to unhealed dissection. Alternatively, residual dissection may represent an innocent marker of adequate therapy. METHODS: Immediate postangioplasty and six-month follow-up IVUS studies of 94 patients in the IVUS substudy of the MultiVitamins and Probucol (MVP) trial and 26 nonstented patients in the Beta Energy Restenosis Trial (BERT) were analyzed for the presence or absence of dissection. RESULTS: Of the 28 patients with postangioplasty dissections in MVP, only one had evidence of residual dissection at six months (95% confidence interval [CI] for failure rate 0.2%; 20.2%). Conversely, 9 of 16 dissections had healed in BERT (95% CI for failure rate 30.6%; 79.2%) (p < 0.0002). Nevertheless, an index based on dissection arc and length demonstrated improvement in the irradiated patients. Irradiated patients with residual dissections showed significant increase in lumen area at six-months (5.10 +/- 0.98 to 7.11 +/- 2.61 mm2, p < 0.02) not noted when there was resolution of the dissection (6.03 +/- 2.38 to 6.36 +/- 3.33 mm2, p = NS). In both groups the external elastic membrane area was unchanged at follow-up. CONCLUSIONS: Resolution appears to be the natural history of IVUS-detected dissections in most cases. Significant resolution of dissection occurs following intracoronary beta-radiation as reflected in reduced dissection index at six-months in these patients, although significant impairment of vessel wall healing was noted.

Influence of postangioplasty beta-irradiation on endothelial function in porcine coronary arteries.

BACKGROUND: Postangioplasty (PTCA) intracoronary radiation therapy (ICRT) has been demonstrated to limit restenosis. The consequences of these procedures on coronary reactivity are unknown. METHODS AND RESULTS: Porcine coronary arteries were studied after PTCA immediately (n=5) and 6 weeks (n=5) after ICRT (n=5 and 5, respectively), after combined PTCA+ICRT (n=5 and 7, respectively), and after no intervention (n=11). A 3-cm-long source train of Sr/Y(90) was used in vivo to deliver 16 Gy at a depth of 2 mm from the source center, as used in clinical trials. Arterial rings were mounted on myographs to record isometric tension. After achieving steady-state contraction to depolarizing physiological solution containing 40 mmol/L KCl, measured baseline tension was significantly elevated immediately after all interventions. It returned to normal levels 6 weeks after PTCA and ICRT alone but was significantly reduced if combined. Active contractions induced by 40 mmol/L KCl were maintained after combined therapy both immediately after and at 6 weeks. In these depolarizing conditions, nitric oxide-dependent relaxation to substance P was trivial after PTCA+ICRT and reduced after ICRT, whereas in the presence of physiological solution and N(omega)-nitro-L-arginine, substance P-induced relaxation was reduced after PTCA and abolished after PTCA+ICRT 6 weeks after intervention. In rings without endothelium, the relaxation mediated by sodium nitroprusside (0.1 micromol/L) was reduced immediately after PTCA and at 6 weeks. CONCLUSIONS: PTCA+ICRT altered the passive mechanical properties of porcine coronary arterial wall. Furthermore, at 6 weeks, receptor-operated release of endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor was reduced by ICRT and PTCA alone, respectively, and was prevented by their combination.

Double vessel occlusions after balloon angioplasty treated by stenting and subsequently by abciximab infusion.

Stent thrombosis is a serious complication after percutaneous coronary intervention. A patient is presented with a double vessel occlusion after balloon angioplasty and subsequent stenting. He was then managed by abciximab therapy alone. Control angiography showed complete resolution of the thrombotic occlusions. His subsequent clinical course was uneventful.

Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations--animal and clinical studies in stented and non-stented coronary arteries.

BACKGROUND: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. METHODS: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. RESULTS: Both systems correlated well for areas (r > or = 0.90, p < 0.0001) and diameters (r > or = 0.84. p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: -0.24 and 0.96 mm2, p < 0.055) and diameter (-0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r > or = 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. CONCLUSIONS: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.

Study of catheter designs and drug mixing processes using 2D steady numerical simulations.

The effectiveness of substance delivery through catheters is an important issue in interventional radiology, especially for infusion therapies where the pharmacokinetic advantage of local intra-arterial drug administration has been firmly established. In principle, the procedure is used to provide appropriate local concentrations while maintaining low systemic values so as to minimise the global effect and toxicity of the intervention. However, poor drug mixing may produce excessive local concentrations potentially damaging for the surrounding tissues and may lead to unsuccessful therapies. These phenomena have been observed in the infusion therapies of liver cancers through the hepatic artery and with brain tumour therapies through the carotid artery. Many aspects of the drug delivery methodology have been explored in order to determine the infusion conditions that would provide optimal mixing: the catheter tip design is considered one of the most important characteristics to be investigated for this purpose. Interestingly, it turns out that angiographic procedures could also benefit from this, because better mixing properties are associated with designs that provide potentially less harmful flow conditions such as jets, whipping and recoil of the catheter on the vascular wall. A 2D steady numerical model is proposed, to simulate the main physical processes occurring during catheter substance infusion: blood dynamics is taken into account with the Navier-Stokes equations and substance dispersion by the flowing blood with the advection-diffusion equation. The model is used to evaluate mixing properties of certain catheter designs in different flow conditions. In particular, two types of side hole catheter are compared in the context of water bath injection and in the context of vessel injection. The simulations suggest that the improved mixing reported with water bath experiments would not be maintained in the clinical context of arterial circulation.

Effects of low-dose-rate beta-irradiation on vascular smooth muscle cells: comparison with high-dose-rate exposure.

PURPOSE: Radiation therapy is undergoing extensive preclinical and clinical testing as a new tool to reduce restenosis after vessel injury. To date, however, no definite dose threshold has been identified after radioactive stent implantation. In this study, we compared the in vitro response of pig vascular smooth muscle cells (SMC) to conventional high-dose-rate (HDR) irradiation with the response to continuous low-dose rate (LDR) that could result from exposure to a radioactive stent. MATERIALS AND METHODS: Catheter-based radiotherapy delivers single doses at HDR whereas radioactive stents use a continuous LDR approach. Single doses in excess of 10 Gy have clearly shown a reduction in neointima formation and negative vessel remodeling in several animal models. Because dose rate is an important parameter modulating the overall biological response to ionizing radiation, we have compared the in vitro response of pig aortic SMC at conventional HDR (1.5 Gy/min) and at LDR (0.675 Gy/h). RESULTS: SMC showed significant repair of sublethal DNA damage and about twice the dose was necessary at the LDR to produce the same effect as that seen at the HDR. CONCLUSION: In vitro SMC exhibit a significant dose-rate effect that indicates that radioactive stents could deliver the dose at a sufficiently high dose rate to compensate for cell proliferation while at the same time the total dose should be increased to account for sublethal damage repair. This finding has important implications for the design of a radioactive stent.

Biocompatibility aspects of new stent technology.

Stent implantation represents a major step forward since the introduction of coronary angioplasty. As indications continue to expand, better understanding of the early and late biocompatibility issues appears critical. Persisting challenges to the use of intracoronary stents include the prevention of early thrombus formation and late neointima development. Different metals and designs have been evaluated in animal models and subsequently in patients. Polymer coatings have been proposed to improve the biocompatibility of metallic stents or to serve as matrix for drug delivery and they are currently undergoing clinical studies. The promises of a biodegradable stent have not yet been fulfilled although encouraging results have recently been reported. Continuous low dose-rate brachytherapy combining the scaffolding effect of the stent with localized radiation therapy has witnessed the development and early clinical testing of radioactive stents. The combined efforts of basic scientists and clinicians will undoubtedly contribute to the improvement of stent biocompatibility in the future.

Development of coronary aneurysm after cutting balloon angioplasty: assessment by intracoronary ultrasound.

We report the case of a coronary aneurysm observed 6 mo after cutting balloon angioplasty complicated by a mild perforation. Intravascular ultrasound allowed characterization of the malformation as a true aneurysm. The clinical course was uneventful.

Angioscopic evaluation of thrombus removal by the POSSIS AngioJet thrombectomy catheter.

Coronary angioplasty in a thombotic vein graft is associated with a low success rate and a high risk of periprocedural complications. The aspiration thrombectomy catheter is a new device designed to treat such cases. We report a first angioscopic description of thrombus removal by the AngioJet thrombectomy catheter.

Prevention of restenosis after angioplasty in small coronary arteries with probucol.

BACKGROUND: Restenosis remains the major limitation of coronary angioplasty. Coronary stents have reduced the incidence of restenosis in selected patients with relatively large vessels. No strategies to date have demonstrated a beneficial effect in vessels < 3.0 mm in diameter. We have shown in the MultiVitamins and Probucol (MVP) Trial that probucol, a potent antioxidant, reduces restenosis after balloon angioplasty. The purpose of this study was to determine whether the benefit of probucol therapy is maintained in the subgroup of patients with smaller coronary vessels. METHODS AND RESULTS: We studied a subgroup of 189 patients included in the MVP trial who underwent successful balloon angioplasty of at least one coronary segment with a reference diameter < 3.0 mm. One month before angioplasty, patients were randomly assigned to one of four treatments: placebo, probucol (500 mg), multivitamins (beta-carotene 30000 IU, vitamin C 500 mg, and vitamin E 700 IU), or probucol plus multivitamins twice daily. The treatment was maintained until follow-up angiography was performed at 6 months. The mean reference diameter of this study population was 2.49+/-0.34 mm. Lumen loss was 0.12+/-0.34 mm for probucol, 0.25+/-0.43 mm for the combined treatment, 0.35+/-0.56 mm for vitamins, and 0.38+/-0.51 mm for placebo (P=.005 for probucol). Restenosis rates per segment were 20.0% for probucol, 28.6% for the combined treatment, 45.1% for vitamins, and 37.3% for placebo (P=.006 for probucol). CONCLUSIONS: Probucol reduces lumen loss and restenosis rate after balloon angioplasty in small coronary arteries.