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Aims: To report the 4-month angiographic and 6-month clinical follow-up in first-in-man study using the tacrolimus-eluting bioabsorbable polymer-coated cobalt-chromium MAHOROBA stent., Methods and Results: A total of 47 patients with either stable angina or unstable angina, or silent myocardial ischaemia, based on a de novo coronary stenosis that could be covered by a single 18 mm stent in a native coronary artery with a diameter between 3.0 and 3.5 mm were enrolled at three sites. The primary endpoint was in-stent late loss at 4 months. The secondary endpoints include %volume obstruction of the stents assessed by intravascular ultrasound (IVUS) at 4 months and major adverse cardiac events (MACE) at 6 months. Forty-seven patients were enrolled. Procedural success was achieved in 97.9%. At 4-month follow-up, in-stent late loss was 0.99 +/- 0.46 mm, whereas in-stent %volume obstruction in IVUS was 34.8 +/- 15.8%. At 6 months, there were no deaths, but 2 patients suffered from a myocardial infarction and 11 patients required ischaemia-driven repeat revascularization. The composite MACE rate was 23.4%., Conclusion: This tacrolimus-eluting stent failed to prevent neointimal hyperplasia, despite the theoretical advantages of the tacrolimus, which has less inhibitory effects on endothelial cells than smooth muscle cells.

Exposure to Epicoccum purpurascens is implicated in respiratory allergies and asthma. Several allergens of clinical importance were identified in Epicoccum extract (EE), but only one allergen has been isolated and characterized. In the present study, a 12-kDa allergen was isolated from an Epicoccum spore-mycelial extract by concanavalin-A sepharose, reverse-phase hydrophobic and gel filtration chromatography. The purified protein was recognized as a single 12-kDa allergen on immunoblot with a serum pool of Epicoccum-sensitive patients. Of the 94 respiratory allergy patients tested intradermally, 17 showed marked positive skin reactions to EE and 12 of them reacted with the 12-kDa protein, indicating a diagnostic sensitivity of 70%. More than 80% patients' sera showed immunoglobulin E (IgE) reactivity to the purified protein in enzyme-linked immunosorbent assay and immunoblot, identifying it as a major allergen. Preincubation of pooled serum with the protein led to inhibition of IgE binding to solid-phase-bound EE (effective concentration 50%=180 ng). Twelve of the 17 serum samples showed significant basophil histamine release upon stimulation with purified protein. The protein induced significant proliferation of peripheral blood mononuclear cells of 13 patients. A high level of interleukin-4 in the culture supernatant of these cells indicated induction of a T-helper type 2 response. The purified 12-kDa protein is a clinically relevant allergen and has potential for the diagnosis and therapy of Epicoccum allergies.

Aims: To report long-term outcome data on the V technique using drug-eluting stents., Methods and Results: From April 2002 to December 2006, 31 consecutive patients were successfully treated with V stenting of a de novo bifurcation lesion. The technique involves the deployment of two stents in the two branches of a bifurcation, the proximal edges of the stents just touching one another. Patients exclusively received either sirolimus- (10), paclitaxel- (20) or biolimus-eluting (one) stents. On average, 1.5 +/- 0.8 stents with a total length of 26.6 +/- 17.2 mm and 1.1 +/- 0.4 stents with a total length of 18.3 +/- 7.6 mm were deployed in the distal main vessel and side branch respectively. Mean duration of follow-up was 853 +/- 553 days. Within 30 days, three patients died; two other patients had definite stent thrombosis involving the V stents, both requiring re-PCI. Beyond 30 days and within one year, there was one death and three cases of target vessel revascularisation, including one target lesion revascularisation. There were a further three deaths (one cardiac) beyond one year. Eleven patients (35.5%) had angiographic follow-up, exhibiting a binary restenosis rate of 9.1% at 203 +/- 33 days., Conclusions: In this real-world cohort, late clinical events stand in accord with studies on competitive techniques, but early outcome was less encouraging, probably due to the baseline risks.

Aims: Previous randomised studies have shown a significant reduction in restenosis when oral rapamycin (OR) is administered to patients undergoing bare metal stent (BMS) implantation. How this regimen compares to drug eluting stents (DES) is unknown., Methods and Results: Two-hundred patients with de novo coronary lesions were randomised to treatment with OR plus BMS (100 pts) or with DES (100 pts). OR was given as a bolus of 10 mg per day before PCI followed by daily doses of 3 mg during following 13 days. Primary endpoints were to compare hospital, follow-up and overall cost at one, two, three and five years of follow-up. The secondary endpoints included death, myocardial infarction (MI) and stroke and were analysed as major adverse cardiovascular events (MACCE). Target vessel (TVR) and target lesion revascularisation (TLR) were independently analysed. Costs included procedural resources, hospitalisation, medications, repeat revascularisation procedures and professional fees. Baseline demographic, clinical and angiographic characteristics were similar. At 18.3 +/- 7 months of follow-up, the initial strategy of OR plus BMS resulted in significant cost saving when compared to DES (p=0.0001). TLR rate was 8.2% with DES and 7.0% with OR plus BMS (p=0.84), similarly no differences in TVR rate in both groups was seen (10.6% and 10.5% in OR and DES group respectively, p=0.86). Non-inferiority testing, determined that DES therapy failed to be cost saving compared to OR in all possible cost scenarios., Conclusions: A strategy of OR plus BMS is cost saving compared to DES in patients undergoing PCI for de novo coronary lesions.

Objectives: We aimed to evaluate the risk of definite stent thrombosis with bare-metal stents (BMS) and drug-eluting stents (DES) in patients treated for acute coronary syndromes., Background: Acute coronary syndromes (ACS) have been reported as increasing the risk for stent thrombosis., Methods: Between January 2000 and December 2005, 5,816 consecutive patients underwent percutaneous coronary intervention for de novo lesions with a single stent type. These patients consisted of 3 sequential groups of BMS (n = 2,248), sirolimus-eluting stents (n = 822) and paclitaxel-eluting stents (n = 2,746). In total, 3,485 patients presented with an ACS., Results: After a median follow-up of 1,394 days, patients with ACS had a definite stent thrombosis rate of 2.5% versus 1.0% in patients with stable angina (propensity score-adjusted hazard ratio [HR]: 2.80, 95% confidence interval [CI]: 1.72 to 4.56). ACS patients had a higher risk of early and late stent thrombosis, although the increased risk of very late stent thrombosis was only present in ACS patients treated with DES. In stable patients, any stent thrombosis resulted in a significant increase in mortality (adjusted HR: 4.0, 95% CI: 1.7 to 9.3), although this was particularly evident for late or very late stent thrombosis; in contrast only early stent thrombosis significantly increased mortality in patients with acute coronary syndrome patients (adjusted HR: 2.0, 95% CI: 1.0 to 4.1)., Conclusions: Patients with acute coronary syndromes are at higher risk of early and late stent thrombosis with either BMS or DES, although very late stent thrombosis seems to be uniquely associated with DES. The clinical sequelae of late and very late stent thrombosis are more pronounced in stable patients.

Rationale: Studies with mite allergens demonstrated that proteolytic activity augments allergic airway inflammation. This knowledge is limited to few enzyme allergens., Objective: The objective of this study is to investigate the effect of serine protease Cur l 1 from Curvularia lunata in airway inflammation/hyper-responsiveness., Methods: Cur l 1 was purified and inactivated using a serine protease inhibitor. Balb/c mice were sensitized with enzymatically active Cur l 1 or C. lunata extract. Sensitized mice were given booster dose on day 14 with active or inactivated Cur l 1. Intranasal challenge was given on day 28, 29, and 30. Airway hyper-responsiveness was measured by plethysmography. Blood, bronchoalveolar lavage fluid (BALF), spleen, and lungs from mice were analyzed for cellular infiltration, immunoglobulins, and cytokine levels., Results: Mice challenged with enzymatically active Cur l 1 demonstrated significantly higher airway inflammation than inactive Cur l 1 group mice (p < 0.01). There was a significant difference in serum IgE and IgG1 levels among mice immunized with active Cur l 1 and inactive Cur l 1 (p < 0.01). IL-4 and IL-5 were higher in BALF and splenocyte culture supernatant of active Cur l 1 than inactive Cur l 1 mice. Lung histology revealed increased eosinophil infiltration, goblet cell hyperplasia and mucus secretion in active group., Conclusion: Proteolytic activity of Cur l 1 plays an important role in airway inflammation and the inactivated Cur l 1 has potential to be explored for immunotherapy.

Drug-eluting stents are widely used for the treatment of coronary artery disease to reduce the risk of restenosis found with bare-metal stents. Nevertheless, there are concerns about device deliverability and safety with the initial generation of drug-eluting stents. The second-generation Xience V everolimus-eluting stent incorporates advanced design features such as a cobalt-chromium stent platform coated with an antirestenotic drug, everolimus, incorporated into a biocompatible polymer with a long history of medical use. The efficacy of the stent has been demonstrated with low rates of angiographic restenosis, whilst randomized trials comparing the Xience V everolimus-eluting stent to the first-generation Taxus paclitaxel-eluting stent have found a reduction in repeat revascularization rates. Further randomized trials, including 'all-comer' patients and registries of unselected patients are currently further evaluating the efficacy and safety of the Xience V stent in high-risk, complex cases.

Drug-eluting stents (DESs) have been shown to reduce the rate of repeat revascularization compared with bare-metal stents (BMSs) after multivessel percutaneous coronary intervention in carefully selected patients. However, the long-term safety and efficacy of DESs in patients with multivessel disease outside the setting of randomized trials was unknown. Therefore, all patients undergoing multivessel percutaneous coronary intervention with BMSs, sirolimus-eluting stents (SESs), or paclitaxel-eluting stents (PESs) from January 2000 to December 2005 were investigated. The primary end point was all-cause mortality. A total of 1,720 patients were recruited in 3 consecutive sequential groups of BMS (n=701; January 2000 to April 2002), SES (n=293; April 2002 to February 2003), and PES (n=726; February 2003 to December 2005). Overall median follow-up was 1,440 days. There was improved 3-year survival in the SES group (93.7%) compared with both the BMS (86.1%) and PES groups (87.3%), which remained significant after propensity score adjustment for differences in baseline and procedural characteristics (SES vs BMS, adjusted hazard ratio 0.53, 95% confidence interval 0.30 to 0.94; SES vs PES, adjusted hazard ratio 0.49, 95% confidence interval 0.28 to 0.87). There was no difference in mortality between the PES and BMS groups. Both DES types significantly reduced the need for clinically driven target-vessel and target-lesion revascularization without an excess in myocardial infarction or stent thrombosis. In conclusion, both SESs and PESs significantly reduced the need for repeated revascularization in these patients with no excess in mortality. SESs might reduce mortality in patients undergoing multivessel percutaneous coronary intervention.

Aims: The main objective was to use IVUS-backscatter radiofrequency (IVUS-RF) to assess the degradation of a bioabsorbable stent by measuring serial changes in dense calcium (DC) and necrotic core (NC) as assessed by intravascular ultrasound-Virtual Histology (IVUS-VH) and in the strain as assessed by palpography., Methods and Results: In the ABSORB trial, 27 patients treated with a single bioabsorbable everolimus-eluting stent (BVS, Abbott Vascular, Santa Clara, CA, USA) were all imaged with IVUS-RF post-stenting and at 6-month follow-up, and 13 and 12 patients were also investigated pre-stenting with IVUS-VH and palpography respectively. From pre- to post-stenting, with VH (n = 13), there was an increase in mean "DC" (9.8 vs. 25.4%, p = 0.0002) and "NC" (15.5 vs. 30.5%, p = 0.0002). In palpography (n = 12), the mean number of frames with Rotterdam Classification (ROC) III/IV per cm decreased from 1.22 +/- 1.91 to 0.12 +/- 0.31 (p = 0.0781) and the mean cumulative strain values (all frames with ROC I-IV scores) changed from 0.50 +/- 0.27 to 0.20 +/- 0.10% (p = 0.0034). Comparing post-stenting with follow-up (n = 27), VH showed a decrease in "DC" (29.7% vs. 21.1%, p = 0.0001). "NC" also decreased (26.9 vs. 21.5%, p = 0.0027). For palpography (n = 25 patients), an increase in the mean number of frames with ROC III/IV per cm was observed from 0.09 +/- 0.26 to 0.22 +/- 0.36 (p = -0.1563) while the mean cumulative strain values (all frames with ROC I-IV scores) changed from 0.15 +/- 0.10 to 0.26 +/- 0.12% (p < 0.0001)., Conclusions: IVUS-VH changes at 6 months suggest alteration of the BVS with reduction of RF backscattering by polymeric struts. Strained plaques on the palpograms were almost abolished following stent implantation. However, strain values reappeared within 6 months suggesting an increase in endoluminal deformability of the stented vessel.

Aims: Sirolimus- and paclitaxel- eluting stents (SES and PES respectively) have been shown to produce a sustained reduction in restenosis and repeat revascularisations as compared to bare-metal stents (BMS) up to four years. There is still limited data about the long-term safety and efficacy of DES in high-risk subgroups., Methods and Results: A total of 6,129 consecutive patients were treated during three sequential periods with BMS (n = 2,428; January, 2000 to April, 2002), SES (n = 866; April 2002 to February 2003) or PES (n = 2,835; February 2003 to December 2005). A stratified analysis (including age, gender, diabetes, clinical presentation, treated vessel, multivessel disease, AHA lesion class, bifurcation, in-stent restenosis, average stent diameter < or = 2.5 mm and total stented length < or = 30 mm) was performed to evaluate possible heterogeneities in treatment effect. At four years, all-cause mortality was identical between the drug-eluting stent (DES) and BMS cohorts (13.5% vs. 13.4%, respectively; Adjusted HR 1.10, 95% CI 0.90 - 1.34) without evidence of heterogeneity in the high-risk patient subsets. Both DES significantly reduced the risk for target vessel revascularisation (TVR) as compared to BMS (TVR: 11.9% vs. 15.7% respectively; Adjusted HR 0.69, 95% CI 0.58 - 0.82) along with a reduced risk for post-operative MI (adjusted HR 0.75, 95% CI 0.57 - 0.98), but counterbalanced by a non-significantly higher risk for stent thrombosis (3.1% vs. 1.6%; adjusted HR 1.26, 95% CI 0.82 - 1.95). DES failed to show superiority to BMS in patients with acute myocardial infarction (TVR 10.5% vs. 9.2% respectively; Adjusted HR 1.26, 95% CI 0.82 - 1.93)., Conclusions: In a real world patient population, after four years, the overall use of DES was associated with similar all-cause mortality rates and a significantly reduced risk for post-operative MI and TVR as compared to BMS.

Objectives: Recently, concerns were raised about the relative long-term safety and efficacy of drug-eluting stents (DES) in saphenous vein bypass grafts (SVG). Our objective was to assess the 4-year relative safety and efficacy of the unrestricted use of drug-eluting stents (DES) as compared to bare metal stents (BMS) in saphenous vein bypass grafts (SVG)., Methods: Between April 16, 2002 and December 2005 a total of 122 consecutive patients were treated with either sirolimus- or paclitaxel-eluting stents for saphenous vein graft disease. These patients were compared with 128 consecutive patients treated with BMS in the immediate preceding period (January 1, 2000 to April 2002)., Results: At 4-years the cumulative survival rate in the DES group was 77.5% versus 73.0% in the BMS group (adjusted HR 1.09; 95% CI 0.63-1.90, Logrank p=0.65). The cumulative survival free of major adverse cardiac events (MACE: death, myocardial infarction and target vessel revascularisation) was 61.5% vs. 46.8% in the DES and BMS groups respectively (adjusted HR 0.77, 95% CI; 0.51-1.16) due to a higher event free survival of clinically driven target vessel revascularisation in the DES group as compared to the BMS group (81.6% vs. 69.0%; adjusted HR 0.53; 95% CI 0.27-1.05)., Conclusions: In the present study, the use of DES for SVG PCI was associated a similar safety profile and there was a trend towards lower rates of TVR and MACE at four years as compared to BMS.

Background: Percutaneous treatment of stenoses involving aorto-ostial lesions is technically demanding and has been associated with lower procedural success and poorer clinical and angiographic outcomes when compared with non-ostial lesions. This study evaluated the immediate and long-term (2-year) outcome of aorto-ostial stenoses treated with paclitaxel-eluting stents (PES)., Methods: From February 2003 to December 2004, a total of 76 consecutive patients with 76 lesions underwent percutaneous intervention with PES for aorto-ostial lesions (right coronary artery, 37; left main, 26; saphenous vein graft, 13). All patients were clinically followed for the occurrence of major adverse cardiac events (MACE), defined as cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR)., Results: All stents (1.7/lesion) were successfully deployed. Three lesions (3.9%) were pre-treated with debulking devices. Thirty-seven lesions (48.7%) were post-dilated with non-compliant balloons (balloon/artery ratio, 1.2). Stents were positioned protruding into the aortic lumen in 29 lesions (38.2%). Cumulative 2-year event-free survival was 68.4%. There was one angiographically-proven stent thrombosis occurring 427 days after TLR for restenosis after the index procedure. The restenosis rate at 7 months (median) was 20.0% and in-stent late lumen loss was 0.48 mm in 40 patients with angiographic follow-up., Conclusions: Utilization of PES in this complex lesion subset is feasible and associated with favorable angiographic results at 7 months. However, the gradual increase in later events up to 2 years suggests that aorto-ostial disease remains problematic even in the era of drug-eluting stents.

Background: Primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction with bare metal stents (BMS) is well established, while randomized trials suggest equivalent safety and reduced repeat revascularization with drug-eluting stents (DES) in this setting. However, long-term data on DES in PPCI is lacking, especially in those ineligible for inclusion in randomized trials. Our aim was to investigate the long-term outcomes of unselected patients undergoing PPCI with BMS and DES., Methods and Results: We analyzed all patients (n=1738) undergoing PPCI for a de novo lesion in our institution from 2000 to 2005. Patients from 3 sequential consecutive cohorts of BMS (n=531), sirolimus-eluting (SES, n=185) or paclitaxel-eluting stents (PES, n=1022) were included. The median duration of follow-up was 1185 days (interquartile range, 746 to 1675). There were no differences in all-cause mortality or repeat revascularization between DES and BMS, although there was a nonsignificant trend toward improved survival with SES compared with both BMS (propensity score-adjusted hazard ratio, 0.63; [95%CI, 0.33 to 1.18]) and PES (hazard ratio, 0.71; [95% CI, 0.40 to 1.26]). SES were associated with lower rates of the composite end point of all-cause death, nonfatal myocardial infarction, or target vessel revascularization (hazard ratio, 0.62; 95%CI, 0.40 to 0.96) when compared with PES. Very late stent thrombosis only occurred in the DES groups., Conclusions: Although DES are not associated with an increase in adverse events compared with BMS when used for PPCI, neither DES reduced repeat revascularizations. Appropriately powered randomized trials with hard clinical end points and an "all-comer" design are required to further assess the benefit of DES in PPCI.

Stent thrombosis is one of the major concerns after drug-eluting stent implantation. Multiple mechanical causes (i.e., stent under-expansion, edge dissection, geographic miss, residual stenosis, incomplete stent apposition and aneurysm) have been postulated. These features are easily identifiable by intravascular ultrasound. However, it is uncertain which of them are inextricably related to stent thrombosis, primarily due to the low number of such patients studied by IVUS in case control studies. Complementary to greyscale IVUS, tissue characterisation by IVUS radiofrequency data (RFD) analysis has the potential to add valuable information on the pathogenesis of stent thrombosis by providing information on plaque composition, specifically on the amount of necrotic core and its location (superficial or deep). However, the clinical utility of IVUS-RFD analysis in this context has yet to be demonstrated.

Aims: There have been recent concerns regarding the long-term safety of the first generation of drug-eluting stents, which utilised a permanent polymer coating for drug delivery. SERIES I is a prospective, non-randomised, first-in-man open label study with the biodegradable polymer-based Supralimus sirolimus eluting stent (Sahajanand Medical Technologies Pvt. Ltd, India) for the treatment of patients with coronary artery lesions., Methods and Results: One hundred patients were treated with 126 Supralimus stents (mean lesion length 10.5 +/- 4.3 mm, mean reference vessel diameter 2.66 +/- 0.62 mm). The pre-specified primary endpoint was angiographic binary in-stent restenosis at six months. Secondary endpoints were device-orientated major adverse clinical events (MACE; defined as a composite of cardiac death, nonfatal myocardial infarction [Q-wave and Non-Q wave], or clinically-justified target vessel revascularisation) at 30 days, nine months and 30 months. Angiographic follow-up in a pre-specified subgroup of 60 patients at six months showed binary angiographic restenosis rates of 0% (in-stent) and 1.7% (in-segment). The in-stent late loss was 0.09 +/- 0.37 mm. MACE rates were 0% after one month, 6% at 9-month follow-up and 7% after 30 months follow-up., Conclusions: The biodegradable-polymer-based sirolimus-eluting stent (Supralimus) is effective in inhibiting neointimal hyperplasia.

Although the safety of drug-eluting stents has been under considerable scrutiny, limited real-world follow-up data extending up to 4 years are available. The randomized clinical trials carefully selected patients and are not reflective of everyday practice. From April to October 2002, 508 consecutive patients treated with sirolimus-eluting stents (SES) were enrolled. The control group consisted of 450 patients treated with bare-metal stents during the preceding 6 months. After 4 years of follow-up, the incidence of composite major adverse clinical events (all-cause death, myocardial infarction, or target vessel revascularization) was found to be significantly lower in the SES group (23.0% vs 28.7%, adjusted hazard ratio 0.66, 95% confidence interval 0.51 to 0.86), as were rates of target vessel revascularization (12.2% vs 17.8%, adjusted hazard ratio 0.57, 95% confidence interval 0.39 to 0.83). There were no differences in all-cause mortality (10.5% for SES vs 10.6% for bare-metal stents, p = 0.9) or in the rates of cardiac death (4.5% vs 6.9%, p = 0.1). Although there was no difference in overall stent thrombosis (2.3% vs 2.2%, p = 1.0), SES had a higher rate of very late stent thrombosis (1.4% vs 0%, p = 0.02), balanced by a lower rate of early stent thrombosis (0.4% vs 1.8%, p = 0.05). In conclusion, after 4 years, SES were found to remain safe and effective compared with bare-metal stents. Nevertheless, the higher rate of very late stent thrombosis remains a concern. Longer term follow-up will be required to determine the extent of this problem.

This review aims to provide a glimpse into the future of drug-eluting stents (DES). Since their arrival in 2002, DES have transformed the practice of interventional cardiology by drastically reducing restenosis and the need for repeat revascularization. However, data about the potentially fatal long-term risk of stent thrombosis have spurred on research and development to improve upon the first generation of devices. The initial commercially available DES used a stainless steel platform coated with a permanent polymer to provide controlled release of the anti-restenotic drug. The platform, polymer and drug are all targets for improvement. More advanced metallic and fully biodegradable stent platforms are currently under investigation. The permanent polymer coating, a likely contributor adverse events, is being superseded by biocompatible and bioabsorbable alternatives. New drugs and drug combinations are also a research goal, as interventional cardiologists and the industry strive towards safer anti-restenotic DES.

Sensitization to allergens of Epicoccum purpurascens is reported from many places world over. Previously, the IgE binding proteins of Epicoccum were studied by one-dimensional immunoblotting (1-DE). However, the allergens recognized by 1-DE may be a mixture of proteins appearing at the same molecular weight. In the present study, IgE-binding components of E. purpurascens were detected using two-dimensional immunoblotting and mass spectrometry. Approximately 250 protein spots were identified by Coomassie staining in the range of 14-110kDa and pI 3.5-9.5. Of these, 147 showed specific IgE reactivity with pooled patients' sera whereas 16 protein components reacted with more than 50% of the individual patients' sera. The frequency of IgE reactivity was highest (87.5%) for a 25-kDa protein (pI-7.85). Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of 16 protein components led to identification of 6 important allergens as phospho-glycerate kinase (PGK), RNA-dependent RNA polymerase, pyrroline-5-carboxylate dehydrogenase, 40S ribosomal protein and two proteins of unknown functions. The major allergens identified may be assessed for cross reactivity with other fungi. In conclusion, 2-DE followed by immunoblotting allowed characterization of E purpurascens allergens. Six new allergens have been identified using this technique and mass spectrometry. The availability of such relevant allergens would help in component-based diagnosis and therapy of fungal allergy.

Background: We previously reported that the 1-year survival-free from target lesion revascularization was 97.4% in patients with chronic total occlusion (CTO) treated with sirolimus-eluting stents (SES). There are currently no long-term results of the efficacy of SES in this subset of lesions. We assessed the 3-year clinical outcomes of 147 patients with CTO treated with either SES or bare metal stents (BMS)., Methods and Results: A total of 147 (BMS = 71, SES = 76) patients were included. Four patients died in the BMS group while five patients died in the SES group, P = 0.8; two myocardial infarctions occurred in both groups, P = 0.9; and target vessel revascularization was performed in nine patients in the BMS and seven in the SES group, P = 0.5. The cumulative event-free survival of MACE was 81.7% in BMS group and 84.2% in SES group, P = 0.7. Two patients of the SES group had a coronary aneurism at 3-year angiographic follow-up., Conclusions: The use of SES was no longer associated with significantly lower rates of target vessel revascularization and major adverse cardiac events in patients with CTOs after 3 years of follow-up compared with BMSs., ((c) 2007 Wiley-Liss, Inc.)

The aim of this article is to review the treatment of patients with multi-vessel coronary artery disease. Percutaneous coronary intervention (PCI) has been challenging coronary artery bypass grafting (CABG) as the gold standard of care for patients with multi-vessel disease; however, the application of PCI to these patients has been mainly limited by restenosis. Up to the late 1990s, numerous large-scale, randomized trials addressed this issue comparing CABG to PCI with balloon angioplasty or bare-metal stents. These studies demonstrated similar rates of death and myocardial infarction in both groups, while the need for revascularization remained significantly lower in the CABG group. Drug-eluting stents (DES) have dramatically reduced restenosis and repeat revascularization rates. CABG has also progressed with improvements in perioperative management, a higher use of arterial grafting, and advanced techniques with the implementation of minimally invasive and off-pump surgery as options. Therefore, the results of previous trials in the pre-DES era can no longer be extrapolated into the ''real world''. As intermediate steps preceding a fully-fledged, randomized trial, several trials have compared PCI with DES and the historical control of CABG, but the results are still inconclusive. Several dedicated randomized trials are currently ongoing to compare PCI with DES and CABG using contemporary techniques. Until the results of these randomized trials are presented, the choice for each strategy should be based on the patients' individual risk and anatomy.

Aims: To describe the contemporary approach of chronic total occlusion (CTO) treatment of patients at the Thoraxcenter, Rotterdam, The Netherlands. Additionally, to make a critical appraisal of the performance of state-of-the-art CTO dedicated guidewires and devices in a prospective registry of patients., Methods and Results: During 20 months, a total of 160 consecutive patients (165 CTOs) were enrolled. The mean age was 61.5+/-11.1 years and 83.6% were male. In 91.5% of the patients this was the first attempt to open the CTO and 93.8% were de novo. The overall success rate was 60.6%. A median of 1 guiding catheter was used per case (Range: 1 to 9) and a median of 4 guidewires (Range: 1 to 11; 13 different types). 74.5% patients required more than one guidewire/device for the treatment of the CTO. The guidewires that most frequently crossed the CTO were the following: PT Graphix intermediate 33.0%, Miracle 3 g 27.4% and Crosswire NT 25.5%. The only device tested as a first option for the treatment of the CTOs was the CROSSER. Overall, the CROSSER system was used in 23 (13.9%) patients with a success rate of 60.9%. The Point 9(R) X-80 Laser catheter was used in 10 (6.1%) patients with a success rate of 60%. Another 3 patients were treated with the Point 7(R) laser catheter. Both were used either to facilitate the crossing of the balloon, or to treat primarily in-stent restenosis occlusions. The SafeCross(R) System was used in 15 (9.1%) patients and the success rate in these patients was 46.7%. The most common strategy used in this registry was the use of an over-the-wire balloon in 81.5% of the cases. The parallel wire technique was used in 27.3% of the cases and in 12.7% was converted into a "see-saw" technique. When a large false lumen was created, re-entry into the true lumen was attempted in 21.2% of the cases, by means of IVUS guided approach and/or the use of stiffer guidewires, such as a Confianza guidewire. Retrograde recanalisation was attempted in 10 cases (6.1%), in three cases a graft was used; the remaining cases were treated either via collaterals or the septal branches., Conclusions: The treatment of CTOs requires the use of a high number of guiding catheters and guidewires, as well as the use of sophisticated devices. The procedure must be carefully planned in advance as far as possible, as well as considering a prompt change in approach during the performance of the procedure to prevent complications derived from long procedures by using specific techniques such as parallel wire, see-saw, anchoring balloon, etc.

Objective: To compare the postprocedural and long-term clinical outcomes of two groups of patients, all presenting with chronic saphenous vein graft (SVG) occlusion, who underwent either SVG or native vessel reopening., Background: Chronic total occlusions (CTO) treatment in patients who underwent previous surgical revascularization is a dilemma and the choice of performing native vessel or SVG recanalization is not always easy., Methods: Between July 2002 and October 2004, a total of 260 patients were successfully treated for a CTO. Of them, we selected all patients (n = 24) who had previous bypass surgery with graft occlusion. Of this final group, 13 patients underwent a percutaneous graft recanalization while 11 underwent native vessel reopening., Results: Primary end points were in-hospital and 3-year rates of death, myocardial infarction, target lesion revascularization, and target vessel revascularization. No events occurred in either group during the in-hospital period. Cumulative 3-year event-free survival in the native vessel and SVG group was 81.8% and 83.9% respectively (P = NS). One death and one TVR occurred in each group., Conclusion: In selected cases, SVG reopening instead of the native vessel is feasible. In such a high-risk population, drug-eluting stent implantation in both SVG and native CTO lesions is associated with good long-term outcomes., ((c) 2007 Wiley-Liss, Inc.)

Chronic total occlusions remain one of the last frontiers in interventional cardiology, with far lower procedural success rates compared with other lesion subsets. The benefits of successful treatment include improvements in angina and survival. One method, which may improve technical success rates, is the use of a retrograde approach. We report three cases employing a retrograde approach and describe the technique in detail., ((c) 2006 Wiley-Liss, Inc.)

Objective: Attachment to host matrix is an important provisory step for the institution of any fungal infection. The present study investigates the role of glycoproteins of Epicoccum purpurascens in host-fungal adherence., Methods: Epicoccum spore-mycelial extract was fractionated on a concanavalin A-Sepharose column. Three glycoproteins of 12, 17 and 33 kDa (Epi p 1) were electroeluted and checked for hemagglutination and hemagglutination inhibition. The monosaccharide content of the highly potent protein Epi p 1 was determined by high-performance anion exchange chromatography and pulsed amperometric detection. The interaction of Epi p 1 with mannose-binding lectin (MBL) leading to the activation of the complement system was studied by immunoblot, ELISA and ELISA inhibition techniques. Immunoblot and immunoblot inhibition were carried out with culture filtrate to determine the nature of Epi p 1., Results: 33 (Epi p 1)-, 17- and 12-kDa proteins were 58, 46 and 38 times more potent than crude extract in hemagglutination activity (HA). The HA of Epi p 1 was inhibited by N-acetyl glucosamine, glucose and laminin. Epi p 1 had a high mannose content, showed MBL binding in ion-dependent manner and caused complement activation. The protein was detected in culture filtrate and thus seems to play a significant role in fungal invasion., Conclusion: Epi p 1, an allergenic glycoprotein of E. purpurascens, is involved in host-fungal interactions through MBL.

Aims: To investigate the outcome of a real world diabetic patient cohort treated with bare metal stents (BMS), sirolimus-, or paclitaxel-eluting stents (SES and PES, respectively). Due to the different mechanisms of action of both drugs it is currently unknown which device is the best option to treat these high-risk patients., Methods and Results: The study compares the 2-year clinical outcome of 708 consecutive diabetic patients (25% insulin treated) treated with either a BMS (n = 252), a SES (n = 206), or a PES (n = 250), as part of the RESEARCH and T-SEARCH registries. Target vessel revascularization was 19.5% in the BMS group, vs. 15.3% in the SES group and 9.7% in the PES group. PES (21.2%), but not SES (28.9%), were superior to BMS (29.7%) in reducing major adverse cardiac events. After propensity analyses, none of the differences remained significant. The incidence of stent thrombosis (ST) was high in both DES groups., Conclusion: There was a trend towards a more favourable outcome associated with the use of PES over BMS. There was no significant difference between SES and PES in each of the clinical endpoints, and neither in the NIDDM patients, which are hypothesized to be better-off with PES.

Background: Virtual histology (VH) uses intravascular ultrasound (IVUS) radiofrequency spectral analysis to locally identify the morphology and composition of atherosclerotic plaques. We sought to explore in vivo the relation between IVUS-derived thin cap fibro-atheroma (IDTCFA) and remodelling index in patients with acute coronary syndromes using IVUS-VH., Methods and Results: Twenty-one patients (63 vessels) were enrolled. When compared to cross sectional areas (CSAs) without necrotic core in contact with the lumen (NCCL), CSAs with NCCL had a larger plaque burden 42.8+/-11.5% vs. 32.8+/-11.5%, p<0.001; higher overall necrotic core content [13.8+/-10.7% vs. 2.3+/-7.9% (p<0.001)] and calcified tissue [4.7+/-6.5 vs. 0.66+/-2.1% (p<0.001)]. On average there were 2 IVUS-derived thin cap fibro-atheroma (IDTCFA) per patient. Nearly half of the IDTCFAs had positive remodelling., Conclusions: CSAs with NCCL had worse morphological profiles than those with no NCCL. The simultaneous and more detailed assessment of IDTCFA and remodelling index identifies a reduced number of allegedly high-risk plaques. The findings of this study may have important clinical implications, since they shed light into a possible method of identiying potentially high-risk plaques suitable for pharmacological and/or local treatment.

Aims: To investigate the medium term (2 year) clinical outcome of the use of the paclitaxel-eluting stent (PES) compared to the sirolimus-eluting stent (SES). To date, there are no direct comparative data on the efficacy of these stents over medium term follow-up. Furthermore, a possible late restenotic phenomenon has not been excluded., Methods and Results: The Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) registry compared 576 consecutive "all-comer" patients, exclusively treated with PES, with 508 patients who received SES from the RESEARCH registry in the preceding period. Patients were enrolled irrespective of clinical or angiographic features. At 2 years, major adverse cardiac event (death, myocardial infarction or target vessel revascularisation) rates were comparable in the two groups: 15.4% in the SES group versus 18.9% in the PES group (HR 1.26, 95% CI 0.94-1.69, p=0.12). Correcting for differences in both groups resulted in an adjusted HR of 1.11 (95% CI 0.82-1.50, p=0.51, using significant univariate variables). Target vessel revascularisation was 8.0% in the SES group compared with 9.6% in the PES group (HR 1.23, 95% CI 0.81-1.86, p=0.33)., Conclusions: The unrestricted use of SES and PES was safe at two years of follow-up. No significant difference was found between the two devices in terms of death or MI, MACE, TVR or TLR. No late clinical restenotic phenomenon was observed.

Coronary artery disease is the leading cause of mortality and morbidity in the Western world and an ever-increasing problem in developing countries. Unheralded acute coronary syndromes (ACS) are common initial manifestations of coronary atherosclerosis and are often caused by lesions which have previously not generated symptoms. Histopathological studies have identified several plaque morphologies associated with ACS. However, the natural history of these high-risk or vulnerable lesions remains unknown and the limited knowledge about their eventual prognosis is provided by retrospective histopathological studies. Detection of these vulnerable plaques in vivo is essential to study their natural history and to evaluate potential treatment modalities and, therefore, may ultimately have an important impact on the prevention of acute myocardial infarction and death. Currently, there are several diagnostic imaging tools capable of evaluating determinants of plaque vulnerability. These techniques can provide information on the vessel lumen and wall size, tissue composition and the status of inflammation. This article aims to review the current status of these imaging techniques.

Background: The uptake of medical treatment in patients with coronary artery disease may be suboptimal. Our intention was to review the medical treatment of these patients in the light of current evidence., Methods: One hundred ninety six consecutive patients with known or suspected coronary artery disease attending a tertiary centre for day case cardiac catheterisation were assessed. Fasting blood samples were sent for glucose and cholesterol. The results of coronary angiography and left ventriculography and any changes in medications were noted., Result: One hundred eighty two patients (93%) had fasting blood samples taken. The management of cholesterol in patients with coronary artery disease has improved since 1994. We have demonstrated the benefit of taking fasting blood samples in patients attending for day case angiography: 10% of non-diabetics actually had fasting blood glucose levels of greater than 7.0 mmol/l. All of these newly diagnosed diabetics had coronary artery disease. A further 9% of non-diabetics had impaired fasting glycaemia; 69% had coronary artery disease and 8% had left ventricular dysfunction. Among patients with coronary artery disease, there was a statistically significant increase on most categories of medications on discharge compared to admission. For those with left ventricular dysfunction, there was a statistically significant increase in the use of Angiotensin-Converting-Enzyme (ACE)-inhibitors., Conclusion: Diabetes mellitus is under-diagnosed in patients with coronary heart disease. They are at higher risk of coronary artery disease and therefore need intensive management. Testing all patients attending for day case cardiac catheterisation for fasting glucose would enable diagnosis and initiation of treatment of a high-risk group., (Copyright 2003 Elsevier Ireland Ltd.)