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The use of bare stents for the percutaneous intervention of saphenous vein bypass grafts (SVGs) is associated with a high subsequent rate of restenosis. To assess the impact of the sirolimus-eluting stent (SES), we studied 19 consecutive patients who underwent de novo SVG intervention treated solely with SES. Mean graft age was 10 years. Clinical presentation was an acute coronary syndrome in 68%. In total, twenty-two de novo lesions were treated with 35 SESs (mean=1.6 stents per lesion). Use of glycoprotein IIb/IIIa inhibitor therapy and distal embolization protection device were at operator discretion and were 42% and 32%, respectively. The rate of in-hospital major adverse cardiac events (MACE) was 11%, related to 2 patients with a creatine kinase rise consistent with peri-procedural acute myocardial infarction (AMI); a distal protection device was not utilized in either. Over a mean 12.5+/-2.6 month follow-up, one patient died from a non-cardiac cause, and there were no further AMIs. Target lesion revascularization was undertaken in 1 patient (5%); survival free of MACE was 84%. In conclusion, utilizing SESs for percutaneous intervention of degenerate SVGs is associated with a low rate of target vessel revascularization. Increased utilization of distal protection devices might reduce the peri-procedural rate of AMI.

No abstract is provided for this article.

BACKGROUND--Recruitment of inflammatory cells in the lungs may contribute to tissue injury as a result of mediators released from these cells. Interleukin 1 beta (IL-1 beta) is a potent inducer of neutrophil accumulation, a process that may require local protein biosynthesis. Macrophage inflammatory protein 2 (MIP-2) is a approximately 6 kD heparin binding protein and is a member of the C-X-C superfamily that causes significant neutrophil chemotaxis and activation in vitro. A study was performed to determine whether IL-1 beta could induce the expression of MIP-2 in the lungs of Brown-Norway rats. METHODS--rhIL-1 beta (500 U) or 0.9% NaCl was injected intratracheally and bronchoalveolar lavage (BAL) cells and lung tissues were evaluated for MIP-2 mRNA expression after RNA extraction by Northern blot analysis. MIP-2 probe was prepared from cDNA obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) of BAL cells obtained from a rat treated with lipopolysaccharide. RESULTS--There was no detectable MIP-2 mRNA in the lungs of control rats but a marked enhancement of the expression at four hours with no expression at 12 hours and a slight expression at 24 hours. IL-1 beta induced a significant influx of neutrophils into BAL fluid with a transient increase in macrophages. In situ hybridisation of lungs using MIP-2 cDNA probe labelled with digoxigenin showed expression of MIP-2 mRNA in airway mononuclear cells and airway epithelium at four hours after IL-1 beta; at 24 hours the signal had nearly gone. CONCLUSION--IL-1 beta induces the expression of MIP-2 mRNA in rat lung. MIP-2 may be one chemokine that could contribute to IL-1 beta induced neutrophil influx.

Background In the GLOBAL LEADERS trial, the intention-to-treat (ITT) effect of ticagrelor monotherapy after 1 month of dual antiplatelet therapy (DAPT) was not superior to that of 12-month DAPT followed by aspirin alone in the prevention of 2-year all-cause mortality or new Q-wave myocardial infarction (MI) after coronary stenting. Intention-to-treat analyses can be affected by incomplete protocol adherence. We present a pre-specified per-protocol analysis. Purpose To determine whether 1 month of ticagrelor plus aspirin followed by 23 months of ticagrelor monotherapy is superior to 12 months of DAPT followed by aspirin alone in the per-protocol population of the GLOBAL LEADERS (NCT01813435). Methods The GLOBAL LEADERS compared two antiplatelet strategies after drug-eluting stenting for stable coronary artery disease or acute coronary syndromes. Per-protocol population consisted of randomized patients fulfilling enrollment criteria and receiving protocol-mandated treatment. Adherence to the allocated antiplatelet therapy was evaluated at discharge, 30 days, and 3, 6, 12, 18, and 24 months, with non-adherence reasons categorized following a hierarchical approach. A protocol-deviation was defined in the case of high perceived bleeding/thrombotic risk, a medical decision without evident clinical reason, patients unwilling to take study drugs, prescription error, logistical issues, unclear reasons. Baseline characteristics, including (but not limited to) age, sex, diabetes, prior PCI, were used to construct time-varying inverse probabilities for not deviation from the protocol to reconstruct a study population with no protocol-deviations. Protocol deviators were artificially censored at the time at which they deviated. The primary endpoint was the composite of 2-year all-cause mortality or non-fatal new Q-wave MI. We used a weighted pooled logistic regression to estimate the per-protocol rate ratio (RR) of experimental vs. control treatment for the primary endpoint. Results Of the 15,968 randomized patients, 805 out of 7,980 (10.1%) in experimental group and 537 out of 7,988 (6.7%) in control group were classified as protocol deviators and artificially censored by month 12, not contributing events in the second year. The events for the adherence-adjusted analysis were 279 in experimental group and 325 in control group (25 and 24 less than in ITT analysis, respectively). The estimated adherence-adjusted RR was 0.87 (95% CI: 0.74–1.02; p=0.09), comparable to the ITT RR (0.87; 95% CI: 0.75–1.01; p=0.07). Conclusion At per-protocol analysis, ticagrelor monotherapy after 1 month of DAPT was not superior to conventional treatment, in line with the previously reported ITT effect. Similar per-protocol and ITT effects can be accounted for similar per-protocol and ITT populations, as a substantial proportion of patients were non-adherent due to clinically grounded reasons (anticipated in the protocol) and, accordingly, not considered as protocol deviators. Funding Acknowledgement Type of funding source: Other. Main funding source(s): GLOBAL LEADERS was sponsored by the European Clinical Research Institute, which received funding from Biosensors International, AstraZeneca, and the Medicines Company.

Objectives. To characterize predictors of restenosis after successful directional atherectomy, we reviewed the clinical, angiographic and procedural data obtained 132 consecutive procedures. Methods. Clinical and angiographic follow-up data were obtained in a prospectively collected and consecutive series of 125 patients who underwent 132 atherectomy procedures for de novo (89%) or restenotic (11%) lesions in native coronary arteries. Restenosis was assessed clinically and by quantitative coronary angiography. A dual approach to data analysis was taken to gain insight into factors affecting the clinical outcome and vessel wall healing response. Therefore, multivariate analysis was performed to 1) determine the correlates of residual lumen diameter at follow-up (angiographic outcome), and 2) characterize the determinants of the late lumen loss (renarrowing process). Results. Clinical and angiographic follow-up data after successful atherectomy were obtained in 100% and 95%, respectively. Atherectomy achieved an acute lumen gain of 1.28 ± 0.48 mm (mean ± SD), resulting in a minimal lumen diameter of 2.44 ± 0.47 mm. At follow-up, the minimal lumen diameter decreased to 1.78 ± 0.64 mm. The angiographic restenosis rate was 28% if the traditional 50% stenosis cutoff criterion was applied. Larger vessel size and postatherectomy minimal lumen diameter and right coronary or left circumflex artery lesions were independent predictors of a larger minimal lumen diameter (angiographic outcome). Lumen loss during follow-up (renarrowing process) was independently predicted by relative lumen gain and preprocedural minimal lumen diameter. Conclusions. In analyzing the long-term results of new interventional techniques such as directional atherectomy, the late lumen loss during follow-up (renarrowing process), which is characterized by the vessel wall healing response after an intervention, should be considered together with the residual lumen at follow-up (clinical outcome). It is clear that whereas improved clinical outcome is associated with larger vessel size and postprocedural lumen diameter and non-left anterior descending artery location, greater relative gain at intervention is predictive of more extensive lumen renarrowing.

Objectives. This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus. Background. It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both imaging methods have to be compared directly to assess the additional diagnostic value of angioscopy. Methods. The angiograms and videotapes of 52 patients who had undergone angioscopy were reviewed independently by two observers unaware of other findings. Classic angiographic definitions were used for dissection and thrombus. Angioscopic dissection was defined as visible cracks or fissures on the lumen surface or mobile protruding structures that are contiguous with the vessel wall. Angioscopic thrombus was defined as a red, white or mixed red and white intraluminal mass. Results. Angiography and angioscopy were in agreement in 40.4% of cases in the absence of thrombus and in 11.5% in the presence of thrombus. No fewer than 25 (48.1%) angioscopically observed thrombi remained undetected at angiography. With angioscopy as the standard, although the specificity of angiography for thrombus was 100%, sensitivity was very low at 19%. Angioscopic dissection was present in 40 patients (76.9%) versus angiographic dissection in 15 patients (28.8%). With regard to dissection, there was no correlation between the two imaging methods (rΦ= 0.15, p = 0.29). Conclusions. Coronary angiography underestimates the presence of intracoronary thrombus. Angioscopy and angiography are complementary techniques for detecting and grading intima1dissections.

The composition and morphology of an atherosclerotic lesion are currently considered more important determinants of acute coronary ischemic syndromes that the degree of stenosis. When a lesion is unstable, it can rupture and cause an acute thrombotic reaction. An unstable plaque can be characterized by a lipid core that is covered by a thin fibrous cap, which has been locally weakened by inflammatory cells. Intravascular Ultrasound Palpography is an intravascular ultrasound based technique that is capable to measure the local strain in coronaries and atherosclerotic plaque. This strain is induced by varying intraluminal pressure. This lecture will show principles of the technology and how this technology is used in clinical trials. Results from a trial with traditional lipid lowering treatment (IBIS1) and from a trial on the efficacy of a new medication (IBIS2) will be presented. Furthermore the potential of Intravascular Ultrasound Modulography will be discussed. This work is financially supported by the Dutch Technology Foundation, The Dutch Heart Foundation and a research grants from Volcano Corporation and Glaxo Smith Kline

The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear.This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62-1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057).Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years.SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972.

Background: Few data are available on long-term follow-up of drug-eluting stents in the treatment of chronic total occlusion (CTO). The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9™-eluting stent (BES) with a sirolimus-eluting stent (SES). Methods: Among 1,707 patients enrolled in the prospective, multi-center, all-comers LEADERS trial, 81 with CTOs were treated with either a BES (n = 45) or a SES (n = 36). The primary endpoint was the occurrence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI) and clinically-indicated target vessel revascularization (TVR). Results: At 5 years, the rate of MACE was numerically higher in the CTO group than in the non-CTO group (29.6% vs. 23.3%; p = 0.173), with a significant increase in the incidence of target lesion revascularization (TLR) (21.0 vs. 12.6; p = 0.033), but no difference in stent thrombosis (ST). Patients with CTO receiving a BES demonstrated a lower incidence of MACE (22.2% vs. 38.9%; p = 0.147) with a significant reduction in TLR compared to patients receiving a SES (11.1% vs. 33.3%, p = 0.0214) with an incidence similar to that observed in the non-CTO group treated with BES (11.6%). Definite ST at 5 years nearly halved in the BES group (4.4% vs. 8.3%, p = 0.478) with no ST in the BES group after the first year (0% vs. 8.3%, p for interaction = 0.009). Conclusions: The use of a BES showed a reduction in MACE, TVR, TLR, and ST over time in the CTO subset with similar outcome as for non-CTO lesions.

A selection of fifty-one artificial aggregates, manufactured with different proportions of kaolinite, an iron phase (Fe⁰, Fe₂O₃, Fe₃O₄ or FeS₂), cork powder and sodium carbonate in three previous works, have been studied mineralogically using the quantitative Rietveld XRD method. Comparisons between the mineral percentage in the raw materials and the phase percentage in the aggregate have been carried out. Additionally, independence contrast tests have been conducted to determine if significant relationships exist between the raw material mineralogical composition and the aggregate phase composition. Based on these statistical results, the mineralogical evolution, the possible reactions that may have taken place and the type of atmosphere required for them have been presented. Mullite, metallic iron, cristobalite, hematite, magnetite, hercynite, fayalite, clinopyroxenes, troilite, nepheline and amorphous material were new phases produced in the aggregates. The presence and/or percentage of the majority of them were greatly influenced by the added iron phase and by the type of atmosphere in the aggregates.