Publications

Background: This prospective study investigated the association between preprocedural biomarker levels and incident major adverse cardiac events (MACE) in complex patients undergoing percutaneous coronary intervention (PCI) with sirolimus‐eluting stenting. Hypothesis: Lipoprotein(a) (Lp[a]), interleukin‐10 (IL‐10), and high‐sensitivity C‐reactive protein (CRP) have long‐term prognostic value in patients undergoing PCI. Methods: Between April 2002 and February 2003, 161 patients were included in the study. Blood was drawn before the procedure, and biomarkers were measured. Patients were followed‐up for MACE (death, nonfatal myocardial infarction, and repeat revascularization). Cox proportional hazard models were used to determine risk of MACE for tertiles of biomarkers. Both 1‐year and long‐term follow‐up (median, 6 years; maximum, 8 years) were evaluated. Results: Mean age was 59 years, and 68% were men. During long‐term follow‐up, 72 MACE occurred (overall crude cumulative incidence: 45% [95% confidence interval (CI): 37%‐52%]). Lp(a) was associated with a higher 1‐year risk of MACE, with an adjusted hazard ratio (HR) of 3.1 (95% CI: 1.1‐8.6) for the highest vs the lowest tertile. This association weakened and lost significance with long‐term follow‐up. IL‐10 showed a tendency toward an association with MACE. The 1‐year HR was 2.1 (95% CI: 0.92‐5.0). Long‐term follow‐up rendered a similar result. The association of CRP with MACE did not reach statistical significance at 1‐year follow‐up. However, CRP was associated with long‐term risk of MACE, with an HR of 1.9 (95% CI: 1.0‐3.5). Conclusions: In this prospective study, preprocedural Lp(a) level was associated with short‐term prognosis after PCI. The preprocedural CRP level was associated with long‐term prognosis after PCI. Clin. Cardiol. 2012 DOI: 10.1002/clc.21988 The authors have no funding, financial relationships, or conflicts of interest to disclose.

Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNF<i>α</i> (tumor necrosis factor <i>α</i>) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-<i>κ</i>B (nuclear factor-<i>κ</i>B) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNF<i>α</i>/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNF<i>α</i> release and MMP9 activity in PBMC from COPD patients at 10 <i>µ</i>M, which is 10 times more potent than the other macrolides tested. Activated NF-<i>κ</i>B by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future.

Aims:The aim of the POLBOS II randomised trial was to compare any regular drug-eluting stents (rDES) with the dedicated bifurcation sirolimus-eluting stent BiOSS LIM for the treatment of coronary bifurcation lesions.The secondary aim was to study the effect of final kissing balloon inflation (FKBI) on clinical outcomes.Methods and results: Between December 2012 and December 2013, 202 patients with stable coronary artery disease or non-ST-segment elevation acute coronary syndrome were randomly assigned 1:1 to treatment of the coronary bifurcation lesions either with the BiOSS LIM stent (n=102) or with an rDES (n=100).Coronary re-angiography was performed at 12 months.The primary endpoint was the composite of cardiac death, myocardial infarction (MI), and target lesion revascularisation (TLR) at 12 months.The target vessel was located in the left main in one third of the cases (35.3% in BiOSS and 38% in rDES).Side branch treatment was required in 8.8% (rDES) and 7% (BiOSS).At 12 months, the cumulative MACE incidence was similar in both groups (11.8% [BiOSS] vs. 15% [rDES, p=0.08]), as was the TLR rate (9.8% vs. 9% [p=0.8]).The binary restenosis rates were significantly lower in the FKBI subgroup of the BiOSS group (5.9% vs. 11.8%,p<0.05).Conclusions: MACE rates as well as TLR rates were comparable between the BiOSS LIM and rDES.At 12 months, cumulative MACE incidence was similar in both groups (11.8% vs. 15%), as was the TLR rate (9.8% vs. 9%).Significantly lower rates of restenosis were observed in the FKBI subgroup of the BiOSS group.

BACKGROUND: Coronary stents have been used with increasing frequency and in increasingly complex coronary lesions for the treatment of symptomatic coronary artery disease. A new stainless steel coronary stent, the R Stent, has been designed to provide maximum flexibility for tracking and high radial strength post-deployment. AIMS: To assess the safety and feasibility of the R Stent in patients with coronary artery disease. Specific objectives were to assess the R Stent's deployment success, angiographic and procedural success (< 20% residual stenosis and TIMI 3 flow), safety (absence of complications), 30-day and six-month clinical follow-up. METHODS: Between April 1998 and January 1999, stent deployment was attempted in 36 lesions in 30 patients with stable (43%) or unstable (57%) angina pectoris and 29/36 of the lesions were anatomically complex. Treated lesions were in the LAD (n = 15), RCA (n = 13) or LCX (n = 8). RESULTS: Stent deployment was achieved in 97% with one crossing failure in a patient with a long, calcified, proximal LAD lesion. After the procedure, patients were scheduled for one- and six-month clinical follow-up. One patient experienced a non-Q-wave myocardial infarction in hospital. At one month, there were no additional complications. Only one patient experienced recurrence of angina (CCS class 2) within the 30 days. At six-month follow-up, one sudden death had occurred. Three (10%) patients had anginal complaints, one of them received target lesion repeat PTCA. All other patients (87%) were event- and angina-free. CONCLUSION: This first clinical experience with the R Stent shows acceptable feasibility and safety with good long-term clinical results.

Objectives The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary intervention with drug-eluting stents (DES). Background The clinical correlates and the prognostic significance of CAC in women undergoing percutaneous coronary intervention with DES remain unclear. Methods Patient-level data from female participants in 26 randomized trials of DES were pooled. Study population was categorized according to the presence of moderate or severe versus mild or no target lesion CAC, assessed through coronary angiography. Co–primary endpoints of interest were the composite of death, myocardial infarction (MI), or target lesion revascularization and death, MI, or stent thrombosis at 3-year follow-up. Results Among 11,557 women included in the pooled dataset, CAC status was available in 6,371 women. Of these, 1,622 (25.5%) had moderate or severe CAC. In fully adjusted models, independent correlates of CAC were age, hypertension, hypercholesterolemia, smoking, previous coronary artery bypass graft surgery, and worse left ventricular and renal function. At 3 years, women with CAC were at higher risk for death, MI, or target lesion revascularization (18.2% vs. 13.1%; adjusted hazard ratio: 1.56; 95% confidence interval: 1.33 to 1.84; p < 0.0001) and death, MI, or stent thrombosis (12.7% vs. 8.6%; adjusted hazard ratio: 1.48; 95% confidence interval: 1.21 to 1.80; p = 0.0001). The adverse effect of CAC on ischemic outcomes appeared to be consistent across clinical and angiographic subsets of women, including new-generation DES. Conclusions Women undergoing PCI of calcified lesions tend to have worse clinical profile and remain at increased ischemic risk, irrespective of new-generation DES.

<b>Background:</b> Patients with chronic obstructive pulmonary disease (COPD) have increased numbers of neutrophils and macrophages in their lungs. Growth related oncogene-α (GROα) attracts neutrophils, whereas monocyte chemoattractant protein-1 (MCP-1) attracts monocytes that can differentiate into macrophages. The aim of this study was to determine the concentration of GROα and MCP-1 in bronchoalveolar lavage (BAL) fluid and sputum from non-smokers, healthy smokers and patients with COPD, and to see if there was a correlation between the concentrations of these chemokines, lung function, and numbers of inflammatory cells. <b>Methods:</b> BAL fluid and sputum from non-smokers (n=32), healthy smokers (n=36), and patients with COPD (n=40) were analysed for the presence of GROα and MCP-1 using ELISA. Cells counts were performed on the samples and correlations between the concentrations of these chemokines, lung function, and inflammatory cells observed. <b>Results:</b> Median (SE) GROα and MCP-1 levels were significantly increased in sputum from patients with COPD compared with non-smokers and healthy smokers (GROα: 31 (11) <i>v</i> 2 (2) <i>v</i> 3 (0.8) ng/ml; MCP-1: 0.8 (0.4) <i>v</i> 0.2 (0.1) <i>v</i> 0.1 (0.04) ng/ml, p&lt;0.05), but not in BAL fluid. There were significant negative correlations between both GROα and MCP-1 levels in sputum and forced expiratory volume in 1 second (FEV₁) % predicted (GROα: <i>r</i>=–0.5, p&lt;0.001; MCP-1: <i>r</i>=–0.5, p&lt;0.001), together with significant positive correlations between GROα and MCP-1 and neutrophil numbers in sputum (GROα: <i>r</i>=0.6, p&lt;0.001; MCP-1: <i>r</i>=0.4, p&lt;0.01). <b>Conclusion:</b> These results suggest that GROα and MCP-1 are involved in the migration of inflammatory cells, thus contributing to the inflammatory load associated with COPD.

Background: Stent malapposition is anticipated to be associated with unfavorable long-term outcomes, but data from patients treated by primary percutaneous coronary intervention (PCI) are rare.According to our previous data, stent restenosis or uncovered struts are more frequent in patients with more than 2% malapposed struts in baseline analysis.Purpose: To evaluate association of baseline stent malapposition to death, myocardial infarction or target vessel revascularization in six-year follow-up.Methods: 105 patients with acute ST segment elevation myocardial infarction underwent OCT guided primary PCI.In 100 of these patients the OCT record was eligible for malapposition analysis.Either biolimus A9 or everolimus eluting stents were used in the trail.The OCT study was performed with C7-XRTM intravascular imaging system employing a non-occlusive technique.It was intended to maintain complete stent apposition, if feasible.Subsequent offline pullback analysis was performed using OCTivat-Stent software.Data in groups were compared by logrank test.Results: Mean follow-up was 6.3 (5.2 -7.8 years).More than 2% of malapposed struts were present in 13 (13%) of study patients.Of these patients, 1 (7.7%) patient died, 1 suffered myocardial infarction and 3 (23.1%)patients underwent target lesion revascularization.In patients with <2% of malapposed struts, 5 (5.7%) died, 2 (2.3%) suffered myocardial infarction and 4 (4.6%)underwent target lesion revascularization (p<0.01 for combined endpoint of death, myocardial infarction and target lesion revascularization). Conclusion:Stent malapposition is associated with unfavorable results in longterm follow-up in patients treated by primary coronary angioplasty.

High-strength aluminum alloys are emerging and gaining increasing prominence in structural engineering. The structural behavior and design of 7A04-T6 high-strength aluminum alloy equal-leg angle-section columns under axial compression are investigated in this study. Eighteen experiments on extruded high-strength aluminum alloy angle-section columns with various lengths were carried out. Complementary material tests and initial geometric imperfection measurements were also performed. The test setup, procedure, and results, including failure modes, load-carrying capacities, and load–end shortening responses, are fully reported. The test program was followed by a numerical study, where refined finite-element (FE) models were first developed and validated against the test results and then utilized to carry out parametric analyses covering a wide range of cross-section dimensions and column lengths. Finally, the load-carrying capacities obtained from the tests and numerical analyses were used to evaluate the accuracy of existing design provisions in European, Chinese, and American standards for aluminum alloy structures and the direct strength method (DSM). The results show that the existing design methods generally yield good capacity predictions for fixed-ended members failing by flexural buckling, but rather conservative and scattered predictions when failure is by flexural-torsional buckling. Improved resistance predictions were achieved through application of a revised DSM-based approach.

Today, drug-eluting metal stents are considered the gold standard for interventional treatment of coronary artery disease. While providing inhibition of neointimal hyperplasia, drug-eluting metal stents have many limitations such as the risk of late and very late stent thrombosis, restriction of vascular vasomotion and chronic local inflammatory reaction due to permanent implantation of a ‘metallic cage’, recognized as a foreign body. Bioresorbable scaffold stents (BRS) are a new solution, which is trying to overcome the limitation of the ‘metallic cage’. This structure provides short-term scaffolding of the vessel and then disappears, leaving nothing behind. The purpose of this review is to present the theoretical rationale for the use of BRS and to outline the clinical outcomes associated with their use in terms of data obtained from RCTs, clinical trials, registries and real life use. We have also tried to answer all questions on this intervention based on available data, with a focus on ABSORB BVS (Abbott Vascular, Santa Clara, USA). We consider that this new technology can be the “magic bullet” to treat coronary artery disease.