Publications

Optimized stent expansion by high-pressure inflations of oversized balloons has initially been derived from experience obtained with the Palmaz-Schatz stent, whereas there is little experience with this strategy in the Wallstent. By using this approach with quantitative coronary angiographic guidance, 20 Wallstents and 20 Palmaz-Schatz stents were implanted in 34 patients and consecutively examined by conventional two-dimensional (2D) intracoronary ultrasound (ICUS) and three-dimensional (3D) ICUS on the basis of the application of a pattern recognition algorithm. Ultrasound criteria of adequate stent expansion were defined as a complete apposition of the stent to the vessel wall, a stent symmetry index (SSI = minimum/maximum lumen diameter) ≥0.7, and a stent-reference lumen area ratio (SRR = Minimum intrastent lumen area/Average of proximal and distal reference lumen area) ≥0.8. In all cases a smooth angiographic lumen and a negative diameter stenosis, on the basis of a distal reference, was achieved. For the Wallstents ICUS showed a higher SSI (2D, 0.95 ± 0.04 vs 0.85 ± 0.09; p < 0.001; 3D, 0.90 ± 0.09 vs 0.82 ± 0.11, p < 0.05) and a lower SRR (2D, 0.66 ± 0.12 vs 0.81 ± 0.13, p < 0.005; 3D, 0.63 ± 0.14 vs 0.74 ± 0.15, p < 0.05) than for the Palmaz-Schatz stents. Ninety percent of failure in meeting these criteria resulted from a low SRR. The incidence of incomplete stent apposition (one in both stents) or SSI <0.7 was low and generally associated with an SRR <0.8. The Wallstents met the ICUS criteria less often (2D, 2 (10%) vs 10 (50%), p < 0.01; 3D, 3 (15%) vs 9 (45%), p < 0.05), were significantly longer (35.1 ± 7.7 mm and 14.3 ± 3.3 mm, p < 0.0001), and generally demonstrated a larger vessel tapering, measured as proximal minus distal ICUS reference lumen area (1.33 ± 2.91 mm2 vs 0.44 ± 1.97 mm2, not significant). Wallstents meeting the ICUS criteria, however, showed less vessel tapering (0.18 ± 1.64 mm2). Thus optimized stent expansion was followed by excellent angiographic results for both Palmaz-Schatz and Wallstent. Although angiographic results and visual assessment of the ICUS examination suggested a good outcome, few Wallstents met the ICUS criteria in contrast to the Palmaz-Schatz stents. The low value of the SRR in the Wallstents is likely to be caused by vessel tapering, suggesting that this criterion may be unsuitable in assessing the adequacy of the expansion of relatively long stents such as the Wallstent.

Background Although it has been suggested that elevation of CK-MB after percutaneous coronary intervention is associated with adverse clinical outcomes, limited data are available in the setting of coronary bypass grafting. The aim of the present study was to determine the incidence, predictors, and prognostic significance of CK-MB elevation following multivessel coronary bypass grafting (CABG). Methods and Results The population comprises 496 patients with multivessel coronary disease assigned to CABG in the Arterial Revascularization Therapies Study (ARTS). CK-MB was prospectively measured at 6, 12, and 18 hours after the procedure. Thirty-day and 1-year clinical follow-up were performed. Abnormal CK-MB elevation occurred in 61.9% of the patients. Patients with increased cardiac-enzyme levels after CABG were at increased risk of both death and repeat myocardial infarction within the first 30 days ( P =0.001). CK-MB elevation was also independently related to late adverse outcome ( P =0.009, OR=0.64). Conclusions Increased concentrations of CK-MB, which are often dismissed as inconsequential in the setting of multivessel CABG, appear to occur very frequently and are associated with a significant increase in both repeat myocardial infarction and death beyond the immediate perioperative period.

Postmortem studies have described the association between the thin-cap fibroatheroma (TCFA) and the occurrence of acute coronary syndrome (ACS). Both noninvasive and invasive techniques have been refined and used as a research tool to visualize the plaque at a high risk of disruption. There has been a considerable effort to develop the imaging modalities that offer detailed visualization of coronary pathology and accurately predict the adverse cardiac outcomes. This chapter provides an overview of the current and experimental coronary imaging methods to detect vulnerable plaque and discuss the potential implication of multimodality imaging in clinical practice.

No abstract is provided for this article.

In 37 patients (28 men, 58±10 years) following conventional PTCA heparin (H) (n=37) and Octreotide (O) (n=10) was infused through the Dispatch™ (Scimed) at the site of angioplasty. Mean drug infusion time was 30±7min (range: 7–39min). A volume of 16±6ml (range: 1.4–23.4mil corresponding to 1660±656 IU H and 0.39±0.02 μg O was infused with a mean pressure of 110±48mmHg. Radio-isotopic studies with infusion of technetium labelled H (Tc-99m H; n=2) or of indium labelled O (In-111 O; n=5) were performed to assess efficacy of local drug delivery. During infusion a linear accumulation was observed for Tc-99m Hand In-111 O (linear fitting: H: r=0.97±0.02; O: r=0.98±0.02) followed at infusion stop by a biexponential washout (biexponential fitting: H; r=0.96±0.02; O: r=0.98±0.02). Local retention time, defined as 5 concentration half-lives and derived from the 2nd slow washout phase, thought to reflect tissular washout, was for H 18±2 h and for a 7±3 h. Of the totally infused dose for H 6.8% and 0.5% (123 and 11 IU; 644 and 58 Itg) and for O 0.3%±0.2% (0.55±0.37 μg) remained at the site of delivery. In conclusion administration of radiolabelled drugs allows to assess local pharmacokinetics and to quantify local drug retention-time and local retained amount of drug.

Abstract Background Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers. Methods Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients. Results Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry ( p &lt; 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum ( p &lt; 0.05) and tended to have more sputum eosinophils. Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD. Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD. There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid. Conclusions Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.

Objective: K lotho is an anti-aging protein which also possesses anti-inflammatory actions and modulates the cellular responses to oxidative stress. Knock out of klotho in the mouse caused the formation of emphysema. The aim of this study is to investigate the expression of klotho in human emphysema and factors affecting its expression and activity in human bronchial epithelial cells. Methods: Lung tissue from 5 COPD patients, 8 smokers without COPD and 13 non-smoking, non-COPD. Klotho expression was determined by quantitative real-time PCR, Western blotting and immunohistochemistry. Human bronchial epithelial cells (HBE) were treated with tumor necrosis factor (TNF)-α and hydrogen peroxide (H 2 O 2 ), and the expression of klotho mRNA in cells and protein in cell supernatants was detected by RT-PCR and enzyme-linked immune sorbent assay (ELISA) respectively. Exogenous klotho was also added to HBE and A549 cell cultures and MTT assays were used to detect cell apoptosis. Results: Klotho was detected in human lung tissue with a clear localization to airway epithelial cells. The level of klotho mRNA and protein in smokers with normal lung function was similar to that in non-smokers but was reduced in COPD patients The level of klotho expression was similar in COPD patients with emphysema compared with that in non-emphysematous COPD patients. In addition, we found that both TNF-α and H 2 O 2 could significantly inhibit the expression and release of klotho in HBE cells. Exogenous klotho inhibited apoptosis in HBE) and A549 cells). Conclusions: Klotho may play an important role in the formation and development of emphysema in COPD. However, further research is needed to explore the underlying mechanism.

The aim of the present study was to determine the long-term effects of percutaneous transluminal septal myocardial ablation (PTSMA) on systolic and diastolic left ventricular (LV) functions in patients with obstructive hypertrophic cardiomyopathy (HC). Ten consecutive patients with symptomatic HC despite optimal medical treatment were referred for PTSMA at our center. LV systolic and diastolic functions were assessed by online LV pressure–volume loops obtained by conductance catheter at baseline and at 6 months after the procedure. At follow-up, the mean gradients at rest and after extrasystole were significantly decreased compared with baseline (88 ± 29 to 21 ± 11 mm Hg and 130 ± 50 to 35 ± 22 mm Hg, respectively, p <0.01 for the 2 comparisons). End-systolic and end-diastolic pressures significantly decreased (p <0.01), whereas end-systolic and end-diastolic LV volumes significantly increased (p <0.01 for the 2 comparisons). Cardiac output and stroke volume were unchanged, as were ejection fraction (p = 0.25) and maximum dP/dt (p = 0.13). The slope of the end-systolic pressure–volume relation was not decreased, indicating a preserved contractility. The relaxation constant time, end-diastolic stiffness, projected volume of the end-diastolic pressure–volume relation at 30 mm Hg, and diastolic stiffness constant showed a significant improvement of active and passive myocardial diastolic properties. In conclusion, PTSMA is an effective method in the treatment of symptomatic patients with HC. At 6-month follow-up, the LV–aortic gradient was decreased and active and passive LV diastolic properties were increased. Myocardial contractility was not decreased and general hemodynamics was maintained.

Introduction: We have reported that formoterol (FM), a long-acting β2- adrenoceptor agonist, restores corticosteroid (CS) sensitivity by activation of a serine/threonine protein phosphatase PP2A (ERJ 2009;34:583s). However, the molecular mechanisms how FM activates PP2A and restores CS sensitivity have not been elucidated. Aims: To investigate the mechanism of PP2A activation by FM and the involvement of PP2A in glucocorticoid receptor (GR) nuclear translocation induced by CS budesonide (BUD). Methods: Phosphatase activity of immunopurified PP2A from U937 monocytic cells was measured by fluorescence-based assay. A549 lung epithelial cells, without functional β2-adrenoceptor, were used as control cells. Direct effect of FM was evaluated using PP2A immunopurified from cell membrane and recombinant PP2A. Nuclear/cytoplasmic GR ratios under PP2A inhibition by okadaic acid (OA) or overexpression were determined by western-blot. Results: FM enhanced PP2A activity in both U937 and A549 cells and the effects were not blocked by a β2-adrenoceptor inhibitor (ICI-118551). FM directly activated PP2A-immunoprecipitates in the membrane and recombinant PP2A. PP2A was detected in GR-immunoprecipitates. PP2A inactivation by OA reduced GR nuclear translocation by BUD and abrogated FM-mediated increase of GR translocation while PP2A overexpression enhanced BUD-induced GR translocation and further increased enhancement of GR translocation by FM. Conclusions: FM directly activates PP2A in a β2-adrenoceptor-independent manner. PP2A associated with GR enhances GR nuclear translocation by BUD. This mechanism may contribute to the clinical benefits of BUD+FM combination therapy.

Little information is available on the specific role of alveolar macrophages (AMs) in modulating local cellular reactions to inhaled allergens in atopic asthma. We investigated the influence of alveolar macrophages obtained by bronchoalveolar lavage (BAL) on the proliferative responses of lavage and peripheral lymphocytes from 12 patients with atopic asthma, 6 nonasthmatic symptomatic atopic subjects, and 6 nonatopic normal volunteers, in the context of in vitro exposure to relevant and nonrelevant allergens. Fresh nonadherent bronchoalveolar lavage cells from atopic asthmatic patients, depleted of alveolar macrophages, proliferated spontaneously more than nonadherent bronchoalveolar lavage cells from normal subjects. Addition of autologous asthmatic alveolar macrophages reduced this endogenous "activation". Asthmatic and normal alveolar macrophages also inhibited phytohaemagglutinin-stimulated proliferation of both autologous and allogeneic nonadherent peripheral blood mononuclear cells (PBMC). In contrast, autologous asthmatic alveolar macrophages induced strong proliferation of peripheral blood mononuclear cells when stimulated with allergen to which the patient was skin test and radio allergosorbent test (RAST) reactive; however, no response was seen with allergens to which the patient was insensitive. No such allergen-specific proliferation was seen with alveolar macrophages from nonasthmatic atopic subjects. These data support the presence of functionally-active alveolar macrophages within the airways of atopic asthmatic patients, that under normal stable conditions suppress the induction of peripheral blood mononuclear cell responses, and which only on contact with specific allergen appear to switch to inducer alveolar macrophages, with consequent peripheral blood mononuclear cell hyperactivation.

Background: The efficacy of drug-coated balloons (DCB) for treating de novo coronary stenoses in non-small lesions remains unclear.Methods: Patients treated with paclitaxel-DCB were compared with patients from two second-generation drug eluting stent (DES) registries. Only patients having DES-only or DCB-only strategies were included; those with in-stent restenosis, a device diameter<2.5mm, DES bailout post-DCB treatment, or combined use of DES and DCB were excluded. The primary endpoint was a patient-oriented composite endpoint (PoCE) defined as all-cause death, any non-fatal myocardial infarction (MI), any stroke, and any revascularization at 2-year. Differences in the risk of PoCE between cohorts were compared and adjusted by propensity score matching (PSM).Findings: The study included 6,284 patients with 5,399 treated with DES and 885 with DCB. The mean device diameters were 3.05mm and 2.88mm in the DES and DCB cohort, respectively. At 2-year follow-up, the primary endpoint occurred in 531 (9.8%) patients receiving DES and 92 (10.4%) patients treated with DCB (HRPSM:1.16, 95%CI:0.83-1.64,P=0.385). All-cause death occurred in 230 (4.3%) patients in the DES group and 11 (1.2%) patients in the DCB group (HRPSM:0.36, 95%CI:0.16-0.81), any non-fatal MI occurred in 56 (1.0%) patients in the DES group and 13 (1.5%) patients in the DCB group (HRPSM:1.04, 95%CI:0.41-2.62), and any repeat revascularization occurred in 199 (3.7%) patients in the DES arm and 69 (7.8%) patients in the DCB group (HRPSM:2.02, 95%CI:1.27-3.21).Interpretation: We did not observe DCB to be associated with a higher rate of PoCE than DES in patients with de novo coronary lesions which were ≥2.5mm in diameter.Trial Registration: Registered on clinicaltrial.gov (NCT02929030, NCT03916432, and NCT05133921)Funding: The Innovation Support Program of Shaanxi Province of China (No. 2022GHJD-03).Declaration of Interests: Dr. Serruys reported receiving personal fees from Philips/Volcano, SMT, Novartis, Xeltis, Merillife outside the submitted work. No other disclosures were reported.Ethics Approval: The study was performed in accordance with the Declaration of Helsinki and was approved by the ethics committees of participant centers of each study. All the patients signed the written informed consent prior to participation.