Publications

Introduction: New Generation drug eluting stents (DES) have overcome the limitations of bare metal stents and first generation DES resulting in lower risk of ischemic events in women. Hypothesis: We sought to compare increasing total stent length per patient for 3-yr outcomes in DM and non-DM women after percutaneous coronary intervention (PCI) with new generation DES. Methods: The WIN-DES collaboration is a pooled database of women undergoing PCI with coronary stents in 26 randomized trials. We compared total stent length per patient treated with new generation DES in quartiles (Among DM - Q1: 8-18mm, Q2: 18-24mm, Q3: 24-38mm and Q4: 38+mm; among non-DM Q1: 8-18mm, Q2: 18-24mm, Q3: 24-36mm and Q4: 36+mm). 3-yr outcomes were analyzed in a time to event manner and adjusted using multivariable methods. Major adverse cardiovascular events (MACE) were defined as a composite of death, myocardial infarction (MI) or target lesion revascularization (TLR). Results: The study sample comprised 5403 patients, of which 31.8% (n = 1719) had DM. In both DM and non-DM groups, patients in Q4 had greater prevalence of B2/C type and calcified lesions with smaller stent diameter compared to others. 3-yr MACE increased from Q1-Q4 in DM and non-DM patients, albeit DM patients experienced higher event rates ( Figure ). After multivariable adjustment, findings were unchanged, and increasing stent length remained associated with greater risk of 3-yr MACE in DM (p-trend=0.003) and non-DM (p-trend <0.0001) patients. No interaction was observed between DM status and stent length for any outcomes. Conclusions: Despite the use of new generation DES, increasing total stent length per patient was associated with greater risk of MACE in both DM and non-DM women undergoing PCI. Women with DM experienced worse outcomes, and a greater risk of TLR regardless of total stent length. Meticulous attention to stent optimization and post PCI pharmacotherapy is needed to mitigate long-term adverse outcomes in women.

To assess the possible relation between catecholamine responses and adrenoceptor affinity and density, we compared the effect of noradrenaline, isoprenaline and ouabain on right ventricular muscle strips from normal and cardiomyopathic hamsters with α1− and β-adrenoceptor characteristics assessed by radioligand binding methods. At concentrations of 1.28, 2.56, 5.0 and 10 × 10−6 mol·litre−1 noradrenaline raised isometric tension by 27 ± 4, 39 ± 5, 52 ± 5 and 61 = 6% in normal animals (n = 6). Corresponding increases of 65 ± 8, 92 ± 8, 109 ± 9 and 115 ± 10% occurred in cardiomyopathic hamsters (n = 11, all P < 0.02). The responses to isoprenaline (EmaK = 82%) and ouabain did not differ between the two groups of hamsters. [3H]-prazosin, a new radioligand, and [−3H]-dihydroalprenolol were used to assess α1− and β-adrenoceptors in cardiac membranes. By Scatchard analysis, the KD values for both ligands did not differ between normal and cardiomyopathic hamsters, but the maximum number of binding sites was higher in the myopathic group: 5.5 vs 3.9 fmol·mg−1 protein for [3H]-prazosin and 27 vs 20 fmol·mg−1 protein for [−3H]-dihydroal-prenolol (both P < 0.05). Histochemically, oxidative and glycolytic activity were normal but lyso-zosomal acid phosphatase was high. Possible explanations for the raised response to noradrenaline in cardiomyopathic hamsters include an increased concentration of noradrenaline in the synaptic cleft due to defective neuronal uptake and / or stimulation of an augmented population of α1-(postsynaptic) adrenoceptors.

Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking.To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease.In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant.In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23).In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

Aims:The aim of this meta-analysis was to compare the midterm clinical outcomes of patients treated with an everolimus-eluting bioresorbable vascular scaffold (BVS) versus an everolimus-eluting metallic stent (EES) for percutaneous coronary interventions. Methods and results:We performed a meta-analysis of aggregate data by searching Medline, EMBASE, Cochrane databases and proceedings of international meetings for randomised trials reporting the clinical outcomes beyond one year of patients treated with BVS versus EES.The primary efficacy and safety outcomes were target lesion failure (TLF) and definite/probable stent (scaffold) thrombosis (ST), respectively.Secondary outcomes were the individual components of the primary efficacy outcome (cardiac death, target vessel myocardial infarction [MI], and ischaemia-driven target lesion revascularisation [ID-TLR]).A total of 5,583 patients randomly received BVS (n=3,261) or EES (n=2,322) in seven trials.Weighted median follow-up was 26.6 months.Patients treated with BVS versus EES showed a higher risk of TLF (odds ratio [OR] 1.35, 95% confidence interval [CI]: 1.11-1.65;p=0.0028) due to a higher risk of target vessel MI (OR 1.68, 95% CI: 1.21-2.33;p=0.008) and ID-TLR (OR 1.42, 95% CI: 1.10-1.84;p=0.007) though the risk for cardiac death was not statistically different (OR 0.89, 95% CI: 0.55-1.43;p=0.56).Patients treated with BVS versus EES showed a higher risk of definite/probable ST (OR 3.24, 95% CI: 1.92-5.49;p<0.0001), particularly in the period beyond one year after implantation (OR 4.03, 95% CI: 1.49-10.87;p=0.006).Conclusions: At midterm follow-up, patients treated with BVS as compared to those treated with EES display a higher risk of target lesion failure and scaffold thrombosis.

To evaluate the hypothesis that furosemide inhibits indirect bronchoconstrictor challenges by altering airway epithelial ion transport, we studied its effects on indirect bronchoconstriction induced by inhaled metabisulfite (MBS) and nasal potential difference (PD) in seven subjects with mild asthma. Its effect on direct bronchoconstriction by the inhaled muscarinic agonist methacholine (MC) was studied in six of these subjects. Each subject inhaled furosemide, 30 mg, in a randomized, double-blind, placebo-controlled fashion immediately before challenge with MBS (0.3 to 160 mg/ml in increasing doubling concentrations) and, in another study, MC (0.125 to 32 mg/ml) aerosols from a nebulizer attached to a dosimeter. PC20MBS and PC20MC, the concentration of each agent needed to lower FEV1 by 20%, were calculated by linear interpolation of the log dose-response curves. Furosemide had no effect on resting lung function, but it caused a significant threefold reduction in sensitivity to MBS (PC20MBS: GM ± GSEM, 15.1 ± 1.6 mg/ml after placebo and 40.7 ± 1.7 mg/ml after furosemide; p < 0.001) with a protective index of 64.8 ± 10.7%. Furosemide caused no change in sensitivity to MC (PC20 MC: GM ± GSEM, 2.37 ± 1.61 mg/ml after placebo and 2.19 ± 1.751 mg/ml after furosemide; NS). In a third study, furosemide, 30 mg, and placebo were inhaled through the nose in a randomized double-blind fashion immediately prior to inhalation of a PC20 concentration of MBS through the nose. Nasal PD was measured before and after placebo or furosemide, and again after MBS inhalation. Neither placebo nor furosemide had any effect on nasal PD compared with the same-day baseline; likewise, MBS had no effect on nasal PD whether preceded by placebo or furosemide. A positive control, 10−3 M amiloride inhaled nasally using the same apparatus, reduced nasal PD by 36.3 ± 5.4% in six normal subjects (p < 0.05). We conclude that inhaled furosemide inhibits MBS-induced bronchoconstriction but does not directly reduce smooth-muscle contractility or affect electrogenic epithelial ion transport. The mechanism whereby furosemide protects against MBS challenge remains uncertain.

No abstract is provided for this article.

To quantitatively analyze a coronary arterial segment from a cineangiogram, an enddiastolic or neighboring cineframe is usually selected, such that a possibly existing coronary lesion is visualized optimally, as judged by the cardiologist. However, different cardiologists may select different (although usually neighboring) frames, even when following the same selection criteria. It is also possible that the frames are selected from different cardiac cycles. In this study the effects of such phase shifts on the reproducibility of the quantitative measurements were studied. In a total of 38 consecutive patient films obtained at a filmspeed of 25 frames/sec, the frame O demonstrating the severity of a lesion optimally, as judged by a senior cardiologist, the three preceding frames, the three following frames and one frame exactly one cycle prior to or following frame O were selected; frame O was always chosen in the end‐diastolic phase of the cardiac cycle. In each film one coronary arterial segment with a focal lesion was analyzed quantitatively in these eight frames with the Cardiovascular Angiography Analysis System (CAAS). No significant differences were found in the mean difference and the standard deviations of the differences (variabilities) in the obstruction diameter, interpolated reference diameter, percent diameter stenosis, extent of the obstruction and area of atherosclerotic plaque obtained in the various frames with respect to frame O. Therefore, it may be concluded that the selection of a cineframe for quantitative analysis in the end‐diastolic phase of the cardiac cycle is not very critical; in other words, the obstruction measurements are not time‐dependent for frames in the end‐diastolic phase. It is argued that the quality of mixing of the contrast agent in the arterial segment is a major source of the observed variations; filling artefacts are potentially present in each of the selected frames.

Reactive nitrogen species (RNS) have been reported to be involved in the inflammatory process in chronic obstructive pulmonary disease (COPD). However, there are no studies on the modulation of RNS in COPD. It was hypothesised that inhibition of xanthine oxidase (XO) might decrease RNS production in COPD airways through the suppression of superoxide anion production. Ten COPD and six healthy subjects participated in the study. The XO inhibitor allopurinol (300 mg·day −1 p.o. for 4 weeks) was administered to COPD patients. RNS production in the airway was assessed by 3‐nitrotyrosine immunoreactivity and enzymic activity of XO in induced sputum as well as by exhaled nitric oxide (eNO) concentration. XO activity in the airway was significantly elevated in COPD compared with healthy subjects. Allopurinol administration to COPD subjects significantly decreased XO activity and nitrotyrosine formation. In contrast, eNO concentration was significantly increased by allopurinol administration. These results suggest that oral administration of the xanthine oxidase inhibitor allopurinol reduces airway reactive nitrogen species production in chronic obstructive pulmonary disease subjects. This intervention may be useful in the future management of chronic obstructive pulmonary disease.