6,963 publications from this institution
Objectives This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe. Background Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients. Methods In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined. Results A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (<1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p < 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mm2, or TCFA), high anatomic risk, and low ESS were prognostically synergistic: 3-year nc-MACE rates were 52.1% versus 14.4% versus 0.0% in high-anatomic risk/low-ESS, low-anatomic risk/low-ESS, and physiological/high-ESS lesions, respectively (p < 0.0001). No lesion without low ESS led to nc-MACE during follow-up, regardless of PB, MLA, or lesion phenotype at baseline. Conclusions Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.
A new 100 cm long 16.5 French valvuloplasty introducer was used in 12 consecutive patients (mean age 73 years, five males and seven females) undergoing aortic balloon valvuloplasty for severe aortic stenosis. The long‐sheath was introduced into the ascending aorta along the stiff part of an exchange guidewire. The valvuloplasty procedure, which included a complete diagnostic catheterization in three patients, lasted 113 ± 47 min (211 ± 81 min in the previous 18 procedures performed with a conventional approach, P < 0.05). Introduction of balloon catheters (3 × 12 mm trefoil balloon in the 12 cases and 2 × 19 mm bifoil balloon in 2 of these cases) was possible in all patients and an increased stability of the balloon during inflation was observed. No systemic embolization or vascular complications occurred at the puncture site. The long‐sheath technique appears to be a valuable adjunct for aortic valvuloplasty in that it provides easier and quicker access for even the largest balloons and additional support and stability during balloon inflation. In our experience, this reduced the practical difficulties and the duration of the procedure.
4indicate that nicotine-dependent smokers are particularly prone to relapse. Second, the chance of a successful quit attempt can be decreased by the presence of psychiatric disorders. Depression is independently associated with inability to stop smoking, and results of research show that patients with COPD are at a greater risk of developing depression than individuals without COPD (unpublished data). In view of these factors, how successful are interventions used to help the general population to stop smoking when used by patients with COPD? Only five trials have assessed the efficacy of smoking cessation interventions in patients with COPD. 5 Results of the Lung Health Study 5 showed that intensive behavioural counselling combined with nicotine replacement therapy resulted in much higher 5-year abstinence rates than no intervention. Furthermore, contrary to what has been stated in many reviews, bupropion has not yet been shown to be effective in smokers with COPD. 5 However,
Key Points Anatomical evaluation is of paramount importance in the treatment of bifurcation lesions. Left main coronary artery bifurcation geometry differs from left anterior descending artery/diagonal and circumflex artery/obtuse marginal bifurcations. Individualized approach with pre‐procedural planning has the potential to improve outcomes after bifurcation treatment.
Abstract Previously, we found that IL-22 produced by NK cells inhibits intracellular mycobacterial growth in human macrophages (Mϕ) by enhancing phagolysosomal fusion. In the current study, we determined the mechanism/s by which IL-22 inhibits virulent M. tuberculosis H37Rv (M. tb) growth in Mϕ. First we asked whether IL-22 restricts M. tb growth in phagosomes that leads to enhanced phagolysosomal fusion. W7, a phagolysosomal fusion inhibitor abrogated IL-22 dependent M. tb growth in Mϕ (11.38 ± 3.3 x 106 vs 2.95 ± 1.7 x 106 CFU per well, p=0.05) suggesting IL-22 inhibits M. tb growth after phagolysosomal fusion. In microarray analysis we found that mRNA expression for 41 genes was &gt;1-fold higher in rIL-22 cultured infected Mϕ compared to infected Mϕ. Of these genes, we selected Indolamine 2,3-dioxegenase (IDO1) and Calgranulin A for further study. rIL-22 enhanced Calgranulin A expression in M. tb infected Mϕ by three fold (3.3 ± 0.83 vs 1.0 arbitrary units, p=0.04) compared to infected Mϕ as measured by real time PCR and confirmed by confocal microscopy. In contrast, IDO1 expression of infected Mϕ was not effected by rIL-22. Calgranulin A siRNA abrogated rIL-22 dependent growth inhibition of M. tb in macrophages (18.4 ± 1.8 x 106 vs 7.97 ± 0.8 x 106 CFU per well, p=0.0005). Studies are underway to determine the effect of Calgranulin A siRNA on phagolysosomal fusion using early endosomal, late endosomal and lysosomal markers.
Background Diabetes increases the risk of developing cardiovascular disease. Patients with diabetes undergoing percutaneous coronary intervention (PCI) show poorer outcomes compared with nondiabetic patients. The aim of this study was to determine the clinical benefit of long-term fluvastatin in patients with diabetes who had undergone a successful PCI. Methods This subanalysis of a prospective, multicenter, randomized, double-blind, placebo-controlled trial of patients who had undergone PCI and were treated with fluvastatin determined the impact of fluvastatin on the survival-free period of major adverse cardiac events (MACE) (defined as cardiac death, nonfatal myocardial infarction, and reintervention procedure [coronary artery bypass grafting, repeat PCI, PCI for a new lesion]). Patients with baseline total cholesterol levels of 135 to 270 mg/dL (3.5-7.0 mmol/L) and triglyceride levels of 400 mg/dL (4.5 mmol/L) were randomized at discharge either to fluvastatin (n = 844) or to placebo (n = 833); follow-up was 3 to 4 years. Among these patients, there were 202 with diabetes (120 on fluvastatin, 82 placebo) and 1475 without diabetes (724 on fluvastatin, 751 on placebo). The primary clinical outcome was survival time free of MACE and MACE excluding restenosis. Results The presence of diabetes increased the risk of MACE by almost 2-fold in placebo-treated patients (RR 1.78, 95% CI 1.20-2,64, P = .0045). In contrast, in diabetic patients treated with fluvastatin, the risk of MACE was not significantly different from that in patients without diabetes. Fluvastatin reduced the risk of MACE in diabetic patients by 51% (P = .0088). Conclusions Diabetes is a consistent clinical predictor of cardiovascular complications and fluvastatin reduces the increased incidence of long-term adverse complications associated with the presence of diabetes.
No abstract is provided for this article.
We studied the tussive effects of a chloride-deficient solution (1.26% sodium bicarbonate). Nine normal volunteers and 10 mild asthmatic subjects were studied. In two double-blind, placebo-controlled, cross-over studies, we assessed the profile of any inhibitory effects that inhaled frusemide had over these responses. Baseline cough challenge was followed by inhalation of either frusemide (40 mg), or 0.15 M NaCl control. Cough was then induced at 0.5, 2, 4 and 6 h after treatment. Forced expiratory volume in one second (FEV1) was measured before and after each challenge. Changes from the baseline cough response due to drug or control were compared nonparametrically at each time point. There was no difference in the sensitivity of normal and asthmatic subjects to the cough challenge (median cough response 15 and 14.5 on control day, 12 and 15 on frusemide day). Frusemide caused sustained inhibition of the cough response in normal subjects (p < 0.05 at 2 h, p < 0.01 at 4 h), but had only a small, nonsignificant effect in asthmatic subjects at 30 min. Falls in FEV1 of asthmatic subjects due to the chloride-deficient solution were not significant, and did not correlate with number of coughs. We conclude that mild asthmatic subjects are less sensitive than normal subjects to the influence of frusemide against low chloride challenge. This observation is not explained by bronchoconstrictor effects of the cough challenge in asthmatic subjects.
