Publications

Both quantitative flow ratio (QFR) and fractional flow reserve derived from computed tomography (FFRCT) have shown significant correlations with invasive wire-based fractional flow reserve. However, the correlation between QFR and FFRCT is not fully investigated in patients with complex coronary artery disease (CAD). The aim of this study is to investigate the correlation and agreement between QFR and FFRCT in patients with de novo three-vessel disease and/or left main CAD. This is a post-hoc sub-analysis of the international, multicenter, and randomized SYNTAX III REVOLUTION trial, in which both invasive coronary angiography and coronary computed tomography angiography were prospectively obtained prior to the heart team discussion. QFR was performed in an independent core laboratory and compared with FFRCT analyzed by HeartFlow™. The correlation and agreement between QFR and FFRCT were assessed per vessel. Furthermore, independent factors of diagnostic discordance between QFR and FFRCT were evaluated. Out of 223 patients, 40 patients were excluded from this analysis due to the unavailability of FFRCT and/or QFR, and a total of 469 vessels (183 patients) were analyzed. There was a strong correlation between QFR and FFRCT (R ​= ​0.759; p ​< ​0.001), and the Bland-Altman analysis demonstrated a mean difference of -0.005 and a standard deviation of 0.116. An independent predictor of diagnostic concordance between QFR and FFRCT was the lesion location in right coronary artery (RCA) (odds ratio 0.395; 95% confidence interval 0.174-0.894; P ​= ​0.026). In patients with complex CAD, QFR and FFRCT were strongly correlated. The location of the lesion in RCA was associated with the highest diagnostic concordance between QFR and FFRCT.

Evidence from the first prospective studies of coronary atherosclerosis demonstrated that intravascular imaging has limited accuracy in detecting lesions that are likely to progress and cause future events, and divided the scientific community into experts who advocate abandoning this quest and others who suggest intensifying our efforts improve and optimise the available imaging techniques. Although the current evidence may not justify the use of invasive or non-invasive imaging in the clinical setting for the detection of vulnerable, high-risk lesions, it is apparent that imaging has provided unique insights about plaque pathophysiology and evolution. Recent evidence indicates that both invasive and non-invasive imaging also provides useful prognostic information in patients with established coronary artery disease and in asymptomatic individuals and is likely to enable more accurate risk stratification. Future studies are anticipated to provide further insights about the value of novel hybrid imaging techniques, which are expected to enable complete assessment of plaque pathophysiology, in detecting vulnerable lesions and identifying high-risk patients that would benefit from new aggressive treatments targeting coronary atherosclerosis.

Abstract Adenosine is a potent endogenous regulator of airway inflammation that acts through specific receptor subtypes that can either cause constriction (A1R, A2BR, and A3R) or relaxation (A2AR) of the airways. We therefore examined the effects of key inflammatory mediators on the expression of the A2AR in a lung epithelial cell line (A549). IL-1β and TNF-α increased the expression of the A2AR gene at the mRNA and protein levels. In contrast, LPS had no effect on A2AR gene expression. IL-1β and TNF-α rapidly activated p50 and p65, but not C-Rel, RelB, or p52, and both IL-1β- and TNF-α-stimulated A2AR expression was inhibited by the IκB kinase 2 inhibitor AS602868 in a concentration-dependent manner. Using chromatin immunoprecipitation assays, we demonstrate that IL-1β can enhance p65 association with putative κB binding sites in the A2AR promoter in a temporal manner. In contrast, TNF-α failed to enhance p65 binding to these putative sites. Functionally, the two most 5′ κB sites were important for IL-1β-, but not TNF-α-, induced A2AR promoter reporter gene activity. Finally, neither TNF-α nor Il-1β had any effect on A2AR mRNA transcript degradation. These results directly implicate a major role for NF-κB in the regulation of A2AR gene transcription by IL-1β and TNF-α but suggest that the effects of TNF-α on A2AR gene transcription are not mediated through the proximal promoter.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y

No abstract is provided for this article.

Background. Nitrosative and oxidative stress are involved in the pathogenesis of COPD but their role in acute exacerbations of COPD (AECOPD) is unclear. We used experimental rhinovirus (RV) infection to examine the role of RNS and oxidative stress in AECOPD. Methods. 9 COPD subjects, 9 smokers (SMK) and 8 non-smokers (NS) were successfully infected with RV. Induced sputum (IS) was collected prior to infection and on days 3, 5, 9, 12, 15, 21 and 42 post-infection. Markers of nitrosative and oxidative stress 3-nitrotyrosine (3-NT), 8-hydroxy-29-deoxyguanosine (8-OHDG) and 8-isoprostane, and inflammatory mediators were measured in IS supernatants. Results. At baseline 3-NT levels were significantly higher in the COPD group compared to both NS (P Conclusions. Following RV infection nitrosative and oxidative stress are increased in COPD. The marker of nitrosative stress 3-NT correlates with levels of inflammatory mediators in sputum. Oxidative and nitrosative stress are potential targets for the development of novel therapies for AECOPD.

No abstract is provided for this article.

Objectives We investigated the impact of total stent length (TSL) and average nominal stent diameter (ASD) on 10‐year mortality after percutaneous coronary intervention (PCI) in the SYNTAXES trial. Background TSL and ASD in patients treated with PCI are associated with major adverse cardiovascular events. However, the treatment effect of PCI with extensive and/or small stenting as compared with coronary artery bypass grafting (CABG) for complex coronary artery disease has not been fully evaluated. Methods Impacts on mortality of extensive stenting defined as TSL &gt;100 mm and small stenting as ASD &lt;3 mm were analyzed in 893 PCI patients and were compared to 865 CABG patients. Results TSL as a continuous variable was significantly associated with 10‐year mortality (adjusted hazard ratio [HR], 1.05 [1.01–1.09] per 10 mm increase). PCI patients with extensive stenting had a higher 10 year mortality than CABG patients (adjusted HR, 1.97 [1.41–2.74]) or not‐ extensive stenting PCI (adjusted HR, 1.94 [1.36–2.77]). Although ASD did not have a significant association with 10 year mortality (adjusted HR, 0.97 [0.85–1.11] per 0.25 mm increase), PCI with small stents was associated with a higher 10 year mortality, compared to CABG (adjusted HR, 1.66 [1.23–2.26]) and PCI performed with large stents (adjusted HR, 1.74 [1.19–2.53]). Patients treated with not‐extensive and large stents had similar mortality rates (24.0 versus 23.8%) as those treated with CABG. Conclusions Extensive and small stenting were associated with higher 10 year mortality, compared with CABG. When patients have to be treated with extensive or small stenting, revascularization with CABG should be preferred.

From September 1991 until November 1993 we randomized 103 patients with functional and total coronary occlusions to Excimer Laser Coronary Angioplasty (ELCA, n=49) or Balloon Angioplasty (BA, n=54) as part of a multi-center trial (AMRO) comparing ELCA versus BA in type B or C-Iesions. We report on the longterm clinical and angiographic outcome of this subgroup. Procedural success (PS) was defined as &lt;50% residual stenosis at the end of the procedure. Clinical endpoints were: death (D), myocardial infarction (MI), coronary bypass surgery (CABG) or repeat angioplasty (re-PTCA) of the randomized segment within 6 months follow-up. Angiographic endpoint was the net gain (NG) in minimal lumen diameter at six months follow-up relative to the pre-procedural baseline determined by a computer-assisted automated edge detection algorithm (CAAS II). Functional status (FS) at six months was graded according to the Canadian Cardiovascular Society classification. Results Baseline patient characteristics were similar in both groups. ELCA was followed by BA in all patients. Re-occlusion of the treated segment during 6 months follow-up was 33% in the ELCA group versus 23% in the BA group (not significant). n PS(%) D/MI/CAB/re-PTCA NG±SD FS(0-IV) ELCA 49 65 0/1/4/10 0.7±0.7 29/6/10/4/0 BA 54 61 0/3/2/8 0.7±0.7 27/5/12/8/2 None of the comparisons were significantly different. Conclusion Excimer Laser Angioplasty compared to Balloon Angioplasty in functional and total coronary occlusion yields similar results with respect to longterm clinical and angiographic outcome.

The effect of bradykinin was studied by inhalation in normal and asthmatic human subjects, as well as on human bronchial smooth muscle in vitro. Bradykinin caused cough and retrosternal discomfort in all subjects and bronchoconstriction in asthmatic subjects. Bradykinin was approximately 10 times more potent than histamine and methacholine, and there was a significant correlation between the subjects' sensitivity to histamine and bradykinin. Bradykinin-induced bronchoconstriction was prolonged when compared with that of histamine and the C-fiber stimulant capsaicin. This bronchoconstriction was subject to tachyphylaxis, which was also associated with desensitization of the subjects to inhaled histamine. The provocative dose causing a 35% fall in specific airway conductance (PD35) was unaffected by aspirin (1 g orally). However, ipratropium bromide (0.25 mg by nebulizer) significantly inhibited the effect of bradykinin, the PD35 being 0.8 mumol (range, 0.16 to 3.4) and 0.15 mumol (range, 0.047 to 1.15) after active dose and placebo, respectively (p less than 0.05). Likewise, cromolyn sodium (40 mg dry powder) also significantly reduced response to bradykinin, with a PD35 of 0.04 mumol (range, 0.13 to 0.31) after placebo and 0.39 mumol (range, 0.05 to 4.45) after SCG (p less than 0.05). Bradykinin only weakly constricted human bronchial smooth muscle in vitro. Bradykinin at 10(-4) caused only 21.5 +/- 5.5% of the maximal carbamylcholine contraction in 11 of 18 airways. Captopril did not enhance the effect of bradykinin. Bradykinin is a potent bronchoconstrictor of human airways in vivo, acting in part through cholinergic mechanisms but not because of the formation of prostaglandins.