Publications

Abstract IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(I:C). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.

No abstract is provided for this article.

Objectives The aim of this study was to assess sirolimus-eluting stent (SES) implantation for the treatment of chronic total coronary occlusions (CTO). Background Long-term results after percutaneous coronary intervention (PCI) in the treatment of CTOs is hindered by a significant rate of restenosis and reocclusion. In the treatment of relatively simple nonocclusive lesions, SESs have shown dramatically reduced restenosis rates compared with bare metal stents (BMS), but whether these results are more widely applicable is unknown. Methods From April 2002, all patients at our institution were treated with SES as the device of choice during PCI. During the first six months, 563 patients were treated solely with SES, with treatment of a de novo CTO in 56 (9.9%). This CTO cohort was compared with a similar group of patients (n = 28) treated in the preceding six-month period with BMS. Results At one year, the cumulative survival-free of major adverse cardiac events was 96.4% in the SES group versus 82.8% in the BMS group, p < 0.05. At six-month follow-up, 33 (59%) patients in the SES group underwent angiography with a binary restenosis rate (>50% diameter stenosis) of 9.1% and in-stent late loss of 0.13 ± 0.46 mm. One patient (3.0%) at follow-up was found to have reoccluded the target vessel. Conclusions The use of SESs in the treatment of chronic total coronary occlusions is associated with a reduction in the rate of major adverse cardiac events and restenosis compared with BMS.

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The use of coronary stents decreases the morbidity associated with acute closure and restenosis after balloon angioplasty. Intracoronary ultrasound (ICUS) guidance of stent implantation has been advocated to improve stent deployment and thereby to further improve the clinical outcome after stenting, over and above balloon angioplasty. Whereas the merits of intracoronary ultrasound in this respect still remain to be proven, the present paper illustrates that ICUS itself may also entail complications. This paper repoorts on three cases of stent damage induced or aggravated by the ICUS procedure. Cathet. Cardiovasc. Diagn. 40:265–270, 1997. © 1997 Wiley-Liss, Inc.

When patients choose percutaneous coronary intervention (PCI) over coronary artery bypass grafting (CABG), they accept an increased long-term risk of repeat revascularisation in exchange for short-term morbidity benefits. This paper quantifies the risk-benefit trade-off faced by patients with multiple vessel coronary artery disease.Data from the Arterial Revascularisation Therapies Study are used to generate risk-benefit acceptability curves for PCI versus CABG. Risks are measured by the long-term likelihood of repeat revascularisation while benefits are measured by short-term reductions in pain or improvements in health-related quality of life (HRQL). PCI patients faced a risk of 0.81 additional revascularisation events over three years in exchange for being pain-free at one month. A patient would need to be willing to tolerate a risk of 1.06 additional revascularisation events at three years, in exchange for being pain free at one month to be 95% confident that choosing PCI over CABG is risk-effective for him/her.The risk-benefit framework outlined in this study provides information to enable physicians to help their patients weigh directly each procedure's risks and benefits. While trade-offs are typically measured in quality-adjusted life years, using pain reduction to reflect benefits may provide a more tangible framework for patients.

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints. This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

The influence of target lesion length, measured by an automated edge detection system (CAAS), on late angiographic and clinical outcome after successful coronary balloon angioplasty (SA), was investigated among 3124 patients with 3513 non-occlusive native coronary lesions. Quantitative angiography was performed before and after BA and at 6 month follow up. Visually assessed post-BA diameter stenosis&lt;50% was considered successful. Late clinical outcome was considered as occurrence of or freedom from, major adverse cardiac events (“MACE”: death, myocardial infarction, coronary artery bypass graft surgery, re-intervention), or target lesion reocclusion at follow up angiography, within 6 months of BA. In univariate analysis, longer lesions were associated with larger reference vessel diameter (p&lt;0.0001) and greater acute luminal gain (p&lt;0.01), but also greater late loss (p&lt;0.001) and greater % stenosis at follow up (p&lt;0.0001). To determine whether lesion length is an independent determinant of late loss or late luminal diameter, multiple linear regression analysis was carried out, including the influence of lesion location, vessel size, pre-procedural minimal luminal diameter and procedural luminal gain. Although lesion length was associated with larger vessel size, which is an independent determinant of less luminal loss (p&lt;0.0001), longer lesions were found to be independently associated with greater late loss and a smaller luminal diameter at follow up. Dividing the lesion population in 9 equal groups (noniles), the shortest lesions (mean 2.98±0.66 mm) had a loss of 0.25±0.49 mm and a % stenosis at follow up of 43±20% while the longest (mean 10.86±1.70 mm) had a loss of 0.37±0.55 mm and a % stenosis at follow up of 50±19% (p&lt;0.0001). Despite these angiographic findings of poorer late angiographic results, the frequency of major adverse cardiac events, total occlusion or binary restenosis (diameter stenosis≥50%) at follow up, did not vary with lesion length. Conclusion Although longer coronary lesions are independently associated with less favourable late angiographic results after successful balloon angioplasty, this does not appear to translate into poorer late clinical outcome. The long term clinical implications of angiographically quantified preinterventionallesion length remain to be determined.

The outcomes from real-life clinical studies regarding the optimal revascularization strategy in patients with multivessel coronary artery disease (MVD) are still poorly investigated. In this retrospective study we assessed 5-year outcomes: primary, secondary endpoints and quality of life of 1035 individuals with severe coronary artery disease (CAD) treated either with coronary artery bypass grafting (CABG)—356 patients or percutaneous coronary intervention (PCI)—679 patients according to the recommendation of a local Heart Team (HT). At 5 years no significant difference in overall mortality and rates of myocardial infarctions (MI) were observed between CABG and PCI cohorts (11.0% vs. 13.4% for PCI, P = 0.27 and 9.6% vs. 12.8% for PCI, P = 0.12, respectively). The incidence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by increased rates of repeat revascularization (RR) were higher in PCI-cohort than in CABG-group (56.1% vs. 40.4%, P &lt; 0.01 and 26.8% vs. 12.6%, P &lt; 0.01, respectively), while CABG-patients experienced stroke more often (7.3% vs. 3.1% for PCI, P &lt; 0.01). In real-life practice with long-term follow-up, none of the two revascularization modalities implemented following HT decisions showed overwhelming superiority: occurrence of death and MI were similar, rates of RR favoured CABG, while incidence of strokes advocated PCI.

A new device (prostarTm, Perclose, Inc.) was developed to close femoral artery access sites percutaneously following coronary interventions in fully anticoagulated patients. The catheter deploys four needles with two pairs of sutures around the hole of femoral artery access sites. The sutures are then tied to close the arteriotomy site mechanically to achieve immediate hemostasis. As a pilot phase, the device was tested in six centers. The device was used immediately following coronary intervention in 91 access sites. Despite an average ACT at the time of the procedure of &gt;300 seconds, immediate complete hemostasis was achieved in 82 sites (90%). The devices were not appropriately positioned in 8 cases and procedures were aborted followed by reinsertion of a sheath or manual compression. Two patients (2.2%) required surgical repair of the femoral artery; one with device mechanical failure and one with bleeding from the initial puncture site in the posterior wall despite successful closure of the sheath site in the front wall. There were no AV fistulae or pseudoaneurysms requiring surgery and no infection, distal embolism or need for blood transfusion. In conclusion, this pilot study suggests that this suture mediated closure device appears to provide safe and effective hemostasis at the femoral access site in fully anticoagulated patients following coronary interventions.

To compare clinical outcomes after percutaneous coronary intervention (PCI) between patients with acute coronary syndromes (ACS) and those with stable ischaemic heart disease (SIHD) stratified by anatomic disease complexity (SYNTAX score).Patient-level data from three all-comers PCI trials were pooled. Patients (n=4,204) were stratified by clinical presentation (i.e., ACS or SIHD) and by SYNTAX score (i.e., lowest vs. two highest tertiles). The major adverse cardiac event (MACE) rates of patients with low-risk SIHD (n=531) and high-risk SIHD (n=1,066) were compared with ACS patients (n=2,607), respectively. At two years, the risk of MACE was higher for high-risk SIHD patients (OR 1.34, 95% CI: 1.08-1.66) and lower for low-risk SIHD patients (OR 0.61, 95% CI: 0.43-0.87) compared with ACS patients, respectively. This difference between high-risk SIHD patients and ACS patients was primarily driven by a higher risk of myocardial infarction (OR 1.64, 95% CI: 1.21-2.21), while there was no difference for cardiac death (OR 0.77, 95% CI: 0.49-1.21) or target lesion revascularisation (OR 1.21, 95% CI: 0.91-1.62).In this pooled analysis, the majority of patients undergoing PCI for SIHD (i.e., with SYNTAX score >8) had a higher risk of MACE than patients with ACS.URL: http://www.ClinicalTrials.gov; unique identifier: NCT00297661 (Sirtax), NCT00389220 (Leaders), NCT00114972 (Resolute-AC).

No abstract is provided for this article.