Long-term comparison of everolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for percutaneous coronary intervention of saphenous vein grafts

Aims: Newer-generation everolimus-eluting stents (EES) have been shown to improve clinical outcomes compared with early-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in patients undergoing percutaneous coronary intervention (PCI). Whether this benefit is maintained among patients with saphenous vein graft (SVG) disease remains controversial. Methods and results: We assessed cumulative incidence rates (CIR) per 100 patient years after inverse probability of treatment weighting to compare clinical outcomes. The pre-specified primary endpoint was the composite of cardiac death, myocardial infarction (MI), and target vessel revascularisation (TVR). Out of 12,339 consecutively treated patients, 288 patients (5.7%) underwent PCI of at least one SVG lesion with EES (n=127), SES (n=103) or PES (n=58). Up to four years, CIR of the primary endpoint were 58.7 for EES, 45.2 for SES and 45.6 for PES with similar adjusted risks between groups (EES vs. SES; HR 0.94, 95% CI: 0.55-1.60, EES vs. PES; HR 1.07, 95% CI: 0.60-1.91). Adjusted risks showed no significant differences between stent types for cardiac death, MI and TVR. Conclusions: Among patients undergoing PCI for SVG lesions, newer-generation EES have similar safety and efficacy to early-generation SES and PES during long-term follow-up to four years.

Multivessel versus culprit vessel percutaneous coronary intervention in ST-elevation myocardial infarction: is more worse?

Aims: We examined what type of STEMI patients are more likely to undergo multivessel PCI (MPCI) in a "real-world" setting and whether MPCI leads to worse or better outcomes compared with single-vessel PCI (SPCI) after stratifying patients by risk. Methods and results: Among STEMI patients enrolled in the Swiss AMIS Plus registry between 2005 and 2012 (n=12,000), 4,941 were identified with multivessel disease. We then stratified patients based on MPCI use and their risk. High-risk patients were identified a priori as those with: 1) left main (LM) involvement (lesions, n=263); 2) out-of-hospital cardiac arrest; or 3) Killip class III/IV. Logistic regression models examined for predictors of MPCI use and the association between MPCI and in-hospital mortality. Three thousand eight hundred and thirty-three (77.6%) patients underwent SPCI and 1,108 (22.4%) underwent MPCI. Rates of MPCI were greater among high-risk patients for each of the three categories: 8.6% vs. 5.9% for out-of-hospital cardiac arrest (p<0.01); 12.3% vs. 6.2% for Killip III/IV (p<0.001); and 14.5% vs. 2.7% for LM involvement (p<0.001). Overall, in-hospital mortality after MPCI was higher when compared with SPCI (7.3% vs. 4.4%; p<0.001). However, this result was not present when patients were stratified by risk: in-hospital mortality for MPCI vs. SPCI was 2.0% vs. 2.0% (p=1.00) in low-risk patients and 22.2% vs. 21.7% (p=1.00) in high-risk patients. Conclusions: High-risk patients are more likely to undergo MPCI. Furthermore, MPCI does not appear to be associated with higher mortality after stratifying patients based on their risk.

The HeartQoL: Part II. Validation of a new core health-related quality of life questionnaire for patients with ischemic heart disease

Background: Evaluation of health-related quality of life (HRQL) is important in improving the quality of patient care. The aim of this study was to determine the psychometric properties of the HeartQoL in patients with ischemic heart disease (IHD), specifically angina, myocardial infarction (MI), or ischemic heart failure. Methods: Data for the interim validation of the HeartQoL questionnaire were collected in (a) a cross-sectional survey and (b) a prospective substudy of patients undergoing either a percutaneous coronary intervention (PCI) or referred to cardiac rehabilitation (CR) and were then analyzed to determine the reliability, validity, and responsiveness of the HeartQoL questionnaire. Results: We enrolled 6384 patients (angina, n = 2111, 33.1%; MI, n = 2351, 36.8%; heart failure, n = 1922, 30.1%) across 22 countries speaking 15 languages in the cross-sectional study and 730 patients with IHD in the prospective substudy. The HeartQoL questionnaire comprises 14-items with physical and emotional subscales and a global score (range 0–3 (poor to better HRQL). Cronbach’s α was consistently ≥0.80; convergent validity correlations between similar HeartQoL and SF-36 subscales were significant (r ≥ 0.60, p < 0.001); discriminative validity was confirmed with predictor variables: health transition, anxiety, depression, and functional status. HeartQoL score changes following either PCI or CR were significant (p < 0.001) with effect sizes ranging from 0.37–0.64. Conclusion: The HeartQoL questionnaire is reliable, valid, and responsive to change allowing clinicians and researchers to (a) assess baseline HRQL, (b) make between-diagnosis comparisons of HRQL, and (c) evaluate change in HRQL in patients with angina, MI, or heart failure with a single IHD-specific HRQL instrument.

Monitoring Programmes, Multiple Stress Analysis and Decision Support for River Basin Management

The identification of plausible causes for water body status deterioration will be much easier if it can build on available, reliable, extensive and comprehensive biogeochemical monitoring data (preferably aggregated in a database). A plausible identification of such causes is a prerequisite for well-informed decisions on which mitigation or remediation measures to take. In this chapter, first a rationale for an extended monitoring programme is provided; it is then compared to the one required by the Water Framework Directive (WFD). This proposal includes a list of relevant parameters that are needed for an integrated, a priori status assessment. Secondly, a few sophisticated statistical tools are described that subsequently allow for the estiation of the magnitude of impairment as well as the likely relative importance of different stressors in a multiple stressed environment. The advantages and restrictions of these rather complicated analytical methods are discussed. Finally, the use of Decision Support Systems (DSS) is advocated with regard to the specific WFD implementation requirements.

First Clinical Experience With Celt ACD(®) : A Femoral Arterial Puncture Closure Device

Introduction This prospective nonrandomized study compared the safety and efficacy of a novel arterial closure device (ACD) in common femoral artery procedures to that of the FDA submitted historical manual pressure control group, who underwent either a diagnostic angiogram (DA) or a percutaneous coronary intervention (PCI) procedure. Methods and Results A total of 55 patients were enrolled in this study of the novel ACD. Of the 55 patients, 39 were enrolled in the DA group and 16 were enrolled in the PCI group. Six patients were excluded. A device was deployed in 49 patients. Time to hemostasis (TTH), time to ambulation (TTA), device function, and device-related vascular complications were measured. In the device group, the TTH for the combined DA and PCI patients was 32 seconds (0.54 ± 0.93 minutes), significantly lower when compared with 16.0 ± 12.2 minutes (P < 0.0001) for the control group. Overall major vascular complication rate did not differ significantly, device group (1/49) and the historical control group (1/217). TTA in the combined PCI and DA device group was 226.4 ± 231.9 at the German site (site ambulation policy). In the Irish site, the average TTA in the PCI group was 187 minutes (n = 8) and 85 minutes (n = 14) in the DA group. Conclusion The Celt ACD® device is safe, effective, and significantly decreases the TTH compared to manual pressure and has a low vascular complications rate. The device may be effective in early ambulation and discharge of patients postcoronary intervention procedures.

Clinical outcome of patients with stable ischaemic heart disease as compared to those with acute coronary syndromes after percutaneous coronary intervention

Aims: 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). Methods and results: 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). Conclusions: 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. Trial registration: URL: http://www.ClinicalTrials.gov; unique identifier: NCT00297661 (Sirtax), NCT00389220 (Leaders), NCT00114972 (Resolute-AC).

A 700-Year Record of Atmospheric Circulation Developed from the Law Dome Ice Core, East Antarctica

A 700-year, high-resolution, multivariate ice core record from Dome Summit South (DSS) (66degrees46'S, 112degrees48'E; 1370 m), Law Dome, is used to investigate sea level pressure (SLP) variability in the region of East Antarctica. Empirical orthogonal function (EOF) analysis reveals that the first EOF (LDEOF1) of the combined glaciochemical, oxygen isotope ratio, and accumulation rate record from DSS represents most of the variability in sea salt seen in the record. LDEOF1 is positively correlated (at least 95% confidence level) to instrumental June mean SLP across most of East Antarctica. Over the last 700 years, LDEOF1 levels at Law Dome were the highest during the nineteenth century, suggesting an increase in intensification of winter circulation during this period. The Law Dome DSS oxygen isotope ratio series also indicates that the nineteenth century had the coldest winters of any century in the record. In contrast, LDEOF1 levels were the lowest at Law Dome during the eighteenth century, suggesting a significant shift in the patterns and/or intensity of East Antarctic atmospheric circulation between the eighteenth and the nineteenth centuries. The LDEOF1 sea salt record is characterized by significant decadal-scale variability with a strong 25-year periodic structure.

Post-Depositional Movement of Methanesulphonic Acid at Law Dome, Antarctica, and the Influence of Accumulation Rate

A series of ice cores from sites with different snow-accumulation rates across Law Dome, East Antarctica, was investigated for methanesulphonic acid (MSA) movement. The precipitation at these sites (up to 35 km apart) is influenced by the same air masses, the principal difference being the accumulation rate. At the low-accumulation-rate W20k site (0.17 in ice equivalent), MSA was completely relocated from the summer to winter layer. Moderate movement was observed at the intermediate-accumulation-rate site (0.7 in ice equivalent), Dome Summit South (DSS), while there was no evidence of movement at the high-accumulation-rate DE08 site (1.4 in ice equivalent). The main DSS record of MSA covered the epoch AD 1727-2000 and was used to investigate temporal post-depositional changes. Co-deposition of MSA and sea-salt ions was observed of the surface layers, outside of the main summer MSA peak, which complicates interpretation of these peaks as evidence of movement in deeper layers. A seasonal study of the 273 year DSS record revealed MSA migration predominantly from summer into autumn (in the up-core direction), but this migration was suppressed during the Tambora (1815) and unknown (1809) volcanic eruption period, and enhanced during an epoch (1770-1800) with high summer nitrate levels. A complex interaction between the gradients in nss-sulphate, nitrate and sea salts (which are influenced by accumulation rate) is believed to control the rate and extent of movement of MSA.

The Early Activation Marker CD69 Regulates the Expression of Chemokines and CD4 T Cell Accumulation in Intestine

Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+) T cells and/or CD4(-) cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/-) CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS)-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/-) CD4 T cell accumulation in colonic lamina propria (cLP) was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/-) mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/-) CD45RB(high) CD4 T cells into RAG(-/-) hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

Predictors of adverse events among patients undergoing primary percutaneous coronary intervention: insights from a pooled analysis of the COMFORTABLE AMI and EXAMINATION trials

Aims: The aim of this study was to identify predictors of adverse events among patients with ST-elevation myocardial infarction (STEMI) undergoing contemporary primary percutaneous coronary intervention (PCI). Methods and results: Individual data of 2,655 patients from two primary PCI trials (EXAMINATION, N=1,504; COMFORTABLE AMI, N=1,161) with identical endpoint definitions and event adjudication were pooled. Predictors of all-cause death or any reinfarction and definite stent thrombosis (ST) and target lesion revascularisation (TLR) outcomes at one year were identified by multivariable Cox regression analysis. Killip class III or IV was the strongest predictor of all-cause death or any reinfarction (OR 5.11, 95% CI: 2.48-10.52), definite ST (OR 7.74, 95% CI: 2.87-20.93), and TLR (OR 2.88, 95% CI: 1.17-7.06). Impaired left ventricular ejection fraction (OR 4.77, 95% CI: 2.10-10.82), final TIMI flow 0-2 (OR 1.93, 95% CI: 1.05-3.54), arterial hypertension (OR 1.69, 95% CI: 1.11-2.59), age (OR 1.68, 95% CI: 1.41-2.01), and peak CK (OR 1.25, 95% CI: 1.02-1.54) were independent predictors of all-cause death or any reinfarction. Allocation to treatment with DES was an independent predictor of a lower risk of definite ST (OR 0.35, 95% CI: 0.16-0.74) and any TLR (OR 0.34, 95% CI: 0.21-0.54). Conclusions: Killip class remains the strongest predictor of all-cause death or any reinfarction among STEMI patients undergoing primary PCI. DES use independently predicts a lower risk of TLR and definite ST compared with BMS. The COMFORTABLE AMI trial is registered at: http://www.clinicaltrials.gov/ct2/show/NCT00962416. The EXAMINATION trial is registered at: http://www.clinicaltrials.gov/ct2/show/NCT00828087.