ObjectivesTo analyse adverse events requiring or prolonging hospitalisation in the Stent or Surgery (SoS) trial.BackgroundMany adverse events following coronary revascularisation are non-major adverse cardiovascular events (non-MACE). Trials comparing percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) have reported rates of mortality and MACE only.Material and methodsComparisons between PCI and CABG groups in the SOS trial were by intention to treat. For patients with non-fatal/non-MACE, number of events per 100 patient years follow-up and duration of hospital stay were assessed. Competing risk analysis was used to illustrate temporal pattern of adverse outcomes.ResultsDuring 2y median follow up, 1 one or more adverse event occurred in 47.3% (231) of the PCI group and 53% (265) of the CABG group (p=0.086). Non-fatal/non-MACE occurred in 11.9% of the PCI group and 38.6% of the CABG group (p<0.001). Non-fatal/non-MACE per 100 patient years follow-up was 17.49 (PCI) and 35.04 (CABG), rate ratio 2.0, 95% CI 1.7 to 2.4, p<0.001. Cumulative non-fatal/non-MACE associated hospital stays were 1387 and 3287days in PCI and CABG groups respectively. Median duration of hospitalisation per non-fatal/non-MACE was 5days (interquartile range 2 to 11.75days) in the PCI group and 6days (interquartile range 2 to 12days) in the CABG group, p=0.245.ConclusionsCABG had lower cumulative incidence of fatal or MACE outcomes, higher cumulative incidence of non-fatal/non-MACE outcomes, and longer cumulative hospitalisation periods compared to the PCI group.

Background Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure.Methods In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs >= 75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0.75 mg/kg; infusion 1.75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518.Findings Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8.7%) of 905 patients in the bivalirudin group and 52 (5.7%) of 907 patients in the heparin group (absolute risk difference 3.0%; relative risk [RR] 1.52, 95% CI 1.09-2.13, p=0.01). The primary safety outcome occurred in 32 (3.5%) of 905 patients in the bivalirudin group and 28 (3.1%) of 907 patients in the heparin group (0.4%; 1.15, 0.70-1.89, p=0.59).Interpretation Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially.

AIMS Post-mortem pathological studies have shown that a "vulnerable" plaque is the dominant patho-physiological mechanism responsible for acute coronary syndromes (ACS). One way to improve our understanding of these plaques in vivo is by using histological "surrogates" created by intravascular ultrasound derived virtual histology (IVUS-VH). Our aim in this analysis was to determine the relationship between site-specific differences in individual plaque areas between ACS plaques and stable plaques (SP), with a focus on remodelling index and the pattern of calcifying necrosis. METHODS AND RESULTS IVUS-VH was performed before percutaneous intervention in both ACS culprit plaques (CP) n=70 and stable disease (SP) n=35. A total of 210 plaque sites were examined in 105 lesions at the minimum lumen area (MLA) and the maximum necrotic core site (MAX NC). Each plaque site had multiple measurements made including some novel calculations to ascertain the plaque calcification equipoise (PCE) and the calcified interface area (CIA). CP has greater amounts of positive remodelling at the MLA (RI@MLA): 1.1 (±0.17) vs. 0.95 (±0.14) (P<0.001); lower values for PCE 30% vs. 54% (P<0.001) but a higher CIA 5.38 (±2.72) vs. 3.58 (±2.26) (P=0.001). These features can provide discriminatory ability between plaque types with area under the curve (AUC) measurements between 0.65-0.86. The cut-off values with greatest sensitivity and specificity to discriminate CP morphologies were: RI @ MLA >1.12; RI @ MAX NC >1.22; PCE @ MLA <47.1%; PCE @MAX NC <47.3%; CIA @ MLA >2.6; CIA @ MAX NC >3.1. CONCLUSIONS Determining the stage of calcifying necrosis, along with the remodelling index can discriminate between stable and ACS related plaques. These findings could be applied in the future to help detect plaques that have a vulnerable phenotype.

AIMS New markers to help stratify coronary atherosclerosis are needed. Although attempts have been made to differentiate active lesions from those that are stable, none of these has ever been formalised into a discriminatory score. The aim of this study was to analyse the differences between culprit ACS lesions and culprit stable angina lesions with intravascular ultrasound-derived virtual histology and to construct and validate a plaque score. METHODS AND RESULTS Prior to percutaneous coronary intervention (PCI), we performed volumetric, intravascular ultrasound-derived virtual histology (IVUS-VH) analysis in acute coronary syndrome (ACS) culprit lesions (AC - n=70) and stable angina culprit lesions (SC - n=35). A direct statistical comparison of IVUS-VH data and multiple logistic regression analysis was undertaken. Four main factors were found to be associated (p<0.05) with an AC lesion phenotype: necrotic core/dense calcium (NC/DC) ratio; minimum lumen area <4 mm2 (MLA <4); remodelling index @MLA >1.05 and VH-TCFA presence. Calculation of each logistic regression coefficient and the equation produces an active plaque discrimination score with an AUC of 0.96 on receiver operating characteristics (ROC) analysis. Validation of the score in 50 independent plaques from the Thoraxcenter in Rotterdam revealed an AUC of 0.71, confirming continued diagnostic ability. CONCLUSIONS We have found four features on IVUS and VH that can predict and discriminate ACS culprit lesion phenotypes from those that are clinically stable. Subsequently, we have constructed and validated the Liverpool Active Plaque Score based upon these features. It is hoped this score may help diagnose active coronary plaques, in the future, to help prevent major adverse cardiac events.

Angiographically-guided stent deployment is the conventional, albeit imperfect, approach in the setting of real world Percutaneous Coronary Intervention (PCI). Recently, the ADAPT-DES study and a large meta-analysis have suggested there may be a benefit to both clinical outcomes and major adverse

In 2002, a 60-year-old man suffered an inferior ST elevation myocardial infarction (STEMI), which was initially successfully treated with thrombolysis. He was then referred to our center for percutaneous coronary intervention (PCI) due to post-infarct angina. In his past history he was a very heavy smoker with an 80-pack-per-year history. He also had established hypertension, a family history of ischemic heart disease and hypercholesterolemia.

Background Composite (Y/T) coronary artery bypass graft surgery (CABG) confers full arterial revascularisation, and “hands off” aorta compared to conventional bypass graft surgery. However, the composite surgical configuration could lead to preferential blood flow down one arm than the other (left internal mammary artery LIMA or radial artery RA) with its potential impact on graft patency. Aim To investigate the impact of bypass graft configuration on short-term grafts patency and cardiac related quality of life. Methods and Results This is a single centre randomised, controlled trial Between March 2006 and July 2007, 322 patients undergoing isolated bypass graft surgery at our institution were screened and 89 (27%) met the inclusion criteria and were randomised. Patients were allocated to conventional (conv n=46) or composite (comp n=43). The two primary end points were graft patency defined as (Thrombolysis In Myocardial Infarction) TIMI III flow in distal anastomosis at angiography 12–24 months after surgery, and cardiac-related health status assesses by Seattle angina questionnaire (SAQ). Baseline characteristics were similar between the two groups apart from diabetes where there were more diabetic patients in the composite arm than the conventional one (15(35%) vs 5(11%) p<0.01 respectively). Trial was stopped prematurely following 18 months interim analysis which showed significant graft failure in the composite arm (40%). Final Analysis was performed on intention to treat basis. Sixty-five (73%) had follow-up angiography (34 conv, 31 comp), with total of 116 graft in conventional arm and 100 grafts in composite arm. All patients in both groups had LIMA graft to left anterior descending artery (LAD). Graft patency rate was significantly higher in the conventional compared to composite arm (95(82%) vs 59(59%) p<0.001 respectively). Three main domains of the SAQs there was significant improvement between before and 6 months after surgery in both groups. There were no significant differences between the two groups in the percentage of improvement in these four domains (Physical limitation, Angina stability, Angina frequency, Quality of life). Conclusions In our randomised trial, composite bypass graft surgery was associated with higher graft failure rate at 12–24 months after surgery compared to conventional type. This difference may be due to the composite conduit configuration. Further blood flow characteristics study in this configuration can help understand such an important finding and its implication on our clinical practice. Despite the difference in graft patency there were no differences in physical limitation, angina stability, angina frequency, or quality of life between the two groups.

Introduction In current practice angiographic assessment of the culprit lesion is the main approach to planning the percutaneous revascularisation strategy in high-risk acute coronary syndromes (ACS) patients. Previous histopathology studies in ACS patients have highlighted the presence of multiple vulnerable plaques along the length of the proximal coronary tree. Furthermore, it is suggested that the most vulnerable part of a culprit lesion does not occur at the most stenotic point, as it may lie in adjacent remodelled disease, not visualised by conventional angiography. We determined the relationship of the most vulnerable region to the minimum lumen area using intravascular ultrasound derived virtual histology (IVUS-VH) and compared this to areas of non-culprit disease. Methods This was a single centre, prospective, observational study that had received local ethical approval. The CL was predetermined by two operators based upon ECG changes and angiographic appearance. Successful IVUS-VH imaging of the entire culprit lesion (CL) (n=15) and non-culprit disease (NCD) (n=15) was undertaken using a phased array catheter (EagleEye catheter, 2.9 F/20 MHz; Volcano Corp) with a continuous motorised pullback of 0.5 mm/s. The plaque composition and analysis was determined by off-line analysis (PC VIAS 3.0.394 software; Volcano Corporation). Plaque constituents were measured over the entire length of a lesion and each individual frame of IVUS-VH was analysed to find the position of both the Minimum Lumen Area (MLA) and the distance to the site of maximum necrotic core % (MAX NC). Necrotic core is the IVUS-VH interpretation of high risk histological tissue that is soft, has no real structure and contains dead cells. Results A total of 30 lesions and 1774 IVUS-VH frames were included in the analysis. The mean length of the segment analysed in millimetres (mm) did not differ between the two groups (CL=30.5±11.7 vs NCD=25.6±11.9 p=0.18) all of the MAX NC sites lay proximal to the lesion MLA. In the CL the following percentages of MAX NC frames were within the following distances from the MLA: 0–5 mm (26.7%) 5–10 mm (26.7%) 10 mm+(46.7%). The mean distance at which the MAX NC site lay proximal to the MLA site in the CL was 10.4±8.9 mm (95% CI 5.5 to 15.3). For NCD this distance was statistically less at 4.6±2.9 (95% CI 3 to 6.3) p=0.03. MAX NC frames were positioned at the following distances: 0–5 mm (53.3%) 5–10 mm (46.7%). Conclusions Angiographic assessment alone cannot define the full extent of the culprit lesion. Generally, the most vulnerable areas of plaque are remotely positioned from the most stenotic region. In some cases 46.7% are over 10 mm proximal. Inadequate lesion coverage due to inappropriate stent length selection and placement in the culprit lesion (‘longitudinal geographic miss’) may be one explanation for the significant recurrent event rate in high-risk ACS patients.

Background : The transradial route for coronary intervention has proven to be safe, effective, and widely applicable in different clinical situations. Several compressive hemostatic devices have been introduced that have shown to be safe and are effective in achieving hemostasis. Methods : Seven hundred ninety patients were randomly assigned to receive either TR band or Radistop hemostatic compression devices after transradial coronary procedure. The outcome measures were patient tolerance of the device, local vascular complications, and the time taken to achieve hemostasis. Results : The mean age was 62.88 years, and 74.2% of the patients were men. Patient age, height, weight, wrist circumference, body mass index, male sex, hypertension, diabetes, hypercholesterolemia, and smoking incidences were similar in both groups. There were significantly more patients reporting no discomfort in the TR band group compared to the Radistop group (77% vs. 61%; P = 0.0001). Patients in the Radistop group reported significantly more pain across all categories of severity and three patients in the Radistop group were crossed over to TR band because of severe discomfort. Oozing and ecchymosis were seen in about 16% of the patients. Local small hematoma and large hematoma were seen in 5.4% and 2.2% patients respectively, and similar in both groups. Radial artery occlusion at the time of discharge was seen in 9.2% of the patients though only 6.8% showed persistent occlusion at the time of follow‐up. The time taken to achieve hemostasis was significantly longer in the TR Band group (5.32 ± 2.29 vs. 4.83 ± 2.23 hr; P = 0.004). There was significantly higher incidence of radial artery occlusion in patients with smaller wrist circumference, the patients who experienced radial artery spasm during the procedure, and patients with no heparin administration during the procedure. Conclusions : We have shown in a randomized comparison of Radistop and TR band that both devices are safe and effective as hemostatic compression devices following transradial procedures. However, more patients felt discomfort with the Radistop device and the time taken to achieve hemostasis was longer with TR band. © 2010 Wiley‐Liss, Inc.

Introduction Rupture of a vulnerable plaque is the most important mechanism leading to acute coronary syndromes (ACS). Studies have shown that the most common feature of these plaques is the presence of a thin-cap fibroatheroma (TCFA). Previous studies have also shown the presence of TCFA and healed plaque rupture in some stable lesions. We sought to compare directly the frequency of TCFA and volume of necrotic core present in stable angina (SA) patients, referred for PCI, to those from patients presenting with high-risk ACS. Intravascular Ultrasound (IVUS) derived Virtual Histology (VH) was used to determine plaque morphology as it is validated against post-mortem histological findings. Methods This single centre, prospective, observational study received ethical approval locally. 15 SA and 45 ACS patients (CD=30; NCD=15) were recruited. IVUS-VH imaging was undertaken using a phased array catheter (EagleEye catheter, 2.9 F/20 MHz; Volcano Corp) with a continuous motorised pullback of 0.5 mm/s. Plaque composition and analysis was determined by off-line analysis (PC VIAS 3.0.394 software; Volcano Corporation) From post-mortem correlation data, the highest risk VH-Thin Cap Fibroatheroma (TCFA) consists of three or more IVUS-VH frames with a confluent necrotic core greater than 20% and no evidence of a fibrous cap. Each lesion pullback was examined frame by frame for VH-TCFA and the overall mean percentage of necrotic core present in each lesion type was calculated. An unpaired t-test was used to compare normally distributed data. Results Sixty lesions and 3543 IVUS-VH frames were analysed in total (15 SA/30 CD/15 NCD) We found no statistical differences between SA and NCD plaque volume constituents (mm3): Fibrous=51.4±33.6 vs 66.7±48.7 p=0.32; Fibrofatty=8.7±6.3 vs 12.5±11.9 p=0.3; Necrotic Core=22.5±15.8 vs 29.3±40.1 p=0.5 and Dense Calcium=13.8±11.8 vs 11.2±14.4 p=0.6) SA lesions had on average 1.86 TCFA per lesion which was very similar to 1.88 TCFA per lesion in unstable CD (p=ns). NCD had a trend towards more TCFA per patient (2.33 vs 1.86, p=0.2). SA lesions typically had a reduced mean total plaque volume (mm3) compared to ACS culprit lesions (SA=162±93 < CD=261±138 p=0.02) and therefore a significantly reduced mean volume (mm3) of all plaque constituents except dense calcium. However, the mean percentage of unstable necrotic core, per lesion type, was not different: SA 22.7% vs CD 21.9% vs NCD 21.3% p=0.75. Conclusions Stable coronary artery lesions differ from culprit ACS lesions in terms of the quantity of plaque present. However, they do not differ from culprit or non-culprit lesions in the percentage contribution of unstable plaque. Importantly, high risk VH-TCFA appears to occur with similar prevalence across the groups. There are structural similarities between SA and NCD lesions suggesting that some SA lesions that contain increased numbers of TCFA are not benign.

Background and aim of the study: Aortic stenosis (AS) is thought to be caused by calcific degeneration of the aortic valve. Clinical observations suggest an association between a left dominant coronary circulation and AS, a situation previously investigated at necropsy and with small observational studies. Mitral regurgitation (MR) and aortic regurgitation (AR) are both disorders with multiple etiologies, but neither has any known association with coronary artery dominance.Methods: The coronary angiogram database of a tertiary referral centre was reviewed for consecutive left heart catheter data acquired over a six-year period. The severity of AS was classified by measured pressure gradient (in mmHg) as none (0), mild (<30), moderate (30-49), or severe (>49). Both, MR and AR were assessed visually by the operator.Results: A total of 1,891 patients was included. In the AS group there was a significant association with a left dominant coronary circulation (p<0.0001), and the proportion of patients with left dominance increased with the severity of AS (p<0.005). There was no significant association of AR with coronary artery dominance (p = 0.84). MR was associated with a reduced prevalence of left dominance (p<0.005).Conclusion: AS was associated with a left dominant coronary circulation, and the incidence of left dominance was increased with the severity of AS, but the opposite situation was true for MR. The reasons for these observations remain unclear.

BACKGROUND:Previous angiographic lesion classification systems were derived from analysis of outcomes and lesion complexity in the early stent era. Advances in equipment design and techniques have altered the association between lesion and target vessel characteristics and procedural outcome in modern percutaneous coronary intervention (PCI). We evaluated the precise relationship between lesion characteristics and technical outcome on a lesion by lesion basis in a large dataset. We developed a multivariate model to predict technical failure in PCI.METHODS:Analysis of prospectively collected data on 10,800 lesions in 6,719 consecutive PCI cases between January 2000 and December 2004. Multivariate logistic regression was undertaken to identify predictors of angiographic outcome at each treated lesion (success/failure). Statistical model validation was carried out using data from a further 3,340 treated lesions in 1,940 consecutive cases.RESULTS:Independent variables associated with an increased risk of technical failure included total occlusion, severe calcification, proximal vessel tortuosity >90 degrees, lesion in a degenerate vein graft, and lesion angulation > or =90 degrees. The receiver operating characteristics (ROC) curve for the predicted probability of technical failure was 0.85. Failure occurred in 2.2% of treated lesions in the validation set (ROC curve 0.82, model predicted 2.5%).CONCLUSIONS:We have re-evaluated the association between lesion characteristics and technical outcome in modern PCI. We have thereby developed a contemporary prediction model for angiographic outcome at each treated lesion.

Background— The safety and efficacy of drug-eluting stents (DES) among more generalized “real-world” patients than those enrolled in pivotal randomized controlled trials (RCTs) are controversial. We sought to perform a meta-analysis of DES studies to estimate the relative impact of DES versus bare metal stents (BMS) on safety and efficacy end points, particularly for non–Food and Drug Administration–labeled indications. Methods and Results— Comparative DES versus BMS studies published or presented through February 2008 with ≥100 total patients and reporting mortality data with cumulative follow-up of ≥1 year were identified. Data were abstracted from studies comparing DES with BMS; original source data were used when available. Data from 9470 patients in 22 RCTs and from 182 901 patients in 34 observational studies were included. RCT and observational data were analyzed separately. In RCTs, DES (compared with BMS) were associated with no detectable differences in overall mortality (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81 to 1.15; P =0.72) or myocardial infarction (HR, 0.95; 95% CI, 0.79 to 1.13; P =0.54), with a significant 55% reduction in target vessel revascularization (HR, 0.45; 95% CI, 0.37 to 0.54; P <0.0001); point estimates were slightly lower in off-label compared with on-label analyses. In observational studies, DES were associated with significant reductions in mortality (HR, 0.78; 95% CI, 0.71 to 0.86), myocardial infarction (HR, 0.87; 95% CI, 0.78 to 0.97), and target vessel revascularization (HR, 0.54; 95% CI, 0.48 to 0.61) compared with BMS. Conclusions— In RCTs, no significant differences were observed in the long-term rates of death or myocardial infarction after DES or BMS use for either off-label or on-label indications. In real-world nonrandomized observational studies with greater numbers of patients but the admitted potential for selection bias and residual confounding, DES use was associated with reduced death and myocardial infarction. Both RCTs and observational studies demonstrated marked and comparable reductions in target vessel revascularization with DES compared with BMS. These data in aggregate suggest that DES are safe and efficacious in both on-label and off-label use but highlight differences between RCT and observational data comparing DES and BMS.

Several baseline and angiographic features have been reported as predictors of long-term mortality after percutaneous coronary intervention (PCI) over the years. Women in particular are reported to be at high risk for poor outcome after PCI. We analyzed the predictors of long-term mortality following PCI in large population of patients undergoing PCI in current era.

OBJECTIVE To assess the impact of diabetes on 2-year mortality in current PCI practice. BACKGROUND In patients with coronary artery disease undergoing revascularization, diabetes mellitus is associated with higher mortality. METHODS A retrospective analysis was done of all patients undergoing PCI at our tertiary center between January 2000 and December 2004. There were 6,160 PCI procedures performed in 5,759 patients who received at least one stent. Of these patients, 801 (13.9%) were diabetic and 4,958 (86.1%) were nondiabetic. The primary outcome measure of the study was all-cause mortality. All patients were followed up for a period of 2 years. Multivariate logistic regression analysis was used to test for a potential independent association between diabetic status and follow-up mortality. RESULTS Before adjustment, a trend toward higher mortality was observed in diabetic patients compared to non-diabetics at 1 year (3.2% vs 2.4%) and 2 years (5.1% vs 3.8%), P = 0.12. Independent predictors for mortality were increasing age, renal dysfunction, peripheral vascular disease, NYHA class >2, urgent PCI, treating left main stem lesions, vessel diameter < or = 2.5 mm, and 3-vessel disease. The use of drug-eluting stent was associated with a reduction in mortality. Diabetes was found to have no independent impact on mortality following PCI (odds ratio = 1.08; 95% confidence intervals = 0.73-1.60; P = 0.71). CONCLUSION The presence of diabetes was not an independent predictor of mortality following PCI. A diabetic patient that does not require insulin treatment and has no evidence of macro- or microvascular diabetic disease could enjoy a PCI outcome similar to nondiabetic subjects.

Background: Long-term safety of drug-eluting stent (DES) is still a concern. We aimed to assess the impact of DES use on all-cause mortality and target-lesion revascularisation (TLR) in routine clinical practice.Methods: Retrospective analysis of all patients undergoing percutaneous coronary intervention with stent implantation at our institution between January 2003 and December 2004. To account for differences in patient characteristics, logistic regression was used to produce a propensity score for DES group membership. Patients receiving DES were then matched to patients receiving bare metal stents (BMS) with identical propensity scores. These two groups were then compared with respect to the incidence of TLR and all-cause mortality.Results: During the study period 995 patients received DES. Of these, 82 patients had combined DES and BMS use and were therefore excluded; leaving 913 DES patients compared to 2105 BMS patients. Patients who received DES were more likely to be diabetic, hypertensive, had more lesions treated, restenotic lesions treated, left anterior descending and left main stem interventions, long lesions treated, small diameter lesions treated, and American Heart Association C-type lesions treated. After performing propensity-matching, to account for differences in patient characteristics, we were able to successfully match 777 DES patients to 777 BMS patients. The TLR rates at 24 months were significantly lower for DES patients (DES-4.2% vs BMS-9.2%, p < 0.001). All-cause mortality was also significantly lower for DES patients (DES-1.8% vs BMS-4.0%, p=0.01).Conclusions: In routine clinical practice DES implantation continued to demonstrate a significant reduction in the need for repeat intervention at 24 months. All-cause and cardiac mortality was also significantly lower for DES patients compared to BMS patients. (C) 2008 Elsevier Ireland Ltd. All rights reserved.