Bifurcation PCI with a hybrid strategy with drug- eluting balloons versus a stepwise provisional two- stent strategy: Rationale and design of the hybrid DEB study.

The optimal treatment strategy for coronary bifurcation lesions by percutaneous coronary intervention (PCI) is complex and remains a subject of debate. Current guidelines advise a stepwise provisional approach with optional two-stent strategy. However, a two-stent strategy, both upfront and stepwise provisional, is technically demanding. Therefore, there is increasing interest in the use of drug-eluting balloons (DEB) in bifurcation lesions, mainly after a provisional approach with unsatisfactory result of the side branch. Some small pilot studies already showed that the use of DEB in bifurcation lesions is safe and feasible. However, a randomized comparison of this hybrid DEB strategy with a two-stent strategy is currently lacking. TRIAL DESIGN: The Hybrid DEB study is a prospective, multicenter, randomized controlled trial investigating noninferiority of a hybrid DEB approach, using a combination of a drug-eluting stent (DES) in the main vessel and DEB in the side branch, compared to stepwise provisional two-stent strategy in patients with true bifurcation lesions. A total of 500 patients with de novo true coronary bifurcation lesions, treated with a stepwise provisional approach and an unsatisfactory result of the side branch after main vessel stenting (≥ 70% stenosis and/or < thrombolysis in myocardial infarction III flow), will be randomized in a 1:1 ratio to receive either treatment with a DEB or with a DES in the side branch. The primary endpoint is a composite endpoint of the occurrence of all-cause death, periprocedural or spontaneous myocardial infarction and/or target vessel revascularization at the anticipated median 2-year follow-up. CONCLUSION: The Hybrid DEB study will compare in a multicenter, randomized fashion a hybrid DEB approach with a stepwise provisional two-stent strategy in patients with true bifurcation lesions. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT05731687.

Transoral Outlet Reduction to Tackle Weight Regain After Roux-en-Y Gastric Bypass: a Single Center Initial Experience.

BACKGROUND: Long-term failure after Roux-en-Y gastric bypass (RYGB) is well known and occurs in 10-15% of patients according to the literature. Causes are multifactorial and dilatation of the gastro-jejunal anastomosis (GJA) is only one of these. A transoral outlet reduction (TORe) with endoscopic sutures to reinstall more restriction could be a valid and safe alternative to reduce regained weight after failed gastric bypass surgery. The objective of this article is to describe our single-center experience and discuss the adverse events of the technique. OBJECTIVES: To describe our single-center case series and adverse events after TORe for weight regain after RYGB. METHODS: We report a case series of 20 patients referred due to weight regain after RYGB with a dilated GJA. TORe was performed using an endoscopic full-thickness suture device (Apollo OverStitch®) to reduce the diameter of the GJA and the volume of the gastric reservoir. Prospectively collected data on technical feasibility, safety and efficacy are described with a median follow-up of 22 (6-38) months. RESULTS: Mean BMI was 44.5 kg/m2 at the time of RYGB. Postoperative nadir BMI was 27,7 kg/m2. The average time to TORe was 12.1 years after initial RYGB. Patients regained a mean 45.9% of excess body weight loss (EWL) before TORe and had a mean preprocedural BMI of 35.3 kg/m2. The aim was to reduce the aperture of the GJA to 5 mm which was done with a mean of 1.7 sutures and 3.5 stitches. The mean absolute weight loss was 13 kg and BMI reduction was 3.9 kg/m2 after 6 months. After a median follow-up of 22 months, a BMI of 31.4 kg/m2 was observed. Dumping symptoms resolved in four of our patients 6 weeks after TORe. Procedural adverse events were nausea and vomiting, sore throat, mild transient abdominal pain, diarrhea and constipation. All of them were treated conservatively. Due to a lack of weight loss, a suture failure was assumed in two of our patients. We describe one case of postprocedural mediastinitis, presumably due to a distal esophageal perforation, treated with a laparoscopic drainage without clinical evidence for perforation. CONCLUSIONS: Endoscopic TORe by narrowing the dilated GJA appears to be an efficient and safe minimal invasive option to tackle weight regain after RYGB and should be more used in clinical practice.

Synthetic Versus Biological Mesh in Laparoscopic and Open Ventral Hernia Repair (LAPSIS): Results of a Multinational, Randomized, Controlled, and Double-blind Trial.

OBJECTIVE: The aim of this study was to investigate the approach (open or laparoscopic) and mesh type (synthetic or biological) in ventral hernias in a clean setting.Summary of Background Data: The level of evidence on the optimal surgical approach and type of mesh in ventral hernia repair is still low. METHODS: Patients with a ventral abdominal hernia (diameter 4-10 cm) were included in this double-blind randomized controlled trial across 17 hospitals in 10 European countries. According to a 2 × 2-factorial design, patients were allocated to 4 arms (open retromuscular or laparoscopic intraperitoneal, with synthetic or Surgisis Gold biological mesh). Patients and outcome assessors were blinded to mesh type used. Major postoperative complication rate (hernia recurrence, mesh infection, or reoperation) within 3 years after surgery, was the primary endpoint in the intention-to-treat population. RESULTS: Between September 1st, 2005, and August 7th, 2009, 253 patients were randomized and 13 excluded. Six of 61 patients (9.8%) in the open synthetic mesh arm, 15 of 66 patients (22.7%) in the open biological mesh arm, 7 of 64 patients (10.9%) in the laparoscopic synthetic mesh arm and 17 of 62 patients (27.4%) in the laparoscopic biological mesh arm had a major complication. The use of biological mesh resulted in significantly more complications (P = 0.013), also after adjusting for hernia type, body mass index, and study site. The trial was prematurely stopped due to an unacceptable high recurrence rate in the biological mesh arms. CONCLUSIONS: The use of Surgisis Gold biological mesh is not recommended for noncomplex ventral hernia repair. TRIAL REGISTRATION: This trial was registered at controlled-trials.com (ISRCTN34532248).

Beta-blocker effect on ST-segment: a prespecified analysis of the EARLY-BAMI randomised trial.

OBJECTIVE: The effect of early intravenous (IV) beta-blockers (BBs) administration in patients undergoing primary percutaneous coronary intervention (pPCI) on ST-segment deviation is unknown. We undertook a prespecified secondary analysis of the Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction (EARLY-BAMI) trial to investigate the effect of early IV BB on ST-segment deviation. METHODS: The EARLY-BAMI trial randomised patients with ST-elevation myocardial infarction (STEMI) to IV metoprolol (2×5 mg bolus) or matched placebo before pPCI. The prespecified outcome, evaluated by an independent core laboratory blinded to study treatment, was the residual ST-segment deviation 1 hour after pPCI (ie, the percentage of patients with >3 mm cumulative ST deviation at 1 hour after pPCI). RESULTS: An ECG for the evaluation of residual ST-segment deviation 1 hour after pPCI was available in 442 out of 683 randomised patients. The BB group had a lower heart rate after pPCI compared with placebo (71.2±13.2 vs 74.3±13.6, p=0.016); however, no differences were noted in the percentages of patients with >3 mm cumulative ST deviation at 1 hour after pPCI (58.6% vs 54.1%, p=0.38, in BB vs placebo, respectively) neither a significant difference was found for the percentages of patients in each of the four prespecified groups (normalised ST-segment; 1-3 mm; 4-6 mm;>6 mm residual ST-deviation). CONCLUSIONS: In patients with STEMI, who were being transported for primary PCI, early IV BB administration did not significantly affect ST-segment deviation after pPCI compared with placebo. The neutral result of early IV BB administration on an early marker of pharmacological effect is consistent with the absence of subsequent improvement of clinical outcomes.

Macrostylis metallicola spec. nov.-an isopod with geographically clustered genetic variability from a polymetallic-nodule area in the Clarion-Clipperton Fracture Zone.

BACKGROUND: The Clarion-Clipperton Fracture Zone (CCFZ) in the Northeast Central Pacific Ocean is a region of heightened scientific and public interest because of its wealth in manganese nodules. Due to a poor ecological understanding at the abyssal seafloor and limited knowledge of the organisms inhabiting this area, huge efforts in alpha taxonomy are required. To predict and manage potential hazards associated with future mining, taxonomy is an essential first step to grasp fundamental ecosystem traits, such as biogeographic patterns, connectivity, and the potential for post-impact recolonization. Amongst samples from the Global Sea Mineral Resources NV exploration area (EA) in the CCFZ an undescribed species of the isopod crustacean family Macrostylidae was discovered. Previously, it has been reported from two other nearby regions, the Institut Français de Recherche pour l'Exploitation de la Mer and BGR EAs. There it was one of the more widely distributed and abundant species of the benthic macrofauna and exhibited geographically structured populations. It nevertheless remained taxonomically undescribed so far. METHODS: The new species is described by means of integrative taxonomy. Morphologically, macro photography, confocal microscopy, scanning electron microscopy and light microscopy were used to describe the species and to get first insights on its phylogenetic origin. Additionally, mitochondrial DNA markers were used to test the morphological allocation of the two dimorphic sexes and juvenile stages, to analyze geographic patterns of genetic differentiation, and to study intra-and inter-species relationships, also in light of previously published population genetics on this species. RESULTS: The new species, Macrostylis metallicola spec. nov., is a typical representative of Macrostylidae as recognizable from the fossosoma, prognathous cephalothorax, and styliform uropods. It can be morphologically distinguished from congeners by a combination of character states which include the autapomorphic shape of the first pleopod of the copulatory male. A sexual dimorphism, as expressed by a peculiar sequence of article length-width ratios of the male antennula, indicates a relationship with M. marionae Kniesz, Brandt & Riehl (2018) and M. longipes Hansen (1916) amongst other species sharing this dimorphism. Mitochondrial genetic markers point in a similar direction. M. metallicola appears to be amongst the more common and widely distributed components of the benthic macrofauna in this region which may suggest a resilience of this species to future mining activities because of its apparent potential for recolonization of impacted sites from adjacent areas of particular environmental interest. The genetic data, however, show geographic clustering of its genetic variability, pointing towards a limited potential for dispersal. Local extinction of populations could potentially not be compensated quickly and would mean a loss of genetic diversity of this species.

Foreign body granuloma reaction following SIRT mimicking peritoneal metastases: a word of caution.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with poor survival rates. Surgical resection is the only curative treatment option, yet only a small portion of cases are resectable. In unresectable situations, suggested therapy consists of a systemic chemotherapy regimen with cisplatinum and gemcitabine. Selective internal radiation therapy (SIRT) has been proposed as an alternative treatment option and may lead to downstaging of unresectable iCCA to surgery. We present a case of a female patient diagnosed with an unresectable iCCA treated with SIRT in order to obtain downstaging. Explorative laparoscopy three months later showed multiple peritoneal lesions in the left upper quadrant, mimicking peritoneal metastases. Anatomopathological investigation showed a foreign body granuloma surrounding the SIRT resin particles. These findings have important consequences, as the presence of peritoneal metastases implies a palliative situation. Anatomopathological confirmation of any intra-abdominal lesion mimicking peritoneal metastases should be carried out.

Forgotten pathogen: tetanus after gastrointestinal surgery.

A previously healthy 79-year-old woman underwent an urgent laparotomy and resection of a strangulated loop of small bowel. On the second postoperative day, she developed symptoms suspicious for postoperative tetanus. A transfer to the intensive care unit was necessary for aggressive supportive therapy. The patient required 5 months of intensive physiotherapy and rehabilitation and was successfully discharged home. New cases of tetanus have become rare in developed countries. This potentially lethal disease affects both non-immunised and inadequately immunised patients. The occurrence of tetanus after gastrointestinal surgery is extremely rare. Prevention is key and can be achieved with correct immunoprophylaxis. Older patients are often inadequately immunised. Should tetanus immunoprophylaxis routinely be checked for elderly patients undergoing gastrointestinal surgery? Or can we limit the immunisation to severe cases of ischaemic bowel injury with necrosis and/or soiling of the abdominal cavity?

The Effect of Dumping on Weight Loss in Conversion of Failed Restrictive Surgery: a Cross-Sectional Pilot Study.

PURPOSE: Dumping is currently seen as a negative side effect of Roux-en-Y gastric bypass (RYGB). However, it may help patients to comply with their prescribed diet. In this study, we assess the role of dumping on weight loss in patients who have undergone conversion of failed restrictive surgery into RYGB. METHODS: An analysis was performed of 100 consecutive patients who underwent revisional RYGB (rRYGB) between 2006 and 2011 due to inadequate weight loss or band intolerance after laparoscopic adjustable gastric banding (LAGB). The percentage of excess weight loss (%EWL) was used to evaluate weight reduction. The Sigstad clinical diagnostic index was used to detect dumping symptoms. RESULTS: Fifty-five patients (59.1%) suffered from dumping. Overall, dumpers showed a greater %EWL than non-dumpers (83.8 ± 48.0 vs 66.9 ± 44.1%, respectively, p = 0.0725). When rRYGB was performed because of inadequate weight loss following LAGB, dumping played a crucial role in weight loss (88.0 ± 21.2 vs 68.9 ± 34.5%, p = 0.0137). This effect positively correlates to post-LAGB body mass index (BMI) with a statistically significant result at BMI > 35 kg/m2 (82.4 ± 15.7 vs 58.4 ± 32.4%, p = 0.00341). A regression analysis of the Sigstad dumping score and %EWL shows that dumping tends to increase the %EWL. CONCLUSIONS: This study provides new insights into the effect of dumping on weight loss in patients who underwent conversion of failed restrictive surgery into RYGB. Based on the findings in our patient group, we suggest that dumping helps patients achieve sustainable weight loss. Therefore, dumping can be regarded as a positive side effect rather than a complication.

Moderating the Enthusiasm of Sleeve Gastrectomy: Up to Fifty Percent of Reflux Symptoms After Ten Years in a Consecutive Series of One Hundred Laparoscopic Sleeve Gastrectomies.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a popular one-stage bariatric procedure with a proven efficacy on weight loss. However, the relationship between LSG and gastroesophageal reflux disease (GERD) remains a subject of debate. The objective is to determine the long-term effect of LSG on weight loss and reflux disease. METHODS: A retrospective analysis of 100 consecutive patients who underwent an LSG between January 2005 and March 2009 was performed. The effect of LSG on weight evolution and the relationship between preoperative and postoperative GERD symptoms and PPI dependency was analyzed. RESULTS: A mean follow-up of 8.48 years (range 6.1-10.3) was achieved. We observed a long-term % excess weight loss (%EWL) of 60%. A significant increase in reflux symptoms and use of PPIs was seen. Seventeen percent suffered from reflux disease preoperatively versus 50% at the end of the postoperative follow-up (RR = 2.5882, 95% CI [1.6161-4.1452], p value = 0.0001). The chance of developing de novo reflux after LSG was 47.8% (32/67). Reflux disease was present in 7 of the 26 patients who underwent a secondary Roux-en-Y gastric bypass (RYGB). In four of these seven patients, reflux disease disappeared completely after the secondary RYGB (57.1%). CONCLUSIONS: A satisfactory long-term effect on weight loss was achieved. However, a significant increase in GERD and PPI dependency after LSG was noted. New onset GERD was seen in more than 40% of the study population. Conversion to RYGB is a good option in patients with refractory reflux disease after LSG.

Pooled Analysis Comparing the Efficacy of Intracoronary Versus Intravenous Abciximab in Smokers Versus Nonsmokers Undergoing Primary Percutaneous Coronary Revascularization for Acute ST-Elevation Myocardial Infarction.

Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We pooled data from 5 randomized trials comparing intracoronary versus intravenous abciximab bolus in patients undergoing primary PCI. The primary end point was the composite of death or reinfarction at a mean follow-up of 292 ± 138 days. Of 3,158 participants, 1,369 (43.3%) were smokers, and they had a lower risk of the primary end point in crude, but not in adjusted analyses (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.63 to 1.21, p = 0.405). Intracoronary versus intravenous abciximab was associated with a significant reduction in the risk of primary end point among smokers (3.6% vs 8.0%; HR 0.43, 95% CI 0.26 to 0.72, p = 0.001), but not in nonsmokers (10.2% vs 9.9%; HR 0.99, 95% CI 0.72 to 1.36, p = 0.96), with a significant interaction (p = 0.009). Furthermore, intracoronary abciximab decreased the risk of reinfarction in smokers (HR 0.30, 95% CI 0.15 to 0.62, p = 0.001), with no difference in nonsmokers (HR 1.20, 95% CI 0.71 to 2.01, p = 0.50). Stent thrombosis was lowered by intracoronary abciximab in smokers (HR 0.28, 95% CI 0.06 to 0.66, p = 0.009), but was ineffective in nonsmokers (HR 1.04, 95% CI 0.54 to 2.00, p = 0.903). Interaction testing showed heterogeneity in treatment effect for reinfarction (p = 0.002) and stent thrombosis (p = 0.018) according to smoking status. In conclusion, among patients with STEMI undergoing primary PCI, smoking status did not affect the adjusted risk of clinical events. Intracoronary abciximab bolus improved clinical outcomes by reducing the risk of death or reinfarction.

Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention.

BACKGROUND: The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. OBJECTIVES: This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population. METHODS: STEMI patients presenting <12 h from symptom onset in Killip class I to II without atrioventricular block were randomized 1:1 to IV metoprolol (2 × 5-mg bolus) or matched placebo before PPCI. Primary endpoint was myocardial infarct size as assessed by cardiac magnetic resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct size and incidence of ventricular arrhythmias. Safety endpoints included symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock. RESULTS: A total of 683 patients (mean age 62 ± 12 years; 75% male) were randomized to metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ between the metoprolol (15.3 ± 11.0%) and placebo groups (14.9 ± 11.5%; p = 0.616). Peak and area under the creatine kinase curve did not differ between both groups. LV ejection fraction by CMR was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group (p = 0.68). The incidence of malignant arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050). The incidence of adverse events was not different between groups. CONCLUSIONS: In a nonrestricted STEMI population, early intravenous metoprolol before PPCI was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events. (Early-Beta blocker Administration before reperfusion primary PCI in patients with ST-elevation Myocardial Infarction [EARLY-BAMI]; EudraCT no: 2010-023394-19).

Outcome after percutaneous coronary intervention for different indications: long-term results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

AIMS: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up. METHODS AND RESULTS: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients. CONCLUSIONS: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.

Integrating Ecosystem Engineering and Food Web Ecology: Testing the Effect of Biogenic Reefs on the Food Web of a Soft-Bottom Intertidal Area.

The potential of ecosystem engineers to modify the structure and dynamics of food webs has recently been hypothesised from a conceptual point of view. Empirical data on the integration of ecosystem engineers and food webs is however largely lacking. This paper investigates the hypothesised link based on a field sampling approach of intertidal biogenic aggregations created by the ecosystem engineer Lanice conchilega (Polychaeta, Terebellidae). The aggregations are known to have a considerable impact on the physical and biogeochemical characteristics of their environment and subsequently on the abundance and biomass of primary food sources and the macrofaunal (i.e. the macro-, hyper- and epibenthos) community. Therefore, we hypothesise that L. conchilega aggregations affect the structure, stability and isotopic niche of the consumer assemblage of a soft-bottom intertidal food web. Primary food sources and the bentho-pelagic consumer assemblage of a L. conchilega aggregation and a control area were sampled on two soft-bottom intertidal areas along the French coast and analysed for their stable isotopes. Despite the structural impacts of the ecosystem engineer on the associated macrofaunal community, the presence of L. conchilega aggregations only has a minor effect on the food web structure of soft-bottom intertidal areas. The isotopic niche width of the consumer communities of the L. conchilega aggregations and control areas are highly similar, implying that consumer taxa do not shift their diet when feeding in a L. conchilega aggregation. Besides, species packing and hence trophic redundancy were not affected, pointing to an unaltered stability of the food web in the presence of L. conchilega.

Intracoronary abciximab in diabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. OBJECTIVES: To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. RESULTS: Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26-0.99; p=0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26-1.20; p=0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07-0.99; p=0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n=2574). CONCLUSIONS: In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial.

Soluble interleukin 6 receptor levels are associated with reduced myocardial reperfusion after percutaneous coronary intervention for acute myocardial infarction.

AIMS: Interleukin-6 receptor (IL-6R) signalling has been suggested to play a causal role in the development and outcome of coronary heart disease (CHD). The aim of this study was to investigate the association of sIL-6R levels with myocardial reperfusion after percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI). METHODS: Blood was sampled from 70 patients presenting with STEMI at 6 different time-points (baseline, post-PCI, t=1h, t=6h, t=24h, t=2w). Coronary angiograms post-PCI were analysed for myocardial blush grade (MBG) as indicator of myocardial reperfusion. Serum IL-6 and sIL-6R were measured using IL-6 and sIL-6R enzyme-linked immunosorbent assays (ELISA). RESULTS: sIL-6R levels fluctuated biphasic during the two weeks after STEMI. Reduced MBG was associated with a larger change in sIL-6R levels between baseline and post-PCI compared to optimal MBG (-13.40; SEM 2.78ng/ml vs -1.99; SEM 2.35ng/ml, respectively; p<0.001). Patients with reduced MBG also showed a larger increase in sIL-6R levels after PCI and 1h after myocardial infarction (MI) compared to optimal MBG (respectively 11.56; SEM 2.68ng/ml vs 3.02; SEM 2.39ng/ml; p=0.018). IL-6/sIL-6R ratio was also more increased in patients with reduced MBG at 24h after myocardial infarction (0.23; SEM 0.08-0.51 vs 0.10; SEM 0.05-0.21; p=0.024). An optimal MBG was associated with a 10ng increase in sIL-6R level between baseline and post-PCI (OR 1.687, CI 1.095-2.598; p=0.018). CONCLUSIONS: sIL-6R levels fluctuate biphasic during the two weeks after MI with larger changes and increased IL-6/sIL-6R ratio in patients with reduced MBG. Further research is needed to increase our understanding of the possible causality of these associations.

Appropriate use of bioresorbable vascular scaffolds in percutaneous coronary interventions: a recommendation from experienced users : A position statement on the use of bioresorbable vascular scaffolds in the Netherlands.

Percutaneous coronary interventions (PCI) have become a reliable revascularisation option to treat ischaemic coronary artery disease. Drug-eluting stents (DES) are widely used as first choice devices in many procedures due to their established good medium to long term outcomes. These permanent implants, however, do not have any residual function after vascular healing following the PCI. Beyond this initial healing period, metallic stents may induce new problems, resulting in an average rate of 2 % reinterventions per year. To eliminate this potential late limitation of permanent metallic DES, bioresorbable coronary stents or 'vascular scaffolds' (BVS) have been developed. In a parallel publication in this journal, an overview of the current clinical performance of these scaffolds is presented. As these scaffolds are currently CE marked and commercially available in many countries and as clinical evidence is still limited, recommendations for their general usage are needed to allow successful clinical introduction.

Uninterrupted oral anticoagulation versus bridging in patients with long-term oral anticoagulation during percutaneous coronary intervention: subgroup analysis from the WOEST trial.

AIMS: To investigate the optimal periprocedural antithrombotic strategy in patients on long-term oral anticoagulation (OAC) who require percutaneous coronary intervention with stenting. METHODS AND RESULTS: The WOEST study was a randomised controlled trial which recruited 573 patients on long-term OAC who underwent PCI. The periprocedural treatment strategy was left to the operator's discretion. To assess the safety and feasibility of uninterrupted oral anticoagulation (UAC) and bridging therapy (BT), bleeding complications and MACCE were assessed in patients treated according to UAC (n=241) and BT (n=322) regimen. After 30 days, as well as after one year, there were no significant differences in bleeding complications (HR 1.14, 95% CI: 0.77-1.69, p=0.51, and HR 1.26, 95% CI: 0.94-1.69, p=0.12, respectively) and MACCE. MACCE tended to be less frequent in the UAC group (respectively HR 0.48, 95% CI: 0.15-1.51, p=0.21, and HR 0.72, 95% CI: 0.46-1.14, p=0.16). Additionally, adjustment with a propensity score revealed no significant differences. Periprocedural INR was not associated with bleeding or MACCE. CONCLUSIONS: In the WOEST study, UAC was not associated with an increase of bleeding or MACCE compared to bridging therapy. This is the largest study up to now to support the current guidelines. The WOEST trial is registered with ClinicalTrials.gov, number NCT00769938.

Rationale and design of a double-blind, multicenter, randomized, placebo-controlled clinical trial of early administration of intravenous ß-blockers in patients with ST-elevation myocardial infarction before primary percutaneous coronary intervention: EARLY ß-blocker administration before primary PCI in patients with ST-elevation myocardial infarction trial.

BACKGROUND: ß-Blockers have a class 1a recommendation in the treatment of patients with ST-elevation myocardial infarctions (STEMIs), as they are associated with a reduced mortality, recurrent myocardial infarction, life-threatening arrhythmias, and with prevention of unfavorable left ventricular remodeling. Whether early administration before primary percutaneous coronary intervention (PCI) of intravenous ß-blockers reduces the infarct size in the current era is unknown. HYPOTHESIS: We postulate that the early administration of ß-blockers will reduce the myocardial infarcted area as assessed by magnetic resonance imaging (MRI) at 30 days. DESIGN: In a multinational, multicenter, double-blind, placebo-controlled, randomized trial, patients with symptoms and signs of STEMI and transferred to a hospital for primary PCI will be randomized in a 1:1 fashion to intravenous metoprolol (5 mg twice daily) administration or placebo. Before admission, study treatment will be started as soon as possible after the diagnosis of STEMI. After admission, primary PCI will be performed as per standard of care. After primary PCI, medical treatment will occur as per current guidelines in all patients, including the use of oral ß-blockers. The primary end point is the myocardial infarct size as assessed by MRI at 30 days. Based on a superiority design and assuming an 18% relative infarct size reduction (from 28% to 23.5%), 408 patients are required to be enrolled, accounting for 20% drop-out (α = .05 and power = 80%). SUMMARY: The EARLY-BAMI trial is a multinational, multicenter, double-blind, placebo-controlled, randomized clinical trial that will investigate the impact of intravenous metoprolol administration before primary PCI for STEMI on myocardial infarct size as measured with MRI at 30 days.

Effects of baseline coronary occlusion and diabetes mellitus in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI). However, the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied. The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of randomized trials comparing intracoronary with intravenous abciximab bolus administration. A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included. Diabetes was present in 578 patients (19%). The primary outcome was mortality after a median follow-up period of 375 days. Secondary end points were reinfarction and stent thrombosis. In patients without diabetes, IRA occlusion versus no occlusion was not associated with increased rates of mortality (4.3% vs 2.7%, p = 0.051) and reinfarction (3.3% vs 2.5%, p = 0.33). Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality (10.6% vs 4.6%, p = 0.01) and reinfarction (5.6% vs 2.1%, p = 0.03). Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic (2.1% vs 1.0%, p = 0.04) and diabetic (3.2% vs 0.8%, p = 0.05) cohorts. Interaction analysis demonstrated that the risk for death and reinfarction was significantly increased when diabetes and IRA occlusion occurred concomitantly. In conclusion, patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfarction. Preprocedural IRA occlusion increased the risk for stent thrombosis, irrespective of diabetic status.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.