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Background: Five to 10% of patients with acute myocardial infarction develop cardiogenic shock and the majority of these patients are expected to die within the first few weeks. In this study, we review our recent experience in the management of patients with cardiogenic shock complicating MI and examine the effect of early invasive revascularisation on mortality. Methods: Thirty-six consecutive patients who developed cardiogenic shock less than 48 h after MI were retrospectively evaluated and divided into two treatment groups. One group received early invasive revascularisation (n=24) and the other group had no early invasive revascularisation, but received similar conventional intensive care medical treatment (n=12). Results: Baseline characteristics and hemodynamic variables were similar in both groups. Apart from invasive revascularisation and the use of intra aortic balloon counterpulsation (IABP), treatment strategies did not differ between the two groups. Thirty-day mortality was 21% in the revascularised group of patients and 58% in the non-revascularised group (P<0.05). Conclusions: Our data support previous observations suggesting that an aggressive treatment strategy including early invasive revascularisation and IABP is associated with improved short and long-term survival in patients with cardiogenic shock. Since early revascularisation appears safe with a considerable treatment benefit, this approach must be considered in patients with short shock duration early after MI. [Copyright &y& Elsevier]

The number of coronary arteriographies (CAG) has increased tremendously all over the industrialised world over the past years. Even though the potential benefit is high in patients with angina pectoris, for example, with expected life prolongation in case of three-vessel disease or left main stenosis with subsequent coronary artery bypass grafting (CABG), the indication for treatment is not as dramatic in all patients and at the same time CAG is a procedure with at least, some risk, and costs are not negligible. It is therefore pertinent, and hence also the purpose of the present analysis, to make observations on indications, clinical and angiographic findings and their combinations which could be helpful in clinical practice/decision-making. Furthermore, the purpose was to analyse the consequences of CAG with respect to revascularisations such as percutaneous transluminal coronary angioplasty (PTCA) or CABG.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: We aimed to relate the amount of jeopardized myocardium to mortality in shocked patients presenting to the catheterization laboratory with ST-elevation myocardial infarction (STEMI) and cardiogenic shock.Background: In contrast with historical data and previous professional guidance, contemporary randomized data suggest that multi-vessel revascularization in such patients does not improve survival; mechanistic insight is incomplete.Methods: Clinical databases identified cases of STEMI and shock triaged for primary percutaneous coronary intervention (PPCI) in Eastern Denmark from June 2011 to December 2014 (n = 128). British Cardiovascular Intervention Society (BCIS)-1 jeopardy scores were calculated from angiography. The study endpoint was 30-day mortality.Results: Median lactate values were 6.0 [2.9-10.7] mmol/L. 30-day mortality was 53.9%. 68% of patients had multi-vessel coronary disease. Median pre-PCI BCIS-1 myocardial jeopardy scores were 8 [6-10]. After multiple logistic regression increasing age (p = 0.008; odds ratio [OR] 1.06), lactate values (p = 0.017; OR 1.02), mechanical ventilation (p = 0.011; OR 1.25) and a systolic blood pressure ≤ 90 mmHg at end-case (p = 0.005; OR 1.26) were predictive of 30-day mortality. Post-PPCI culprit vessel TIMI 3 flow was associated with reduced mortality (p < 0.001; OR 0.66). There was no association between pre-PCI jeopardy scores and the primary endpoint.Conclusions: In patients with STEMI and shock, myocardial jeopardy scores do not relate to patient outcomes. Jeopardy scores may be applied to existing datasets in order to understand why multi-vessel revascularization does not lead to the anticipated clinical benefits in cardiogenic shock. [ABSTRACT FROM AUTHOR]

• SuPAR was a strong prognostic biomarker of non-cardiac mortality after STEMI. • The suPAR level was independent of sampling time < 12 h after revascularization. • SuPAR may identify patients in risk of non-cardiac mortality prior to discharge. Identification of patients at high risk of non-cardiac mortality following ST-segment elevation myocardial infarction (STEMI) could guide clinicians to identify patients who require attention due to serious non-cardiac conditions after the acute phase of STEMI. The purpose of this study was to evaluate if the non-specific and prognostic biomarker of inflammation and comorbidity, soluble urokinase receptor (suPAR), could predict non-cardiac mortality in a cohort of STEMI patients. SuPAR was measured in 1,190 STEMI patients who underwent primary percutaneous coronary intervention (pPCI). The primary endpoint was non-cardiac mortality, secondary endpoints were cardiac mortality, all-cause mortality, reinfarction and periprocedural acute kidney injury. Backwards elimination of potential confounders significantly associated with the respective outcome was used to adjust associations. Patients were followed for a median of 3.0 years (interquartile range 2.5– 3.6 years). Multivariate cox regression revealed that a plasma suPAR level above 3.70 ng mL−1 was associated with non-cardiac and cardiac mortality at hazard ratios 3.33 (95% confidence interval 1.67–6.63, p = 0.001, adjusted for age) and 0.99 (0.18–5.30, p = 0.98, adjusted for previous myocardial infarction and left ventricular ejection fraction), respectively. In patients with pPCI treated STEMI, suPAR was an independent prognostic biomarker of non-cardiac but not cardiac mortality and may identify patients with high risk of non-cardiac mortality. [ABSTRACT FROM AUTHOR]

To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization. • Irreversible damage to the myocardium after STEMI can be predicted in 47% of the patients. • ICD implantation can be considered in these patients with irreversible damage to the myocardium. • Cardiac MRI during admission for STEMI can help directing the future treatment in selected patients. • 77% of STEMI patients with LVEF <35% will experience increase in their LVEF to >35% within three months. [ABSTRACT FROM AUTHOR]

To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT) of ST-elevation myocardial infarction (STEMI). We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%) and 617 contemporary non-participants (22%) had died (Log-Rank: P < 0.001) after a median follow-up of 1333 days (range: 1–2021 days). In an unadjusted Cox regression model all groups of non-participants had a higher hazard ratio to predict mortality compared to participants: eligible excluded (n = 144) (hazard ratio: 3.41 (95% CI: (2.69–4.32)), ineligible excluded (n = 472) (hazard ratio: 3.42 (95% CI: (2.44–4.80), eligible non-screened (n = 154) (hazard ratio: 3.37 (95% CI: (2.36–4.82)), ineligible non-screened (n = 154) (hazard ratio: 6.48 (95% CI: (4.77–8.80). Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias. • Participants in the DANAMI-3 trial were not representative to the background population with STEMI. • Participants in the DANAMI-3 trial were not representative to the per protocol target population. • Sampling bias and unreported screening had occurred. • Screening logs may not be suitable for addressing issues of external validity. [ABSTRACT FROM AUTHOR]

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes.Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure.Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023).Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effect of intramyocardial injections of autologous VEGF-A165-stimulated adipose-derived stromal cells (ASCs) in patients with refractory angina. MyStromalCell trial is a randomized double-blind placebo-controlled study including sixty patients with CCS/NYHA class II-III, left ventricular ejection fraction > 40%, and at least one significant coronary artery stenosis. Patients were treated with ASC or placebo in a 2 : 1 ratio. ASCs from the abdomen were culture expanded and stimulated with VEGF-A165. At 6 months follow-up, bicycle exercise tolerance increased significantly in time duration 22 s (95%CI −164 to 208 s) (P=0.034), in watt 4 (95%CI −33 to 41, 0.048), and in METs 0.2 (95%CI −1.4 to 1.8) (P=0.048) in the ASC group while there was a nonsignificant increase in the placebo group in time duration 9 s (95%CI −203 to 221 s) (P=0.053), in watt 7 (95%CI −40 to 54) (P=0.41), and in METs 0.1 (95%CI −1.7 to 1.9) (P=0.757). The difference between the groups was not significant (P=0.680, P=0.608, and P=0.720 for time duration, watt, and METs, resp.). Intramyocardial delivered VEGF-A165-stimulated ASC treatment was safe but did not improve exercise capacity compared to placebo. However, exercise capacity increased in the ASC but not in the placebo group. This trial is registered with ClinicalTrials.gov NCT01449032. [ABSTRACT FROM AUTHOR]

Background: Although some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3-DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and deferred stenting.Objectives: This study sought to evaluate the effect of deferred stent implantation on infarct size, myocardial salvage, and microvascular obstruction (MVO) in patients with STEMI.Methods: In the present DANAMI-3 substudy, a total of 510 patients with STEMI were randomized to PCI with deferred versus immediate stent implantation. The patients underwent a cardiac magnetic resonance examination before discharge after the index procedure and again 3 months later. The primary endpoint was final infarct size.Results: Deferred stenting did not reduce final infarct size (9% left ventricle [LV]; interquartile range [IQR]: 3% to 18% vs. 10% LV; IQR: 3% to 18%; p = 0.67). Similarly, deferred stenting was not associated with myocardial salvage index (66%; IQR: 50% to 89% vs. 67%; IQR: 49% to 88%; p = 0.80) or presence of MVO (43% vs. 42%; p = 0.78). In a post hoc analysis, stent length was the only subgroup of 7 that had an effect on outcome. In patients with a stent length ≥24 mm, deferred stenting reduced the final infarct size (6% LV; IQR: 2% to 18% vs. 13% LV; IQR: 7% to 23%; p = 0.006; and p for interaction = 0.005).Conclusions: In the DANAMI-3-DEFER cardiac magnetic resonance substudy, routine deferred stenting did not reduce infarct size or MVO and did not increase myocardial salvage. These results do not support the use of routine deferred stenting in STEMI patients treated with primary PCI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408). [ABSTRACT FROM AUTHOR]

Background: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI.Methods: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408.Findings: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups.Interpretation: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population.Funding: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research. [ABSTRACT FROM AUTHOR]

Background: The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event.Methods and Results: Between August 2010 and December 2014, 64 patients were investigated at the time point of VLST as part of an international optical coherence tomography registry. Optical coherence tomography pullbacks were performed after restoration of flow and analyzed at 0.4 mm. A total of 38 early- and 20 newer-generation drug-eluting stents were suitable for analysis. VLST occurred at a median of 4.7 years (interquartile range, 3.1-7.5 years). An underlying putative cause by optical coherence tomography was identified in 98% of cases. The most frequent findings were strut malapposition (34.5%), neoatherosclerosis (27.6%), uncovered struts (12.1%), and stent underexpansion (6.9%). Uncovered and malapposed struts were more frequent in thrombosed compared with nonthrombosed regions (ratio of percentages, 8.26; 95% confidence interval, 6.82-10.04; P<0.001 and 13.03; 95% confidence interval, 10.13-16.93; P<0.001, respectively). The maximal length of malapposed or uncovered struts (3.40 mm; 95% confidence interval, 2.55-4.25; versus 1.29 mm; 95% confidence interval, 0.81-1.77; P<0.001), but not the maximal or average axial malapposition distance, was greater in thrombosed compared with nonthrombosed segments. The associations of both uncovered and malapposed struts with thrombus were consistent among early- and newer-generation drug-eluting stents.Conclusions: The leading associated findings in VLST patients in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent underexpansion without differences between patients treated with early- and new-generation drug-eluting stents. The longitudinal extension of malapposed and uncovered stent was the most important correlate of thrombus formation in VLST. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis.Methods: In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis.Results: HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily,n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373–746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p < 0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90–4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59–1.99).Conclusion: Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI. [ABSTRACT FROM PUBLISHER]

We aimed to assess the risk factors and outcome of ventricular fibrillation (VF) before and during primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction. From 1999 to 2012, we consecutively enrolled 5,373 patients with ST-segment elevation myocardial infarction. In total, 410 of the patients had VF before and 88 had VF during PPCI. During a mean follow-up of 4.2 years, 1,196 subjects died. A logistic regression model identified younger age, anterior infarct, Killip class >I at admission, and a preprocedural Thrombolysis In Myocardial Infarction flow grade of 0 to I to be significantly associated with VF before PPCI, whereas inferior infarct, a preprocedural Thrombolysis In Myocardial Infarction flow grade of 0 to I, and Killip class >I at admission were significantly associated with VF during PPCI. All-cause mortality was evaluated using the Cox regression model. Compared with the patients without VF, those with VF before or during PPCI had a significantly increased 30-day mortality, with an adjusted hazard ratio = 3.40 (95% confidence interval 1.70 to 6.70) and 4.20 (95% confidence interval 1.30 to 13.30), respectively. Importantly, there was no tendency of 30-day mortality difference between VF before and during PPCI (p = 0.170). In patients with VF before or during PPCI who survived for at least 30 days, there was no increase in the long-term mortality. In conclusion, our data suggest that 30-day mortality is the same for patients with VF before PPCI compared with VF during PPCI, and the occurrence of VF before or during PPCI was associated with increased 30-day mortality but not with long-term mortality. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a novel approach to estimate the illumination and reflectance of an image. The approach is based on illumination-reflectance model and wavelet theory. We use a homomorphic wavelet filter (HWF) and define a wavelet quotient image (WQI) model based on dyadic wavelet transform. The illumination and reflectance components are estimated by using HWF and WQI, respectively. Based on the illumination and reflectance estimation we develop an algorithm to segment sows in grayscale video recordings which are captured in complex farrowing pens. Experimental results demonstrate that the algorithm can be applied to detect the domestic animals in complex environments such as light changes, motionless foreground objects and dynamic background. [ABSTRACT FROM AUTHOR]

Background: Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only.Methods: We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933.Findings: From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004).Interpretation: In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints.Funding: Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research. [ABSTRACT FROM AUTHOR]

Background Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. Methods We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. Findings From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004). Interpretation In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. INSET: Research in context.. [ABSTRACT FROM AUTHOR]

Previous studies have shown a poor correlation between angiographic assessment of stenosis grade (%) and its functional assessment by fractional flow reserve (FFR). This study aimed to investigate whether a more comprehensive evaluation of the coronary angiogram may contribute to a better identification of flow-limiting stenoses. Coronary angiograms of 1,350 patients (1,883 lesions) were retrospectively analyzed for stenosis grade (eyeballing, %) and matched with FFR values. Angiography-derived optimal cut-off values and intervals delineating the [90% sensitivity--90% specificity] range were 50.8% [42.5-- 65.0%] for the left main (LM), 62.2% [50.0--72.5%] for the proximal (prox)/mid left anterior descending (LAD) artery, 66.3% [57.5--77.5%] for the prox/mid right coronary artery (RCA), 70.5% [60.0--80.0%] for the prox left circumflex/first obtuse marginal (LCX/OM1), and 71.4% [62.5--82.5%] for the more distal segments. In patients with intermediate LAD lesions, 5 angiographic parameters were identified as independent predictors of flow limitation: (1) a 30--50% lesion prox to the lesion of interest, (2) lesion length >20 mm, (3) distal take-off of all diagonal branches ≥2 mm diameter, (4) "apical wrap" of LAD, and (5) collaterals to an occluded LCX/RCA. Based on these results, a risk score (P20-DAC2) for prediction of flow limitation in intermediate LAD lesions was derived. In conclusion, a comprehensive evaluation of the coronary angiogram--in which besides stenosis grade also other lesion/vessel characteristics are evaluated--can lead to a more accurate identification of functionally significant coronary stenoses. [ABSTRACT FROM AUTHOR]

Background Short-term mortality has been studied thoroughly in patients undergoing primary percutaneous coronary intervention (PCI), whereas long-term cause of death in patients with ST-segment elevation myocardial infarction (STEMI) remains unknown. Objectives The goal of this study was to describe the association between time and cause of death in patients with STEMI undergoing primary PCI. Methods A centralized civil registration system, patient files, and public disease and death cause registries with an accurate record linkage were used to trace time and cause of death in 2,804 consecutive patients with STEMI (age 63 ± 13 years, 72% males) treated with primary PCI. Results Patients were followed up for a median of 4.7 years. During a total of 13,447 patient-years, 717 patients died. Main causes of death within the first 30 days were cardiogenic shock and anoxic brain injury after cardiac arrest. Age, culprit vessel size and flow, and the presence of heart failure and diabetes were independent predictors of mortality. After 30 days, the annual cardiac mortality rate was <1.5%. Causes of death beyond 30 days were noncardiac in 65% of cases (mainly malignancies and pulmonary diseases). The 30-day, 1-year, and 5-year all-cause (and cardiac) mortality rates were 7.9% (7.3%), 11.4% (8.4%), and 23.3% (13.8%), respectively. Conclusions Patients who survive the first month after an STEMI treated with primary PCI have an excellent prognosis, with a <1.5% annual risk of successive cardiac death. Noncardiac causes are responsible for the majority of later deaths in these patients. [ABSTRACT FROM AUTHOR]

High on-treatment platelet reactivity (HTPR) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). The antiplatelet effect and safety of prasugrel was compared to that of double-dose clopidogrel in patients with stable coronary artery disease or acute coronary syndrome (ACS) exhibiting HTPR on clopidogrel and treated with PCI, using multiple electrode aggregometry (MEA) to assess platelet reactivity. Of 923 patients screened, 237 (25.7%) exhibited HTPR. Of these, 106 were eligible for participation in a randomized trial comparing two intensified antiplatelet regimen: 52 were assigned to double maintenance-dose clopidogrel and 54 to standard-dose prasugrel. At 1 month, tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1% of patients. Prasugrel entailed greater platelet inhibition ( p = 0.02) and a lower rate of persisting HTPR at follow-up compared to double-dose clopidogrel (HTPR persisted in 20.4% and 42% respectively, p = 0.02). Within the 30-day follow-up, no major bleeds were observed and the incidence of major adverse cardiovascular events (MACE) was similar in the two treatment arms. Prasugrel demonstrated superiority to double-dose clopidogrel in overcoming HTPR and reducing platelet activity. Intensifying antiplatelet therapy in both ACS and stable angina pectoris (SAP) patients exhibiting HTPR prior to PCI was well tolerated. [ABSTRACT FROM AUTHOR]

Aims. To investigate the incidence of contrast media-induced nephropathy (CIN) in patients with stable coronary artery disease (CAD) referred for elective coronary intervention following hydration routines. The reversibility of CIN was followed in a 6 month-period. Methods and results. A total of 447 patients referred for elective coronary intervention due to suspected CAD were included. Blood samples were collected before and 24 h after intervention and medical records were obtained. Patients had no drinking fluid restrictions and were routinely treated with a 1000 ml saline infusion. All patients were invited to a 6-month examination and collection of blood samples. Results. A total of 19 patients (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated glomerular filtration rate (eGRF), lower level of kidney failure and lower creatinine level than non-CIN patients. Kidney function was not normalized in CIN patients 6 months after the intervention. Two patients still met the definition of CIN. Conclusion. With no restriction in fluid intake and supplementary infusion of saline, only a few patients with stable CAD developed early indications of CIN during elective coronary interventions. Kidney function and the amount of contrast media used was not a predictor of CIN development. The induced CIN was not completely normalized in a 6-month follow-up period. [ABSTRACT FROM AUTHOR]

Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index and infarct size adjusting for area at risk did not differ between the groups. Treatment with exenatide resulted in increased salvage index both among patients with normoglycemia and hyperglycemia. Thus, we conclude that the association between hyperglycemia upon hospital admission and infarct size in STEMI patients is a consequence of a larger myocardial area at risk but not of a reduction in myocardial salvage. Also, cardioprotection by exenatide treatment is independent of glucose levels at hospital admission. Thus, hyperglycemia does not influence the effect of the reperfusion treatment but rather represents a surrogate marker for the severity of risk and injury to the myocardium. [ABSTRACT FROM AUTHOR]

Abstract: The purpose was to elucidate the mechanism of action of sodium dodecyl sulphate (SDS) on drug dissolution from discs under physiologically relevant conditions. The effect of incorporating SDS (4–30%, w/w) and drug into discs on the dissolution constant and solubility were evaluated for the poorly soluble drugs griseofulvin and felodipine in a biorelevant dissolution medium (BDM). Dissolution constants from dissolution profiles of drug discs with and without SDS were measured using miniaturized rotating disc dissolution. Solid state changes were investigated by X-ray diffraction. Solubility was determined using HPLC-UV. The interaction between micelles in BDM and SDS was investigated by isothermal titration calorimetry and dynamic light scattering. Isothermal titration calorimetry showed that SDS formed mixed micelles with bile salt:phospholipid (BS:PC) micelles in BDM. Dynamic light scattering showed that the addition of SDS made the BS:PC micelles grow up to 2.5 times in volume. As a function of SDS addition, the dissolution constant showed an apparent exponential increase, while drug solubility showed a weak linear dependence. The pronounced effect on dissolution constant with SDS in the discs is not caused by an increased surface area as SDS dissolves, micelles in the bulk medium or changes in the solid state properties of the drugs. The proposed mechanism involves a high local concentration of SDS at the solid–liquid interface as SDS dissolves and this solubilizes the drug. The improved solubility at the solid–liquid interface provided a much steeper concentration gradient resulted in a faster dissolution. The total amount of SDS in the discs only gave a minor increase in total surfactant concentration in the dissolution medium and did therefore not to any large extent affect the drug solubility in the bulk. [Copyright &y& Elsevier]

The correct segmentation of a foreground object in video recordings is an important task for many surveillance systems. The development of an effective and practical algorithm to segment sows in grayscale video recordings captured under commercial production conditions is described. The segmentation algorithm combines a modified adaptive Gaussian mixture model for background subtraction with the boundaries of foreground objects, which is obtained by using dyadic wavelet transform. This algorithm can accurately extract the shapes of a sow under complex environments, such as dynamic background and illumination changes as well as motionless foreground objects. About 97% of the segmented binary images in the validation data sets can be used to track sow behaviours, such as position, orientation and movement. The experimental results demonstrate that the proposed algorithm is able to provide a basis to detect and classify the sow behaviours in farrowing pens. [ABSTRACT FROM AUTHOR]

This paper develops a simple and effective method for detection of sows and piglets in grayscale video recordings of farrowing pens. This approach consists of three stages: background updating, calculation of pseudo-wavelet coefficients and foreground object segmentation. In the first stage, the texture integration is used to update the background modelling (i.e. the reference image). In the second stage, we apply an “à trous” wavelet transform on the current reference image and then perform subtraction between the current original image and the approximation of the current reference image. In the third stage, the pairwise relationships between a pixel and its neighbours on a factor graph are modelled based on the pseudo-wavelet coefficients, and the image probabilities are approximated by using loopy belief propagation. Experiments have shown promising results in extracting foreground objects from complex farrowing pen scenes, such as sudden light changes and dynamic background as well as motionless foreground objects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coronary in-stent restenosis (ISR) continues to be a therapeutic challenge especially after drug eluting stent (DES) implantation. We studied patients with ISR to investigate safety and efficacy of a novel drug coated balloon (DCB) incorporating paclitaxel into a microcrystalline structure by applying the inert excipient butyryltri-n-hexyl citrate (BTHC) in a prospective First-in-Man trial. Methods and Materials: Eighty-one patients were enrolled at 9 European sites, thereof 43 (53.1%) presenting with bare metal stent (BMS)-ISR and 38 (46.9%) with DES-ISR. The primary study endpoint was in-stent late lumen loss (LLL) independently assessed by a quantitative coronary angiography laboratory at 6 months. A secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, non-fatal myocardial infarction, clinically driven target vessel revascularization after 6 and 12 months. Results: At 6 months, overall LLL was 0.07±0.31 mm showing differences in BMS-ISR and DES-ISR treatment (−0.05±0.28 mm vs. 0.19±0.29 mm, respectively, P=.001). Overall MACE rates at 6 and 12 months were 6.5% and 11.8%. At the 12-month follow-up, one myocardial infarction, and no cardiac death nor stent thrombosis had occurred. Conclusion: Application of a novel paclitaxel coated balloon using BTHC as an excipient in patients with ISR is safe and results in very low LLL, revascularization- and MACE-rates at follow-up. (ClinicalTrials.gov:NCT00961181). [Copyright &y& Elsevier]

Aims. We evaluated the feasibility, safety and efficacy of intra-myocardial injection of autologous mesenchymal stromal cells derived endothelial progenitor cell (MSC) in patients with stable coronary artery disease (CAD) and refractory angina in this first in man trial. Methods and results. A total of 31 patients with stable CAD, moderate to severe angina and no further revascularization options, were included. Bone marrow MSC were isolated and culture expanded for 6--8 weeks. It was feasible and safe to establish in-hospital culture expansion of autologous MSC and perform intra-myocardial injection of MSC. After six months follow-up myocardial perfusion was unaltered, but the patients increased exercise capacity (p < 0.001), reduction in CCS Class (p < 0.001), angina attacks (p < 0.001) and nitroglycerin consumption (p < 0.001), and improved Seattle Angina Questionnaire (SAQ) evaluations (p < 0.001). For all parameters there was a tendency towards improved outcome with increasing numbers of cells injected. In the MRI substudy: ejection fraction (p < 0.001), systolic wall thickness (p == 0.03) and wall thickening (p == 0.03) all improved. Conclusions. The study demonstrated that it was safe to treat patients with stable CAD with autologous culture expanded MSC. Moreover, MSC treated patients had significant improvement in left ventricular function and exercise capacity, in addition to an improvement in clinical symptoms and SAQ evaluations. [ABSTRACT FROM AUTHOR]

Objectives. Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse. Design. Survival and SCD in 77 PTSMA-treated patients (follow-up 3.5 ±± 2.8 years) were analyzed. The future risk of SCD was assessed by risk stratification for SCD in 57 PTSMA patients at long-term follow-up (3.8 ±± 2.8 years). Results. The five years survival of the PTSMA cohort (age 61 ±± 12 years) was 83% compared to 79% in a control cohort (n == 90) of patients (age 52 ±± 17 years) with hypertrophic cardiomyopathy (HCM) (Log Rank p == 0.8), and 91% (p == 0.01) in the background population. Five-year survival free of SCD was 94% after PTSMA compared to 99% (p == 0.13) in the HCM control cohort. Eight percent of patients had two or more risk factors for SCD at follow-up. Conclusion. The survival in the PTSMA-treated patients and in the HCM control cohorts was similar. The incidence of SCD and the future risk of SCD assessed by risk factors were not increased in the PTSMA cohort compared to the HCM control cohort. The excess mortality in the PTSMA cohort compared to the background population seems to be related to HCM rather than PTSMA. [ABSTRACT FROM AUTHOR]

It is unknown whether high-sensitivity C-reactive protein (hs-CRP) predicts outcome depending on implanted stent type. We investigated the prognostic value of hs-CRP in relation to type of stent implanted in patients with ST-segment elevation myocardial infarction (STEMI). Immediately before primary percutaneous coronary intervention (pPCI), 301 patients had blood drawn. Patients were categorized according to hs-CRP levels and combination of hs-CRP (≤2 vs >2 mg/L) and stent type (bare metal stent [BMS] vs drug-eluting stent [DES]). Hs-CRP >2 mg/L (median, hazard ratio 2.7, 95% confidence interval 1.3 to 5.6, p = 0.007) and the combined variable of hs-CRP >2 mg/L and BMS (hazard ratio 2.4, 95% confidence interval 1.2 to 4.5, p = 0.006) independently predicted the composite end point of death and MI at 36-month follow-up. There was a significant interaction (p = 0.006) for hs-CRP and stent type. Survival analysis demonstrated significant differences for occurrence of death and MI: 4.8% in BMS + CRP ≤2 mg/L, 11.9% in DES + CRP ≤2 mg/L, 17.6% in DES + CRP >2 mg/L, and 27.9% in BMS + CRP >2 mg/L. None of the 14 stent thromboses occurred in patients with BMS + CRP ≤2 mg/L. In conclusion, preprocedure hs-CRP predicts outcome after pPCI in patients with STEMI. Our hypothesis-generating data indicate that BMS implantation should be preferred when hs-CRP is ≤2 mg/L and DES when hs-CRP is >2 mg/L to decrease long-term adverse outcomes including stent thrombosis in patients with STEMI treated with pPCI. These findings need confirmation in larger randomized clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: In semi-natural environments sows often select a protected nest site at farrowing. Investigations of nest site selection under indoor conditions are scarce but suggest that sows prefer to nest and farrow under a covered area. Since feed-back from a functional nest may improve maternal behaviour and thus piglet survival we investigated if access to a covered area and ad libitum access to straw would improve maternal behaviour of importance for piglet survival. We used forty-four primiparous sows housed in large individual pens from approximately 2 weeks prior to expected parturition. The sows were randomly distributed to four treatment groups of +/− ad libitum access to straw combined with +/− access to a covered area in the pen. The sows’ position in the pen (left or right side) was observed from 24h prior to birth of the first piglet until 24h after using 10-min interval scan sampling and the temporal pattern of sow position in relation to position of the cover (left or right side of the pen) was studied. Furthermore, postural and nest-building behaviours were observed, as well as situations where the piglets were either at risk of being crushed or were crushed. The results showed no significant influence of cover on sow position. Odds-ratio for choosing the covered farrowing position was 1.4 (95% creditability interval (0.4–5.1)). The temporal pattern of sow position showed that the probability of observing the sows in the part of the pen classified as the farrowing position increased from close to 0.5 to 1 as parturition approached and stayed high during the 24h observation period after birth of the first piglet, except for a small drop around 12h after birth of the first piglet. However, the tendency to stay in the nest during farrowing was not increased neither by cover nor by ad libitum access to straw. Access to cover significantly increased prepartum nest-building behaviour (F 1,29 =4.27, P =0.05) whereas there was no significant influence of access to straw. However, it should be taken into account that all sows had access to sawdust on the floor, which may also serve as a nesting material. The number of crushing and near crushing situations within 24h after birth of first piglet (BFP) was significantly decreased in pens with access to straw (F 1,25 =4.50, P =0.04), whereas there was no significant influence of cover on this variable. Neither the number of scan intervals with lateral lying nor the number of postural changes were significantly influenced by cover or straw. In conclusion, the sows did select a specific nest site within the farrowing pen, but neither the choice of nest site nor the temporal consistency of staying in the nest were significantly affected by cover or ad libitum access to straw. Access to a covered area increased the occurrence of nest-building behaviour whereas access to straw reduced the number of near crushing situations. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). Background: The evidence of long-term efficacy and safety after implantation of DES in patients with complex lesions is scarce. Methods: We randomly assigned 626 patients with STEMI referred within 12 h to have a DES or a BMS implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Results: At 3 years, target lesion revascularization was 6.1% in the DES group compared with 16.3% in the BMS group (p < 0.001), and the rate of major adverse cardiac events was 11.5% versus 18.2%, respectively (p = 0.02). Whereas all-cause mortality did not differ significantly, the rate of cardiac death was higher in the DES group, 6.1% versus 1.9% for the BMS group (p = 0.01). The occurrence of reinfarction, stroke, and stent thrombosis was similar. Conclusions: Implantation of DES in patients with STEMI reduces the long-term rate of major adverse cardiac events compared with BMS, but patients with DES had a higher risk of cardiac death not attributed to myocardial infarction or stent thrombosis. (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction [DEDICATION]; NCT00192868) [ABSTRACT FROM AUTHOR]

Abstract: Background: Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial. Methods: Timing of G-CSF treatment was analyzed in the STEMMI MRI subpopulation including 54 patients with STEMI treated with primary percutaneous coronary intervention (PCI) <12 h after symptom onset. Patients were randomized to double blind treatment with G-CSF (10 µg/kg/day) or placebo. Treatment was initiated from 17 to 65 h (mean 30) after PCI. Left ventricular ejection fraction (LVEF) was evaluated with MRI. Results: Recovery of LVEF from baseline to 6 months was not associated with time from PCI to G-CSF. An identical improvement in LVEF was found in the placebo group and the G-CSF group (p =0.8). There was no correlation between time from PCI to G-CSF and maximum plasma concentration of CD34+ cells (r =−0.3, p =0.1). Similar results were found from data on recovery of the infarction size and change in the systolic wall thickening. Conclusions: In the time window from 17 to 65 h after STEMI treated with PCI, the timing of G-CSF treatment does not seem to affect the recovery of LVEF. It remains to be determined if very early, or very late G-CSF treatment might be effective. [Copyright &y& Elsevier]

Background: Plasma YKL-40 is increased early in patients with ST-elevation myocardial infarction (STEMI). It is not known whether plasma YKL-40 is related to infarct size and recovery of ventricular function after primary percutaneous coronary intervention (PCI) of STEMI and whether granulocyte colony-stimulating factor (G-CSF) therapy influence plasma YKL-40 concentration. Materials and methods: A total of 72 patients (age: 56 ± 9 years (mean ± SD), 56 men and 16 women) with STEMI treated with PCI were included in a double-blind, randomized, placebo-controlled trial with subcutaneous G-CSF or placebo injections from day 1 to 7 after the STEMI. Plasma YKL-40, high-sensitivity C-reactive protein (hs-CRP) and CK-MB concentrations were measured at baseline and during the first month. Infarct size and left ventricular ejection fraction (LVEF) were measured by magnetic resonance imaging at baseline and after 6 months. Results: Baseline plasma YKL-40 was increased (median 92 μg/L) compared to healthy subjects (median 34 μg/L, p <0.001). In the placebo group hs-CRP and YKL-40 correlated at baseline ( p = 0.04) and day 3 ( p = 0.01), but not at day 7 and 30. Moreover, YKL-40 correlated negatively to LVEF recovery ( p = 0.04) but not infarct size. G-CSF injections increased YKL-40 compared to placebo ( p <0.001), but were not associated with infarct size or LVEF recovery. Conclusion: Plasma YKL-40 was significantly increased in STEMI patients at admission and G-CSF treatment caused a further increase in YKL-40. Plasma YKL-40 may be an indirect marker of LVEF recovery, independent of hs-CRP, and higher plasma YKL-40 indicates a lower recovery. [ABSTRACT FROM AUTHOR]

The selective thrombin inhibitor bivalirudin with a provisional glycoprotein IIb/IIIa inhibitor (GPI) has been shown to be comparable to heparin plus GPI in the rates of ischemic events but to significantly reduce the risk of bleeding complications in patients with acute coronary syndromes. The aim of this preliminary study was to describe the feasibility and safety of a switch from prehospital administration of unfractionated heparin to bivalirudin in ST-elevation acute myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention. Patients with STEMI treated with a 1-mg/kg bivalirudin bolus in the ambulance followed by infusion during angiography/primary percutaneous coronary intervention were compared with a STEMI control group (from the preceding year) treated with 10,000 U unfractionated heparin in the ambulance followed by in-hospital treatment with a GPI. A total of 102 patients (59%) receiving bivalirudin and 72 receiving heparin were followed during hospitalization. The baseline characteristics and prehospital treatment times were comparable between the 2 groups. The thrombolysis in myocardial infarction flow before and after primary percutaneous coronary intervention was similar. Stents were used significantly more often in the heparin-treated patients (90% versus 76%; p = 0.04), with bailout GPI for those receiving bivalirudin occurring in 30% compared with 83% of those receiving heparin (p <0.001). Significant bleeding complications were seen in <10% of all patients undergoing angiography with no difference between groups. Bivalirudin was easy to administer in the prehospital setting and did not affect the prehospital run times. In conclusion, the results suggest that prehospital bivalirudin administration is as safe and effective as heparin in the treatment of patients with STEMI. Prehospital administration seemed to reduce the need for GPI. [Copyright &y& Elsevier]

Background. YKL-40 is involved in remodelling and angiogenesis in non-cardiac inflammatory diseases. Aim was to quantitate plasma YKL-40 in patients with ST-elevation myocardial infarction (STEMI) or stable chronic coronary artery disease (CAD), and YKL-40 gene activation in human myocardium. Methods and results. We included 73 patients: I) 20 patients with STEMI; II) 28 patients with stable CAD; III) 15 CAD patients referred for coronary by-pass surgery. YKL-40 mRNA expression was measured in myocardium subtended by stenotic or occluded arteries and areas with no apparent disease; and IV) 10 age-matched healthy controls. Plasma YKL-40 was significantly increased in patients with STEMI (88 µg/l, median) and CAD (66 µg/l) compared to controls (16 µg/l, p<0.01 for both). Plasma YKL-40 correlated with CRP at baseline in STEMI (r=0.53, p=0.02) and CAD patients (r=0.41, p=0.031).YKL-40 gene expression was similar in ischemic and non-ischemic myocardium. Conclusions. Plasma YKL-40 was significantly increased in patients with STEMI and stable CAD. Further studies will define the role of YKL-40 as a clinically useful marker for myocardial ischemia, remodelling and maybe prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this experiment was to investigate pigs’ preferences for rooting materials. Eighteen materials were allocated to six categories each of which consisted of three similar materials based on characteristics such as structure, size of particles, complexity, destructibility and digestibility. Twelve pairs of pigs chose among the three materials of each of the six categories in a balanced design. Within each category each pair was given four instantaneous choices among the three materials in a three-armed maze. ‘No choice’ was scored if the pigs did not enter one of the maze-arms within 90s. Thus there were four options in each choice situation. The results were analysed using a random utility model incorporating random intercepts to account for the repeated testing of the same animals. The pigs expressed clear preferences within the category EARTH, where compost and peat were preferred to wood-shavings and no choice. In the category CHIP the most probable rank-order was spruce chip, willow chip, fir chip and no choice, while in the category ROUGH the most probable rank-order was maize-silage, grass silage, sugar beets and no choice. However, in these two categories none of the probabilities were sufficiently large to signify a preference for any of the three materials although the probabilities of the ‘no choice’ option were low. The pigs expressed no preferences among any of the four options including ‘no choice’ in the categories TOY (sisal robe, Bite-Rite, wooden beam), HAY (alfalfa hay mixed with straw, seed grass hay, barley straw with under-seed), and STRAW (long straw, chopped straw and straw pellets). [Copyright &y& Elsevier]

Objectives: Our purpose was to evaluate the long-term use of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with complex coronary artery lesions. Background: Although the use of SES has proved to be effective in patients with simple coronary artery lesions, there are limited data of the long-term outcome of patients with complex coronary artery lesions. Methods: We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted. Results: At 3 years, major adverse cardiac events had occurred in 20 patients (12%) in the SES group and in 59 patients (38%) in the BMS group (p < 0.001). Four versus 2 patients suffered a cardiac death (p = NS), and 5 versus 1 died of a noncardiac disease (p = NS) in the SES versus the BMS group. Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (p < 0.05) during the 3-year observation period, and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (p < 0.001); of these, 4 in the SES versus 7 in the BMS group were performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient. Conclusions: A continued benefit was observed up to 3 years after implantation of SES in patients with complex coronary artery lesions. The rate of late adverse events was similar in the 2 groups, and stent thromboses occurred rarely after 1 year. (Sirolimus Eluting Stents in Complex Coronary Lesions [SCANDSTENT]; NCT00151658) [Copyright &y& Elsevier]

Aim: Analyze clinical, temporal and procedural characteristics from 7,528 consecutive percutaneous coronary intervention (PCI) patients in one of the largest published contemporary European PCI-database during a 6-year period. Method: Retrospective study design. Period: 1998–2004. Temporal and referral changes in a Danish PCI-registry were analyzed. Demographic and angiographic variables were compared with data from randomized clinical trials, US-registries and current guidelines. Results: 22,214 patients were examined with coronary angiography and 7,528 patients were treated with PCI. The annual number of PCI’s increased by 15%. Over time, the fraction of patients with risk factors increased, median age increased from 61 to 64 years and the coronary pathology was significantly worsened. ST-elevation myocardial infarction patients primarily admitted to hospitals without facilities for primary angioplasty, were less likely to receive primary PCI. Baseline-data were in general in par with randomized clinical trial study populations and large-scale US data-registries. Interestingly, 14% of all PCI-procedures were performed on patients with a clinical presentation, for which coronary artery bypass grafting would be recommended by guidelines. Conclusion: PCI is performed in an increasingly sicker population, but generally in accordance with randomized trials and similar to US tradition. However, 14% were treated with PCI even though coronary artery bypass grafting was recommended by guidelines. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the use of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in native coronary vessels. Background: Embolization of material from the infarct-related lesion during PCI may result in impaired myocardial perfusion and worsen the prognosis. Previous attempts to protect the microcirculation during primary PCI have had conflicting results. Methods: We randomly assigned 626 patients with STEMI referred within 12 h to have PCI performed with (n = 312) or without (n = 314) distal protection. The primary end point was complete (≥70%) ST-segment resolution detected by continuous ST-segment monitoring. Blood levels of troponin-T and creatine kinase-MB were monitored before and after the procedure, and echocardiographic determination of the left ventricular wall motion index (WMI) was performed before discharge. Results: Patients were well matched in terms of demographic and angiographic baseline characteristics. There was no significant difference in the occurrence of the primary end point (76% vs. 72%, p = 0.29), no difference in maximum troponin-T (4.8 μg/l and 5.0 μg/l, p = 0.87) or maximum creatine kinase-MB (185 μg/l and 184 μg/l, p = 0.99), and no difference in median WMI (1.70 vs. 1.70, p = 0.35). The rate of major adverse cardiac and cerebral events (MACCE) 1 month after PCI was 5.4% with distal protection and 3.2% with conventional treatment (p = 0.17). Conclusions: The routine use of distal protection by a filterwire system during primary PCI does not seem to improve microvascular perfusion, limit infarct size, or reduce the occurrence of MACCE (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction; NCT00192868). [Copyright &y& Elsevier]

An abstract of the article "Exploring the Cost-Benefit of Vaccines for Infectious Diseases in Slaughter Pig Production," by Nils Toft and colleagues is presented.

Abstract: Background: Angiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease. Methods: Fifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects. Results: Plasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34−/CD45−cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p <0.005−0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p =0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea. Conclusions: Plasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden. [Copyright &y& Elsevier]

Abstract: The most critical period for the survival of piglets is during the first 2 days of life. Causes of early piglet mortality include reduced vitality due to hypoxia during parturition, hypothermia and lack of adequate colostrum intake. Besides, low vitality piglets may run a larger risk of being crushed by the sow. In the light of the thermoregulatory challenges facing newborn piglets and the possible sow-piglet interactions under loose housing, we investigated whether floor heating around parturition affected early piglet vitality and behaviour related to survival. Twenty-three Landrace×Yorkshire sows of 2nd parity were housed individually in 7.5m2 pens in a climate controlled facility. HEAT sows (n =12) were exposed to pen floor heating (33.5°C) from 12h after onset of nest building and until 48h after birth of 1st piglet, whereas CONT sows (n =11) received no floor heating (21.2°C). The concentration of lactate in umbilical cord blood at birth—an indicator of hypoxia—increased with the birth duration (P <0.001) and with declining piglet weight (P <0.001), with no significant effect of floor heating. After the initial drop in body temperature at birth, floor heating resulted in an earlier recovery of piglet temperatures (P <0.001), i.e. the piglet''s period for experiencing hypothermia after birth was reduced. HEAT piglets also suckled sooner than CONT piglets after the 1st hour post partum (with ratios between HEAT/CONT hazard functions being 2.9–6.4 for latency to suckle in the period 1–3h after birth). Moreover, fewer live-born piglets died during the first 3 days (P =0.047), as well as during the first week in the floor heated litters (mean (S.E.) HEAT 8.7 (2.8)% versus CONT 15.5 (5.2)%, P =0.014). We did not find any effect of floor heating on duration of parturition, inter-birth intervals, litter size, early piglet weight gains, blood glucose and lactate concentrations at birth, heart rate at birth, piglet activity from birth to first suckling or amount of parvovirus antibodies transferred from sow to piglets. In conclusion, floor heating around parturition had no evident effect on the innate piglet vitality, but it had favourable effects on the early recovery of piglet body temperature, latency to first suckle and survival of piglets in the loose house system. [Copyright &y& Elsevier]

Objectives: The purpose of the SCANDSTENT study was to evaluate the use of sirolimus-eluting stents (SES) in complex coronary lesions. Background: The use of SES improves angiographic and clinical outcomes compared with bare-metal stents (BMS) in simple coronary artery lesions, but there is limited evidence of their safety and efficacy when implanted in complex lesions. Methods: We randomly assigned 322 patients with symptomatic complex coronary artery disease to receive either SES or BMS. The lesions were occluded (36%), bifurcational (34%), ostial (22%), or angulated (8%) in morphology. The primary end point was the difference in minimal lumen diameter six months after stent implantation. Results: The patients were well matched in terms of demographic and angiographic baseline characteristics; 18% had diabetes. The reference vessel diameter was 2.86 mm in mean, and the lesion length 18.0 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.48 mm compared with 1.65 mm in those who received BMS (p < 0.001), a diameter stenosis of 19.3% versus 43.8% (p < 0.001), and 2.0% versus 31.9% developed restenosis (p < 0.001). The rate of major adverse cardiac events was 4.3% with SES versus 29.3% with BMS (p < 0.001), and stent thrombosis was observed in 0.6% in the SES group versus 3.1% in the BMS group (p = 0.15). Conclusions: The use of SES markedly reduced restenosis and the occurrence of major adverse cardiac events in patients with complex coronary artery lesions without increasing the risk of stent thrombosis. [Copyright &y& Elsevier]

Abstract: The aim of the present experiment was to measure pigs’ preferences for four different rooting materials using a set-up where pigs were given the opportunity to consider the relative attractiveness of two different materials simultaneously. Ten pigs had access to work for 50min daily in an operant conditioning experiment using concurrent schedules of reinforcement. During the 50min two different rooting materials were available after completing a fixed number of presses on two different operant panels inside a test pen. Long straw was always used as reinforcement on one panel, while one of four alternative rooting materials (chopped straw, fir branches, peat or long straw) was used as reinforcement on the other panel. The cost of access to the resources varied on both panels according to five pairs of Fixed Ratio schedules (FR8/FR40, FR16/FR32, FR24/FR24, FR32/FR16, FR40/FR8). For each material all pigs went through three test runs of the five FR pairs. Measures of preferences were based both on the generalized matching law (bias) and on the cross-points between the demand curves for the reference material and for the alternative material. Both the bias and the cross-point was significantly affected by type of alternative material in that the cross-point for peat (FR9.0) was significantly lower (P &#60;0.05) and bias (−0.34) significantly higher (P &#60;0.05) than for all other alternative materials (cross-point: branches FR18.3, chopped straw FR23.8, long straw FR29.2; log(bias): branches −0.27, chopped straw −0.01, long straw 0.40). The intercept of the demand curves for the alternative materials were significantly affected (P &#60;0.05) by type of material in that it was higher for peat (1.73±0.14)(lsmeans±std. err.) than for all other materials. The intercept for branches (1.31±0.14) was higher than for chopped straw (0.92±0.14) and long straw (0.54±0.17). The slopes of the alternative demand curves were unaffected by type of material as were the intercepts and slopes of the reference curves. The number of times of pressing the alternative panel in succession before shifting to the reference panel was significantly higher (P &#60;0.001) across all FR''s for peat (11±0.7 at FR24) and branches (9.4±0.7 at FR24) than for chopped straw (8.2±0.6 at FR24) and long straw (7.0±0.6 at FR24). The pigs achieved a new reward sooner following delivery of the previous one (P &#60;0.05) when the alternative material was either peat (1.3±0.13min) or branches (1.3±0.13min) compared to long straw (1.8±0.19min) and chopped straw (1.7±0.13min). All three alternatives were able to substitute completely for long straw, in that the slope of the demand curve of the reference material was not influenced by type of alternative material. In conclusion, both measures of cross-points and bias indicated a preference for peat and branches over chopped straw and long straw. [Copyright &y& Elsevier]

Abstract: Objectives: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. Design, patients and results: 29 patients with IHD participated in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were “poor mobilizers” with a maximal increase in CD34+ cells to 5,000±700/mL blood (mean±S.D.) compared to 28,900±5,100/mL blood in “mobilizers”. At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in “mobilizers” compared to controls. Myocardial perfusion was unchanged at adenosine stress single photon emission computerized tomography (SPECT) or magnetic resonance images (MRI). Left ventricular ejection fraction decreased from 57% to 52% (p<0.01, MRI) and from 48% to 44% (p=0.07, SPECT) in G-CSF treated, but was unchanged measured with echocardiography. Conclusions: Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded. [Copyright &y& Elsevier]

Objectives: In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed. Background: Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials. Methods: Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography. Results: No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients. Conclusions: The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to investigate the incidence, risk factors and long-term prognosis of acute kidney injury (AKI) in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (primary PCI). Method: A large-scale, retrospective cohort study based on procedure-related variables, biochemical and mortality data collected between 2009 and 2014 at Rigshospitalet, Copenhagen, Denmark. AKI was defined as an increase in serum creatinine of 25% during the first 72 hours after the index procedure. Results: A total of 4239 patients were treated with primary PCI of whom 4002 had available creatinine measurements allowing for assessment of AKI and inclusion in this study. The mean creatinine value upon presentation for all patients was 84 μmol/l (standard deviation (SD) ±40) and 97 μmol/l (SD ±53) at peak. AKI occurred in a total of 765 (19.1%) patients. Independent risk factors for the occurrence of AKI were age, time from symptom onset to procedure, peak value of troponin-T, female sex and the contrast volume to eGFR ratio. In a multivariable adjusted analysis AKI was independently associated with a higher mortality rate at 5 years follow-up (hazard ratio 1.39 [95%-confidence interval 1.03–1.88]). Conclusion: In STEMI patients treated with primary PCI one in five experiences acute kidney injury, which was associated with a substantial increase in both short- and long-term mortality. [ABSTRACT FROM AUTHOR]