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Aims: Coronary angiography holds a central role in the diagnosis of coronary heart disease. We studied temporal trends in referral patterns 2000-09., Methods and Results: We identified 156 496 first-time coronary angiographies in 2000-09 in nationwide registries. Trends were analyzed in 2-year intervals. Numbers of acute (5943-10 707) and elective (17 294-25 550) procedures increased between 2000-01 and 2008-09. Mean age increased from 61.8 to 63.9 years (P < 0.001) and the proportion of females increased from 33 to 37% (P < 0.001). An increase in the number of patients with prior chronic heart failure (2866 vs. 3197), cerebrovascular disease (1790 vs. 2906), diabetes (2527 vs. 4593), and arrhythmias (2985 vs. 4733) was observed. The proportion of acute patients examined the same day as hospitalized increased from 56.6 to 83.1%. Odds ratios (95% confidence interval) for treatment with statins [3.42(3.27;3.57)], RAS-inhibitors [1.85(1.77;1.93)], and acetylsalicylic acid [1.43(1.37;1.49)] at the time of coronary angiography increased towards 2008-09. Elective patients received medical treatment more often than acute patients (P < 0.001)., Conclusion: During a 10-year period, there was an increase in the mean age of patients and the proportion of female patients, and a 56% increase in number of coronary angiographies performed. The use of prophylactic cardiovascular drugs among these high-risk patients increased during our study period., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objectives: The purpose of this study was to assess the occurrence, predictors, and mechanisms of optical coherence tomography (OCT)-detected coronary evaginations following drug-eluting stent (DES) implantation., Background: Angiographic ectasias and aneurysms in stented segments have been associated with a risk of late stent thrombosis. Using OCT, some stented segments show coronary evaginations reminiscent of ectasias., Methods: Evaginations were defined as outward bulges in the luminal contour between struts. They were considered major evaginations (MEs) when extending ≥3 mm along the vessel length, with a depth ≥10% of the stent diameter. A total of 228 patients who had sirolimus (SES)-, paclitaxel-, biolimus-, everolimus (EES)-, or zotarolimus (ZES)-eluting stents implanted in 254 lesions, were analysed after 1, 2, or 5 years; and serial assessment using OCT and intravascular ultrasound (IVUS) was performed post-intervention and after 1 year in 42 patients., Results: Major evaginations occurred frequently at all time points in SES (∼26%) and were rarely seen in EES (3%) and ZES (2%, P = 0.003). Sirolimus-eluting stent implantation was the strongest independent predictor of ME [adjusted OR (95% CI) 9.1 (1.1-77.4), P = 0.008]. Malapposed and uncovered struts were more common in lesions with vs. without ME (77 vs. 25%, P < 0.001 and 95 vs. 20%, P < 0.001, respectively) as was thrombus [49 vs. 14%, OR 7.3 (95% CI: 1.7-31.2), P = 0.007]. Post-intervention intra-stent dissection and protrusion of the vessel wall into the lumen were associated with an increased risk of evagination at follow-up [OR (95% CI): 2.9 (1.8-4.9), P < 0.001 and 3.3 (1.6-6.9), P = 0.001, respectively]. In paired IVUS analyses, lesions with ME showed a larger increase in the external elastic membrane area (20% area change) compared with lesions without ME (5% area change, P < 0.001)., Conclusion: Optical coherence tomography-detected MEs are a specific morphological footprint of early-generation SES and are nearly absent in newer-generation ZES and EES. Evaginations appear to be related to vessel injury at baseline; are associated with positive vessel remodelling; and correlate with uncoverage, malapposition, and thrombus at follow-up.

Objective: To test the hypothesis that mutations in the vascular endothelial growth factor (VEGF) gene are associated with plasma concentration of VEGF and subsequently the ability to influence coronary collateral arteries in patients with coronary heart disease (CHD)., Methods: Blood samples from patients with chronic ischemic heart disease (n=53) and acute coronary syndrome (n=61) were analysed. Coronary collaterals were scored from diagnostic biplane coronary angiograms., Results: The plasma concentration of VEGF was increased in patients with acute compared to chronic CHD (p=0.01). The genotype frequencies differed significantly from Hardy-Weinberg equilibrium in three of 15 examined loci. Four new mutations in addition to the already described were identified. The VEGF haplotype did not seem to predict plasma VEGF concentration (p=0.5). There was an association between the genotype in locus VEGF-1154 and coronary collateral size (p=0.03) and a significant association between the VEGF plasma concentration and the collateral size (p=0.03)., Conclusion: VEGF plasma concentration seems related to coronary collateral function in patients with CHD. The results did not support the hypothesis that polymorphisms in the untranslated region of the VEGF gene were associated with the concentration of circulating VEGF. Increased understanding of VEGF in the regulation of myocardial collateral flow may lead to new therapies in CHD.

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)

Background: Sirolimus-eluting stent implantation improves the outcome in simple coronary artery lesions compared with bare metal stents, but there is limited evidence of their safety and efficacy when implanted in complex lesions like coronary bifurcations., Methods: SCANDSTENT was a randomized controlled study comparing implantation of sirolimus-eluting stents with bare-metal stents in patients with complex coronary artery disease. This substudy evaluates the angiographic and clinical outcome of 126 patients with lesions located in a coronary bifurcation., Results: The baseline characteristics of the patients were comparable: 15% had diabetes, and 1.7 stents were implanted per lesion. At follow-up, the minimum lumen diameter of the main branch was 2.35 mm in patients who received sirolimus-eluting stents compared with 1.68 mm in those who received bare-metal stents, and that of the side branch was 1.70 versus 1.19 mm (both P < .001). The late lumen loss in the main branch was 0.12 mm in the sirolimus-eluting stent group versus 0.99 mm in the bare-metal stent group and 0.03 versus 0.56 mm in the side branch (both P < .001). Thus, sirolimus-eluting stents reduced the restenosis rate from 28.3% to 4.9% in the main branch and from 43.4% to 14.8% in the side branches (both P < .001). Major adverse cardiac events occurred in 9% with sirolimus-eluting stents versus 28% with bare-metal stents (P = .01), and stent thrombosis was observed in 0% versus 9% (P = .02)., Conclusion: Sirolimus-eluting stent implantation improves both the angiographic and clinical outcomes considerably compared with that of bare-metal stents in patients with stenoses located in coronary bifurcations.

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.

In patients with stable CAD, PCI can be considered a valuable initial mode of revascularization in all patients with objective large ischaemia in the presence of almost every lesion subset, with only one exception: chronic total occlusions that cannot be crossed. In early studies, there was a small survival advantage with CABG surgery compared with PCI without stenting. The addition of stents and newer adjunctive medications improved the outcome for PCI. The decision to recommend PCI or CABG surgery will be guided by technical improvements in cardiology or surgery, local expertise, and patients' preference. However, until proved otherwise, PCI should be used only with reservation in diabetics with multi-vessel disease and in patients with unprotected left main stenosis. The use of drug-eluting stents might change this situation. Patients presenting with NSTE-ACS (UA or NSTEMI) have to be stratified first for their risk of acute thrombotic complications. A clear benefit from early angiography (<48 h) and, when needed, PCI or CABG surgery has been reported only in the high-risk groups. Deferral of intervention does not improve outcome. Routine stenting is recommended on the basis of the predictability of the result and its immediate safety. In patients with STEMI, primary PCI should be the treatment of choice in patients presenting in a hospital with PCI facility and an experienced team. Patients with contra-indications to thrombolysis should be immediately transferred for primary PCI, because this might be their only chance for quickly opening the coronary artery. In cardiogenic shock, emergency PCI for complete revascularization may be life-saving and should be considered at an early stage. Compared with thrombolysis, randomized trials that transferred the patients for primary PCI to a 'heart attack centre' observed a better clinical outcome, despite transport times leading to a significantly longer delay between randomization and start of the treatment. The superiority of primary PCI over thrombolysis seems to be especially clinically relevant for the time interval between 3 and 12 h after onset of chest pain or other symptoms on the basis of its superior preservation of myocardium. Furthermore, with increasing time to presentation, major-adverse-cardiac-event rates increase after thrombolysis, but appear to remain relatively stable after primary PCI. Within the first 3 h after onset of chest pain or other symptoms, both reperfusion strategies seem equally effective in reducing infarct size and mortality. Therefore, thrombolysis is still a viable alternative to primary PCI, if it can be delivered within 3 h after onset of chest pain or other symptoms. Primary PCI compared with thrombolysis significantly reduced stroke. Overall, we prefer primary PCI over thrombolysis in the first 3 h of chest pain to prevent stroke, and in patients presenting 3-12 h after the onset of chest pain, to salvage myocardium and also to prevent stroke. At the moment, there is no evidence to recommend facilitated PCI. Rescue PCI is recommended, if thrombolysis failed within 45-60 min after starting the administration. After successful thrombolysis, the use of routine coronary angiography within 24 h and PCI, if applicable, is recommended even in asymptomatic patients without demonstrable ischaemia to improve patients' outcome. If a PCI centre is not available within 24 h, patients who have received successful thrombolysis with evidence of spontaneous or inducible ischaemia before discharge should be referred to coronary angiography and revascularized accordingly--independent of 'maximal' medical therapy.

Background. While regenerative stem cell therapy for ischemic heart disease has moved into phase 3 studies, little is still known about retention and migration of cell posttransplantation. In human studies, the ability to track transplanted cells has been limited to labeling with radioisotopes and tracking using nuclear imaging. This method is limited by low resolution and short half-lives of available radioisotopes. Longitudinal tracking using magnetic resonance imaging (MRI) of myocardial injected cells labeled with iron oxide nanoparticles has shown promising results in numerous preclinical studies but has yet to be evaluated in human studies. We aimed to evaluate MRI tracking of mesenchymal stromal cells (MSCs) labeled with ultrasmall paramagnetic iron oxide (USPIO) nanoparticles after intramyocardial transplantation in patients with ischemic heart disease (IHD). Methods. Five no-option patients with chronic symptomatic IHD underwent NOGA-guided intramyocardial transplantation of USPIO-labeled MSCs. Serial MRI scans were performed to track labeled cells both visually and using semiautomated T2∗ relaxation time analysis. For safety, we followed symptoms, quality of life, and myocardial function for 6 months. Results. USPIO-labeled MSCs were tracked for up to 14 days after transplantation at injection sites both visually and using semiautomated regional T2∗ relaxation time analysis. Labeling of MSCs did not impair long-term safety of treatment. Conclusion. This was a first-in-man clinical experience aimed at evaluating the utility of MRI tracking of USPIO-labeled bone marrow-derived autologous MSCs after intramyocardial injection in patients with chronic IHD. The treatment was safe, and cells were detectable at injection sites up to 14 days after transplantation. Further studies are needed to clarify if MSCs migrate out of the injection area into other areas of the myocardium or if injected cells are washed out into the peripheral circulation. The trial is registered with ClinicalTrials.gov NCT03651791. [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]

The article discusses a randomized, double-blind, placebo-controlled study which hypothesized that the effect of exenatide is more pronounced in patients with short system delay. Patients 18 years old and above and presented within 12 hours from the onset of symptoms and signs of ST-segment-elevation myocardial infarction (STEMI) were eligible. It suggests an association between exenatide treatment with a 30% decrease in final infarct size in patients with short system delay.

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]

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]

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. To investigate the mobilization of non-haematopoietic and haematopoietic cells from the bone marrow induced by intramyocardial VEGF gene therapy and G-CSF treatment alone or in combination in patients with chronic ischemic heart disease (IHD). Secondly, we tested the hypothesis that the quantity of circulating stem cells correlated with improvement in symptoms. Design. We treated I) 16 patients with intramyocardial placebo injections, II) 16 patients with intramyocardial VEGF-A165 gene injections, III) 13 patients with low dose G-CSF, and IV) 16 patients with intramyocardial VEGF-A165 gene followed by high dose G-CSF. Results. Circulating CD34+ cells and CD45 - CD34 - cells increased by G-CSF in a dose-dependent manner, but did not increase with VEGF gene therapy. The CD45 - /CD34- cells subgroups increased in both G-CSF treated groups. No association was found between the concentration of mobilized stem cells in the circulation and improvement in symptoms. Conclusions. G-CSF mobilized both haematopoietic and non-haematopoietic cells from the bone marrow in a dose-dependent manner in patients with chronic IHD. However, even high levels of circulating stem cells did not improve symptoms of IHD. [ABSTRACT FROM AUTHOR]

Aims Increased plasma concentrations of B-type natriuretic peptide (BNP) and its precursor (proBNP) provide important prognostic information in patients presenting with acute coronary syndromes. Although a majority of these patients undergo early invasive assessment, the effects of coronary angiography per se on plasma BNP and proBNP concentrations are not known. We therefore sought to determine whether coronary angiography and ventriculography affect the cardiac secretion of these prognostic markers. [ABSTRACT FROM PUBLISHER]

Examines clinical impact of vascular growth factors and endothelial progenitor cells in the acute coronary syndrome. Vascular growth factors which are of clinical relevance; Categories of endothelium-specific vascular endothelial growth factors (VEGF); Characteristics of fibroblast growth factor polypeptides; Role of VEGF in stimulating the development of collateral arteries in an ischemic area of the myocardium.

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]

Investigates the therapeutic angiogenesis of vascular growth factors in patients with ischemic coronary artery disease in Scandinavia. Prevention and treatment of atherosclerotic vascular heart disease; Causes of morbidity and mortality in industrialized countries; Methods for gene therapy.

Background: Stem cell therapy is investigated as a treatment option for patients with ischemic heart disease. In this study, long-term safety and efficacy of autologous intra-myocardial injections of adipose-derived stromal cells (ASCs) was studied in patients with refractory angina.Methods: Sixty patients with coronary artery stenosis and preserved left ventricular ejection fraction were 2:1 randomised to intramyocardial injections of ASCs or saline and followed for 3 years.Results: For patients in the ASC group, the bicycle exercise time and the exercise performance in watt were un-changed (383 ± 30 s to 370 ± 44 s, P = 0.052 and 81 ± 6 to 78 ± 10, P = 0.123, respectively), but the performance in METs was reduced significantly (4.2 ± 0.3 to 4.0 ± 0.4, P = 0.027) during the follow-up period. However, in the same period, there was in the placebo group a significant decline in bicycle exercise time (437 ± 53 s to 383 ± 58 s, P = 0.001), the exercise performance measured in watt (87 ± 12 W to 80 ± 12 W, P = 0.019) and in METs (4.5 ± 0.4 to 4.1 ± 0.4, P = 0.002). Moreover, angina measured as CCS class was significantly reduced in the ASC group but not in the placebo group (2.5 ± 0.9 to 1.8 ± 1.2, P = 0.002 and 2.5 ± 0.8 to 2.1 ± 1.3, P = 0.186, respectively). However, no significant change was observed between the two groups.Conclusions: Patients receiving ASCs had improved cardiac symptoms and unchanged exercise capacity, in opposition to deterioration in the placebo group. Trial registration ClinicalTrials.gov Identifier: NCT01449032. Registered 7 October 2011-Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT01449032?term=jens+kastrup&rank=7. [ABSTRACT FROM AUTHOR]

Objective To investigate whether distance from a patient's home to the nearest invasive centre influenced the invasive treatment strategy in acute coronary syndrome (ACS). Methods This was an observational cohort study using nationwide registries involving 24910 patients admitted with ACS (median age 67, range 30-"90⇔…years). All persons were grouped in tertiles according to the distance from their residence to the invasive centre. Cox proportional hazard models were applied to estimate the differences in coronary angiography and revascularisation rate within 60⇔…days of admission according to the distance to the centre. The end points were coronary angiography and subsequent revascularisation. Results Of 24910 patients with a first ACS, 33% resided <21⇔…km from one of the five invasive centres in Denmark, 33% lived between 21 and 64⇔…km away and 34% lived >64⇔…km away. The incidence of coronary angiography was 68% for long distance versus 77% for short distance (p<0.05), with an HR of 0.78 (95% CI 0.75 to 0.81, p<0.0001). Adjustment for patient characteristics such as age, sex, co-morbidity and socioeconomic status did not attenuate the difference (HR 0.74, 95% CI 0.71 to 0.77, p<0.0001). Furthermore, revascularisation in the subgroup examined with coronary angiography was less likely for those residing a long distance from the invasive centre compared with those living nearer (adjusted HR of 0.82 (95% CI 0.78 to 0.85, p<0.0001). Conclusions In patients hospitalised with ACS, invasive examination and treatment were less likely the further away from an invasive centre the patients resided, thus equal and uniform invasive examination and treatment was not found. [ABSTRACT FROM AUTHOR]

Abstract: Background: The study assessed long-term safety and efficacy of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells (BMMSCs) in patients with severe stable coronary artery disease (CAD) and refractory angina. Methods: Thirty-one patients with severe stable CAD and refractory angina were included. Patients had reversible myocardial ischemia and no further revascularization options. Autologous BMMSCs were isolated, culture expanded and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation. BMMSCs were injected into an ischemic, viable region of the myocardium. Patients were followed for 3years. Results: We found significant clinical improvements in exercise time (p=0.0016), angina class (CCS) (p<0.0001), weekly number of angina attacks (p<0.0001) and use of nitroglycerine from (p=0.0017). In the Seattle Angina Questionnaire there were significant improvements in physical limitation score, angina stability score, angina frequency score and quality of life score (all p<0.0001). When comparing all hospital admissions from 3years before to 3years after treatment, we observed highly reduced admission rates for stable angina (p<0.0001), revascularization (p=0.003) and overall cardiovascular disease (p<0.0001). No early or late side-effects of the treatment were observed. Conclusions: The final 3-year follow-up data after intramyocardial injection of autologous BMMSCs, in patients with severe CAD and refractory angina, demonstrated sustained clinical effects, reduced hospital admissions for cardiovascular disease and excellent long-term safety. The results indicate that autotransplantation of BMMSCs to the heart does not only improve symptoms but also slows down disease progression. [Copyright &y& Elsevier]

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 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]

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]