A contemporary look at pericardiocentesis.

Percutaneous drainage is the default strategy for evacuating a pericardial effusion. A pericardiocentesis can be necessary or required in a wide variety of clinical settings ranging from urgent tamponade to relieve in iatrogenic hemorrhagic effusions in the electrophysiology or catheterization room, to planned diagnostic procedures in patients with suspected or known malignancy or infections. With the help of several procedural improvements over the past decades, echocardiography and fluoroscopy-guided percutaneous pericardiocentesis has become the standard intervention for evacuating pericardial effusions, as well as an essential tool in the diagnostic work-up of an unexplained pericardial effusion. When performed by skilled physicians assisted by appropriate imaging it is a very safe procedure, and provided that an indwelling catheter is placed, it is also very effective with an acceptably low risk of recurrences. In this review, the indications and standard techniques for pericardiocentesis are discussed, as well as their consequences for patients with iatrogenic and malignant effusions.

5-Year clinical follow-up of the COBRA (complex coronary bifurcation lesions: Randomized comparison of a strategy using a dedicated self-expanding biolimus A9-eluting stent vs. a culotte strategy using everolimus-eluting stents) study.

OBJECTIVES: We evaluated healing responses with optical coherence tomography, and long-term clinical outcomes after treatment with a dedicated stent versus a conventional culotte technique. BACKGROUND: Dedicated bifurcation stents have been proposed as an alternative treatment for coronary bifurcation lesions. The long-term performance of dedicated stents versus conventional dual-stent techniques for the treatment of complex coronary bifurcation lesions is unknown. METHODS: Forty patients with true coronary bifurcation lesions were randomized to treatment with a dedicated Axxess bifurcation stent in the proximal main vessel and additional Biomatrix stents in branches versus culotte stenting using Xience stents. RESULTS: The percentage of uncovered struts in each bifurcation segment at 9 months (primary endpoint) was similar between groups. Five-year clinical follow-up was available for all patients and included major adverse cardiac events [MACE; a composite of cardiac death, myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR)], target-vessel (TVR) and non-target-vessel revascularization (non-TVR), non-TLR and stent thrombosis. At 5 years, in the culotte group, one patient had undergone TLR and another suffered a clinical MI, resulting in 10% MACE versus none in the Axxess group. TVR (5% vs. 10%, P = 0.54) and non-TVR (5% vs. 20%, P = 0.39) rates were similar between the Axxess and culotte groups, respectively. There was no stent thrombosis. CONCLUSION: Compared with culotte stenting with Xience, complex coronary bifurcation stenting using a dedicated strategy combining the Axxess and Biomatrix stents results in similar stent strut coverage at 9 months, and excellent clinical outcomes at 5 years.

Air pollution and ST-elevation myocardial infarction: A case-crossover study of the Belgian STEMI registry 2009-2013.

BACKGROUND: Previous studies have shown that air pollution particulate matter (PM) is associated with an increased risk for myocardial infarction. The effects of air pollution on the risk of ST-elevation myocardial infarction (STEMI), in particular the role of gaseous air pollutants such as NO2 and O3 and the susceptibility of specific populations, are still under debate. METHODS: All patients entered in the Belgian prospective STEMI registry between 2009 and 2013 were included. Based on a validated spatial interpolation model from the Belgian Environment Agency, a national index was used to address the background level of air pollution exposure of Belgian population. A time-stratified and temperature-matched case-crossover analysis of the risk of STEMI was performed. RESULTS: A total of 11,428 STEMI patients were included in the study. Each 10µg/m3 increase in PM10, PM2.5 and NO2 was associated with an increased odds ratio (ORs) of STEMI of 1.026 (CI 95%: 1.005-1.048), 1.028 (CI 95%: 1.003-1.054) and 1.051 (CI 95%: 1.018-1.084), respectively. No effect of O3 was found. STEMI was associated with PM10 exposure in patients ≥75y.o. (OR: 1.046, CI 95%: 1.002-1.092) and with NO2 in patients ≤54y.o. (OR: 1.071, CI 95%: 1.010-1.136). No effect of air pollution on cardiac arrest or in-hospital STEMI mortality was found. CONCLUSION: PM2.5 and NO2 exposures incrementally increase the risk of STEMI. The risk related to PM appears to be greater in the elderly, while younger patients appear to be more susceptible to NO2 exposure.

[Rivaroxaban: Xarelto--recommendations for pharmacists]. / Le Rivaroxaban (Xarelto): guide de la pratique officinale.

Rivaroxaban is one of the new oral anticoagulants (NOACs). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

Stroke prevention in elderly patients with atrial fibrillation: challenges for anticoagulation.

Elderly patients with atrial fibrillation (AF), who constitute almost half of all AF patients, are at increased risk of stroke. Anticoagulant therapies, especially vitamin K antagonists (VKA), reduce the risk of stroke in all patients including the elderly but are frequently under-used in older patients. Failure to initiate VKA in elderly AF patients is related to a number of factors, including the limitations of current therapies and the increased risk for major haemorrhage associated with advanced age and anticoagulation therapy. Of particular concern is the risk of intracranial haemorrhages (ICH), which is associated with high rates of mortality and morbidity. Novel oral anticoagulant agents that are easier to use and might offer similar or better levels of stroke prevention with a similar or reduced risk of bleeding should increase the use of antithrombotic therapy in the management of elderly AF patients. Amongst these new agents, the recently approved direct thrombin inhibitor dabigatran provides effective stroke prevention with a significant reduction of ICH, and enables clinicians to tailor the dose according to age and haemorrhagic risk.

Automatic segmentation of in-vivo intra-coronary optical coherence tomography images to assess stent strut apposition and coverage.

The implantation of intracoronary stents is currently the standard approach for the treatment of coronary atherosclerotic disease. The widespread adoption of this technology has boosted an intensive research activity in this domain, with continuous improvements in the design of these devices, aiming at reducing problems of restenosis (re-narrowing of the stented segment) and thrombosis (sudden occlusion due to thrombus formation). Recently, a new, light-based intracoronary imaging modality, optical coherence tomography (OCT), was developed and introduced into clinical practice. Due to its very high axial resolution (10-15 µm), it allows for in vivo evaluation of both stent strut apposition and neointima coverage (a marker of healing of the treated segment). As such, it provides valuable information on proper stent deployment, on the behaviour of different stent types in-vivo and on the effect of new types of stents (e.g. drug-eluting stents) on vessel wall healing. However, the major drawback of the current OCT methodology is that analysis of these images requires a tremendous amount of-currently manual-post-processing. In this manuscript, an algorithm is presented that allows for fully automated analysis of stent strut apposition and coverage in coronary arteries. The vessel lumen and stent struts are automatically detected and segmented through analysis of the intensity profiles of the A-lines. From these data, apposition and coverage can then be measured automatically. The algorithm was validated using manual assessments by two experienced operators as a reference. High Pearson's correlation coefficients were found (R = 0.96-0.97) between the automated and manual measurements while Bland-Altman analysis showed no significant bias with good limits of agreement. As such, it was shown that the presented algorithm provides a robust and fast tool to automatically estimate apposition and coverage of stent struts in in-vivo OCT pullbacks. This will be important for the integration of this technology in clinical routine and for the analysis of datasets of larger clinical trials.

Antiplatelet therapy in the perioperative period.

Antiplatelet drugs are the cornerstone treatment in the secondary prevention of arterial thrombosis. Until recently, their intake was interrupted in the perioperative period because of fear for bleeding, but new insights have challenged this old habit: In patients at high risk for atherothrombotic events who need to undergo surgery or an invasive procedure, the risk for bleeding complications because of a treatment with low-dose acetylsalicylic acid (LD ASA) needs to be balanced against the risk of atherothrombotic events after treatment discontinuation. For patients at high risk of atherothrombotic complications recent guidelines do no longer advocate to interrupt LD ASA routinely. However, the likelihood of bleeding versus atherothrombotic complications should be considered on a case-by-case basis. When continued perioperatively, the bleeding risk associated with thienopyridines (ticlopidine, clopidogrel and prasugrel) is higher than that of LD ASA. It is recommended to stop their intake 1 week before the surgical intervention, except in patients with (recent) coronary stenting.

La hiperglicemia de ingreso se asocia a mayor mortalidad en pacientes con infarto agudo al miocardio y supradesnivel del ST sometidos a angioplastía primaria / Hyperglycemia is associated to increased mortality rate in patients with acute myocardial infarction undergoing primary angioplasty

Antecedentes: La hiperglicemia es habitual en los pacientes graves, tales como quienes cursan con un infarto al miocardio con supradesnivel del ST (IAMSDST). Los registros han demostrado que la hiperglicemia de ingreso es un marcador certero de mortalidad durante un IAM, especialmente en aquellos no diagnosticados previamente como diabéticos. Objetivos: El objetivo de este estudio fue establecer la relación entre los niveles de glicemia al ingreso y la mortalidad intrahospitalaria de pacientes cursando IAMSDST sometidos a angioplastía primaria. Métodos: Se analizaron 273 pacientes consecutivos sometidos a angioplastía primaria o de rescate (después de trombolisis fallida) entre junio de 2003 y mayo de 2005. En 234 de ellos se midió la glicemia dentro de las primeras 6 horas del ingreso. Se dividió a los pacientes en cuatro grupos según la glicemia: hasta 125 mg/dl, 126-150 mg/dl, 151-200 mg/dl y, mayor a200 mg/dl. Se registró la mortalidad intrahospitalaria y la ocurrencia de eventos cardíacos mayores (MACE: muerte, infarto no fatal, revascularización). Resultados: La mortalidad total fue de 9,4 por ciento y la ocurrencia de MACE fue 13,6 por ciento. La mortalidad aumentó significativamente conforme aumentaba la glicemia. Los pacientes con niveles altos de glicemia presentaron un riesgo mayor de shock cardiogénico. Los niveles de glicemia se correlacionaron con el tamaño del infarto medido como niveles de CK total (p<0.001). El análisis multivariado señaló como marcadores independientes de mortalidad intrahospitalaria a la disfunción ventricular (p=0,006) y a la glicemia mayor de 150 mg/dl (p=0,023)Conclusión: Los niveles de glicemia al ingreso se asocian a mayor mortalidad intrahospitalaria en pacientes con IAMSDST sometidos a angioplastía primaria.

Acute ST-elevation myocardial infarction.

Acute ST-elevation myocardial infarction (STEMI) remains the leading cause of death in industrialized countries. For many patients, a myocardial infarction is the first presentation of atherosclerotic coronary artery disease. This often results in delays in obtaining medical attention and subsequently poorer outcome, certainly because symptoms are often misinterpreted. Furthermore, a large proportion of STEMI patients die from lethal arrhythmias even before reaching medical facilities. Numerous studies during the past decades have firmly established the paradigm of achieving early, complete and sustained infarct-related artery patency. Because of a more aggressive therapy and rapid revascularization using either fibrinolysis or primary PCI, many patients do remarkably well after STEMI. Unfortunately, adherence to treatment guidelines is often suboptimal, leading to less favourable outcome. Also, more efficient care for patients with myocardial infarction has led to a rapidly growing population of patients with chronic heart failure.

Will oral antithrombin agents replace warfarin?

The new oral direct thrombin inhibitor ximelagatran is at least equivalent to warfarin for stroke prevention in patients with non-valvar atrial fibrillation, and seems to be a promising adjunct to aspirin after acute coronary syndrome

Thrombolytic therapy. State of the art.

Thrombolytic agents have become the corner stone in the treatment of acute myocardial infarction. However, the current agents are far from perfect. New thrombolytic drugs have been designed to overcome these shortcomings. Development of these agents has focused not only on increasing plasma half-life and thus allowing single-bolus administration, but also on improving fibrin specificity and resistance to plasminogen activator inhibitor. The safety and efficacy of several of these promising thrombolytic drugs have been evaluated in large-scale trials, which are discussed in the present review. Parallel to these advances, alternatives to standard thrombolytic regimens have been developed. New trials evaluating the combination of reduced-dose fibrinolytics with different regimens of antithrombotic agents will optimize future reperfusion strategies.

Soluble guanylate cyclase alpha(1) and beta(1) gene transfer increases NO responsiveness and reduces neointima formation after balloon injury in rats via antiproliferative and antimigratory effects.

In vascular smooth muscle cells, NO stimulates the synthesis of cGMP by soluble guanylate cyclase (sGC), a heterodimer composed of alpha(1) and beta(1) subunits. NO/cGMP signal transduction affects multiple cell functions that contribute to neointima formation after vascular injury. Balloon-induced vascular injury was found to decrease sGC subunit expression and enzyme activity in rat carotid arteries. The effect of restoring sGC enzyme activity on neointima formation was investigated using recombinant adenoviruses specifying sGC alpha(1) and beta(1) subunits (Adalpha1 and Adbeta1). Coinfection of cultured rat aortic smooth muscle cells with Adalpha1 and Adbeta1 increased NO-stimulated intracellular cGMP levels 60-fold and decreased DNA synthesis and migration by 16% and 48%, respectively. Immunoreactivity for alpha(1) and beta(1) subunits colocalized in carotid arteries infected with Adalpha1 and Adbeta1. Molsidomine-stimulated carotid tissue cGMP levels were greater after coinfection with Adalpha1 and Adbeta1 than after infection with a control virus, AdRR5 (0.53+/-0.09 pmol/mg protein, mean+/-SEM, versus 0.23+/-0.09, P<0.05). Mean intima/media ratio, 2 weeks after balloon injury and twice-daily administration of 5 mg/kg molsidomine, was less in rats coinfected with Adalpha1 and Adss1 than in rats infected with AdRR5 or in uninfected rats (0.36+/-0.11 versus 0. 81+/-0.13 and 0.75+/-0.25, respectively, P<0.05). Thus, Adalpha1 and Adbeta1 gene transfer to balloon-injured rat carotid arteries increases NO responsiveness and attenuates neointima formation via a direct antiproliferative and antimigratory effect on vascular smooth muscle cells.

Gene Therapy for Coronary Restenosis: A Promising Strategy for the New Millennium?

Gene therapy is an attractive alternative for reducing restenosis after percutaneous coronary interventions. Several approaches, using genes encoding antiproliferative, antimigratory, cytostatic, or cytotoxic proteins have been successfully tested in relevant animal models. Antiproliferative, gene-based strategies also appear to be good candidates for the highly proliferative lesion responsible for in-stent restenosis. However, several key issues, including vector safety and delivery mechanisms, still have to be resolved before percutaneous gene therapy can be widely applied in the clinic. The amount of experimental research in this field indicates a medical evolution that can (and should) not be ignored by cardiologists.

Polyethylene glycol-derivatized cysteine-substitution variants of recombinant staphylokinase for single-bolus treatment of acute myocardial infarction.

BACKGROUND: Thrombolytic therapy of acute myocardial infarction (AMI) is evolving toward bolus administration. Derivatization of proteins with polyethylene glycol (PEG) may reduce their clearance. METHODS AND RESULTS: A staphylokinase (SakSTAR) variant with 12 amino acid substitutions to reduce its antigenicity, SakSTAR (K35A, E65Q, K74R, E80A, D82A, T90A, E99D, T101S, E108A, K109A, K130T, K135R), and with Ser in position 3 mutated into Cys (code SY161), was derivatized with maleimide-PEG with M:(r) of 5,000 (P5), 10,000 (P10), or 20,000 (P20). The PEGylated variants recognized only one third of the antibodies elicited with wild-type SakSTAR in AMI patients. In experimental animals, plasma clearances were reduced 2. 5- to 5-fold with P5, 5- to 20-fold with P10, and 20-fold with P20, and bolus injection induced pulmonary plasma clot lysis at doses inversely related to their clearance. Intravenous bolus injection of 5 mg of the P5, P10, or P20 variants in AMI patients was associated with plasma half-lives (t(1/2alpha)) of 13, 30, and 120 minutes and clearances of 75, 43, and 8 mL/min, respectively, compared with 3 minutes and 360 mL/min for SakSTAR. Injection of 5 mg P5 variant restored TIMI-3 flow within 60 minutes in 14 of 18 AMI patients (78%, 95% CI 55% to 91%) and of 2.5 mg in 7 of 11 patients (63%, 95% CI 35% to 85%), both in the absence of fibrinogen degradation. The immunogenicity of the variants was significantly (P:<0.002) reduced. CONCLUSIONS: The staphylokinase variant SY161-P5, derivatized with one linear polyethylene glycol molecule of M:(r) 5000, is a promising fibrin-selective agent for single-bolus coronary thrombolysis.

Percutaneous gene therapy using recombinant adenoviruses encoding human herpes simplex virus thymidine kinase, human PAI-1, and human NOS3 in balloon-injured porcine coronary arteries.

Local intracoronary delivery of recombinant adenoviruses expressing anti-migratory or anti-proliferative proteins including human constitutive endothelial nitric oxide synthase (NOS3), plasminogen activator inhibitor 1 (PAI-1), or herpesvirus thymidine kinase (TK) (combined with ganciclovir) was used to prevent neointimal formation in porcine coronary arteries. After balloon injury of the left anterior descending (LAD) coronary artery, animals received an intramural injection of adenovirus (1.5 X 10(9) PFU) carrying either the NOS3 cDNA (AdCMVNOS3, n = 12), the PAI-1 cDNA (AdCMVPAI-1, n = 12), the TK cDNA (AdMLPItk, n = 12), or no cDNA (AdpL+, n = 12). After 28 days, morphometric analysis was performed on coronary sections from all segments demonstrating injury. The internal elastic lamina (IEL) fracture length normalized to the IEL perimeter (initial injury) and the neointimal area normalized to the vessel area (response to injury) were used to generate linear regression lines and calculate an index of stenosis for the respective treatment groups. The response to injury was significantly smaller in AdCMVNOS3- and AdMLPItk-infected animals than in AdpL+-infected animals (slopes = 0.86 +/- 0.05 and 0.69 +/- 0.07 versus 1.11 +/- 0.06, p < 0.005 and p < 0.0001, respectively) but not in AdCMVPAI-1-infected animals (slope = 1.26 +/- 0.04, p = 0.04). No viral shedding was observed and there was no acute systemic toxicity after gene transfer. An increase in neutralizing antibody titers against Ad vectors was observed without any detectable response to the transgene products (NOS3, PAI-1). Local gene transfer of NOS3 and TK may hold promise as a safe and effective adjunctive treatment to reduce neointimal formation after percutaneous coronary intervention in humans.

Percutaneous adenoviral gene transfer into porcine coronary arteries: is catheter-based gene delivery adapted to coronary circulation?

Recombinant adenoviral (Ad) vectors represent an efficient gene transfer system for targeting the cardiovascular system. Phenotypic modulation of coronary vascular cells in vivo is, however, critically dependent on the efficacy of local delivery devices. Four local drug delivery catheters were tested for intracoronary gene transfer efficiency: the Infiltrator (INF, n = 10), the Crescendo (CRE, n = 10), the Infusasleeve (SLE, n = 8), and the Remedy balloon (channel balloon [CHA], n = 8). After balloon injury of the LAD, Ad vector containing the firefly luciferase cDNA (AdCMVluc, 1.5 x 10(10) plaque-forming units) was administered at the site of injury. On day 4, tissue samples from different regions in the heart and from the liver were assayed for luciferase activity to evaluate local and systemic gene transfer. INF, CRE, and SLE catheters showed higher transduction levels of the target LAD segment than did the CHA catheter (median luciferase activity = 4.2 x 10(6), 11 x 10(6), and 1.3 x 10(6) light units [LU]/vessel versus 0.09 x 10(6) LU/vessel, respectively, p < 0.05). Luciferase activity was occasionally observed in nontarget tissues (right and left ventricular free wall, distal LAD, and liver) and was not significantly different between groups. The viral circulatory half-life was similar for the four groups (<1 min). Gene transfer efficiency was positively correlated with the degree of injury for the intralumenal catheters (CRE, SLE, and CHA) but was independent of the vessel wall injury for the intramural INF. Local drug delivery catheters enable efficient vascular gene transfer in balloon-injured coronary arteries, a prerequisite for further development of intracoronary gene therapy for restenosis.

Gene therapy in the cardiovascular system: an update.

This update reviews the remarkable progression in several cardiovascular gene transfer domains. The first chemical gene therapy protocols to stimulate angiogenesis in ischemic myocardium are discussed and both the great expectations as well as remaining hurdle are highlighted. In experimental models of restenosis and heart failure gene therapy shows promising results. Important question regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases.