Perioperative Bridging Anticoagulation in Patients With Atrial Fibrillation

Perioperative Bridging Anticoagulation in Patients With Atrial Fibrillation

JOURNAL OF VASCULAR SURGERY Volume 63, Number 1 ability to generate human myocardial vascular progenitor cells of mesoderm origin and terminally diff...

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JOURNAL OF VASCULAR SURGERY Volume 63, Number 1

ability to generate human myocardial vascular progenitor cells of mesoderm origin and terminally differentiated vascular and endothelial cells. They can be used for potential characterization of lncRNAs. The authors investigated the lncRNAs differentially regulated at key steps during human cardiovascular development with a special focus on vascular and endothelial cells. RNA sequencing led to generation of large data sets that served as a gene expression road map highlighting gene expression changes during human pluripotential cell differentiation. Specific analysis led to identification of three previously uncharacterized lnc RNAs, TERMINATOR, ALIEN, and PUNISHER. These lncRNAs are specifically expressed in undifferentiated pluripotential stem cells, cardiovascular progenitors, and differentiated endothelial cells, respectively. Functional characterization of these lncRNAs included localization studies, dynamic expression analysis, epigenetic modification monitoring, and knock down experiments in lower vertebrates, as well as mirroring embryos, confirmed a critical role for each lncRNA specific for each analyzed developmental stage. Comment: Study of human embryology is now moving beyond the microscope to the genome. Long noncoding RNAs are a new class of regulatory RNA molecules that can modulate diverse processes such as development, pluripotency, and disease by altering post transcriptional and post translational regulation, recombination, protein complex formation and cell signaling. It is therefore clear that identification and characterization of such molecules regulating human development is potentially of major interest. Ultimately there may be new avenues for development of human therapeutics targeting this previously overlooked family of genes. Preservation Solution Impacts Physiologic Function and Cellular Viability of Human Saphenous Vein Graft Wise ES, Hocking KM, Eagle S, et al. Surgery 2015;158:537-46. Conclusion: Preservation of human saphenous veins (HSVs) in normal saline solution causes graft injury and leads to impaired physiologically function and decreased viability of HSVs. Harm can be mitigated by use of buffered salt solutions as preservation media. Summary: Saphenous vein is the most widely used conduit for coronary and peripheral bypass grafts. Typical preparation of the saphenous vein consists of a series of “back table” manipulations. One such manipulation is preservation in a “storage medium” before implantation. Previous studies have suggested that preservation in normal saline may actually harm vascular conduits and promote neointimal hyperplasia (O’Connell TX et al, J Surg Res 1974;16:197-203). In a retrospective examination of coronary artery vein grafts stratified according to preservation solution it was found that the balanced buffered electrolyte solutions preserved grafts had one year vein graft failure rates less than those grafts preserved with normal saline solution or whole blood. In this study, the authors assess the influence of preservation solutions including Plasma-Lyte A, normal saline, University of Wisconsin solution, Celsior solution, autologous whole blood, and glutathione-ascorbic acid L-arginine solution on cellular physiology and viability. Their goal is to provide insights into identifying components of a HSV storage medium that enhances graft function. Unprepared HSVs obtained from coronary artery bypass graft patients were characterized after two hour storage in the six tested solutions. Vascular smooth muscle contraction was assessed after exposure to depolarizing KCl and phenylephrine. The relaxation of phenylephrine-precontracted saphenous veins to sodium nitroprusside and carbachol (endothelial-independent and dependent relaxation, respectively) was also assessed. Cellular viability was determined via methyl thiazolyl tetrazolium (MTT) assay. Preservation of HSVs in normal saline or autologous whole blood impaired contractile responses to KCl relative to unpreserved (UP) tissues, whereas preservation in University of Wisconsin solution and Celsior solution enhanced contractile responses (P < .05). Relative to UP tissues, HSV responses to relaxation treated with Wisconsin solution, Celsior solution, and GALA all potentiated responses (P < .05). Only preservation in normal saline impaired endothelial-independent relaxation (P ¼ .005). Preservation in Plasma-Lyte A (P ¼ .02), normal saline (P ¼ .002), and University of Wisconsin solution (P ¼ .02) impaired endothelial-dependent relaxation. Normal saline preservation decreased MTT viability index relative to UP tissues (0.02 6 0.002 mg10.5 mL1 vs 0.033 6 0.005 mg10.5 mL1; P ¼ .03).

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Comment: How preparation procedures of vein grafts enhance long term patency of the graft and minimize intimal hyperplasia are not precisely known. However, it does appear that during “back-table” preparation there is a potential window of opportunity where vein graft endothelial cells can either be harmed or preserved. The data suggests normal saline alone impairs physiological function and decreases cellular viability of the graft and much of this can be obviated with use of a balanced buffered salt solution potentially with additives such as L-arginine or P2X7 receptor antagonists or antioxidants or other cellular nutrients. A combination of these things may help maintain smooth muscle cell function as well as an intact functional endothelial mono-layer. Whereas, it makes sense that this should contribute to the health of the vein graft as it is implanted, the precise characteristics of a preservation solution and preservation technique to maximize endothelial function and minimize intimal hyperplasia are still unknown and require further study relating relevant clinical end points like graft patency and/or need for revision, to measures of endothelial cell function affected by back table vein preparation. Perioperative Bridging Anticoagulation in Patients With Atrial Fibrillation Douketis JD, Spyropoulos AC, Kaatz S, et al. N Engl J Med 2015;373:823-33. Conclusion: Patients with atrial fibrillation on warfarin therapy and who have warfarin therapy interrupted for an elective operation or other elective or invasive procedures do just as well without bridging anticoagulation as they do when they have bridging anticoagulation with respect to prevention of thromboembolism and they have decreased risk of major bleeding. Summary: Patients undergoing invasive procedures who are on anticoagulation therapy with warfarin for atrial fibrillation are frequently treated with so called bridging therapy in an attempt to prevent thromboembolic complications potentially associated with withholding anticoagulation. The fundamental question of whether bridging anticoagulation is actually necessary during perioperative warfarin interruption has not been answered. Theoretic risk of thromboembolic events during the period of time where anticoagulation is held must be balanced by the potential risk of increased bleeding with bridging therapy. This study was designed to address the relatively simple question: in patients with atrial fibrillation is heparin bridging needed during the interruption of warfarin therapy before and after an operation or other invasive procedure? The hypothesis was that forgoing bridging all together would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative thromboembolism and would be superior to bridging with regard to the outcome of major bleeding. This was a randomized double blind placebo controlled trial in which after perioperative interruption of warfarin therapy patients were randomly assigned to receive bridging anticoagulation therapy with low-molecularweight heparin (100 IU of dalteparin per kg of body weight) or matching placebo administered subcutaneously twice daily from 3 days before the procedure until 24 hours after the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days post-procedure. Primary outcomes were arterial thromboembolism (stroke, systemic embolization, or transient ischemic attack) and major bleeding. There were 1884 patients enrolled, 950 assigned to receive no bridging therapy, 934 assigned to receive bridging therapy. Incidence of thromboembolism was 0.4% in the nonbridging group and 0.3% in the bridging group (risk difference, 0.1%; 95% confidence interval, 0.6 to 0.8; P ¼ .01 for noninferiority). Incidence of major bleeding was 1.3% in a nonbridging group and 3.2% in the bridging group (relative risk, 0.41; 95% confidence interval, 0.20-0.78; P ¼ .005 for superiority). Comment: This paper and that by Steinberg BA et al, Circulation 2015;131:488-94 (also featured in this Abstracts section of the J Vasc Surg) should effectively put the kybosh on the use of routine bridging therapy for low risk patients with atrial fibrillation who require interruption of anticoagulation for an invasive surgical or diagnostic procedure. The results of course do not apply to high-risk patients or patients who are on one of the new novel oral anticoagulants for treatment of atrial fibrillation, as a risk of rebound hypercoagulation in patients when these agents are held is really not known.