Hélène Kremer

Human serum albumin improves endothelial dysfunction and survival during experimental endotoxemia: Concentration- dependent properties*

Objectives: The mechanisms by which human serum albumin might protect against sepsis-induced organ dysfunction and improve survival are not elucidated. The present study was designed to assess the effects of two concentrations of human serum albumin on endotoxin-induced mortality as well as on endothelial and organ dysfunctions in both mouse and cell models. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratories. Subjects: Swiss mice (n = 10–15/group) were injected with either lipopolysaccharide or vehicle. Four and 12 hrs later, mice were infused or not with human serum albumin HSA (4% or 20%, 10 mL/kg) or normal saline (0.9% NaCl, 30 mL/kg). Human uterine vein endothelial cells were exposed to both lipopolysaccharide and tumor necrosis factor-&agr; during 8 hrs in the presence or absence of human serum albumin (4% or 20%). Measurements and Main Results: Mice survival, reactivity of mesenteric arteries, and Western blot protein analysis were assessed. Circulating endothelin-1, gluthatione, gluthatione disulfide, and creatinine plasma levels were measured. Nitric oxide production, oxidative, and nitrosative stresses were also measured in situ in endothelial cells. Human serum albumin 4%, but not human serum albumin 20% or normal saline solution, improved survival time of endotoxemic mice. Furthermore, human serum albumin 4% activated endothelial nitric oxide synthase and restored lipopolysaccharide-impaired flow-dependent endothelial dilation in mesenteric arteries. This was associated with a downregulation of nuclear factor &kgr;B and an upregulation of nuclear respiratory factor-2 and heme oxygenase-1. Human serum albumin 4% reduced lipopolysaccharide-induced renal dysfunction, enhanced endothelin-1 production and glutathione plasmatic levels, whereas human serum albumin 20% increased gluthatione disulfide. Furthermore, human serum albumin 4% but not 20% blunted lipopolysaccharide-tumor necrosis factor-&agr;-induced oxidative and nitrosative stresses in endothelial cells and increased their gluthatione levels. Conclusions: The present data confirm a protective effect of 4% human serum albumin treatment both on mice survival and endothelial dysfunction by inhibiting inflammatory and oxidative stress pathways induced by endotoxins. Conversely, higher concentrations of human serum albumin were detrimental suggesting a dose-dependent effect.

Exclusive Low-Molecular-Weight Heparin as Bridging Anticoagulant After Mechanical Valve Replacement

BACKGROUND Unfractionated heparin has been the standard anticoagulant used immediately after mechanical heart valve replacement (MHVR). The purpose of this study was to assess a postoperative anticoagulation protocol with low-molecular-weight heparin (LMWH) immediately after MHVR without the use of unfractionated heparin or anti-factor Xa monitoring. METHODS We performed a prospective, single-center, observational study of 1,063 consecutive patients undergoing elective MHVR with postoperative LMWH anticoagulation treatment. The exclusion criteria were as follows: renal failure, intraaortic balloon counterpulsation, critical perioperative state, or a recent neurologic event. The postoperative anticoagulation protocol used subcutaneous enoxaparin as a bridging anticoagulant treatment beginning on the first postoperative day and continuing until vitamin K antagonist treatment was fully effective. Patients were followed for 6 weeks. The primary endpoints were the incidence of thromboembolic or major bleeding events. RESULTS Eleven (1%) thromboembolic events occurred. Ten of these events were transient or permanent strokes. Major bleeding events occurred in 44 patients (4.1%), 7 of which were observed before the enoxaparin treatment period. At the time of discharge, 570 patients (53.6%) were no longer receiving LMWH treatment due to achieving the target international normalized ratio. The mean length of hospital stay was 8.5 ± 2.9 days. There were no deaths during the 6-week follow-up period. CONCLUSIONS In our highly selected population, after MHVR, postoperative anticoagulation using LMWH is associated with a low rate of thromboembolic and major bleeding events. This large observational study demonstrates that the use of LMWH as an anticoagulant is effective and safe after MHVR.

Out-of-hospital cardiac arrest survivors sent for emergency angiography: a clinical score for predicting acute myocardial infarction

Background: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Emergency coronary angiography and percutaneous coronary intervention might improve survival, especially when cardiac arrest is caused by acute myocardial infarction (AMI). However, identifying patients with AMI after OHCA remains challenging. The aim of this study was to determine the clinical and ECG criteria in OHCA that may help to identify better the patients with AMI. Methods: Consecutive OHCA patients who underwent emergency coronary angiography in our centre between 2009 and 2013 were included in this retrospective single-centre observational study. Results: A total of 177 patients with complete datasets were included. Significant coronary artery disease was found in 71% of the patients, and 43% presented with AMI. The independent predictors of AMI were ST elevation in any lead including aVR (odds ratio (OR) 18.06; 95% confidence interval (CI) 6.6–49.38), chest pain before cardiac arrest (OR 4.05; 95% CI 1.55–10.54) and an initial shockable rhythm (OR 2.99; 95% CI 1.34–6.45). An additive score that included these three predictors yielded a sensitivity and a specificity for detecting AMI of 93% and 63%, respectively. Conclusions: These data suggest that fewer than half of patients with OHCA undergoing emergency coronary angiography present with AMI. The identification of OHCA patients with AMI might be improved by a simple score using post-resuscitation ECG and simple clinical criteria.

0258: Comparison of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement in very high risk patients, monocentric registry of an early experience

Introduction The PARTNER trial has shown that TAVI is not inferior to surgical aortic valve replacement (AVR) in high-risk aortic stenosis. However, real life registry comparing TAVI and surgery are lacking. Methods monocentric registry of high-risk patients (lEUROSCORE1 ≥15%) undergoing TAVI (114 patients) or AVR (81 patients) between 2009 and 2013 in our institution. Results Mean age was 84,4 and 83,6 yo (p=NS). TAVI patients had higher EUROSCORE1 (31 vs 24.5%, p Conclusion The present registry results confirm that TAVI is a real alternative to surgery in patients with at high surgical risk. Longer follow up is required to confirm these results. Abstract 0258 – Table. AVR TAVI p n 81 114 Age 83.6 84.4 0.21 Euroscore1 (%) 24.5 31 FEV (%) 57.1 48.5 DTVG (mm) 51 54 0.086 Mean Gradient (mmHg) 53 46 0.008 Creatinin pre (microM/L) 111 138 0.003 Hemoglobin pre (g/100) 12.6 11.6 Death (%) 17.3 9.6 0.12 Vascular complication (%) 0 11.4 0.001 Infection (%) 19 11 0.008 Dialysis (%) 13.6 11.4 0.65 AFIB post (%) 41 20 0.002 Pericardial effusion (% ) 2.5 8.8 0.13 Stroke (%) 4.9 1.8 0.23 Pace Maker (%) 4.9 24.6 Transfusions (%) 80 25

0228: Aortic annulus sizing strategy in TAVI, comparison of echocardiography and CT, impact on aortic regurgitation incidence and patients prognosis

Background Aortic regurgitation (AR) after TAVI is the main limitation of this procedure. The aim of this study was to evaluate i) aortic annulus sizing by CT and/or echocardiography (TTE or TEE) ii) the incidence of AR and its determinism iii) the prognostic impact of AR and other survival predictors. Methods 136 consecutive patients undergoing TAVI were included between 2010 and 2013. The aortic annulus sizing for prosthesis choice was done by TEE in 29 patients and by CT in 107 patients. Aortic valve calcium volume was measured by the volume technique in 67% of patients who have got CT. Follow-up was performed at 1, 6, 12 and 24 months. Results Aortic annulus sizing by TTE and TEE echocardiography (TEE) were well correlated (r=0,73, p=0,0001, n=51) but were significantly lower than CT sizing (p 25%, aortic regurgitation ≥ 2/4, renal failure with creatinin> 130μmol/l, anemia after TAVI Conclusion This study showed that aortic annulus sizing by echocardiography is significantly lower than sizing by CT. AR have an independent prognostic on survival. Prevention of aortic regurgitation is an important issue for the future of this technique.