Impact of the indexed effective orifice area on mid-term cardiac-related mortality after aortic valve replacement

Background There has been ongoing controversy as to whether prosthesis-patient mismatch (PPM, defined as indexed effective orifice area (EOAI) <0.85 m(2)/cm(2)) influences mortality after aortic valve replacement (AVR). In most studies, PPM is anticipated by reference tables based on mean EOAs as opposed to individual assessment. These reference values may not reflect the actual in vivo EOAI and hence, the presence or absence of PPM may be based on false assumptions. Objective To assess the impact of small prosthesis EOA on survival after aortic valve replacement AVR. Methods 645 patients had undergone an AVR between 2000 and 2007 entered the study. All patients underwent transthoracic echocardiography for determination of the actual EOAI within 6 months postoperatively. In order to predict time from surgery to death a proportional hazards model for competing risks (cardiac death vs death from other causes) was used. EOAI was entered as a continuous variable. Results PPM occurred in 40% of the patients. After a median follow-up of 2.35 years, 92.1% of the patients were alive. The final Cox regression model showed a significantly increased risk for cardiac death among patients with a smaller EOAI (HR=0.32, p=0.022). The effect of EOAI on the 2-5 year mortality risk was demonstrated by risk plots. Conclusions In contrast to previous studies these EOAI values were obtained through postoperative echocardiography, substantially improving the accuracy of measurement, and the EOAI was modelled as a continuous variable. There was a significantly improved survival for larger EOAIs following AVR. Strategies to avoid PPM should become paramount during AVR

Predictors of mortality following corevalve transcatheter aortic valve implantation: results from the ADVANCE study

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Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

OBJECTIVE: To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. METHODS: A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. RESULTS: Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. CONCLUSION: TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis

Impact of Anesthesia Type on Outcomes of Transcatheter Aortic Valve Implantation (from the Multicenter ADVANCE Study).

Transcatheter aortic valve implantation (TAVI) has become the standard of care for many patients with symptomatic severe aortic stenosis who are at increased risk of morbidity and mortality during surgical aortic valve replacement. However, there is still no general consensus regarding the use of general anesthesia (GA) versus local anesthesia with sedation (non-GA) during the TAVI procedure. Using propensity score-matching analysis, we analyzed the characteristics and outcomes of patients who underwent TAVI with either GA (n = 245) or non-GA (n = 245) in the fully monitored, international, CoreValve ADVANCE Study. No statistically significant differences existed between the non-GA and GA groups in all-cause mortality (25.4% vs 23.9%, p = 0.78), cardiovascular mortality (16.4% vs 16.6%, p = 0.92), or stroke (5.2% vs 6.9%, p = 0.57) through 2-year follow-up. Major vascular complications were more common in the non-GA group. Total hospital stay was similar between the 2 groups. Conversion from non-GA to GA occurred in 13 patients (5.3%) because of procedural complications in 9 patients and discomfort or restlessness in 4 patients. Most procedural complications were related to valve positioning or vascular issues. Two of the 13 converted patients died during the procedure. Both GA and non-GA are widely used in real-world TAVI practice, and the decision appears to be guided by only a few patient-related factors and dominated by local and national practice. The outcomes of both anesthesia modes are equally good. When conversion from non-GA did occur, the complication requiring GA affected outcomes

De novo Generation of an Axially Vascularized Processed Bovine Cancellous-Bone Substitute in the Sheep Arteriovenous-Loop Model

Abstract Background/Aims: The aim of this study was to generate an axially vascularized bone substitute. The arteriovenous (AV)- loop approach in a large-animal model was applied in order to induce axial vascularization in a clinically approved processed bovine cancellous bone (PBCB) matrix of significant volume with primary mechanical stability and to assess the course of increasing axial vascularization. Methods: PBCB constructs were implanted into 13 merino sheep together with a microsurgically created AV loop in an isolation chamber. The vascularization process was monitored by sequential magnetic resonance imaging (MRI) scans. Explants were subjected to micro-computed tomography (micro-CT) analysis, histomorphometry and immunohistochemistry for CD31 and CD45. Results: Increasing axial vascularization in PBCB constructs was quantified by histomorphometry and visualized by micro-CT scans. Intravital sequential MRI scans demonstrated a significant progressive increase in perfused volume within the matrices. Immunohistochemistry confirmed endothelial lining of newly formed vessels. Conclusion: This study demonstrates successful axial vascularization of a clinically approved, mechanically stable bone substitute with a significant volume by a microsurgical AV loop in a large-animal model. Thus microsurgical transplantation of a tissue-engineered, axially vascularized and mechanically stable bone substitute with clinically relevant dimensions may become clinically feasible in the future

New aspects on efficient anticoagulation and antiplatelet strategies in sheep

Background After addressing fundamental questions in preclinical models in vitro or in small animals in vivo, the translation into large animal models has become a prerequisite before transferring new findings to human medicine. Especially in cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important in vivo model for testing innovative therapies or medical devices prior to clinical application. For a wide variety of sheep model based research projects, an optimal anticoagulation and antiplatelet therapy is mandatory. However, no standardised scheme for this model has been developed so far. Thus the efficacy of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in sheep of different ages. Results Responses to antiplatelet and anticoagulant drugs in different concentrations were studied in the sheep. First, a baseline for the measurement of platelet aggregation was assessed in 20 sheep. The effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite carboxylic acid were detected in every plasma sample. High dose ticagrelor (375 mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep, while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti-factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite receiving quadruple dosages (600 mg bid). Conclusion High dosages of clopidogrel inhibited platelet aggregation merely in a low number of sheep despite sufficient absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for platelet inhibition in sheep. Efficient anticoagulation can be ensured using sodium enoxaparin rather than dabigatran etexilate in age-dependent dosages. The findings of this study significantly contribute to the improvement of a safe and reliable prophylaxis for thromboembolic events in sheep. Applying these results in future translational experimental studies may help to avoid early dropouts due to thromboembolic events and associated unnecessary high animal numbers

PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat

Background The Arterovenous Loop (AV Loop) model is a vascularization model in tissue engineering research, which is capable of generating a three dimensional in vivo unit with cells as well as the supporting vessels within an isolation chmaber. In our previous studies the AV loop in the isolation chamber was discovered to undergo hypoxia, characterized by Hypoxia Inducible Factor (HIF) up-regulation. The vascularization followed the increase of HIF-α temporally, while it was spatially positively correlated with the HIF-α level, as well. This study aims to prove that HIF-1a up-regulation is the stimulus for vascularization in the AV loop model. Method The AV loop model in rats was created by interposing a femoral vein graft into the distal ends of the contralateral femoral artery and vein, and the loop was embeded in fibrin matrix and fixed in isolation chamber. PHD (prolyl hydroxylases) inhibitor DMOG (Dimethyloxallyl Glycine) was applied systemically in the rats in 40 mg/KG at day 0 and day 3 (DMOG-1), or in 15 mg/KG at day 8, day10 and day12 (DMOG-2). Two weeks later the specimens were explanted and underwent morphological and molecular evaluations. Results Compared to the control group, in the DMOG-2 group the HIF-1α positive rate was siginicantly raised as shown in immunohistochemistry staining, accompanied with a smaller cross section area and greater vessel density, and a HIF-1α accumulation in the kidney. The mRNA of HIF-1α and its angiogenic target gene all increased in different extends. Ki67 IHC demostrate more positive cells. There were no significant change in the DMOG-1 group. Conclusion By applying DMOG systemically, HIF-1α was up-regulated at the protein level and at the mRNA level, acompanied with angiogenic target gene up-regulateion, and the vascularization was promoted correspondingly. DMOG given at lower dosage constantly after one week tends to have better effect than the group given at larger dosage in the early stage in this model, and promotes cell proliferation, as evidenced by Ki67 IHC. Thus, this study proves that HIF-1a up-regulation is the stimulus for vascularization in the AV loop model and that the process of the vessel outgrowth can be controlled in the AV Loop model utilizing this mechanism

50 years experience with Dupuytren's contracture in the Erlangen University Hospital – A retrospective analysis of 2919 operated hands from 1956 to 2006

<p>Abstract</p> <p>Background</p> <p>Dupuytren's disease (DD) is a hand disorder mainly among the northern population. In contrast it is rare in the mediterranean population. Therefore typical habits and dietetic influences have been discussed as well as genetic predisposition. Still, since the first description by Dupuytren in 1834 only little is known about the etiology and pathogenesis of this disease. Some hints were found for a higher prevalence among people with diabetes, alcohol abuse or smoking. Also, intensive manual work or hand injuries have been discussed to have an influence on DD. To our knowledge this is the largest retrospectively evaluated series of symptomatic patients published to date. The study includes patients from the last 50 years. It was performed to show possible correlations between DD and typical risk factors such as diabetes, alcohol consumption, and smoking.</p> <p>Methods</p> <p>We retrospectively analysed all patient records with DD documented between 1956 and 2006 in the Surgical University Hospital in Erlangen. Data acquisition was conducted by reviewing the medical records from 1956 to 2006 including data from all patients who were surgically treated because of DD.</p> <p>Results</p> <p>We reviewed 2579 male and 340 female surgically treated patients with DD. More than 80% of the patients were between 40 and 70 years old. In 28.9% only the right hand was effected by DD, in 25.3% only the left hand and in 45.8% both hands. In 10.3% of all Patients suffered from Diabetes mellitus. Statistical analysis revealed no significant correlation between diabetes, alcoholism or smoking on the degree of DD in our patients.</p> <p>Conclusion</p> <p>Most data are consistent with previously published results from smaller, comparable retrospective studies with regard to right- or left handedness. We could not confirm a statistically significant correlation of DD with diabetes mellitus, severe alcohol consumption, heavy smoking or epilepsy and the stage of the disease as described in other studies. However, in the whole cohort of our operated patients during the last 50 years the prevalence of the above mentioned risk factors is slightly higher than in the normal population.</p