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Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a newly recognized syndrome mediated by anti-platelet factor 4 antibodies induced by Covid-19 adenovirus-vectored vaccines including ChAdOx1 nCoV-19 and Ad26.COV2.S. This study validated a proposed Brighton Collaboration case definition for VITT. A data collection form was developed and used to capture the variations in VITT criteria and assess their level of diagnostic certainty from adjudicated positive VITT case datasheets in Germany (n = 71), UK (n = 220), Australia (n = 203), and Taiwan (n = 56). We observed high prevalence of each component of the proposed VITT definition in positive cases (84%-100%), except for the occurrence of thrombosis or thromboembolism criterion in only 34% of VITT cases in Taiwan. The sensitivity of this proposed definition was 100% for Germany and UK, 92% for Australia, and 89% for Taiwan cases. These findings support the validity of this case definition for VITT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H. Tran reports project grant funding support outside of the submitted work from AstraZeneca and Sanofi. W.-I. Huang is a member of the national enhanced passive Covid-19 vaccine safety surveillance team in Taiwan. J. Buttery has served as an independent data monitoring committee member for CEPI SPEAC, GSK, Serum Institute of India, SK Biosciences and Clover Vaccines. His employer Murdoch Children’s Research Institute is compensated for his time. A. Greinacher reports grants and non-financial support from Aspen, Boehringer Ingelheim, MSD, Bristol Myers Squibb (BMS), Paringenix, Bayer Healthcare, Gore Inc., Rovi, Sagent, Biomarin/Prosensa, personal fees from Aspen, Boehringer Ingelheim, MSD, Macopharma, BMS, Chromatec, Werfen, nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, GTH e.V. outside the submitted work. No other authors report conflicts of interest. Parts of the German results reported have been obtained in a study conducted by Universitätsmedizin Greifswald under service contract No. EMA/2021/17/TDA. The views expressed are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its Committees or Working Parties. The Taiwan VITT case information was based on data provided by the Vaccine Adverse Event Reporting System, operated by Taiwan Centers for Disease Control., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Postoperative thrombosis is a significant complication in pediatric cardiac surgery patients, contributing to morbidity and mortality. Identifying clinical factors associated with thrombosis can improve patient outcomes by guiding early detection and intervention., Objectives: This study aimed to assess factors associated with postoperative thrombosis or thromboembolism in pediatric patients under 12 months old who underwent surgery for congenital heart disease (CHD). Design, Setting, and Participants: This retrospective cohort study analyzed electronic medical records from pediatric patients admitted to the Pediatric Cardiovascular Intensive Care Unit (PCICU) at the German Paediatric Heart Center, Bonn, between March 1, 2020, and March 1, 2021. A total of 197 children under 12 months old who underwent cardiac surgery were included in the analysis., Main Outcomes and Measures: Thrombosis was diagnosed postoperatively using imaging modalities such as ultrasound, echocardiography, and computed tomography. The primary outcome was the incidence of thrombosis and its association with clinical factors such as age, central venous catheter (CVC) duration, CRP levels, and D-dimer levels., Results: Among 197 patients, the incidence of thrombosis was 8.63%, predominantly venous (70.6%). Initial associations were observed between thrombosis and younger age, lower body weight, higher hematocrit, cyanosis, longer central venous catheter (CVC) use, and elevated C-reactive protein (CRP) and d-dimer levels. Receiver operating characteristic analysis indicated a higher risk in patients with d-dimer levels above 5.47 mg/L. The stepwise multiregression analysis identified longer CVC duration in situ (β = 0.553; p < 0.001), higher CRP levels (β = 0.217; p = 0.022), and younger age at admission (β = -0.254; p = 0.006) as significant predictors of thrombosis. Decision tree analysis identified CVC use longer than 12.5 days and CRP levels above 118.01 mg/L as the most critical risk factors., Conclusions and Relevance: Postoperative thrombosis is a notable risk in pediatric CHD patients, particularly in neonates. Prolonged CVC use and elevated CRP levels are critical risk factors. Routine monitoring of D-dimer and CRP levels, along with timely sonographic screening, can aid early thrombosis detection and intervention. Further research is warranted to optimize thrombosis prevention strategies in this population., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background:  The exact monitoring of the therapeutic-range international normalized ratio (INR) after left ventricular assist device (LVAD) implantation is an important aim to reduce the risk of thrombosis or bleeding complications. Service providers offer a telemedical anticoagulation service (CS)., Methods:  We compared LVAD patients using the CS ( n  = 15) to those who received regular medical care (RMC; n  = 15) to investigate if telemedicine supervision increased the INR-specific time in the therapeutic range (TTR) during anticoagulation. All patients received self-management training for phenprocoumon medication according to their INR value. INR values were documented for 12 months. A survey (scale: 1 = not satisfied and 10 = very satisfied) was used to determine patient's satisfaction and psychological well-being., Results:  A total of 1,798 INR measurements were analyzed. The TTR Rosendaal was higher in patients undergoing RMC (78.1 ± 14.3%) compared with that in patients using the CS (58.3 ± 28.0%, p  = 0.03). The patient's satisfaction with the coagulation setting at the beginning of the study (RMC: 6.7 ± 3.1, CS: 7.2 ± 3.0, p  = 0.74) and psychological wellbeing (RMC: 6.5 ± 1.9, CS: 6.5 ± 2.7, p  = 0.97) were comparable between both groups., Conclusion:  We found that INR self-management is superior regarding the efficiency of post-LVAD anticoagulation therapy when compared with telemedical (CS)-based INR management in a small study cohort. Intensive training by experienced staff was able to replace CS., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Data about the impact of left-atrial appendage thrombosis (LAAT) on early safety and mortality in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) are scarce. We aimed to investigate the prevalence and predictors of LAAT and the outcome associated with this condition in patients treated by TF-TAVI., Methods: Retrospective data analysis was derived from a prospective single-centre registry comparing patients with and without LAAT regarding early safety at 30 days, according to Valve Academic Research Consortium-2 (VARC-2) and 2-year mortality., Results: LAAT was found in 7.6% of the whole cohort (n = 2527) and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort, n = 1099). Compared with controls, patients with LAAT were sicker, indicated by a higher Society of Thoracic Surgeons (STS) score and burden of comorbidities. Neither VARC-2-defined early safety at 30 days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 29.2% vs 24.2%, P = 0.123; stroke: 5.9% vs 4.7%, P = 0.495) and AF cohort (early safety: 29.1% vs 22.9%, P = 0.072; stroke: 5.6% vs 3.3%, P = 0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared with controls (hazard ratio, 1.41; 95% confidence interval, 1.07-1.86; P = 0.014). However, multivariate analysis of the whole cohort and the AF cohort revealed no association between LAAT and 2-year mortality., Conclusions: LAAT was frequent in patients undergoing TF-TAVI- in particular, in patients with histories of AF-but it was not associated with an increase in periprocedural complications and did not predict 2-year mortality., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Calciphylaxis is a life threatening complication in renal patients. Of great importance is the identification of concomitant factors for calciphylaxis. Due to the variability of clinical presentation the evaluation of such factors may be obscured when calciphylaxis diagnosis is based just on clinical features. We aimed to characterize associated factors only in patients with calciphylaxis proven by histomorphological parameters in addition to clinical presentation., Methods: In a single center retrospective study we analyzed 15 patients in an 8 year period from 2008 to 2016. Only patients with clinical features and histomorphological proof of calciphylaxis were included. Criteria for histological diagnosis of calciphylaxis were intimal hyperplasia, micro thrombi or von Kossa stain positive media calcification., Results: The mean age of patients was 64.8 years. Nine patients (60%) were female; 12 (80%) were obese with a Body-Mass-Index (BMI) > 30 kg/m 2 ; 3 (20%) had no renal disease; 12 (80%) had CKD 4 or 5 and 10 (66.7%) had end-stage renal disease (ESRD). One-year mortality in the entire cohort was 73.3%. With respect to medication history, the majority of patients (n = 13 (86.7%)) received vitamin K antagonists (VKA); 10 (66.7%) were treated with vitamin D; 6 (40%) had oral calcium supplementation; 5 (33.3%) had been treated with corticosteroids; 12 (80%) were on proton pump inhibitors (PPI); 13 (86.7%) patients had a clinical proven hyperparathyroidism. Ten (66.7%) patients presented with hypoalbuminemia at diagnosis., Conclusions: The evaluation of biopsy proven calciphylaxis demonstrates that especially treatment with vitamin K antagonists and liver dysfunction are most important concomitant factors in development of calciphylaxis. As progression and development of calciphylaxis are chronic rather than acute processes, early use of DOACs instead of VKA might be beneficial and reduce the incidence of calciphylaxis.

Background: Obstructive thrombosis of bioprosthetic valves is considered rare but may have dramatic consequences for the individual patient including repeat valve replacement, thrombolysis, or long-term anticoagulation. Whether the risk of obstructive thrombosis is dependent on the type of bioprosthesis (porcine versus bovine pericardial) is uncertain., Methods and Results: Between 2007 and 2012 a total of 1751 patients received a single stented bioprosthesis in the aortic valve position, 749 (43%) were porcine and 1002 (57%) bovine. During a mean follow-up of 3.4±1.9years, obstructive thrombosis (identified by an increase in mean pressure gradient≥20mm Hg or a decrease in velocity ratio≥0.05 and confirmed by either ECG-gated computer tomography, a return to baseline of stenosis parameters under treatment with a vitamin K antagonist, or histology in case of reoperation) was diagnosed in 17 patients with a porcine (2.3%) and none with a bovine valve (p<0.001). The cumulative probability of developing an obstructive thrombosis was significantly higher in patients with a porcine valve (p<0.001 log-rank test). Adjusting for differences in baseline variables and stratification by the estimated propensity score showed that strata with a high probability of receiving a bovine valve had the highest number of obstructive thrombosis in porcine valves. These findings were further confirmed in a Poisson model and a competing risk model including all-cause mortality. Treatment of obstructive thrombosis with a vitamin K antagonist was safe and effective in 15/17 patients., Conclusion: The porcine valve type is an independent predictor of obstructive thrombosis in bioprostheses in the aortic position., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: An increasing number of patients are being treated with anticoagulants and platelet inhibitors. Whenever surgical procedures of the skin are required, questions arise regarding the perioperative management of anticoagulation., Methods: Development of S3 guidelines following the requirements of the Association of Scientific Medical Societies, systematic literature search and analysis, use of GRADE methodology, structured consensus conference using a nominal group process., Results: During cutaneous surgery, treatment with acetylsalicylic acid (ASA) should be continued if medically necessary. In procedures with a higher risk of bleeding and a positive bleeding history, INR should be determined preoperatively. Surgical procedures of the skin with a higher risk of bleeding should not be performed if the INR is above therapeutic range. Bridging from vitamin K antagonists (VKA) to heparin should not be performed just because of the surgery of the skin. As to direct-acting oral anticoagulants, the last dose should be taken 24 h preoperatively., Conclusions: The recommendations issued by the German guidelines group are mostly in line with recommendations provided by other guidelines. The American ìChest-Guidelineì recommends continuing VKAs and acetylsalicylic acid during minor dermatologic procedures. In their guidelines, the German College of General Practitioners and Family Physicians considers an INR of 2 to be adequate in surgical procedures on the skin., (© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Background: Inhospital stent thrombosis (ST) and cerebrovascular accidents (CVA) are rare but serious adverse events after percutaneous coronary intervention (PCI). The association of ST or CVA with long-term outcome after PCI remains poorly investigated., Methods: The study included 18,334 consecutive patients who underwent PCI. Patients were divided into 3 groups: the group with ST, the group with CVA, and the group without these events. The primary outcome was all-cause mortality at 3-year follow-up., Results: Inhospital ST or CVA occurred in 59 patients (0.32%) and in 90 patients (0. 49%), respectively. There were 2,149 deaths (11.7%) during the follow-up: 26 deaths among patients with ST, 32 deaths among patients with CVA, and 2,091 deaths among patients without ST or CVA (Kaplan-Meier estimates of 3-year mortality 45.3%, 38.0%, and 12.9%, odds ratio 6.1, 95% CI 3.6-10.2, P < .001 for ST group vs the group without ST or CVA and odds ratio 4.2 [2.7-6.6], P < .001 for CVA group vs the group without ST or CVA). There was no significant difference in the 3-year mortality between CVA and ST groups (P = .29). The Cox proportional hazards model showed that ST (adjusted hazard ratio 4.97, 95% CI 2.58-9.56, P < .001) and CVA (adjusted hazard ratio 2.25 [1.25-4.04], P = .006) were independently associated with the increased risk of 3-year mortality., Conclusion: Inhospital ST and CVA after PCI are associated with the increased risk of 3-year mortality. Both events seem to have a similar impact on long-term survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Second-generation drug-eluting stents (DES) have provided better results over both bare-metal stents and first-generation DES. However, comparative data of different first- and second-generation DES in a clinical setting of all-comers have not been well studied., Methods and Results: Baseline clinical and angiographic characteristics and in-hospital and follow-up events were recorded for enrolled patients. The composite of death, myocardial infarction, and stroke, defined as major adverse cardiac and cerebrovascular events (MACCE), as well as target vessel revascularization (TVR) was used as the primary end point. Between May 2007 and May 2009, 10,852 patients subjected to drug-eluting stent implantation were enrolled at 74 sites. 3,032 patients (27.9 %) were treated with Taxus™, 4,382 (40.4 %) with Cypher™, 1,012 (9.3 %) with Endeavor™, 1,693 (15.6 %) with Xience V™ and 733 (6.8 %) with Promus™ during this period. At 1-year follow-up, the comparison between groups revealed no significant differences with respect to overall death, MACCE, definite stent thrombosis, TVR, stroke and major bleeding. After adjustment for risk factors in final regression models, a modestly significant association of DES type to MACCE was observed (p = 0.046); however, this association could not be attributed to one particular DES. An impact of DES type on TVR was not seen after risk adjustment., Conclusion: Data generated from the prospective German drug-eluting stent (DES.DE) registry confirm that safety and efficacy of different first- and second-generation DES are clinically equivalent in the first year of follow-up, even in a more complex setting.

Background: Vascular access by dialysis graft or fistula is of major importance for hemodialysis treatment. Vascular access occlusion is one main reason for hospitalization of patients on hemodialysis. Thrombophilic risk factors are discussed as one cause for occlusion. The aim of this study was to determine if the presence of thrombophilic factors is associated with a reduced survival rate of vascular dialysis access., Patients and Methods: The following thrombophilic parameters were measured in every hemodialysis patient from five outpatient dialysis centers in Berlin: antithrombin, protein C, protein S, prothrombin mutation (G20210A), factor V mutation (G1691A), lupus anticoagulant, anticardiolipin antibodies, factor VIII, plasminogen activator inhibitor, homocysteine and lipoprotein(a). Vascular access characteristics such as vascular access material (PTFE graft or native fistula) and location were also recorded. Each patient's medical history was documented., Results: 199 patients with a total of 499 vascular accesses in the past (311 native fistulas (62.3 %) and 188 PTFE grafts (33.7 %)) were included in this study. The type of vascular access played an important role, with mean survival times of 34.2 months for native fistulas versus 9.5 months for grafts. There was at least one thrombophilic risk factor present in 69.8 % of the patients. In the univariate analysis thrombophilia had a significant influence on vascular access survival. The effect persisted throughout the multivariate analysis. Multivariate Cox analysis showed that the presence of thrombophilic factors was associated with a 43 % (mild) to 105 % (severe thrombophilia) increased risk of occlusion of the vascular access, corresponding to a 45 % to 68 % reduction of native access survival time. The influence of thrombophilia was evident in fistulas as well as in PTFE grafts., Conclusions: Thrombophilia plays a role in vascular accesses survival in patients on hemodialysis. In hemodialysis patients with recurrent occlusions of vascular access thrombophilia testing should be performed.

Objectives: We compared safety and efficacy outcomes of 3 limus-based drug-eluting stents in the 'all-comers' PROENCY (PROmus/ENdeavor/CYpher) registry., Background: Limited data are available on head-to-head comparisons of the everolimus-eluting stent (EES) with the zotarolimus-eluting stent (ZES) or the sirolimus- eluting stent (SES) in the treatment of patients with coronary artery disease., Methods: PROENCY was a prospective, open-label, multicenter, observational study including consecutive patients undergoing planned treatment with EES, ZES, or SES. Seventeen centers were designated to place an EES or SES, 14 other centers were designated to place EES or ZES. The primary endpoint was the composite of cardiac death, myocardial infarction, and target vessel revascularization (TVR) at 12 months. Unadjusted and propensity-adjusted outcomes were compared between groups., Results: A total of 1921 patients were enrolled in the study from February to December 2008, of which 1704 patients received only study stents and were analyzed. At 12 months, the unadjusted major adverse event rate was significantly lower in the EES group versus the ZES group (3.1% vs 8.7%; P=.001) and the SES group (5.2% vs 9.6%; P=.01). This was mainly driven by lower TVR rates [2.6% with EES vs 8.2% with ZES [P<.001] and 4.1% with EES vs 7.0% with SES [P=.05]. Stent thrombosis rates were low and comparable. Adjusted analyses confirmed the unadjusted results., Conclusion: There were no differences in safety outcomes of EES, ZES, and SES at 12 months in PROENCY. However, differences in efficacy were observed between the 3 "limus"-based stents in a real-world patient population.

Liver cell transplantation (LCT) is considered a new therapeutic strategy for the treatment of acute liver failure and inborn metabolic defects of the liver. Although minimally invasive, known safety risks of the method include portal vein thrombosis and pulmonary embolism. Since no systematic data on these potential side effects exist, we investigated the toxicological profile of repeated intraportal infusion of allogeneic liver cells in 30 rabbits under GLP conditions. Rabbit liver cells were administered once daily for 6 consecutive days at 3 different dose levels, followed by a 2-week recovery period. No test item-related mortality was observed. During cell infusion, clinical findings such as signs of apathy and hyperventilation, moderate elevations of liver enzymes ALT and AST and a slight decrease in AP were observed, all fully reversible. Cell therapy-related macroscopic and histological findings, especially in liver and lungs, were observed in animals of all dose groups. In conclusion, the liver and lungs were identified as potential toxicological target organs of intraportal allogeneic liver cell infusion. A NOAEL (no observed adverse effect level) was not defined because of findings observed also in the low-dose group. No unexpected reactions became apparent in this GLP study. Overall, LCT at total doses up to 12 % (2 % daily over 6 days) of the total liver cell count were tolerated in rabbits. Observed adverse effects are not considered critical for treatment in the intended patient populations provided that a thorough monitoring of safety relevant parameters is in place during the application procedure.

Background: Bypass-graft intervention was associated with worse outcomes in the bare-metal stent era. Without sufficiently powered data from subgroup analyses, and in absence of randomized controlled trials targeting clinical endpoints, controversy is ongoing over safety and efficacy of drug-eluting stents (DES) in saphenous vein graft (SVG) lesions., Methods and Results: Between October 2005 and October 2006, 5,183 patients receiving DES in SVG (n = 251) or native coronary arteries (NCA) (n = 4,932) were enrolled at 98 DES.DE sites. The composite of death, myocardial infarction (MI), and stroke defined as major adverse cardiac and cerebrovascular events (MACCE) and target-vessel revascularization (TVR) were defined as primary endpoints. Baseline clinical and descriptive morphology of coronary artery disease revealed more severe lesions and comorbidities in the SVG group. At 1-year follow-up, the SVG group suffered from higher rates of overall death (6.6 vs. 2.5%; p < 0.0001), myocardial infarction (5.9 vs. 2.2%; p < 0.0001), MACCE (13.6 vs. 5.4%; p < 0.0001), TVR (17.7 vs. 10.4%; p < 0.001) and overall stent thrombosis (10.0 vs. 3.7%; p < 0.0001)., Conclusion: Data collected in DES.DE revealed that first generation DES used in SVG lesions did not offset the worse clinical outcomes of bypass-graft intervention. Such sobering results in SVG may suggest to opt for native vessel PCI preferentially or occasionally for surgical reintervention as decided by the Heart Team.

Objectives: To obtain Western European perspectives on the economic burden of atherothrombosis in patients with multiple risk factors only (MRF), cerebrovascular disease (CVD), coronary artery disease (CAD), and in the under-evaluated group of patients with peripheral arterial disease (PAD), we examined vascular-related hospitalisation rates and associated costs in France and Germany., Design: The prospective REACH Registry enrolled 4693 patients in France, and 5594 patients in Germany (from December 2003 until June 2004)., Methods: For each country, 2-year rates and costs associated with cardiovascular events and vascular-related hospitalisations were examined for patients with MRF, CVD, CAD, and PAD., Results: Two-year hospitalisation costs were highest for patients with PAD (3182.1€ for France; 2724.4€ for Germany) and lowest for the MRF group (749.1€ for France; 503.3€ for Germany). Peripheral revascularizations and amputations were the greatest contributors to costs for all risk groups. Across all PAD subgroups, peripheral procedures constituted approximately half of the 2-year costs., Conclusion: Hospitalisation rates and costs associated with atherothrombotic disease in France and Germany are high, especially so for patients with PAD., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Experience with patients undergoing left ventricular assist device (LVAD) implantation with preexisting mitral valve prostheses is limited. Patients with mechanical heart valves might have an increased risk of thromboembolism; in patients with biologic valves, there might be a risk of structural deterioration of the leaflets. Out of 597 patients supported with a LVAD system between 2000 and 2009, 18 patients had mitral valve surgery prior to implantation. We excluded all patients below 18 years of age, those with postcardiotomy failure, and patients who had had mitral valve reconstruction. Only 1% of the studied patient population (n= 6) had mitral valve replacement. The mitral valve implantation has been performed 7.4 ± 9.4 years prior to LVAD insertion. None of the valves (one biologic, five mechanical) were exchanged or explanted. LVAD implantation was done either with left lateral thoracotomy (n= 5) or with midline resternotomy (n= 1). Temporary right ventricular assist device support was necessary in one case (16.6%); 30-day mortality was 16.6% (n= 1). Median support time was 14 ± 15 months. Two patients received heart transplantation after 6 and 26 months on the device; four patients died on mechanical circulatory support after 1, 2, 5, and 40 months. No valve or pump thrombosis or other clinically relevant thromboembolic events were observed. Only a small number of patients (1%) had a preexisting mitral valve prosthesis prior to LVAD implantation. No severe adverse events were observed when the prosthesis was left in place. Attention should be paid to the anticoagulation regime., (© 2011, Copyright Prof.Dr.Roland Hetzer Deutsches Herzzentrum Berlin. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Object: The predominant mechanism of early graft failure after coronary artery bypass grafting (CABG) is associated with antiplatelet treatment using drugs such as acetylsalicylic acid (ASA). Impaired hemostasis of multiple etiologies is often present in patients undergoing on-pump cardiac surgery. We investigated the impact of intravenous ASA administration on platelet function in this setting., Methods: Forty-two patients were enrolled in the study. Patients received 100 mg oral ASA once daily, beginning in the early postoperative period. Noncompliance was eliminated by the administration of 300 mg ASA intravenously at 6-8 days post-operation. Blood was drawn immediately before, 1 h and 24 h after ASA administration., Results: A platelet function analyzer (PFA-100™) was used to evaluate closure time (CT), turbidimetric platelet aggregation (TPA) and impedance platelet aggregation (IPA) induced by arachidonic acid (AA), collagen and ADP and results were compared with the respective values from 120 healthy individuals. At 1 h and 24 h after administration, we found that intravenous ASA caused CEPI-CT to be significantly prolonged with a reduction of AA and collagen-induced IPA. Despite postoperative oral ASA administration for 6-8 days, PFA-100™ CEPI and CADP-CT were significantly shorter and ADP-TPA and IPA values induced by any agonist were significantly greater in patients than in controls. Intravenous ASA had no significant influence on CADP-CT or ADP-induced IPA (ADP-IPA)., Conclusion: Platelet tests for diagnosing patients as aspirin responders (ASA-R) or aspirin non-responders (ASA-NR) were found to be not comparable. Patients after CABG show augmented platelet dysfunction. Intravenous ASA administration may indicate a promising approach to reduce laboratory resistance after CABG procedure. The reason for this is not clear and requires additional clinical studies., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: This study evaluated the early and intermediate results of endovascular aortic aneurysm repair (EVAR) using the Endurant stent graft (Medtronic Cardiovascular, Santa Rosa, Calif) in patients treated according to device-specific instructions for use (IFU) for the proximal aortic neck compared with those obtained in patients treated in an off-label (OL) situation., Methods: Between November 2007 and March 2010, 177 consecutive patients with abdominal aortic aneurysms (AAAs) were treated with the Endurant stent graft at our centers. The IFU for the Endurant stent graft included a proximal neck of 15 mm in length and <75° of angulation or 10 mm of neck length and <60° of angulation. The 121 patients (68.4%) operated on according to IFU were compared with 56 (31.6%) who underwent EVAR in OL circumstances to evaluate significant differences in demographics, intraoperative technical factors, and early (30 days) and intermediate outcomes (1 year)., Results: Significantly more patients were aged >80 years in the OL group (37.5% vs 19%, P = .008), and they also had larger aneurysms (59 ± 10.6 vs 55.9 ± 10.8 mm, P = .05) and required a longer procedure time (69.3 ± 27.2 vs 60.8 ± 20.4 minutes, P = .02). At 30 days, the risk of type I endoleak was higher in the OL group (2 patients, 3.6% vs 0 in IFU), but this did not reach statistical significance (P = .09). The two groups were similar in rates of perioperative mortality, major morbidity, technical success, clinical success, complications, and reinterventions. At 1 year, there were no differences between the two groups in survival, freedom from any device-related reinterventions, and freedom from graft thrombosis. Estimated 1-year freedom from type I endoleak was 100% in the IFU group vs 93.3% in the OL group (P = .01)., Conclusions: In patients with both normal and complex anatomy of the proximal aortic neck, the Endurant stent graft obtained acceptable results, with no difference in survival, morbidity, or reinterventions. However, there was a greater risk of type I endoleak when OL indications were applied. Longer term follow-up is required to evaluate the effectiveness of this endograft in preventing late aneurysm-related complications., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: A minimal provider volume for total knee replacement (TKR) was introduced in 2006. Does this lead to an improvenment in quality or not? The records of treatment in the compulsory external quality assurance program of the Land of North Rhine-Westphalia (QS-NRW) were evaluated., Method: A total of 125,324 comparable records from the QS-NRW program were available to determine the appearance of general and surgical complications. In a logistical regression model the risk factors age, gender, ASA classification, comorbidity and duration were taken into account., Results: A significant reduction could only be shown for pneumonia, thrombotic events and lung embolisms as well as vascular injury. In 2006 and 2007 malpositioning of implants was significantly higher and from 2005 to 2008 the number of fractures rose compared to 2004. Deep infections and reoperations did not change significantly during the whole study period., Conclusion: This evaluation could not show an improvement in quality due to the minimal provider volume. Thus the minimal provider volume should not be taken into account as a main criterion to improve quality. Further outcome studies and creating an arthroplasty register in Germany are more useful.

Objectives: To evaluate feasibility and safety of MGuard based percutaneous coronary interventions (PCI) in vein grafts (VG) and native coronaries (NC)., Background: Distal embolization is a frequent complication of PCI of VG and NC during acute coronary syndromes (ACS). MGuard was a stent designed to reduce embolization., Methods: Prospective, single arm, two-center trial assessing the feasibility and safety of MGuard-based PCI with post-PCI clinical and laboratory monitoring including: cardiac biomarkers, ECG and 6-month angiography., Results: Forty-one patients with mean age of 68.2±10.1 years were enrolled. Mean VG age (n=23) was 14.4±4.3 years. All patients received heparin, clopidogrel and aspirin; while none received glycoprotein IIb/IIIa inhibitors, or embolic protection device (EPD). Device and procedural success were 100% and 95.1% respectively. Two patients (4.9%) experienced procedure-related creatinine phosphokinase rise. At 6 months one patient had myocardial infarction and 19.5% had target vessel revascularization (TLR). Late follow up (12-27 months) revealed one additional TLR., Conclusion: MGuard based PCI of NC and VG appears encouraging especially in view of unfavorable patient and lesion characteristics. Efficacy needs to be further established in larger randomized trials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Pediatric ventricular assist devices may be superior to extracorporeal membrane oxygenation in some respects, especially for medium- and long-term cardiac support. We present our nearly 20-year experience with pediatric ventricular assist devices., Methods: Between 1990 and April 2009, Berlin Heart EXCOR (Berlin Heart AG, Berlin, Germany) was implanted in 94 children. Patients were compared according to period of treatment: group I, implantation between 1990 and 2001 (n = 45), and group II, implantation since 2002 (n = 49)., Results: Preoperative serum creatinine (1.2 vs 0.7 mg/dL, P = .002) and bilirubin (1.5 vs 1 mg/dL, P = .002) were lower in period II, and fewer patients were artificially ventilated before surgery (26 vs 13, P = .002). In period I, more patients were supported with biventricular assist devices (64% vs 22.5%, P < .001). Median time on support was shorter in period I (10 vs 40 days, P < .001). Success (weaning from system or heart transplant) was achieved in 49% and 69%, respectively (P = .043). Whereas in period I 17% of children younger than 1 year were discharged home after transplant or weaning, rate during period II was 93% (P < .001), in particular because of improvement in discharge rate of patients with postcardiotomy heart failure (13% vs 50%). Rates of pump exchange for thrombus formation were 0.029/d in period I and 0.014/d in period II (P = 0.003)., Conclusions: Recent results show significant improvements in survival and discharge rate, especially for children younger than 1 year. Pediatric Berlin Heart EXCOR ventricular assist device may provide a safe mechanical support strategy in children with cardiogenic shock., (Copyright © 2011. Published by Mosby, Inc.)

Background: According to some current guidelines, extended thromboprophylaxis after hip and knee arthroplasties is recommended. Outpatient prophylaxis with low molecular weight heparins (LMWH) is an important part of this prophylaxis, although the rates of adherence to these regimens is not known., Questions/purposes: We determined (1) the degree of nonadherence (NA) of patients with LMWH outpatient prophylaxis, and (2) whether specific independent factors explain NA., Methods: NA was determined by syringe count and by indirect and direct questions to patients. We defined six different NA indicators. To identify factors explaining LMWH NA, we used three different logistic regression models., Results: NA rates ranged between 13% and 21% depending on the indicator used for measurement. Patients who were nonadherent missed between 38% and 53% of their outpatient LMWH injections. If patients attended an outpatient rehabilitation program, the probability for their NA increased substantially. Moreover, the NA probability increased with each additional day between acute hospitalization and start of rehabilitation (linking days). NA was lower for patients who feared thrombosis or who believed antithrombotic drugs to be the most important measure in thromboprophylaxis., Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Clopidogrel is a prodrug that is converted via the hepatic cytochrome P450 system into its active thiol metabolite. Evidence is accumulating that proton pump inhibitors (PPIs) inhibit this enzymatic pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The objective of this study was to investigate whether patients on clopidogrel therapy after drug-eluting stent (DES) placement who also receive a PPI are at higher risk of stent thrombosis (ST). This is a retrospective analysis of patients who received dual antiplatelet treatment including clopidogrel after DES placement. Outcomes were compared according to PPI therapy. The primary endpoint was the incidence of definite ST at 30 days. Secondary endpoints were death, combined death or ST and myocardial infarction (MI). The study population included 3,338 patients and 698 patients (20.9%) received PPIs. Patients receiving a PPI had a higher risk profile at baseline. Multivariate analysis showed that PPI treatment was not independently associated with the occurrence of ST [adjusted HR 1.8 (95% CI: 0.7-4.7), p=0.23] or MI [adjusted HR 1.3 (0.8-2.3), p=0.11]. PPI treatment was significantly associated with death [adjusted HR 2.2 (1.1-4.3), p=0.02] and death or ST [adjusted HR 3.3(1.7-6.7), p=0.02]. Concomitant treatment with a PPI in patients receiving dual antiplatelet treatment after coronary stenting is not an independent predictor of ST. The higher mortality is probably due to confounding as patients on PPIs had a higher risk profile at baseline.

Platelet dysfunction followed by thromboembolic as well as bleeding complications are severe events in patients with ventricular assist devices (VADs). Microparticles (MP) are cell vesicles with inflammatory and coagulatory potency that are released by cells during activation and can be used as specific cell activation markers. The aim of the study was to establish MP as surrogate markers for platelet, leukocyte and endothelial activation in VAD patients predicting platelet activation and vascular inflammation. Therefore, MP from platelet, leukocyte and endothelial origin were measured in 12 patients with VAD and compared to controls. VAD patients had significantly increased levels of platelet microparticles (PMP) (VAD 1705+/-1100 cpm vs. co: 527+/-238 cpm, P=0.002), leukocyte microparticles (LMP) (VAD 43+/-16 cpm vs. co: 18+/-8 cpm, P<0.001) and endothelial microparticles (EMP) (VAD 135+/-66 cpm vs. co: 46+/-23 cpm, P<0.001) indicating enhanced vascular inflammation and pro-coagulation. Furthermore, LMP correlated well to EMP suggesting that LMP induce endothelial cell dysfunction. In conclusion, VAD patients suffer from enhanced platelet, leukocyte and endothelial activation that can be easily quantified by measuring PMP, LMP and EMP and that may help to estimate the thrombotic risk and contribute to avoid ischemic but also bleeding complications.

Objectives: The prospective multicenter German DES.DE registry provides real world data to evaluate the therapeutic principle of two different drug-eluting stents (DES) [Sirolimus- (SES) and Paclitaxel-eluting stent (PES)] in the context of the German Health System., Background: Differential DES have been effective in randomized trials, but their difference in safety and efficacy in diabetic patients has not been well studied., Methods: Baseline, predefined procedural as well as clinical in-hospital and follow-up events were recorded for all 1,526 diabetic patients. The composite of death, myocardial infarction (MI), and stroke defined as major adverse cardiac and cerebrovascular events (MACCE) and target vessel revascularization (TVR) were defined as primary endpoints., Results: Between October 2005 and October 2006, 1,526 diabetic patients, 34.2% of them being insulin-dependent, were enrolled (SES: n = 612; PES: n = 914) at 98 DES.DE sites. Overall, one third of patients were admitted with acute coronary syndrome (ACS) and 70% had multivessel-disease reflecting a real world scenario. With similar baseline clinical and descriptive morphology of coronary artery disease (CAD) in both DES groups, there were no statistical differences in 1-year follow-up with respect to rates of overall mortality (5.8% vs. 5.4%), TVR (12.0% vs. 11.3%), overall stent thrombosis (5.6% vs. 4.6%) and MACCE (11.4% vs. 10.3%) between both DES., Conclusion: The data collected in DES.DE revealed no differences in clinical outcomes within 1 year between SES and PES in diabetic patients in a "real-world" setting., ((c) 2010 Wiley-Liss, Inc.)

Manipulative therapy of the cervical spine is associated with a considerable risk of stroke. We evaluated all cases with the diagnosis of arterial dissection submitted between 1996 and 2005 to the Schlichtungsstelle für Arzthaftpflichtfragen der Norddeutschen Arztekammern for assessment of the accusations brought against the therapists who conducted the manipulation. Neither in the 7 carotid nor in the 9 vertebral artery cases could a causal link be made between the dissection and the manipulation. However, in 5 of the 7 carotid and 7 of the 9 vertebral artery dissections there was clear evidence or high probability that the dissection was present prior to the manipulation, and had caused neck pain, segmental dysfunction and, in some cases, even neurological symptoms. Stroke after manipulative therapy was due to embolisation of thrombotic material from the dissected artery. As both cervical arterial dissection and cervical spine disorder usually cause similar signs and symptoms physicians must differentiate between these two entities prior to any manipulative therapy. Clinical indicators of pre-existent dissection and the medicolegal implications are discussed in this paper.

Objectives: Percutaneous coronary intervention of unprotected left main (ULM) stenosis is increasing despite surgical revascularisation being the recommended treatment by the current guidelines. We compared the 30-day and 9-month mortality after ULM stenting with the predicted surgical outcome as determined by the EuroSCORE., Methods and Results: We included 81 consecutive patients who underwent ULM stenting. The patient cohort was divided into a normal risk group (EuroSCORE 5, predicted 30-day mortality 11%). Follow-up examinations were scheduled for one and nine months after the initial PCI. The average EuroSCOREs in the normal- and high-risk group were 3.0 (29 patients, 36%) and 10.0 (52 patients, 64%), respectively. Mortality rates at 30 days were 3% in the normal-risk group and 8% in the high-risk group. Subacute stent thrombosis occurred in 3.4% (three patients) undergoing elective PCI. Major adverse cardiac events during the nine months follow-up were registered in 24% of patients in the normal-risk group, and in 27% of the patients in the high-risk group., Conclusion: Short-term outcome of ULM stenting in our high-risk patients is comparable to surgical outcome predicted by the EuroSCORE. Long-term outcome was less favourable due to a high mortality rate. ULM stenting in patients with low surgical risk could be associated with higher mortality rates compared to CABG because of the unpredictable risk of a fatal stent thrombosis.

Background: The purpose of this study was to collect the experience gained from risk assessment of incidents associated with mechanical heart valves as reported to the German Medical Devices Vigilance System., Methods: All events in connection with the use of prosthetic heart valves which had been reported to the Federal Institute for Drugs and Medical Products were identified in the Institute's anonymized database. Subsequently all information that had been obtained and the reports of investigations by the various responsible manufacturer of medical products were retrospectively analysed., Results: Of 53 incident reports the aortic valve position was involved 32 times, the mitral valve position 21 times. 17 cases of leaflet breakage, 12 of leaflet dysfunction, 6 of valve thrombosis, 4 of paravalvular leakage, 4 of damage to the suture ring, 3 of endocarditis and 7 of various other singular defects were reported. The outcome was mostly very serious (re-surgery, prolongation of surgery, death). Corrective actions taken by the manufacturers consisted of recalls, advisory notices and stoppage of production., Conclusions: The Medical Devices Vigilance System is able to detect product failures of mechanical heart valves and to initiate corrective action. As the reporting rate over more than 10 years is relatively low, it can be assumed that in general mechanical heart valves are safe medical devices. The quality of incident reporting by manufactures and users of medical devices should be improved to reduce the number of undetected and unsolved incidents.

About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and getting larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B12, and vitamin B6 deficiencies and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10% of total risk. Elevated plasma homocysteine levels (>12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10% of the general population and in up to 40% of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence over-proportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial anti-thrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stress. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and lifestyle factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine levels in high-risk individuals in general and patients with manifest vascular disease in particular. Subjects of both populations should first have a baseline homocysteine assay. Except where manifestations are already present, intervention, if any, should be guided by the severity of hyperhomocysteinemia. Consistent with other working parties and consensus groups, we recommend a target plasma homocysteine level of <10 micromol/l. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25% of cardiovascular events. Supplementation is inexpensive, potentially effective, and devoid of adverse effects and, therefore, has an exceptionally favorable benefit/risk ratio. The results of ongoing randomized controlled intervention trials must be available before screening for, and treatment of, hyperhomocysteinemia can be recommended for the apparently healthy general population.

Purpose/background: What are the options for early diagnosis, treatment and prevention of the occlusion of microvascular anastomosis after replantations? METHOD AND (CLINICAL) MATERIAL: This is a retrospective analysis of 336 cases involving primary microvascular repair after an injury between 1984 and 2000. In 272 cases this was a revascularisation and in 187 a replantation. In 23 cases the vascular anastomosis was located proximal to the wrist (macroreplantations) and 313 times distal to it (microreplantations/-revascularisations)., Results: Vascular complications developed in seven and 54 cases respectively. 40 % of these 61 patients showed a severe soft tissue compromise or/and had sustained an injury known to cause widespread intima lesions (15 avulsions, six crush injuries, one blast, one gun shoot, one RTA). 37 of the 61 patients had been injured by circulating saws. There were 34 arterial and 22 venous occlusions, four no-reflow-syndromes and one HIT-syndrome. Almost 90 % of these vascular complications occurred within the first four post-operative days, 50 % even within the first 36 hours. Treatment was surgical in 39/61 cases and conservative 22 times. In 55 % (33/61) of all cases this treatment was successful., Conclusion: With an overall incidence of 1 : 6 vascular crisis is not only the most consequential but also the most common post-operative complication after replantations. Timely operative and/or non-operative therapeutic measures can save more than half of the replants affected.

Obesity increases the risk of metabolic complications such as diabetes, dyslipidemia, systemic hypertension and cardiovascular disease. These are mainly responsible for the increased mortality of obese people. Other metabolic consequences of obesity are: gallstones, steatosis of the liver and the polycystic ovary syndrome. Beside the body mass index the distribution of body fat is important. Centralized obesity, as measured by the waist-to-hip circumference ratio (WHR), is associated with increased mortality and morbidity. Insulin resistance and hyperinsulinaemia seem to play a central role in the pathogenesis of this association. Obesity has not only metabolic complications. There is a relationship between obesity and impaired respiratory function. Furthermore is obesity a risk factor for osteoarthrosis of the knee, the hip and even the hand and for pulmonary embolism and venous thrombosis. Obesity can also lead to psycho-social problems such as depression, social discrimination and isolation.