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(1) Background: Inflammatory bowel diseases are complex and multifactorial disorders of unknown etiology. The extravasation of activated leukocytes is a critical step in the pathogenesis of these diseases. Leukocyte integrin Mac-1 (αMβ2; CD11b/CD18) is crucial for the extravasation of myeloid cells, and a novel activation-specific anti-Mac-1 Designed Ankyrin Repeat protein (DARPin F7) is a promising therapeutic agent for inflammatory diseases. In its activated conformation, Mac-1 expresses the high-affinity binding site I-domain, which the DARPin F7 selectively targets. In our study, we aimed to explore the therapeutic potential of anti-Mac-1 DARPin F7 in murine dextrane sodium sulfate (DSS)-induced colitis. (2) Methods: C57BL/6J mice received 3% DSS drinking water for five days, followed by normal drinking water for one week. The mice were treated with DARPin F7 or a control substance daily via intraperitoneal injections. Disease activity index (DAI), colon length, myeloperoxidase (MPO) activity measurements, H&E staining, and qRT-PCR were conducted after euthanizing the mice on day 12. (3) Results: Treatment with DARPin F7 resulted in less pronounced colon shortening and significantly lower histological scores. The DARPin F7-treated animals experienced substantially less disease and myeloperoxidase (MPO) activity. Animals that received DARPin F7 treatment suffered less weight loss and recovered from the weight loss more efficiently. Treatment with DARPin F7 also led to significantly reduced mRNA expression of inflammatory cytokines. (4) Conclusion: Anti-Mac-1 treatment markedly reduced disease activity and inflammatory reaction accompanying DSS-induced colitis in mice.

Introduction The effect of valve type on outcomes in transfemoral transcatheter aortic valve replacement (TF-TAVR) has recently been subject of debate. We investigate outcomes of patients treated with balloon-expanding (BE) vs. self-expanding (SE) valves in in a cohort of all these procedures performed in Germany in 2018. Methods All patients receiving TF-TAVR with either BE (N = 9,882) or SE (N = 7,413) valves in Germany in 2018 were identified. In-hospital outcomes were analyzed for the endpoints in-hospital mortality, major bleeding, stroke, acute kidney injury, postoperative delirium, permanent pacemaker implantation, mechanical ventilation > 48 h, length of hospital stay, and reimbursement. Since patients were not randomized to the two treatment options, logistic or linear regression models were used with 22 baseline patient characteristics and center-specific variables as potential confounders. As a sensitivity analysis, the same confounding factors were taken into account using the propensity score methods (inverse probability of treatment weighting). Results Baseline characteristics differed substantially, with higher EuroSCORE (p p p p = 0.617] major bleeding [aOR 0.91 (0.73;1.14), p = 0.400], stroke [aOR 1.13 (0.88;1.46), p = 0.347], acute kidney injury [OR 0.97 (0.85;1.10), p = 0.621], postoperative delirium [aOR 1.09 (0.96;1.24), p = 0.184], mechanical ventilation > 48 h [aOR 0.98 (0.77;1.25), p = 0.893], length of hospital stay (risk adjusted difference in days of hospitalization (SE instead of BE): − 0.05 [− 0.34;0.25], p = 0.762) and reimbursement [risk adjusted difference in reimbursement (SE instead of BE): − €72 (− €291;€147), p = 0.519)] There is, however, an increased risk of PPI for SE valves (aOR 1.27 [1.15;1.41], p Conclusions We find broadly equivalent outcomes in contemporary TF-TAVR procedures, regardless of the valve type used. Incidence of major complications is very low for both types of valve.

To introduce an RF coil system consisting of an 8-channel transmit (Tx) and 8-channel receive (Rx) coil arrays forThe Tx efficiency and homogeneity of the 8-element loop coil array (loop size: 6 × 15 cmMeasured and simulated Tx efficiency and homogeneity for the 8-channel and 5-channel arrays were in good agreement: 1.87 ± 0.22μT/√kW versus 1.96 ± 0.29μT/√kW, and 2.29 ± 0.39μT/√kW versus 2.41 ± 0.37μT/√kW. An isolation of 38 ± 8 dB is achieved between theA modular and scalable Tx array offers improved Tx efficiency in

Aims P-selectin is an activatable adhesion molecule on platelets promoting platelet aggregation, and platelet–leukocyte complex (PLC) formation. Increased numbers of PLC are circulating in the blood of patients shortly after acute myocardial infarction and predict adverse outcomes. These correlations led to speculations about whether PLC may represent novel therapeutic targets. We therefore set out to elucidate the pathomechanistic relevance of PLC in myocardial ischemia and reperfusion injury. Methods and results By generating P-selectin deficient bone marrow chimeric mice, the post-myocardial infarction surge in PLC numbers in blood was prevented. Yet, intravital microscopy, flow cytometry and immunohistochemical staining, echocardiography, and gene expression profiling showed unequivocally that leukocyte adhesion to the vessel wall, leukocyte infiltration, and myocardial damage post-infarction were not altered in response to the lack in PLC. Conclusion We conclude that myocardial infarction associated sterile inflammation triggers PLC formation, reminiscent of conserved immunothrombotic responses, but without PLC influencing myocardial ischemia and reperfusion injury in return. Our experimental data do not support a therapeutic concept of selectively targeting PLC formation in myocardial infarction.

This study hypothesized that cerebral protection prevents strokes in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) in clinical practice.Preventing strokes is an important aim in TAVR procedures. Embolic protection devices may protect against cardiac embolism during TAVR, but their use and outcomes in clinical practice remain controversial.Isolated transfemoral TAVR procedures performed in Germany with or without cerebral protection devices were extracted from a comprehensive nationwide billing dataset.A total of 41,654 TAVR procedures performed between 2015 and 2017 were analyzed. The overall share of procedures incorporating cerebral protection devices was 3.8%. Patients receiving cerebral protection devices were at increased operative risk (European System for Cardiac Operative Risk Evaluation score 13.8 vs. 14.7; p 0.001) but of lower age (81.1 vs. 80.6 years; p = 0.001). To compare outcomes that may be related to the use of cerebral protection devices, a propensity score comparison was performed. The use of a cerebral protection device did not reduce the risk for stroke (adjusted risk difference [aRD]: +0.88%; 95% confidence interval [CI]: -0.07% to 1.83%; p = 0.069) or the risk for developing delirium (aRD: +1.31%; 95% CI: -0.28% to 2.89%; p = 0.106) as a sign of acute brain failure. Although brain damage could not be prevented, in-hospital mortality was lower in the group receiving a cerebral protection device (aRD: -0.76%; 95% CI: -1.46% to -0.06%; p = 0.034).In this large national database, cerebral embolic protection devices were infrequently used during TAVR procedures. Device use was associated with lower mortality but not a reduction in stroke or delirium. Future studies are needed to confirm these findings.

MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund’s adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes.

X-ray-based fluoroscopy is the standard tool for diagnostics and intervention in coronary artery disease. In recent years, computed tomography has emerged as a non-invasive alternative to coronary angiography offering detection of coronary calcification and imaging of the vessel lumen by the use of iodinated contrast agents. Even though currently available invasive or non-invasive techniques can show the degree of vessel stenosis, they are unable to provide information about biofunctional plaque properties, e.g. plaque inflammation. Furthermore, the use of radiation and the necessity of iodinated contrast agents remain unfavourable prerequisites. Magnetic resonance imaging (MRI) is a radiation-free alternative to X-ray which offers anatomical and functional imaging contrasts fostering the idea of non-invasive biofunctional assessment of the coronary vessel wall. In combination with molecular contrast agents that target-specific epitopes of the vessel wall, MRI might reveal unique plaque properties rendering it, for example, 'vulnerable and prone to rupture'. Early detection of these lesions may allow for early or prophylactic treatment even before an adverse coronary event occurs. Besides diagnostic imaging, advances in real-time image acquisition and motion compensation now provide grounds for MRI-guided coronary interventions. In this article, we summarize our research on MRI-based molecular imaging in cardiovascular disease and feature our advances towards real-time MRI-based coronary interventions in a porcine model.La fluoroscopia con rayos X es la herramienta estándar para el diagnóstico y la intervención de coronariopatías. En los últimos años, la tomografía computarizada se ha convertido en una alternativa atraumática a la coronariografía, ya que se puede detectar la calcificación coronaria y ver a través de imágenes las luces de los vasos sanguíneos mediante el uso de medios de contraste yodados. Si bien las técnicas traumáticas o atraumáticas disponibles actualmente pueden mostrar el grado de la estenosis vascular, no pueden proporcionar información sobre las propiedades biofuncionales de la placa de ateroma, por ejemplo, inflamación de la placa de ateroma. Por otra parte, el uso de radiación y la necesidad de agentes de contraste yodados siguen siendo requisitos desfavorables. La resonancia magnética (RM) es una alternativa sin radiación a los rayos X que proporciona contrates de imagen con información anatómica y funcional, lo cual refuerza la idea del diagnóstico biofuncional atraumático de las paredes de los vasos coronarios. En combinación con medios de contraste molecular que actúan sobre epítopos específicos de las paredes de los vasos, la RM puede poner de manifiesto propiedades particulares de la placa de ateroma mediante su representación, por ejemplo, «vulnerabilidad y predisposición a rotura». La detección precoz de este tipo de lesiones puede facilitar un tratamiento a tiempo o preventivo antes de que tenga lugar una complicación coronaria grave.Además del diagnóstico por imagen, los avances en la adquisición de imágenes en tiempo real y la compensación del movimiento sirven de base para las intervenciones coronarias guiadas por RM. En este artículo, ofrecemos un resumen de nuestra investigación sobre imagen molecular con resonancia magnética en enfermedades cardiovasculares y presentamos nuestros avances hacia las intervenciones coronarias con RM en tiempo real en un modelo porcino.基于 X 射线的荧光检查是诊断和干预冠状动脉疾病的标准工具。近年来, 计算机断层扫描已成为冠状动脉血管造影的一种非侵入性替代方法, 通过使用碘化造影剂来检测冠状动脉钙化和血管腔成像。即使当前可用的侵入性或非侵入性技术可以显示出血管狭窄的程度, 也仍无法提供有关生物功能性斑块特性（例如斑块炎症）的信息。此外, 辐射的使用和碘化造影剂的必要性仍然是不利的先决条件。磁共振成像是 X 射线的无辐射替代方法, X 射线提供了解剖学上和功能上的成像对比, 从而形成了对冠状动脉壁进行无创生物功能评估的想法。结合靶向血管壁特定表位的分子造影剂, MRI 可能会显示出独特的斑块特性, 例如“易损且易破裂”。这些病变的早期发现使在不良冠状动脉事件发生之前就进行早期或预防性治疗成为可能。除了诊断成像外, 实时图像采集和运动补偿方面的进展为 MRI 引导的冠状动脉介入治疗提供了基础。在本文中, 我们总结了对心血管疾病中基于 MRI 的分子成像的研究, 并介绍了在猪模型中基于 MRI 的实时冠状动脉介入治疗的进展。.

ObjectiveTranscatheter aortic valve implantation (TAVI) is the most common aortic valve replacement in Germany. Since 2015, to ensure high-quality procedures, hospitals in Germany and other countries that meet the minimum requirement of 50 interventions per centre are being certified to perform TAVI. This study analyses the impact of these requirements on case number and in-hospital outcomes.MethodsAll isolated TAVI procedures and in-hospital outcomes between 2008 and 2016 were identified by International Classification of Diseases (ICD) and the German Operation and Procedure Classification codes.Results73 467 isolated transfemoral and transapical TAVI procedures were performed in Germany between 2008 and 2016. During this period, the number of TAVI procedures per year rose steeply, whereas the overall rates of hospital mortality and complications declined. In 2008, the majority of procedures were performed in hospitals with fewer than 50 cases per year (54.63%). Until 2014, the share of patients treated in low-volume centres constantly decreased to 5.35%. After the revision of recommendations, it further declined to 1.99%. In the 2 years after the introduction of the minimum requirements on case numbers, patients were at decreased risk for in-hospital mortality when treated in a high-volume centre (risk-adjusted OR 0.62, p=0.012). The risk for other in-hospital outcomes (stroke, permanent pacemaker implantation and bleeding events) did not differ after risk adjustment (p=0.346, p=0.142 and p=0.633).ConclusionA minimum volume of 50 procedures per centre and year appears suitable to allow for sufficient routine and thus better in-hospital outcomes, while ensuring nationwide coverage of TAVI procedures.

Emergency hematopoiesis is the driving force of the inflammatory response to myocardial infarction (MI). Increased proliferation of hematopoietic stem and progenitor cells (LSK) after MI enhances cell production in the bone marrow (BM) and replenishes leukocyte supply for local cell recruitment to the infarct. Decoding the regulation of the inflammatory cascade after MI may provide new avenues to improve post-MI remodeling. In this study, we describe the influence of adenosine diphosphate (ADP)-dependent P2Y12-mediated signaling on emergency hematopoiesis and cardiac remodeling after MI. Permanent coronary ligation was performed to induce MI in a murine model. BM activation, inflammatory cell composition and cardiac function were assessed using global and platelet-specific gene knockout and pharmacological inhibition models for P2Y12. Complementary in vitro studies allowed for investigation of ADP-dependent effects on LSK cells. We found that ADP acts as a danger signal for the hematopoietic BM and fosters emergency hematopoiesis by promoting Akt phosphorylation and cell cycle progression. We were able to detect P2Y12 in LSK, implicating a direct effect of ADP on LSK via P2Y12 signaling. P2Y12 knockout and P2Y12 inhibitor treatment with prasugrel reduced emergency hematopoiesis and the excessive inflammatory response to MI, translating to lower numbers of downstream progeny and inflammatory cells in the blood and infarct. Ultimately, P2Y12 inhibition preserved cardiac function and reduced chronic adverse cardiac remodeling after MI. P2Y12-dependent signaling is involved in emergency hematopoiesis after MI and fuels post-ischemic inflammation, proposing a novel, non-canonical value for P2Y12 antagonists beyond inhibition of platelet-mediated atherothrombosis.

Previous mouse studies have shown the increased presence of platelets in the myocardium during early stages of myocarditis and their selective detection by MRI. Here, we aimed to depict early myocarditis using molecular contrast-enhanced ultrasound of activated platelets, and to evaluate the impact of a P2Y12 receptor platelet inhibition. Experimental autoimmune myocarditis was induced in BALB/c mice by subcutaneous injection of porcine cardiac myosin and complete Freund adjuvant (CFA). Activated platelets were targeted with microbubbles (MB) coupled to a single-chain antibody that binds to the “ligand-induced binding sites” of the GPIIb/IIIa-receptor (=LIBS-MB). Alongside myocarditis induction, a group of mice received a daily dose of 100 g prasugrel for 1 month. Mice injected with myosin and CFA had a significantly deteriorated ejection fraction and histological inflammation on day 28 compared to mice only injected with myosin. Platelets infiltrated the myocardium before reduction in ejection fraction could be detected by echocardiography. No selective binding of the LIBS-MB contrast agent could be detected by either ultrasound or histology. Prasugrel therapy preserved ejection fraction and significantly reduced platelet aggregates in the myocardium compared to mice without prasugrel therapy. Therefore, P2Y12 inhibition could be a promising early therapeutic target in myocarditis, requiring further investigation.

Extracellular adenosine-5'-triphosphate (ATP) acts as an import signaling molecule mediating inflammation via purinergic P2 receptors. ATP binds to the purinergic receptor P2X

Background Emergency hematopoiesis (EH) serves as the foundation of monocyte-derived and macrophage (Mφ) driven efferocytosis and ventricular remodeling after myocardial infarction (MI). Excessive myelopoiesis, however, can stipulate maladaptive wound healing and its therapeutic reduction may be a novel approach to preserve cardiac function. All-trans retinoic acid (ATRA) is a pleiotropic modulator of EH and innate immunity shielding hematopoietic stem cells from activation and driving survival and differentiation of myeloid cells. Purpose This study aimed to investigate this intriguing interplay of ATRA in wound healing after MI. Methods MI was induced by permanent coronary ligation in C57BL/6 mice and treated with daily injections of either ATRA (30mg/kg) or DMSO (vehicle) up to five days, starting 24h after ligation. Flow cytometry (FACS) was used for cell cycle analysis and immunophenotyping of leukocytes in bone marrow (BM), blood and heart. Immunohistochemistry (IH), masson trichrome (MT) staining and echocardiography evaluated inflammatory-fibrotic and functional development. Cytokine expression was analyzed by qPCR in bulk infarct and isolated, polarized Mφ-populations of BM-derived and cardiac resident origin. Results On day 2 after MI, EH was significantly reduced in ATRA-treated mice as compared to vehicle controls by means of cell cycle activity (n=6–13 per group; p Conclusion Despite a beneficial reduction of EH after MI, short-term treatment with ATRA induced profound and persisting changes in the cytokine expression of monocyte-derived Mφ, which significantly altered their function and thus prevented improvements in cardiac function. Our data provide evidence that quantitative and qualitative changes in innate immunity are equally important for cardiac remodeling after MI. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Objectives We aimed to identify risk factors for major transcatheter aortic valve intervention (TAVI) access site complications based on detailed analysis of the preprocedural computed tomography angiogram (CTA). Background Transfemoral TAVI has become the treatment of choice for severe aortic stenosis in elderly patients, especially with increased perioperative risk. Frailty, however, favors complications at the vascular access site due to the large bore vascular sheath devices necessary for valve deployment. Methods In this monocentric study, we retrospectively analyzed the preprocedural CTA of 417 consecutive patients that received transfemoral TAVI between 2015 and 2019 to quantify vessel diameter, calcification volume and calcified plaque location in detail within 10 cm proximal to the femoral bifurcation. Results The mean age of the study cohort was 81.4 ± 6.5 years with a STS of 8 ± 5.2 representing a population at increased periprocedural risk. 54.4% of patients were female. Major vascular access site complications occurred in 8.2% of patients. Major vascular complications correlated statistically with a sheath-to-vessel diameter (SFAR) when measured 1 cm proximal to the femoral bifurcation using a line-derived diameter and ventral calcification within the first 5 cm proximal to the bifurcation. In contrast, overall calcification volume had no influence. Conclusions Transfemoral TAVI harbors a considerable risk for vascular access site complications especially if vessel diameter is too small to comfortably host the sheath diameter at the area of the femoral bifurcation. For preprocedural TAVI planning and risk assessment, location of calcification, especially if located ventrally, seems to be more relevant than consideration of overall calcification alone.

The acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition. The number of ARDS cases has risen dramatically recently but specific treatment options are limited. ARDS is associated with an overshooting inflammatory response and neutrophils play a central role in its pathogenesis. Neutrophils express the integrin Mac-1 on their surface which adopts a resting and activated conformation depending on leukocyte activation. The aim of this study was to investigate the anti-inflammatory effects of the unique activation-specific anti-Mac-1 DARPin ‘F7’ in a mouse model of ARDS. ARDS was induced by intratracheal lipopolysaccharide (LPS) instillation and the acute (day 1–4) and chronic phase (day 5–10) were studied. After expression and purification, F7, a control DARPin and PBS, were applied daily via the intraperitoneal route. Survival and weight loss were recorded. Histological analysis of lung sections, flow cytometric leukocyte analysis of blood and bronchioalveolar lavage (BALF) were performed. Moreover, protein concentration and cytokine levels were determined in the BALF. Treatment with F7 improved survival and reduced weight loss significantly compared to treatment with the control DARPin or PBS. Neutrophil count in the BALF and peripheral blood were significantly reduced in mice treated with F7. Histology revealed significantly reduced pulmonary inflammation in the F7 treated group. Treatment with DARPin F7 inhibited neutrophil accumulation, reduced signs of local and systemic inflammation and improved survival in a mouse model of ARDS. F7 may be a novel anti-inflammatory drug candidate for the treatment of severe ARDS.

Emergency hematopoiesis is the driving force of the inflammatory response to myocardial infarction (MI). Increased proliferation of hematopoietic stem and progenitor cells (LSK) after MI enhances cell production in the bone marrow (BM) and replenishes leukocyte supply for local cell recruitment to the infarct. Decoding the regulation of the inflammatory cascade after MI may provide new avenues to improve post-MI remodeling. In this study, we describe the influence of adenosine diphosphate (ADP)-dependent P2Y

Statins induce plaque regression characterized by reduced macrophage content in humans, but the underlying mechanisms remain speculative. Studying the translational APOE*3-Leiden.CETP mouse model with a humanized lipoprotein metabolism, we find that systemic cholesterol lowering by oral atorvastatin or dietary restriction inhibits monocyte infiltration, and reverses macrophage accumulation in atherosclerotic plaques. Contrary to current believes, none of (1) reduced monocyte influx (studied by cell fate mapping in thorax-shielded irradiation bone marrow chimeras), (2) enhanced macrophage egress (studied by fluorescent bead labeling and transfer), or (3) atorvastatin accumulation in murine or human plaque (assessed by mass spectrometry) could adequately account for the observed loss in macrophage content in plaques that undergo phenotypic regression. Instead, suppression of local proliferation of macrophages dominates phenotypic plaque regression in response to cholesterol lowering: the lower the levels of serum LDL-cholesterol and lipid contents in murine aortic and human carotid artery plaques, the lower the rates of in situ macrophage proliferation. Our study identifies macrophage proliferation as the predominant turnover determinant and an attractive target for inducing plaque regression. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-020-00838-4.

Introduction Inflammation is essential for wound healing after myocardial infarction (MI). Leukocytes, especially neutrophils and monocytes, orchestrate removal of necrosis and regulation of tissue remodeling. Beside local recruitment from the blood, leukocyte supply via increased hematopoiesis is of major relevance for post-ischemic myocardial inflammation. Little is known about the pathways that carry the signals for increased demand for leukocytes from the site of injury to upstream hematopoietic stem cells (LSK) in the bone marrow (BM). In this study, we investigate the role of the P2Y12-ADP-receptor mediated regulation for emergency hematopoiesis after MI. Methods For standardized MI, a model of permanent coronary ligation was used in C57/Bl6 and P2Y12−/− mice. Changes in plasmatic ADP levels after MI were screened using ELISA, whereas the expression of the P2Y12-ADP-receptor in cell populations isolated from the BM was investigated by qPCR. CFU assays added further functional insight on hematopoietic proliferation in vitro. The effect of P2Y12 on the hematopoietic system after MI was investigated by inhibiting the P2Y12-receptor via prasugrel and compared to inhibition of the thromboxane pathway via acetylsalicylic acid (ASA). Proliferation of LSK in BM and leukocyte composition in blood, BM and infarct tissue after MI were assessed via FACS. Leukocyte composition in the infarcted myocardium was validated by immunohistochemistry. Finally, left ventricular function (LV-EF) and remodeling were investigated by echocardiography. Results 24 h after MI, we found a peak of plasmatic ADP levels. LSK as upstream hematopoietic progenitors in the BM express a P2Y12-receptor, which was validated on transcriptional and protein level. Whereas ADP stimulation of LSK led to significantly larger colony growth in vitro on the one hand, percentage of cycling LSK were significantly reduced 48 h after MI in P2Y12−/− mice compared to WT mice, assessed by Ki67/DAPI cell cycle analysis. Prasugrel treatment showed similar effects, translating into reduced numbers of downstream hematopoietic progenitors GMP and MDP 72 h after MI. Treatment with ASA however had no significant effect neither on cycling LSK nor progenitor populations. Consequently, decreased medullary hematopoiesis under P2Y12-inhibition led to reduced infiltration of inflammatory cells in the infarct tissue 7 days after MI, finally resulting in significantly improved outcome in terms of LV-EF 3 weeks after MI. Conclusion In this study, we demonstrate that P2Y12-mediated signaling is involved in emergency hematopoiesis after MI and advocates post-MI inflammation. In turn, inhibition of P2Y12-mediated signaling contributes to improved wound healing and prevention of adverse cardiac remodeling after MI, which adds a yet unknown mechanism to the success story of modern P2Y12-receptor blockers. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Objectives Coronary physiology is increasingly used in evaluating coronary stenosis, but the penetrance of FFR (Fractional Flow Reserve) or resting indices (e.g. iwFR or RFR) in daily clinical routine is not known. Methods The number of coronary angiographies and use of coronary physiology (CP) in patients with chronic coronary syndromes (CCS) in Germany was identified by ICD and OPS codes. Results From 2007 to 2017, there was a constant increase in CP usage, with an application rate of 9.19% in 2017. Patients with use of CP were younger (68.8 vs. 70.8 years), had less often severe co-morbidities (peripheral or carotid disease, chronic obstructive pulmonary disease, pulmonary hypertension, renal disease, atrial fibrillation, diabetes), had milder symptoms (10.4 vs. 14.4% in NYHA class III or IV), and a lower EuroSCORE (6.1 vs. 8.3%). Less coronary stents were implanted in patients with use of CP (0.6 vs. 0.8, 95% CI: −0.14–0.26; p Conclusions In 2017, coronary physiology was used in 9.19% of patients with CCS in Germany. CP resulted in better in-hospital outcomes and less stent implantations. The reasons for a reduced use of CP in patients with significant co-morbidities, and their impact on clinical outcomes require further attention and evaluation in the future. Funding Acknowledgement Type of funding source: None

Aims: Removal of large calibre arterial sheaths, as employed in venoarterial extracorporeal membrane oxygenation, is still associated with a high risk for vascular access site complications. In this study, we investigated the large bore Manta closure device as an option for venoarterial extracorporeal membrane oxygenation decannulation. Methods and results: Sixteen patients weaned from venoarterial extracorporeal membrane oxygenation between January–June 2019 were prospectively included in a registry (eight during extracorporeal cardiopulmonary resuscitation, seven with severe cardiogenic shock and one patient with fulminant pulmonary embolism). All patients had an arterial sheath removed at bedside using the Manta device achieving rapid haemostasis without clinically relevant complications afterwards. A computed tomography angiography was available for 11 patients (68.8%) and reassessed with regards to relevant pathologies at the closure device. Average intraluminal area was 40.4 mm2 (12.2–76.3 mm2) at the closure site. All devices but one were correctly deployed. Three patients (27.3%) had a visible thrombus at the closure device resulting in a >60% stenosis, two of which had a puncture site distal of the femoral artery bifurcation. Conclusion: Decannulation from venoarterial extracorporeal membrane oxygenation using the Manta closure device is a viable approach for rapid haemostasis, but is also associated with a significant risk of thrombotic vessel stenosis. These preliminary findings indicate that puncture in near proximity or distal to the femoral bifurcation might identify patients at risk and further studies are needed.

AIMS:Patients with postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR) are ventilated and hospitalized longer and suffer increased in-hospital mortality. This study hypothesized that a minimalistic approach with conscious sedation during transfemoral aortic valve replacement (TF-AVR) protects against delirium, time of mechanical ventilation, and increased length of stay in intensive care unit (ICU) compared to intubation anaesthesia. METHODS AND RESULTS:308 patients which underwent TF-AVR in our centre between 01/2013 and 08/2017 were retrospectively evaluated regarding postoperative delirium, time of mechanical ventilation, and days in ICU. TF-AVR was performed with intubation anaesthesia in 245 patients and with conscious sedation in 63. The operative risk estimated by the logEUROScore was similar in both groups (intubation: 13.28 +/-9.06%, conscious sedation: 12.24 +/-6.77%, p = 0.395). In the conscious sedation group procedure duration was shorter (0.61 +/-0.91h vs. 1.75 +/-0.96h, p

POD is associated with a worse postoperative course in patients after cardiac surgery, but its incidence and effects after TAVR are not well-understood. The aim of the present study was to analyze incidence, risk factors, and in-hospital outcomes of postoperative delirium (POD) after transfemoral (TF-AVR) and transapical (TA-AVR) transcatheter aortic valve replacement (TAVR) in a nationwide cohort. Administrative data on all patients undergoing isolated TAVR in Germany in 2014 were analyzed. 9038 TF-AVR and 2522 TA-AVR procedures were performed. POD incidence was 7% after TF-AVR and 12% after TA-AVR. Atrial fibrillation (TF: OR 1.35, p

Background and aims Activated platelets are amongst the most attractive imaging targets in atherosclerosis due to their important role in early processes of atherogenesis and thrombus formation. We developed a molecular intravascular ultrasound (IVUS) approach to detect activated platelets ex vivo on the surface of human plaques, using an IVUS system applied in clinical routine. Methods Human carotid endarterectomy specimens were obtained directly from the operating room and exposed to artificial arterial flow conditions for incubation with the contrast agent. This consists of microbubbles (MB), which are linked to an antibody against the ligand induced binding site (LIBS) of the activated platelet glycoprotein IIb/IIa, and a sialyl Lewis polymer (SL), which mediates binding to selectins (LIBS-SL-MB). IVUS was performed pre and post incubation with LIBS-SL-MB and after rinsing with PBS. In comparison, IVUS was performed pre and post incubation with MBs linked to an unspecific control antibody and a dysfunctional polymer (control-MB). All imaging results were correlated to histology findings. Results IVUS imaging showed a high signal enhancement after administration of LIBS-SL-MB. After rinsing with PBS, the signal enhancement remained stable. Immunofluorescence and immunohistochemistry confirmed significant binding of microbubbles to thrombi on the plaque surface. Moreover, thrombus size and number of bound MBs correlated well. Conclusions LIBS-SL-MB allows ex vivo IVUS imaging of even small numbers of activated platelets on the surface of human carotid endarterectomy specimens. This diagnostic approach could deliver valuable additional information for risk stratification of atherosclerotic plaques, especially since we apply a clinically well-established IVUS imaging system.

Aim: The present study analyzes in depth the impact of different calcification patterns on disturbances of the conduction system in transcatheter aortic valve replacement (TAVR) patients. Methods and Results: A total of 169 preprocedural TAVR multislice computed tomography scans from consecutive transfemoral (TF) TAVRs performed between 2014 and 2017 using either Edwards SAPIEN or Medtronic Evolut R valves were retrospectively evaluated. The volume, distribution, and orientation of annular and valvular aortic valve calcification were measured and their impact on postoperative conduction disturbances was determined using linear and logistic regression analyses. The total volume of calcification and distribution at the aortic annulus or valve did not influence the conduction system. Oval calcification of the left aortic cusp was independently associated with an elevated risk for an increase in atrioventricular block degree (+0.6, p = 0.03). Moreover, orthogonal calcifications at the level of the aortic annulus were associated with an increased risk for QRS prolongation (+26 ms, p = 0.004) and an increased risk for permanent pacemaker implantation (OR 4.3, p = 0.03) after TF TAVR. This was more pronounced in patients undergoing TF TAVR using a balloon-expandable Edwards SAPIEN 3 valve (QRS +38.195 ms, p < 0.001; OR permanent pacemaker 15.48, p = 0.013). Conclusion: Orthogonal annular calcification confers an increased risk for conduction disturbances after TAVR. This is even more pronounced after implantation of balloon-expandable valves.

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Background Transfemoral transcatheter aortic valve replacement (TF-TAVR) is the standard therapy for patients with severe aortic valve stenosis at high operative risk. If the transfemoral access is not possible, a transapical access is an alternative. However, it is known from randomized trials and large registries that outcomes after transapical TAVR (TA-TAVR) are inferior to TF-TAVR. Purpose We compared in-hospital outcomes of patients undergoing TA-TAVR or SAVR in a nationwide data-set, in order to identify patients' groups, who benefit from SAVR or TA-TAVR. Methods We identified all 13,151 isolated SAVR and 4,625 TA-TAVR performed in Germany 2014 and 2015 on the basis of ICD- and OPS codes. In order to compare outcomes, we adjusted for risk factors using a covariate adjusted analysis. Results Patients undergoing TA-TAVR were older (68 vs. 80 years), had more co-morbidities, and accordingly an increased logistic EuroSCORE (LogES 5.3 vs 16.7%). However, stroke, acute kidney injuries, relevant bleedings, and prolonged mechanical ventilation occurred less frequently in patients undergoing TA-TAVR (OR TA-TAVR vs SAVR: stroke 0.66, p=0.017; acute kidney injury 0.72, p=0.002; relevant bleeding: 0.38, p48h: 0.5, p≤0.001). The risk for a new permanent pacemaker was higher after TA-TAVR (OR 2.44, p≤0.001). Without adjustment in-hospital mortality was higher after TA-TAVR (2.0% vs. 5.9%). After covariate adjustment, the difference disappeared (OR TA-TAVR vs. SAVR 1.2, p=0.136). In order to identify subgroups, which may benefit from TA-TAVR or SAVR, we compared mortality in different subgroups after risk adjustment. Patients under 75 years (OR TA-TAVR vs. SAVR: 1.86, p=0.01) and female (OR 1.48, p=0.043) patients had a lower risk for in-hospital mortality after SAVR. In all other groups (age 75–79, 80–84, >85, log. EuroScore 9, NYHA III/IV, previous CABG, COPD, pulmonary hypertension, chronic renal failure, Diabetes) none of both treatment strategies was superior. Conclusion TA-TAVR is with regard to in-hospital mortality not superior to SAVR in clinical practice. Younger patients under 75 years and female patients benefit from SAVR. However, complications such as bleeding, stroke, or prolonged ventilation were less frequently in patients undergoing TA-TAVR.

Background Transcatheter aortic valve replacement (TAVR) is recommended for patients suffering from aortic valve stenosis at increased operative risk or age over 75 years. Beyond that patients with different co-morbidities could profit from TAVR. Purpose The present study analyzes in-hospital outcomes of aortic valve replacement procedures in order to identify subgroups of patients in which TAVR might be preferable. Methods For all 33,789 isolated transfemoral TAVR and SAVR procedures performed in Germany in 2014 and 2015, co-morbidities and in-hospital outcomes were identified by ICD- and OPS-codes. Results Patients undergoing TAVR were older with more co-morbidities and at increased estimated risk (logistic EuroSCORE TAVR: 13.9±10.3%; SAVR: 5.3±4.7%; p9: OR 0.62, p=0.001). No significant difference in in-hospital mortality occurs between TAVR and SAVR in patients under 80 and intermediate or low risk (48h, OR 0.21, p Conclusions The present study analyzing over 33.000 real-world procedures confirms that TAVR is the safer procedure in clinical practice for patients with severe aortic valve stenosis at increased operative risk, over 80 years, in NYHA-class III/IV, and with renal failure.