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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。.

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

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

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.