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Home › Herzzentrum › deutsch › Klinik für Kardiologie und Angiologie › Forschung › Forschung Freiburg › Grundlagenforschung › Experimentelle Interventionelle Kardiologie - Prof. Dr. C. v.z. Mühlen

Experimental Interventional Cardiology

Group leader: Prof. Dr. von zur Mühlen

1. Overview

Multiple non-invasive approaches are well established for diagnosis of coronary artery disease, and invasive coronary angiography is the gold standard for treatment of coronary stenoses. However, we are still limited in individualized evaluation of vascular inflammation or plaque progression resulting in coronary artery disease. Furthermore, routine coronary angiography does not provide us with information on plaque characteristics, and involves ionizing radiation – which is potentially harmful to the operator over the course of time.

We are interested in completely new approaches for individualized diagnostics and interventions in coronary artery disease. Our main interest is focused on interventional magnetic resonance imaging including plaque characterization and its specific interventional treatment (SFB).

Furthermore, we are interested in the application of current interventional technologies in the clinical routine, its clinical outcomes in large nationwide cohorts, and economical aspects of these interventional approaches (CeBac).

2. Interventional Magnetic Resonance Imaging

An important step towards individualized therapy in cardiovascular medicine is the specific characterization of disease followed by selective treatment. Interventional Magnetic resonance imaging (MRI) of cardiovascular disease has a high diagnostic potential due to the absence of ionizing radiation, its excellent 3D imaging capabilities, and superior soft tissue contrast compared to x-ray fluoroscopy. Recent technical developments of imaging hard- and software enable us to perform MRI-guided coronary interventions with stents or scaffolds in large animals (Figure 1, Movie 1), without any use of radiation. In addition, specific disease detection is possible by molecular MRI. Molecular imaging allows to image cells or cellular receptors on a molecular level – by dedicated contrast agents, e.g. consisting of target-specific antibodies and contrast-giving moieties.

As a perspective, MRI may constitute an ideal imaging technique for the detection and assessment of pathophysiological changes in atherosclerotic plaques, providing cell-type specificity when using molecular imaging contrast agents, and allowing a step towards an individualized interventional therapy.

This project is funded by the DFG within the SFB 1425.

Figure. 1: Guiding catheters for interventional MRI. Left: guiding catheter. Right: In vivo MRI scan of the guiding catheter in the aortic arch. Modified from Heidt T et al. Sci Rep 2019.

Movie 1: Real-time MRI of intubation of the left coronary artery with a guiding catheter suitable for coronary interventions. From Heidt T et al. Sci Rep 2019

3. Cardiovascular molecular imaging using targeted contrast agents

Atherosclerosis and its resulting cardiovascular complications are the leading cause of morbidity and mortality in the western world. The progression, erosion and rupture of atherosclerotic plaques are regarded as the precipitating event for thrombus formation in myocardial infarction and stroke. Early non-invasive testing in symptomatic or asymptomatic patients can help to guide specific therapies or interventions, and may therefore help to reduce morbidity and mortality. Recent progress in magnetic resonance imaging (MRI) has provided the technical prerequisites to allow imaging of atherosclerotic plaques. There is currently considerable interest in developing contrast-ligand probes to enable imaging of specific molecules, cells and processes that are important to atherosclerosis. We have previously used functionalized microparticles of iron oxide (MPIO) to specifically target activated platelets. Therefore, we used a unique single-chain antibody recognizing ligand-induced binding-sites (LIBS) on activated glycoprotein IIb/IIIa-receptors. Using this technology, we were able to noninvasively detect platelet aggregation in arterial thrombosis of the carotid arteries in mice, and to observe the success of a thrombolytic therapy (Figure 2). In a different approach using the same contrast agent, we were able to detect platelet aggregation in cerebrovascular inflammation before the onset of clinical symptoms, or in thrombosis of coronary vessels in mice. Furthermore, using a dual imaging apporach, we can also non-invasively characterize the presence and extent of a myocardial ischemia/reperfusion injury after temoporary coronary ligation (Figure 3). Currently, research is ongoing to transfer this technique into human settings as well as into ultrasound contrast agent applications.

Imaging of monocytes/macrophages involved into plaque inflammation is another goal of our research. Macrophages are promoters of plaque inflammation and vulnerability, and therefore their timely detection would be of clinical interest. We have examined uptake mechanisms of iron oxide particles into monoctyes/macrophages, which could help to target such inflammatory cells with increased sensitivity. 

Figure 2: In vivo MRI after carotid artery injury. (A) Localizer-sequence with labeled anatomical landmarks: the non-injured left carotid artery (a), the trachea (b) and the injured right carotid artery (c). (B/C) Transverse sections demonstrate the injured right carotid artery (red circle), which is well-perfused despite wall adherent thrombosis (negative control: non-injured left carotid artery (green circle)). After injection of control-MPIO, signal intensity in both vessels is similar at 12, 48 and 72min. After LIBS-MPIO injection, there is increasing signal drop at 12, 24 and 72min compared with pre-injection images and the non-injured left carotid artery. This represents the typical susceptibility artifact caused by MPIOs in T2* weighted MRI, and therefore indicates LIBS-MPIO binding. Taken from: von zur Muhlen et al, Circulation 2008

Figure 3: Dual imaging with LIBS-MPIO and gadolinium for imaging of ischemia/reperfusion injury. Representative sections of a short axis image from the medial ventricular areas are depicted. For animals injected with LIBS-MPIO (A, upper row) and control-MPIO (B, lower row), baseline scans are shown on the left. After contrast agent injection, a continuous signal decrease can be seen in ischemic areas of animals with LIBS-MPIO-injection (red arrows) as the typical susceptibility artifact induced by MPIOs. No signal effect is visible in animals with control-MPIO-injection. After imaging for 37min, gadolinium was injected to observe the late gadolinium enhancement for detection of myocardial necrosis, which is present in both treatment groups (see yellow arrow). Taken from: von zur Muhlen et al, Circulation 2014

4. Coronary magnetic resonance imaging of vascular devices

Bioresorbable vascular scaffolds (BVS) are an evolving technique in interventional cardiology. Due to the non-metallic PLLA-backbone, BVS-therapy might also allow for noninvasive eva­luation of coronary arteries by magnetic resonance imaging (MRI), simultaneously yiel­ding information about anatomy and atherosclerotic plaque dynamics. Conventional metallic stents are known to shield off the radio-frequency (RF) fields during MRI signal excitation and data acquisition, which leads to a severely reduced MRI sensitivity inside the stent. Additionally, the closed metallic ring structures can create unwanted field distortions from susceptibility differences. In contrast, BVS might allow for an artifact-free imaging of the scaffold lumen, so that the patency of the vessel can be directly assessed in a noninvasive manner (Figure 4)

Figure 4. Magnetic resonance imaging of bioresorbable vascular scaffold (BVS) in patient cases. Top, Patient 1 with non-ST–elevation acute coronary syndromes and a soft plaque in the proximal left anterior descending was implanted with a BVS (3.0/18 mm). Left, Coro- nary angiographic result. Middle/Right, 1.5T dark-blood prepared three-dimensional (3D) turbo spin echo (TSE)/bright-blood 3D FLASH imaging shows the patent vessel lumen without any artifacts within the lumen or the vessel wall. Arrows indicate scaffolded area. Bottom, Patient 2 with stable CAD was implanted with 2 BVS overlapping scaffolds (3.0/18 mm and 3.5/28 mm). Left, Coronary angiographic result. Middle/Right, 1.5T dark-blood TSE images of the right coronary artery and a cross-section of the scaffolded area indicated by the arrow. Compared with patient 1, image quality especially in the proximal part slightly degraded because of incomplete dark-blood preparation and motion. Taken from: Reiss et al, Circ Cardiovasc Interventions 2015.

5. Center for Big Data Analysis in Cardiology (CeBAC)

The Center of Big Data Analysis in Cardiology is an association of interventional cardiologists and statisticians in order to analyze interventional procedures. Together we analyze big data sets to evaluate the clinical and economic value of modern interventional therapies. This may help to identify the ideal therapeutic options for individual patients. Beyond that we support health care policy by the evaluation of emerging therapy concepts in clinical practice.

Members

Prof. Dr. med. Constantin von zur Mühlen

constantin.vonzurmuehlen@uniklinik-freiburg.de

Sekretariat Diana Selig

0761 270-34415

0761 270-34426

diana.selig@uniklinik-freiburg.de

Dr. med. Alexander Maier
FA Innere Medizin, Zusatzbezeichnung Notfallmedizin

alexander.maier@uniklinik-freiburg.de

Dr. med. Hana Seung
Post-Doc USA

hana.seung@uniklinik-freiburg.de

Lab manager & technical assistance

  • Carolin Wadle
  • Nathalie Hoppe

Current Medical- and PhD-Student

  • Patrick Huber

Alumni

  • Janine Ender
  • Mario Brasse
  • Julia Möller
  • Verena Berti
  • Christine Sackmann
  • Christina Müller
  • Kristina Wiens
  • Dominik Trübenbach
  • Felix Günther
  • Stephanie Meier
  • Simon Ehrismann
  • Anna Lena Mutscher
  • Hannes Hummel
  • Katharina Bartmann
  • Marvin Krohn-Grimberghe
  • Dr. Tayrin Hopp
  • Dr. Lisa Besch
  • Patricia Plaza-Heck
Publications

Originalarbeiten

2021

Stachon P, Kaier K, Heidt T, Duerschmied D, Staudacher D, Zehender M, Bode C, von Zur Mühlen C. Use and outcomes of cerebral protection devices for patients undergoing transfemoral TAVR in clinical practice. JACC Cardiovasc Interv. 2021 Jan 25; 14(2):161-168. doi: 10.1016/j.jcin.2020.09.047IF: 9,544

2020

Härdtner C, Kornemann J, Krebs K, Ehlert C, Jander A, Zou J, Starz Ch, Rauterberg S, Sharipova D, Dufner B, Hoppe N, Dederichs TS, Willecke F 1 , Stachon P, Heidt T, Wolf D, von zur Mühlen C, Madl J, Kohl P, Kaeser R, Boettler T, Pieterman E, Princen HMG,  Ho-Tin-Noé B, Swirski F K, Robbins C S, Bode C, Zirlik A, Hilgendorf I. Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering. Basic Res Cardiol 2020 Dec 9; 115(6):78. doi: 10.1007/s00395-020-00838-4; IF: 6,620

Lang C, Kaier K, Zotzmann V, Stachon P, Pottgiesser T, von zur Mühlen C, Zehender M, Duerschmied D, Schmid B, Bode C, Wengenmayer T, Staudacher D. Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry; Clin Res Cardiol. 2020 Nov 30. doi: 10.1007/s00392-020-01781-z. Online ahead of print

Lother A, Kaier K, Ahrens I, Bothe W, Wolf D, Zehender M, Bode C, von Zur Mühlen C, Stachon P. Bleeding complications drive in-hospital mortality of patients with atrial fibrillation after transcatheter aortic valve replacement. Thromb Haemost. 2020, in press

Rilinger J, Zotzmann V, Bemtgen X, Schumacher C, Biever P, Duerschmied D, Kaier K, Stachon P, von Zur Mühlen C, Zehender M, Bode C, Staudacher D, Wengenmayer D. Prone positioning in severe ARDS requiring extracorporeal membrane oxygenation. Crit Care. 2020 Jul 8; 24(1):397. doi: 10.1186/s13054-020-03110-2.

Frankenstein L, Kaier K, Katus H, Bode C, Wengenmayer T, von Zur Mühlen C, Bekeredjian R, Täger T, Zehender M, Fröhlich H, Stachon P. Impact of the introduction of percutaneous edge-to-edge mitral valve reconstruction on clinical practice in Germany compared to surgical valve repair. Clin Res Cardiol. 2020 May 27. doi: 10.1007/s00392-020-01675-0. Online ahead of print.

Duerschmied D, Zotzmann V, Rieder M, Bemtgen X, Biever P, Kaier K, Trummer G, Benk C, Busch H, Bode C, Wengenmayer T, Stachon P, von Zur Mühlen C, Staudacher D. Myocardial infarction type 1 is frequent in refractory out-of-hospital cardiac arrest (OHCA) treated with extracorporeal cardiopulmonary resuscitation (ECPR). Sci Rep. 2020 May 21; 10(1):8423. doi: 10.1038/s41598-020-65498-9.

Bemtgen X, Heidt T, Zotzmann V, Rilinger J, Wengenmayer T, Biever P, von Zur Mühlen C, Benk C, Bode C, Staudacher D. Venoarterial extracorporeal membrane oxygenation decannulation using the novel Manta vascular closure device. Eur Heart J Acute Cardiovasc Care. 2020 May 4; 2048872620918707. doi: 10.1177/2048872620918707. Online ahead of print.

Heidt T, Reiss S, Lottner T, Özen A, Bode C, Bock M, von Zur Mühlen C. Magnetic resonance imaging for pathobiological assessment and interventional treatment of the coronary arteries. Eur Heart J Suppl. 2020 Apr; 22(Suppl C):C46-C56. doi: 10.1093/eurheartj/suaa009. Epub 2020 Apr 29.

Stachon P, Kaier K, Heidt T, Bothe W, Zirlik A, Zehender M, Bode C, von Zur Mühlen C. Nationwide outcomes of aortic valve replacement for pure aortic regurgitation in Germany 2008-2015. Catheter Cardiovasc Interv. 2020 Mar 1;95(4):810-816. doi: 10.1002/ccd.28361. Epub 2019 Jun 4.

Stachon P, Kaier K, Oettinger V, Bothe W, Zehender M, Bode C, von Zur Mühlen C. Transapical aortic valve replacement versus surgical aortic valve replacement: A subgroup analyses for at-risk populations. J Thorac Cardiovasc Surg. 2020 Feb 29; S0022-5223(20)30517-1. doi: 10.1016/j.jtcvs.2020.02.078. Online ahead of print.

Oettinger V, Kaier K, Heidt T, Hortmann M, Wolf D, Zirlik A, Zehender M, Bode C, von Zur Mühlen C, Stachon P. Outcomes of transcatheter aortic valve implantations in high-volume or low-volume centres in Germany. Heart. 2020 Feb 18; heartjnl-2019-316058. doi: 10.1136/heartjnl-2019-316058. Online ahead of print.

Maier A, Hammerich B, Humburger F, Brieschal T, Heidt T, Bothe W, Schröfel H, Kaier K, Zehender M, Reinöhl J, Bode C, von Zur Mühlen C, Stachon P. A logistic regression analysis comparing minimalistic approach and intubation anaesthesia in patients undergoing transfemoral transcatheter aortic valve replacement. PLoS One. 2020 Feb 5;15(2):e0227345. doi: 10.1371/journal.pone.0227345. eCollection 2020.

Baumann S, Bojara W, Post H, Rudolph T, Schäufele T, Ong P, Lehmann R, von Zur Mühlen C. Coronary physiology in the catheter laboratory. Herz. 2020 Jan 14. doi: 10.1007/s00059-019-04878-y. Online ahead of print.

Dangas GD, Tijssen JGP, Wöhrle J, Søndergaard L, Gilard M, Möllmann H, Makkar RR, Herrmann HC, Giustino G, Baldus S, De Backer O, Guimarães AHC, Gullestad L, Kini A, von Lewinski D, Mack M, Moreno R, Schäfer U, Seeger J, Tchétché D, Thomitzek K, Valgimigli M, Vranckx P, Welsh RC, Wildgoose P, Volkl AA, Zazula A, van Amsterdam RGM, Mehran R, Windecker S; GALILEO Investigators. A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement. N Engl J Med. 2020 Jan 9;382(2):120-129. doi: 10.1056/NEJMoa1911425. Epub 2019 Nov 16.

2019

Pepin M, Koentges C, Pfei K, Gollmer J, Kersting S, Wiese S, Hoffmann M, Odening K, von Zur Mühlen C, Diehl P, Stachon P, Wolf D, Wende A, Bode C, Zirlik A, Bugger H. Dysregulation of the Mitochondrial Proteome Occurs in Mice Lacking Adiponectin Receptor 1. Front Endocrinol (Lausanne). 2019 Dec 13; 10:872. doi: 10.3389/fendo.2019.00872. eCollection 2019.

Heidt T, Reiss S, Krafft A, Özen A, Lottner T, Hehrlein C, Galmbacher R, Kayser G, Hilgendorf I, Stachon P, Wolf D, Zirlik A, Düring K, Zehender M, Meckel S, von Elverfeldt D, Bode C, Bock M, von Zur Mühlen C. Publisher Correction: Real-time magnetic resonance imaging - guided coronary intervention in a porcine model. Sci Rep. 2019 Nov 29; 9(1):18282. doi: 10.1038/s41598-019-54947-9.

Kaier K, Bode C, Zehender M, von Zur Mühlen C, Stachon P. Modeling the Volume-Outcome Relationship for TAVR. J Am Coll Cardiol. 2019 Oct 22; 74(16):2115-2116. doi: 10.1016/j.jacc.2019.08.999.

Peikert A, Kaier K, Merz J, Manhart L, Schäfer I, Hilgendorf I, Hehn P, Wolf D, Willecke F, Sheng X, Clemens A, Zehender M, von Zur Mühlen C, Bode C, Zirlik A, Stachon P. Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort. Clin Res Cardiol. 2019 Jul. 19. [Epub ahead of print].

Heidt T, Reiss S, Krafft AJ, Özen AC, Lottner T, Hehrlein C, Galmbacher R, Kayser G, Hilgendorf I, Stachon P, Wolf D, Zirlik A, Düring K, Zehender M, Meckel S, von Elverfeldt D, Bode C, Bock M, von zur Mühlen C. Real-time magnetic resonance imaging - guided coronary intervention in a porcine model. Sci Rep. 2019 Jun 17;9(1):8663. doi: 10.1038/s41598-019-45154-7.

Koentges C, Cimolai MC, Pfeil K, Wolf D, Marchini T, Tarkhnishvili A, Hoffmannn MM, Odening KE, Diehl P, von Zur Mühlen C, Alvarez S, Bode C, Zirlik A, Bugger H. Impaired SIRT3 activity mediates cardiac dysfunction in endotoxemia by calpain-dependent disruption of ATP synthesis. J Mol Cell Cardiol. 2019 Aug;133:138-147.

Stachon P, Kaier K, Heidt T, Bothe W, Zirlik A, Zehender M, Bode C, von Zur Mühlen C. Nationwide outcomes of aortic valve replacement for pure aortic regurgitation in Germany 2008-2015. Catheter Cardiovasc Interv. 2019 Jun 4. [Epub ahead of print].

Stachon P, Kaier K, Zirlik A, Bothe W, Heidt T, Zehender M, Bode C, von Zur Mühlen C. Risk-Adjusted Comparison of In-Hospital Outcomes of Transcatheter and Surgical Aortic Valve Replacement. J Am Heart Assoc. 2019 Apr 2;8(7):e011504.

Hehrlein C, Schorch B, Kress N, Arab A, von Zur Mühlen C, Bode C, Epting T, Haberstroh J, Mey L, Schwarzbach H, Kinscherf R, Stachniss V, Schiestel S, Kovacs A, Fischer H, Nennig E. Zn-alloy provides a novel platform for mechanically stable bioresorbable vascular stents. PLoS One. 2019 Jan 2;14(1):e0209111.

Kaier K, von Zur Mühlen C, Zirlik A, Bothe W, Hehn P, Zehender M, Bode C, Stachon P. Estimating the additional costs per life saved due to transcatheter aortic valve replacement: a secondary data analysis of electronic health records in Germany. Eur J Health Econ. 2019 Jun;20(4):625-632.

2018

Merz J, Albrecht P, von Garlen S, Ahmed I, Dimanski D, Wolf D, Hilgendorf I, Härdtner C, Grotius K, Willecke F, Heidt T, Bugger H, Hoppe N, Kintscher U, von Zur Mühlen C, Idzko M, Bode C, Zirlik A, Stachon P. Purinergic receptor Y(2) (P2Y(2))- dependent VCAM-1 expression promotes immune cell infiltration in metabolic syndrome. Basic Res Cardiol. 2018 Oct 18;113(6):45.

Kaier K, von zur Mühlen C, Zirlik A, Schmoor C, Roth K, Bothe W, Hehn P, Reinöhl J, Zehender M, Bode C, Stachon P. Sex-Specific Differences in Outcome of Transcatheter or Surgical Aortic Valve Replacement. Can J Cardiol. 2018, Aug;34(8):992-998.

Kaier K, Oettinger V, Reinecke H, Schmoor C, Frankenstein L, Vach W, Hehn P, von zur Mühlen C, Bode C, Zehender M, Reinöhl J. Volume-outcome relationship in transcatheter aortic valve implantations in Germany 2008-2014: a secondary data analysis of electronic health records. BMJ Open. 2018 Jul 28;8(7):e020204.

Stachon P, Zehender M, Bode C, von zur Mühlen C, Kaier K. Development and In-Hospital Mortality of Transcatheter and Surgical Aortic Valve Replacement in 2015 in Germany. J Am Coll Cardiol. 2018 Jul 24;72(4):475-476.

Stachon P, Kaier K, Zirlik A, Reinöhl J, Heidt T, Bothe W, Hehn P, Zehender M, Bode C, von zur Mühlen C. Risk factors and outcome of postoperative delirium after transcatheter aortic valve replacement. Clin Res Cardiol. 2018 Apr 13. In press.

Wolf D, Anto-Michel N, Blankenbach H, Wiedemann A, Buscher K, Hohmann JD, Lim  B, Bäuml M, Marki A, Mauler M, Duerschmied D, Fan Z, Winkels H, Sidler D, Diehl P, Zajonc DM, Hilgendorf I, Stachon P, Marchini T, Willecke F, Schell M, Sommer B, von zur Mühlen C, Reinöhl J, Gerhardt T, Plow EF, Yakubenko V, Libby P, Bode C, Ley K, Peter K, Zirlik A. A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense. Nat Commun. 2018 Feb 6;9(1):525.

von zur Mühlen C, Reiss S, Krafft AJ, Besch L, Menza M, Zehender M, Heidt T, Maier A, Pfannebecker T, Zirlik A, Reinöhl J, Stachon P, Hilgendorf I, Wolf D, Diehl P, Wengenmayer T, Ahrens I, Bode C, Bock M. Coronary magnetic resonance imaging after routine implantation of bioresorbable vascular scaffolds allows non-invasive evaluation of vascular patency. PLoS One. 2018 Jan 25;13(1):e0191413.

Anto Michel N, Colberg C, Buscher K, Sommer B, Pramod AB, Ehinger E, Dufner B, Hoppe N, Pfeiffer K, Marchini T, Willecke F, Stachon P, Hilgendorf I, Heidt T, von zur Mühlen C, von Elverfeldt D, Pfeifer D, Schüle R, Kintscher U, Brachs S, Ley K, Bode C, Zirlik A, Wolf D. Inflammatory Pathways Regulated by Tumor Necrosis Receptor-Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced Obesity. Circ Res. 2018 Mar 2;122(5):693-700.

2017

Maier A, Plaza-Heck P, Meixner F, Guenther F, Kaufmann BA, Kramer M, Heidt T, Zirlik A, Hilgendorf I, Reinöhl J, Stachon P, Bronsert P, Birkemeyer R, Neudorfer I, Peter K, Bode C, von zur Mühlen C. A molecular intravascular ultrasound contrast agent allows detection of activated platelets on the surface of symptomatic human plaques. Atherosclerosis. 2017 Dec;267:68-77.

Kaier K, von Kampen F, Baumbach H, von zur Mühlen C, Hehn P, Vach W, Zehender M, Bode C, Reinöhl J: Two-year post-discharge costs of care among patients treated with transcatheter or surgical aortic valve replacement in Germany. BMC Health Serv Res. 2017 Jul 11;17(1):473.

Gutmann A, Kaier K, Reinecke H, Frankenstein L, Zirlik A, Bothe W, von zur Mühlen C, Zehender M, Reinöhl J, Bode C, Stachon P: Impact of pulmonary hypertension on in-hospital outcome after surgical or transcatheter aortic valve  replacement. EuroIntervention. 2017 Apr 25. pii: EIJ-D-16-00927. [Epub ahead of print].

Stachon P, Heidenreich A, Merz J, Hilgendorf I, Wolf D, Willecke F, von Garlen S, Albrecht P, Härdtner C, Ehrat N, Hoppe N, Reinöhl J, von zur Mühlen C, Bode C, Idzko M, Zirlik A: P2X(7) Deficiency Blocks Lesional Inflammasome Activity and Ameliorates Atherosclerosis in Mice. Circulation. 2017 Jun 20;135(25):2524-2533.

Htun NM, Magliano DJ, Zhang ZY, Lyons J, Petit T, Nkuipou-Kenfack E, Ramirez-Torres A, von zur Mühlen C, Maahs D, Schanstra JP, Pontillo C, Pejchinovski M, Snell-Bergeon JK, Delles C, Mischak H, Staessen JA, Shaw JE, Koeck T, Peter K: Prediction of acute coronary syndromes by urinary proteome analysis. PLoS One. 2017 Mar 8;12(3):e0172036.

Wolf D, Bukosza N, Engel D, Poggi M, Jehle F, Anto Michel N, Chen YC, Colberg C, Hoppe N, Dufner B, Boon L, Blankenbach H, Hilgendorf I, von zur Muhlen C, Reinöhl J, Sommer B, Marchini T, Febbraio MA, Weber C, Bode C, Peter K, Lutgens E, Zirlik A: Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11b/CD18) in diet-induced obesity (DIO). Thromb Haemost. 2017 Jan 26;117(2):325-338.

2016

Reinöhl J, Kaier K, Reinecke H, Frankenstein L, Zirlik A, Zehender M, von zur Mühlen C, Bode C, Stachon P: Transcatheter Aortic Valve Replacement: The New Standard in Patients With Previous Coronary Bypass Grafting? JACC Cardiovasc Interv. 2016 Oct 24;9(20):2137-2143.

Kaier K, Gutmann A, Baumbach H, von zur Mühlen C, Hehn P, Vach W, Beyersdorf F, Zehender M, Bode C, Reinöhl J: Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement- a model-based longitudinal data analysis. Health Qual Life Outcomes. 2016 Jul 26;14(1):109.

Stachon P, Geis S, Peikert A, Heidenreich A, Michel NA, Ünal F, Hoppe N, Dufner B, Schulte L, Marchini T, Cicko S, Ayata K, Zech A, Wolf D, Hilgendorf I, Willecke F, Reinöhl J, von zur Mühlen C, Bode C, Idzko M, Zirlik A: Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor Y2 in Mice. Arterioscler Thromb Vasc Biol. 2016 Aug;36(8):1577-86.

Wehrum T, Hagenlocher P, Lodemann T, Vach W, Dragonu I, Hennemuth A, von zur Mühlen C, Stuplich J, Ngo BT, Harloff A: Age dependence of pulmonary artery blood flow measured by 4D flow cardiovascular magnetic resonance: results of a population-based study. J Cardiovasc Magn Reson. 2016 May 31;18(1):31.

Marchini T, Wolf D, Michel NA, Mauler M, Dufner B, Hoppe N, Beckert J, Jäckel M, Magnani N, Duerschmied D, Tasat D, Alvarez S, Reinöhl J, von zur Mühlen C, Idzko M, Bode C, Hilgendorf I, Evelson P, Zirlik A: Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages. Basic Res Cardiol. 2016 Jul;111(4):44.

Heidt T, Ehrismann S, Hövener JB, Neudorfer I, Hilgendorf I, Reisert M, Hagemeyer CE, Zirlik A, Reinöhl J, Bode C, Peter K, von Elverfeldt D, von zur Mühlen C: Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging. Sci Rep. 2016 May 3;6:25044.

von zur Mühlen C, Koeck T, Schiffer E, Sackmann C, Zürbig P, Hilgendorf I, Reinöhl J, Rivera J, Zirlik A, Hehrlein C, Mischak H, Bode C, Peter K: Urine proteome analysis as a discovery tool in patients with deep vein thrombosis and pulmonary embolism. Proteomics Clin Appl. 2016 May;10(5):574-84.

Lindau A, Härdtner C, Hergeth SP, Blanz KD, Dufner B, Hoppe N, Anto-Michel N, Kornemann J, Zou J, Gerhardt LM, Heidt T, Willecke F, Geis S, Stachon P, Wolf D, Libby P, Swirski FK, Robbins CS, McPheat W, Hawley S, Braddock M, Gilsbach R, Hein L, von zur Mühlen C, Bode C, Zirlik A, Hilgendorf I: Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression. Basic Res Cardiol. 2016 Mar;111(2):20.

Reinöhl J, Psyrakis D, Kaier K, Kodirov S, Siepe M, Gutmann A, von zur Mühlen C, Moser M, Ahrens I, Pache G, Zirlik A, Langer M, Beyersdorf F, Zehender M, Bode C, Blanke P: Aortic root volume is associated with contained rupture of the aortic annulus in balloon-expandable transcatheter aortic valve replacement. Catheter Cardiovasc Interv. 2016 Mar;87(4):807-17.

2003-2015

Reinöhl J, Kaier K, Gutmann A, Sorg S, von zur Mühlen C, Siepe M, Baumbach H, Moser M, Geibel A, Zirlik A, Blanke P, Vach W, Beyersdorf F, Bode C, Zehender M: In-hospital resource utilization in surgical and transcatheter aortic valve replacement. BMC Cardiovasc Disord. 2015 Oct 22;15:132.

Reinöhl J, Pache G, Ahrens I, Heidt T, Psyrakis D, Latib A, De Marco F, Schröfel H, Beyersdorf F, Zehender M, Bode C, von zur Mühlen C: Preprocedural planning and implantation of a transcatheter aortic valve without the use of contrast agent. EuroIntervention. 2016 Mar;11(12):1433.

Meier S, Pütz G, Massing U, Hagemeyer CE, von Elverfeldt D, Meissner M, Ardipradja K, Barnert S, Peter K, Bode C, Schubert R, von zur Muhlen C: Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis. Biomaterials. 2015 Jun;53:137-48.

Reiss S, Krafft AJ, Zehender M, Heidt T, Pfannebecker T, Bode C, Bock M, von zur Muhlen C. Magnetic resonance imaging of bioresorbable vascular scaffolds: potential approach for noninvasive evaluation of coronary patency. Circ Cardiovasc Interv. 2015 Apr;8(4). pii: e002388. doi: 10.1161/CIRCINTERVENTIONS.115.002388. PubMed PMID: 25794509.

Stachon P, Kaier K, Milde S, Pache G, Sorg S, Siepe M, von zur Mühlen C, Zirlik A, Beyersdorf F, Langer M, Zehender M, Bode C, Reinöhl J: Two-year survival of patients screened for transcatheter aortic valve replacement with potentially malignant incidental findings in initial body computed tomography. Eur Heart J Cardiovasc Imaging. 2015 Jul;16(7):731-7.

Kaier K, Gutmann A, Vach W, Sorg S, Siepe M, von zur Mühlen C, Moser M, Blanke P, Beyersdorf F, Zehender M, Bode C, Reinöhl J: "Heart Team" decision making in elderly patients with symptomatic aortic valve stenosis who underwent AVR or TAVI - a look behind the curtain. Results of the prospective TAVI Calculation of Costs Trial (TCCT). EuroIntervention. 2015 Nov;11(7):793-8.

Gutmann A, Kaier K, Sorg S, von zur Mühlen C, Siepe M, Moser M, Geibel A, Zirlik A, Ahrens I, Baumbach H, Beyersdorf F, Vach W, Zehender M, Bode C, Reinöhl J: Analysis of the additional costs of clinical complications in patients undergoing transcatheter aortic valve replacement in the German Health Care System. Int J Cardiol. 2015 Jan 20;179:231-7.

Stachon P, Peikert A, Michel NA, Hergeth S, Marchini T, Wolf D, Dufner B, Hoppe N, Ayata CK, Grimm M, Cicko S, Schulte L, Reinöhl J, von zur Muhlen C, Bode C, Idzko M, Zirlik A: P2Y6 deficiency limits vascular inflammation and atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2237-45.
Heidt T, Sager HB, Courties G, Dutta P, Iwamoto Y, Zaltsman A, von zur Muhlen C, Bode C, Fricchione GL, Denninger J, Lin CP, Vinegoni C, Libby P, Swirski FK, Weissleder R, Nahrendorf M: Chronic variable stress activates hematopoietic stem cells. Nat Med. 2014 Jul;20(7):754-758.

von Elverfeldt D, Maier A, Duerschmied D, Braig M, Witsch T, Wang X, Mauler M, Neudorfer I, Menza M, Idzko M, Zirlik A, Heidt T, Bronsert P, Bode C, Peter K, von zur Muhlen C: Dual-contrast molecular imaging allows noninvasive characterization of myocardial ischemia/reperfusion injury after coronary vessel occlusion in mice by magnetic resonance imaging. Circulation. 2014 Aug 19;130(8):676-87.

Wolf D, Jehle F, Michel NA, Bukosza EN, Rivera J, Chen YC, Hoppe N, Dufner B, Rodriguez AO, Colberg C, Nieto L, Rupprecht B, Wiedemann A, Schulte L, Peikert A, Bassler N, Lozhkin A, Hergeth SP, Stachon P, Hilgendorf I, Willecke F, von zur Mühlen C, von Elverfeldt D, Binder CJ, Aichele P, Varo N, Febbraio MA, Libby P, Bode C, Peter K, Zirlik A: Coinhibitory suppression of T cell activation by CD40 protects against obesity and adipose tissue inflammation in mice. Circulation. 2014 Jun 10;129(23):2414-25.

Willecke F, Tiwari S, Rupprecht B, Wolf D, Hergeth S, Hoppe N, Dufner B, Schulte L, Anto Michel N, Bukosza N, Marchini T, Jäckel M, Stachon P, Hilgendorf I, Zeschky K, Schleicher R, Langer HF, von zur Muhlen C, Bode C, Peter K, Zirlik A: Interruption of classic CD40L-CD40 signalling but not of the novel CD40L-Mac-1 interaction limits arterial neointima formation in mice. Thromb Haemost. 2014 Aug;112(2):379-89.

Guenther F, Herr N, Mauler M, Witsch T, Roming F, Hein L, Boeynaems JM, Robaye B, Idzko M, Bode C, von zur Muhlen C, Duerschmied D: Contrast ultrasound for the quantification of deep vein thrombosis in living mice: effects of enoxaparin and P2Y12 receptor inhibition. J Thromb Haemost. 2013 Jun;11(6):1154-62.

Fink K, Busch HJ, Bourgeois N, Schwarz M, Wolf D, Zirlik A, Peter K, Bode C, von zur Muhlen C: Mac-1 directly binds to the endothelial protein C-receptor: a link between the protein C anticoagulant pathway and inflammation? PLoS One. 2013;8(2):e53103. doi: 10.1371/journal.pone.0053103. Epub 2013 Feb 7.

Reinöhl J, Gutmann A, Kollum M, von zur Mühlen C, Baumbach H, Avlar M, Moser M, Bode C, Zehender M: Transfemoral aortic valve implantation: bleeding events, related costs and outcomes. J Thromb Thrombolysis. 2013 May;35(4):469-75.

von Elverfeldt D, von zur Muhlen C, Wiens K, Neudorfer I, Zirlik A, Meissner M, Tilly P, Charles AL, Bode C, Peter K, Fabre JE: In vivo detection of activated platelets allows characterizing rupture of atherosclerotic plaques with molecular magnetic resonance imaging in mice. PLoS One. 2012;7(9):e45008.

von Elverfeldt D, Meissner M, Peter K, Paul D, Meixner F, Neudorfer I, Merkle A, Harloff A, Zirlik A, Schöllhorn J, Markl M, Hennig J, Bode C, von zur Muhlen C: An approach towards molecular imaging of activated platelets allows imaging of symptomatic human carotid plaques in a new model of a tissue flow chamber. Contrast Media Mol Imaging. 2012 Mar-Apr;7(2):204-13.

Wolf D, Jehle F, Ortiz Rodriguez A, Dufner B, Hoppe N, Colberg C, Lozhkin A, Bassler N, Rupprecht B, Wiedemann A, Hilgendorf I, Stachon P, Willecke F, Febbraio M, von zur Muhlen C, Binder CJ, Bode C, Zirlik A, Peter K: CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies. PLoS One. 2012;7(3):e33026.

von zur Muhlen C, Schiffer E, Sackmann C, Zürbig P, Neudorfer I, Zirlik A, Htun N, Iphöfer A, Jänsch L, Mischak H, Bode C, Chen YC, Peter K: Urine proteome analysis reflects atherosclerotic disease in an ApoE-/- mouse model and allows the discovery of new candidate biomarkers in mouse and human atherosclerosis. Mol Cell Proteomics. 2012 Jul;11(7):M111.013847.

Wolf D, Hohmann JD, Wiedemann A, Bledzka K, Blankenbach H, Marchini T, Gutte K, Zeschky K, Bassler N, Hoppe N, Rodriguez AO, Herr N, Hilgendorf I, Stachon P, Willecke F, Duerschmied D, von zur Muhlen C, Soloviev DA, Zhang L, Bode C, Plow EF, Libby P, Peter K, Zirlik A: Binding of CD40L to Mac-1's I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis--but does not affect immunity and thrombosis in mice. Circ Res. 2011 Nov 11;109(11):1269-79.

Ta HT, Prabhu S, Leitner E, Jia F, von Elverfeldt D, Jackson KE, Heidt T, Nair AK, Pearce H, von zur Muhlen C, Wang X, Peter K, Hagemeyer CE: Enzymatic single-chain antibody tagging: a universal approach to targeted molecular imaging and cell homing in cardiovascular disease. Circ Res. 2011 Aug 5;109(4):365-73.

Hilgendorf I, Eisele S, Remer I, Schmitz J, Zeschky K, Colberg C, Stachon P, Wolf D, Willecke F, Buchner M, Zirlik K, Ortiz-Rodriguez A, Lozhkin A, Hoppe N, von zur Muhlen C, zur Hausen A, Bode C, Zirlik A: The oral spleen tyrosine kinase inhibitor fostamatinib attenuates inflammation and atherogenesis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):1991-9.

Duerschmied D, Meißner M, Peter K, Neudorfer I, Roming F, Zirlik A, Bode C, von Elverfeldt D, von zur Muhlen C: Molecular magnetic resonance imaging allows the detection of activated platelets in a new mouse model of coronary artery thrombosis. Invest Radiol. 2011 Oct;46(10):618-23.

Willecke F, Zeschky K, Ortiz Rodriguez A, Colberg C, Auwärter V, Kneisel S, Hutter M, Lozhkin A, Hoppe N, Wolf D, von zur Mühlen C, Moser M, Hilgendorf I, Bode C, Zirlik A: Cannabinoid receptor 2 signaling does not modulate atherogenesis in mice. PLoS One. 2011 Apr 26;6(4):e19405.

Heidt T, Deininger F, Peter K, Goldschmidt J, Pethe A, Hagemeyer CE, Neudorfer I, Zirlik A, Weber WA, Bode C, Meyer PT, Behe M, von zur Mühlen C: Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody. PLoS One. 2011 Mar 30;6(3):e18446.

von zur Muhlen C, Fink-Petri A, Salaklang J, Paul D, Neudorfer I, Berti V, Merkle A, Peter K, Bode C, von Elverfeldt D: Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI. Contrast Media Mol Imaging. 2010 Sep-Oct;5(5):268-75.

Delles C, Schiffer E, von zur Muhlen C, Peter K, Rossing P, Parving HH, Dymott JA, Neisius U, Zimmerli LU, Snell-Bergeon JK, Maahs DM, Schmieder RE, Mischak H, Dominiczak AF: Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals. J Hypertens. 2010 Nov;28(11):2316-22.

Guenther F, von zur Muhlen C, Ferrante EA, Grundmann S, Bode C, Klibanov AL: An ultrasound contrast agent targeted to P-selectin detects activated platelets at supra-arterial shear flow conditions. Invest Radiol. 2010 Oct;45(10):586-91.

Stachon P, Missiou A, Walter C, Varo N, Colberg C, Wolf D, Buchner M, von zur Mühlen C, Zirlik K, Bode C, Zirlik A: Tumor necrosis factor receptor associated factor 6 is not required for atherogenesis in mice and does not associate with atherosclerosis in humans. PLoS One. 2010 Jul 14;5(7):e11589.

Fink K, Schwarz M, Feldbrügge L, Sunkomat JN, Schwab T, Bourgeois N, Olschewski M, von zur Mühlen C, Bode C, Busch HJ: Severe endothelial injury and subsequent repair in patients after successful cardiopulmonary resuscitation. Crit Care. 2010; 14(3):R104.

Markl M, Arnold R, Hirtler D, von zur Muhlen C, Harloff A, Langer M, Hennig J, Frydrychowicz A: Three-dimensional flow characteristics in aortic coarctation and poststenotic dilatation. J Comput Assist Tomogr. 2009 Sep-Oct; 33(5):776-8.

Eisenhardt SU, Habersberger J, Murphy A, Chen YC, Woollard KJ, Bassler N, Qian H, von zur Muhlen C, Hagemeyer CE, Ahrens I, Chin-Dusting J, Bobik A, Peter K: Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques. Circ Res. 2009 Jul 17;105(2):128-37.

von zur Muhlen C, Schiffer E, Zuerbig P, Kellmann M, Brasse M, Meert N, Vanholder RC, Dominiczak AF, Chen YC, Mischak H, Bode C, Peter K: Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients. J Proteome Res. 2009 Jan;8(1):335-45.

von zur Muhlen C, von Elverfeldt D, Choudhury RP, Ender J, Ahrens I, Schwarz M, Hennig J, Bode C, Peter K: Functionalized magnetic resonance contrast agent selectively binds to glycoprotein IIb/IIIa on activated human platelets under flow conditions and is detectable at clinically relevant field strengths. Mol Imaging. 2008 Mar-Apr; 7(2):59-67.

von zur Muhlen C, von Elverfeldt D, Moeller JA, Choudhury RP, Paul D, Hagemeyer CE, Olschewski M, Becker A, Neudorfer I, Bassler N, Schwarz M, Bode C, Peter K: Magnetic resonance imaging contrast agent targeted toward activated platelets allows in vivo detection of thrombosis and monitoring of thrombolysis. Circulation. 2008 Jul 15;118(3):258-67.

von zur Muhlen C, Peter K, Ali ZA, Schneider JE, McAteer MA, Neubauer S, Channon KM, Bode C, Choudhury RP: Visualization of activated platelets by targeted magnetic resonance imaging utilizing conformation-specific antibodies against glycoprotein IIb/IIIa. J Vasc Res. 2009; 46(1):6-14.

von zur Muhlen C, Sibson NR, Peter K, Campbell SJ, Wilainam P, Grau GE, Bode C, Choudhury RP, Anthony DC: A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI. J Clin Invest. 2008 Mar; 118(3):1198-207.

McAteer MA, Schneider JE, Ali ZA, Warrick N, Bursill CA, von zur Muhlen C, Greaves DR, Neubauer S, Channon KM, Choudhury RP: Magnetic resonance imaging of endothelial adhesion molecules in mouse atherosclerosis using dual-targeted microparticles of iron oxide. Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):77-83.

McAteer MA, Sibson NR, von zur Muhlen C, Schneider JE, Lowe AS, Warrick N, Channon KM, Anthony DC, Choudhury RP: In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nat Med. 2007 Oct; 13(10):1253-8.

von zur Muhlen C, von Elverfeldt D, Bassler N, Neudorfer I, Steitz B, Petri-Fink A, Hofmann H, Bode C, Peter K: Superparamagnetic iron oxide binding and uptake as imaged by magnetic resonance is mediated by the integrin receptor Mac-1 (CD11b/CD18): implications on imaging of atherosclerotic plaques. Atherosclerosis. 2007 Jul; 193(1):102-11.

Nahrendorf M, Frantz S, Hu K, von zur Mühlen C, Tomaszewski M, Scheuermann H, Kaiser R, Jazbutyte V, Beer S, Bauer W, Neubauer S, Ertl G, Allolio B, Callies F: Effect of testosterone on post-myocardial infarction remodeling and function. Cardiovasc Res. 2003 Feb; 57(2):370-8.

Mentors and Collaborators

  • Prof. Dr. Dirk Westermann, University Heart Center Freiburg, Freiburg, Germany
  • Prof. em. Dr. Christoph Bode, University Heart Center Freiburg, Freiburg, Germany
  • Prof. Dr. Karlheinz Peter, Baker Heart Research Institute, Melbourne, Australia
  • Prof. Dr. Jürgen Hennig, University of Freiburg, Freiburg, Germany
  • Prof. Dr. Michael Bock, University of Freiburg, Freiburg, Germany
  • Prof. Dr. Harald Mischak, Mosaiques Diagnostics, Hannover, Germany
  • Prof. Dr. Philipp Meyer, Dept. of Nuclear Medicine, University Hospital Freiburg
  • Prof. Dr. Robin P. Choudhury, Oxford University, Oxford, UK
  • Prof. Dr. Stefan Neubauer, Oxford University, Oxford, UK
  • Prof. Dr. Matthias Nahrendorf, Harvard Medical School, Boston, USA
  • Prof. Dr. Jean-Etienne Fabre, University of Strassbourg, Strassbourg, Freiburg
  • Prof. Dr. Meinrad Gawaz, University of Tübingen, Tübingen, Germany
  • Prof. Dr. Andreas Zirlik, Universits Hospital Graz, Graz, Austria
  • Prof. Dr. Andreas Harloff, University of Freiburg, Freiburg, Germany
  • Prof. Dr. Uli Massing, Tumor Biology Center Freiburg, Germany
  • Prof. Dr. Jörg Busch, University of Freiburg, Freiburg, Germany
  • Prof. Dr. Dominik v. Elverfeldt [PubMed], University of Freiburg, Freiburg, Germany
  • PD Dr. Beat Kaufmann, Kantonssptial Basel, Schweiz
  • Dr. Martin Behe, PSI/ ETH Zürch, Villigen, Schweiz
  • Dr. Katrin Fink, University of Freiburg, Freiburg, Germany
  • Dr. Gerhard Pütz, University of Freiburg, Freiburg, Germany
  • Dr. Christoph Hagemeyer, Baker Heart Research Institute, Melbourne, Australia
  • Dr. Nicola Sibson, Oxford University, Oxford, UK
  • Dr. Eric Schiffer, Numares, Regensburg, Germany

Prof. Dr. C. von zur Mühlen
Telefon: 0761 270-70420
Telefax: 0761 270-70450
E-Mail: constantin.vonzurmuehlen@uniklinik-freiburg.de

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