Marc W Merx

Robert Koch Institut, Berlín, Berlin, Germany

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Publications (83)490.91 Total impact

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    ABSTRACT: Dual antiplatelet therapy (DAPT) is recommended early after transcatheter aortic valve implantation (TAVI) procedure at the moment despite the lack of evidence. Two small randomized trials failed to demonstrate DAPT to be superior to aspirin alone in TAVI patients. However, it is known that there are substantial response variabilities to antiplatelet medication. We aimed to investigate high on-treatment platelet reactivity (HTPR), respectively low on-treatment platelet reactivity (LTPR) to clopidogrel as well as HTPR to aspirin in patients undergoing TAVI procedure.
    European Journal of Pharmacology. 01/2015;
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    ABSTRACT: Aims: Degenerative aortic valve stenosis (AVS) is independently associated with endothelial dysfunction and increased levels of circulating endothelium-derived microparticles (EMPs) as a marker of compromised endothelial integrity. The aim of this study was to investigate whether therapy for severe AVS by transcatheter aortic valve implantation (TAVI) improves endothelial function and decreases EMPs. Methods and results: Fifty-six patients with indication for TAVI due to symptomatic severe AVS were prospectively enrolled. Brachial wall shear stress (WSS), endothelial function and circulating microparticles (MPs) were measured before and three months following TAVI. Endothelial function was assessed as flow-mediated dilation (FMD) using ultrasound. MP subpopulations were discriminated by flow cytometry according to the expression of established surface antigens: CD31+/CD41-, CD144+ and CD62E+ as EMPs and CD41+ as platelet-derived MPs (PMPs). In patients with severe AVS, decreased brachial WSS was an independent predictor of low FMD. At three-month follow-up after TAVI, WSS and FMD increased along with decreased levels of EMPs as compared to pre TAVI. Decrease of CD31+/CD41-, CD144+ and CD62E+ EMP levels correlated with the increase of FMD. Conclusions: Therapy for AVS by TAVI was associated with improved endothelial function and integrity indicating beneficial effects of TAVI on systemic arterial function.
    10/2014;
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    ABSTRACT: The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.
    PLoS ONE 07/2014; 9(7):e102648. · 3.53 Impact Factor
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    ABSTRACT: Aims: Introduction of a novel contrast injection protocol during rotational C-arm CT (RCT) in cardiac catheterisation of patients with aortic stenosis for aortic root assessment. Methods and results: Fifty-two patients underwent RCT imaging with contrast injection performed either into the aorta (Ao-RCT, n=25) or into the left ventricle (LV-RCT, n=27). Aortic annulus diameters were assessed in a multiplanar reconstruction view and compared with corresponding multidetector computed tomography (MDCT). LV contrast injection additionally enabled measurement of the left ventricular outflow tract (LVOT). LV-RCT improved the accuracy of annulus measurements and correlated well with MDCT data in comparison with Ao-RCT and MDCT (r=0.9 r=0.76, respectively). The Bland-Altman analysis showed smaller differences in MDCT and LV-RCT annulus measurements than between MDCT and Ao-RCT (LV-RCT: mean=0.4 mm, limits of agreement -1.5-2.3 mm vs. Ao-RCT: mean=0.1 mm, limits of agreement -3.4-3.6 mm). The inter-observer agreement for the annulus measurements was significantly increased for LV-RCT as calculated by the intra-class coefficient (ICC=0.85) in comparison with Ao-RCT (ICC=0.52). Conclusions: Cardiac catheterisation including LV-RCT offers complementary assessment of left ventricular function, aortic valve anatomy, coronary angiography and arterial access routes. LV-RCT for aortic root measurements shows better correlation to MDCT than standard Ao-RCT protocols.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 04/2014; · 3.17 Impact Factor
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    ABSTRACT: Pulmonary vascular injury is a rare but life-threatening complication of Swan-Ganz catheterization. We report an 82-year old patient who underwent right heart catheterization by a balloon-tipped catheter because of suspected pulmonary hypertension. After deflation of the catheter in the wedge position, hemoptoe appeared associated with acute respiratory insufficiency requiring respiratory support by intubation and mechanical ventilation. Pulmonary angiography showed the formation of a false aneurysm of a segment artery of the left lower lobe. Immediate interventional therapy was performed by the implantation of two coated coronary stent grafts into the injured pulmonary artery thereby excluding the false aneurysm. Bleeding was stopped by this interventional approach while antegrade blood flow was maintained. Long term follow-up after 3 months showed an effective treatment with a completely thrombotic false aneurysm. However, despite oral anticoagulation and dual antiplatelet therapy, graft patency could not be achieved after 3 months. In summary, implantation of coated stents is a feasible and safe approach for the acute and long term treatment of potentially life-threatening condition of a pulmonary artery false aneurysm while treatment to achieve long term patency of the affected vessel still remains an issue to be resolved.
    Case reports in pulmonology. 01/2014; 2014:893647.
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    ABSTRACT: Nitric oxide (NO) derived from endothelial NO synthase (NOS3) plays a central role in myocardial ischemia/reperfusion (I/R)-injury. Subsets of circulating blood cells, including red blood cells (RBCs), carry a NOS3 and contribute to blood pressure regulation and RBC nitrite/nitrate formation. We hypothesized that the circulating blood born NOS3 also modulates the severity of myocardial infarction in disease models. We cross-transplanted bone marrow in wild-type and NOS3(-/-) mice with wild-type mice, producing chimeras expressing NOS3 only in vascular endothelium (BC-/EC+) or in both blood cells and vascular endothelium (BC+/EC+). After 60-min closed-chest coronary occlusion followed by 24 h reperfusion, cardiac function, infarct size (IS), NOx levels, RBCs NO formation, RBC deformability, and vascular reactivity were assessed. At baseline, BC-/EC+ chimera had lower nitrite levels in blood plasma (BC-/EC+: 2.13 ± 0.27 μM vs. BC+/EC+ 3.17 ± 0.29 μM; *p < 0.05), reduced DAF FM associated fluorescence within RBCs (BC-/EC+: 538.4 ± 12.8 mean fluorescence intensity (MFI) vs. BC+/EC+: 619.6 ± 6.9 MFI; ***p < 0.001) and impaired erythrocyte deformability (BC-/EC+: 0.33 ± 0.01 elongation index (EI) vs. BC+/EC+: 0.36 ± 0.06 EI; *p < 0.05), while vascular reactivity remained unaffected. Area at risk did not differ, but infarct size was higher in BC-/EC+ (BC-/EC+: 26 ± 3 %; BC+/EC+: 14 ± 2 %; **p < 0.01), resulting in decreased ejection fraction (BC-/EC+ 46 ± 2 % vs. BC+/EC+: 52 ± 2 %; *p < 0.05) and increased end-systolic volume. Application of the NOS inhibitor S-ethylisothiourea hydrobromide was associated with larger infarct size in BC+/EC+, whereas infarct size in BC-/EC+ mice remained unaffected. Reduced infarct size, preserved cardiac function, NO levels in RBC and RBC deformability suggest a modulating role of circulating NOS3 in an acute model of myocardial I/R in chimeric mice.
    Archiv für Kreislaufforschung 01/2014; 109(1):398. · 5.96 Impact Factor
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    ABSTRACT: Dietary interventions with flavan-3-ols have shown beneficial effects on vascular function. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. Therefore, in the present study, we assessed the habitual intake of flavan-3-ol monomers, proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined their main food sources using the EFSA (European Food Safety Authority) Comprehensive European Food Consumption Database. Data for adults aged 18-64 years were available from fourteen European countries, and intake was determined using the FLAVIOLA Flavanol Food Composition Database, developed for the present study and based on the latest US Department of Agriculture and Phenol-Explorer databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d) and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main sources were tea (62 %), pome fruits (11 %), berries (3 %) and cocoa products (3 %). Tea was the major single contributor to monomer intake (75 %), followed by pome fruits (6 %). Pome fruits were also the main source of PA (28 %). The present study provides important data on the population-based intake of flavanols in the EU and demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and theaflavins vary significantly across European countries. The average habitual intake of flavan-3-ols is considerably below the amounts used in most dietary intervention studies.
    The British journal of nutrition 12/2013; · 3.45 Impact Factor
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    ABSTRACT: Pulmonary vein isolation (PVI) as a cornerstone for catheter ablation of atrial fibrillation (AF) remains a complex and time consuming procedure. The purpose of this study was to assess feasibility, safety and acute efficacy of a novel irrigated multielectrode ablation catheter guided by an electroanatomical mapping system for PVI in patients with paroxysmal AF. 25 consecutive patients (60 ± 10 years) with paroxysmal AF underwent PVI by using a novel decapolar mapping and ablation catheter (NMARQ). Ablation was guided by electroanatomical mapping allowing radiofrequency (RF) energy delivery in the antral region of pulmonary veins (PV) from 10 irrigated electrodes simultaneously. The day after ablation, cardiac magnetic resonance imaging (MRI) was performed routinely in order to assess for potential acute PV-stenosis. Overall, 97 of 97 targeted PV (100 %) could be isolated with a mean of 27 ± 11 RF applications and a mean total burning time of 15 ± 6 minutes per patient. The total procedure time from femoral vein access to catheter withdrawal was 110 ± 31 minutes including a mean total fluoroscopy time of 23 ± 9 minutes. On average, 6 ± 3 RF impulses with a maximum of 25 Watt were applied per vein. After a short learning curve procedure, fluoroscopy and total burning time decreased to 94 ± 16 minutes, 16 ± 3 minutes and 9 ± 2 minutes respectively (p<0.05). Entrance and exit block could be verified by placing the ablation catheter into 90 of 97 (93%) PVs in 18 of 25 (72%) patients. No procedure-related complications were observed, especially no acute PV stenosis could be detected. Use of a novel irrigated multielectrode ablation system for PVI is feasible and safe, resulting in acute isolation of all targeted PVs with no complications and short procedure times. Sustainability of these initial results has to be confirmed in long term efficacy and follow up trials.
    Heart rhythm: the official journal of the Heart Rhythm Society 12/2013; · 4.56 Impact Factor
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    ABSTRACT: Endothelial nitric oxide synthase (NOS)3-derived nitric oxide (NO) modulates inotropic response and diastolic interval for optimal cardiac performance under non-inflammatory conditions. In sepsis, excessive NO production plays a key role in severe hypotension and myocardial dysfunction. We aimed to determine the role of NOS3 on myocardial performance, NO production, and time course of sepsis development. NOS3(-/-) and C57BL/6 wildtype mice were rendered septic by cecum ligation and puncture (CLP). Cardiac function was analyzed by serial echocardiography, in vivo pressure and isolated heart measurements. Cardiac output (CO) increased to 160 % of baseline at 10 h after sepsis induction followed by a decline to 63 % of baseline after 18 h in wildtype mice. CO was unaltered in septic NOS3(-/-) mice. Despite the hyperdynamic state, cardiac function and mean arterial pressure were impaired in septic wildtype as early as 6 h post CLP. At 12 h, cardiac function in septic wildtype was refractory to catecholamines in vivo and respective isolated hearts showed impaired pressure development and limited coronary flow reserve. Hemodynamics remained stable in NOS3(-/-) mice leading to significant survival benefit. Unselective NOS inhibition in septic NOS3(-/-) mice diminished this survival benefit. Plasma NO( x )- and local myocardial NO( x )- and NO levels (via NO spin trapping) demonstrated enhanced NO( x )- and bioactive NO levels in septic wildtype as compared to NOS3(-/-) mice. Significant contribution by inducible NOS (NOS2) during this early phase of sepsis was excluded. Our data suggest that NOS3 relevantly contributes to bioactive NO pool in developing sepsis resulting in impaired cardiac contractility.
    Archiv für Kreislaufforschung 03/2013; 108(2):330. · 5.96 Impact Factor
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    ABSTRACT: Endothelial nitric oxide synthase (NOS)3-derived nitric oxide (NO) modulates inotropic response and diastolic interval for optimal cardiac performance under non-inflammatory conditions. In sepsis, excessive NO production plays a key role in severe hypotension and myocardial dysfunction. We aimed to determine the role of NOS3 on myocardial performance, NO production, and time course of sepsis development. NOS3(-/-) and C57BL/6 wildtype mice were rendered septic by cecum ligation and puncture (CLP). Cardiac function was analyzed by serial echocardiography, in vivo pressure and isolated heart measurements. Cardiac output (CO) increased to 160 % of baseline at 10 h after sepsis induction followed by a decline to 63 % of baseline after 18 h in wildtype mice. CO was unaltered in septic NOS3(-/-) mice. Despite the hyperdynamic state, cardiac function and mean arterial pressure were impaired in septic wildtype as early as 6 h post CLP. At 12 h, cardiac function in septic wildtype was refractory to catecholamines in vivo and respective isolated hearts showed impaired pressure development and limited coronary flow reserve. Hemodynamics remained stable in NOS3(-/-) mice leading to significant survival benefit. Unselective NOS inhibition in septic NOS3(-/-) mice diminished this survival benefit. Plasma NO( x )- and local myocardial NO( x )- and NO levels (via NO spin trapping) demonstrated enhanced NO( x )- and bioactive NO levels in septic wildtype as compared to NOS3(-/-) mice. Significant contribution by inducible NOS (NOS2) during this early phase of sepsis was excluded. Our data suggest that NOS3 relevantly contributes to bioactive NO pool in developing sepsis resulting in impaired cardiac contractility.
    Archiv für Kreislaufforschung 03/2013; 108(2):330. · 5.96 Impact Factor
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    [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial nitric oxide synthase (NOS)3-derived nitric oxide (NO) modulates inotropic response and diastolic interval for optimal cardiac performance under non-inflammatory conditions. In sepsis, excessive NO production plays a key role in severe hypotension and myocardial dysfunction. We aimed to determine the role of NOS3 on myocardial performance, NO production, and time course of sepsis development. NOS3(-/-) and C57BL/6 wildtype mice were rendered septic by cecum ligation and puncture (CLP). Cardiac function was analyzed by serial echocardiography, in vivo pressure and isolated heart measurements. Cardiac output (CO) increased to 160 % of baseline at 10 h after sepsis induction followed by a decline to 63 % of baseline after 18 h in wildtype mice. CO was unaltered in septic NOS3(-/-) mice. Despite the hyperdynamic state, cardiac function and mean arterial pressure were impaired in septic wildtype as early as 6 h post CLP. At 12 h, cardiac function in septic wildtype was refractory to catecholamines in vivo and respective isolated hearts showed impaired pressure development and limited coronary flow reserve. Hemodynamics remained stable in NOS3(-/-) mice leading to significant survival benefit. Unselective NOS inhibition in septic NOS3(-/-) mice diminished this survival benefit. Plasma NO( x )- and local myocardial NO( x )- and NO levels (via NO spin trapping) demonstrated enhanced NO( x )- and bioactive NO levels in septic wildtype as compared to NOS3(-/-) mice. Significant contribution by inducible NOS (NOS2) during this early phase of sepsis was excluded. Our data suggest that NOS3 relevantly contributes to bioactive NO pool in developing sepsis resulting in impaired cardiac contractility.
    Archiv für Kreislaufforschung 03/2013; 108(2):330. · 5.96 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    ABSTRACT: Introduction Murine arterial graft models are being used to uncover the inflammatory reactions of the vessel wall after surgery and the herein involved mediators. The aim of this study was to establish a model of transplantation-induced atherosclerosis after aortic transplantation. Methods Mice on a C57BL/6-background (n = 14) underwent infrarenal, orthotopic aortic transplantation. A group of sham animals (n = 10) served as controls. These groups of mice were kept on normal chow. In addition, apolipoprotein E-deficient (ApoE-/-) mice were employed (n = 5) that were fed a high fat diet immediately after surgery for 4 weeks. Results Ultrasound analyses and immunohistochemical analyses of the transplanted aorta revealed no major changes in morphology and function of C57BL/6 mice. In contrast, ApoE-/- mice developed marked intimal hyperplasia, with signs of monocyte/macrophage and smooth muscle cell infiltrations. Conclusion While C57BL/6 mice showed no significant changes in the aorta after transplantation, ApoE-/- mice on a high fat diet displayed signs of transplant atherosclerosis. Hence, this model provides an experimental basis for studying the pathogenesis of chronic atherosclerotic vessel wall remodeling after transplantation. This may also be useful for elucidating new therapeutic targets for the treatment of this disease.
    Gefässchirurgie 12/2012; · 0.24 Impact Factor
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    Free Radical Biology and Medicine 11/2012; 53:S13. · 5.71 Impact Factor
  • Marc Merx, Malte Kelm
    Free Radical Biology and Medicine 11/2012; 53:S11. · 5.71 Impact Factor
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    ABSTRACT: Transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve (MCV) system might represent an alternative to conventional redo surgery in older high-risk patients with a failing aortic valve bioprosthesis. Symptomatic patients with failing aortic valve bioprosthesis, aged ≥65 years with a logistic EuroSCORE ≥10 % were considered for treatment. Local anesthesia was used to retrogradely implant the MCV system into the failing bioprosthetic valve. Clinical events were recorded and a transthoracic echocardiography was performed to evaluate the impact of MCV on hemodynamics after transcatheter aortic valve implantation. A total of 27 patients (aged 74.8±8 years, logistic EuroSCORE of 31±17%) were treated. In those with AS and AS and AR (n=25), the mean gradient declined from 42±16 mm Hg before to 18±8 mm Hg after MCV implantation (P<0.001), in those with AR the level declined by 2. There was no intraprocedural death and no procedural myocardial infarction. On the basis of the definitions of the Valvular Academic Research Consortium, the rate of major stroke was 7.4 %, of life-threatening bleeding 7.4%, of kidney failure stage III 7.4%, and of major access site complication 11.1 %, respectively. Within 30 days after the procedure, 2 patients died; 1 from stroke and 1 from cardiac failure (30-day mortality: 7.4%). THESE RESULTS SUGGEST THAT TRANSFEMORAL MCV IMPLANTATION INTO A WIDE RANGE OF DEGENERATED AORTIC BIOPROSTHETIC VALVES: IRRESPECTIVE OF THE FAILURE MODE: is feasible, safe, and improves hemodynamics in older patients with higher risk for conventional aortic valve redo surgery.
    Circulation Cardiovascular Interventions 10/2012; 5(5):689-97. · 6.54 Impact Factor
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    ABSTRACT: To characterize the time course of tumor necrosis factor-α (TNF-α) serum levels along with myocardial perfusion and contractile function in patients with ST-segment elevation myocardial infarction (STEMI) and successful primary percutaneous coronary intervention (PCI). Serum levels of TNF-α, interleukin 6 (IL-6), and C-reactive protein (CRP) were measured in 42 patients with STEMI before, one and 6 days after successful PCI. Myocardial perfusion was assessed by contrast-enhanced echocardiography (ceEcho), contractile function by unenhanced two-dimensional (2DE) and real-time three-dimensional echocardiography. In a subset of 18 patients, infarct size was quantified by late gadolinium enhancement cardiovascular magnetic resonance imaging (LGE-CMR) on day six. TNF-α serum levels were in the upper normal range within the first 12 h from symptom onset and increased continuously until day six, while IL-6 and CRP increased subsequently with a peak on day one after STEMI. Serum TNF-α on day one after PCI correlated with perfusion defects, wall motion abnormalities, and infarct size (ceEcho: r = 0.52, p = 0.005; 2DE: r = 0.56, p = 0.002; LGE-CMR: r = 0.83-0.86; p < 0.0001). Using multiple regression linear analysis, infarct size on day six was predicted by serum TNF-α 1 day after PCI (p = 0.006, adjusted R (2) 0.638). Our data reflect the clinical significance of early TNF-α elevation in patients with STEMI and primary PCI (Controlled Clinical Trials number, NCT00529607).
    Clinical Research in Cardiology 05/2012; 101(10):815-27. · 4.17 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P97. · 4.44 Impact Factor
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    ABSTRACT: Here we assess the intrinsic functions of the chemokine receptor CXCR4 in remodeling after myocardial infarction (MI) using Cxcr4 heterozygous (Cxcr4(+/-)) mice. Myocardial necrosis triggers complex remodeling and inflammatory changes. The chemokine CXCL12 has been implicated in protection and therapeutic regeneration after MI through recruiting angiogenic outgrowth cells, improving neovascularization and cardiac function, but the endogenous role of its receptor CXCR4 is unknown. MI was induced by ligation of the left descending artery. Langendoff perfusion, echocardiography, quantitative immunohistochemistry, flow cytometry, angiogenesis assays, and cardiomyocyte analysis were performed. After 4 weeks, infarct size was reduced in Cxcr4(+/-) mice compared with wild-type mice and in respective bone marrow chimeras compared with controls. This was associated with altered inflammatory cell recruitment, decreased neutrophil content, delayed monocyte infiltration, and a predominance of Gr1(low) over classic Gr1(high) monocytes. Basal coronary flow and its recovery after MI were impaired in Cxcr4(+/-)mice, paralleled by reduced angiogenesis, myocardial vessel density, and endothelial cell count. Notably, no differences in cardiac function were seen in Cxcr4(+/-)mice compared with wild-type mice. Despite defective angiogenesis, Cxcr4(+/-) mouse hearts showed no difference in CXCL12, vascular endothelial growth factor or apoptosis-related gene expression. Electron microscopy revealed lipofuscin-like lipid accumulation in Cxcr4(+/-) mouse hearts and analysis of lipid extracts detected high levels of phosphatidylserine, which protect cardiomyocytes from hypoxic stress in vitro. CXCR4 plays a crucial role in endogenous remodeling processes after MI, contributing to inflammatory/progenitor cell recruitment and neovascularization, whereas its deficiency limits infarct size and causes adaptation to hypoxic stress. This should be carefully scrutinized when devising therapeutic strategies involving the CXCL12/CXCR4 axis.
    Journal of the American College of Cardiology 11/2011; 58(23):2415-23. · 15.34 Impact Factor

Publication Stats

2k Citations
490.91 Total Impact Points

Institutions

  • 2014
    • Robert Koch Institut
      Berlín, Berlin, Germany
  • 2010–2014
    • Universitätsklinikum Düsseldorf
      • Klinik für Kardiologie, Pneumologie und Angiologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2001–2013
    • Heinrich-Heine-Universität Düsseldorf
      • • Nuklearmedizinische Klinik
      • • Institut für Herz- und Kreislaufphysiologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1999–2012
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1995–2011
    • RWTH Aachen University
      • • Department of Cardiology, Pneumology, Angiology and Intensive Care (Internal Medicine I)
      • • Institute of Medical Statistics
      • • Institute for Molecular Cardiovascular Research
      • • Institute of Clinical Chemistry and Pathobiochemistry
      Aachen, North Rhine-Westphalia, Germany