Thorax Center

Berlin, Germany

Thorax Center

Berlin, Germany

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Jansen K.,Thorax Center | Jansen K.,Interuniversity Cardiology Institute of the Netherlands Netherlands Heart Institute | Van Der Steen A.F.W.,Thorax Center | Van Der Steen A.F.W.,Interuniversity Cardiology Institute of the Netherlands Netherlands Heart Institute | And 11 more authors.
Journal of Biomedical Optics | Year: 2014

The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue. © 2014 Society of Photo-Optical Instrumentation Engineers.


PubMed | University of Southern California, National University of Singapore, Erasmus University Rotterdam and Thorax Center
Type: Journal Article | Journal: Journal of biomedical optics | Year: 2014

The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.


Semper H.,Thorax Center | Muehlberg F.,Max Delbrück Center for Molecular Medicine | Schulz-Menger J.,Max Delbrück Center for Molecular Medicine | Allewelt M.,Thorax Center | Grohe C.,Thorax Center
Lung Cancer | Year: 2016

Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response. © 2016 Elsevier Ireland Ltd


Vos H.J.,Thorax Center | Vos H.J.,TNO | Goertz D.E.,Thorax Center | Goertz D.E.,University of Toronto | And 5 more authors.
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control | Year: 2011

This study investigates the use of an acoustic parametric array as a means for microbubble excitation. The excitation wave is generated during propagation in a nonlinear medium of two high-frequency carrier waves, whereby the frequency of the excitation wave is the difference frequency of the carrier waves. Carrier waves of around 10 and 25 MHz are used to generate low-frequency waves between 0.5 and 3.5 MHz at amplitudes in the range of 25 to 80 kPa in water. We demonstrate with high-speed camera observations that it is possible to induce microbubble oscillations with the low frequency signal arising from the nonlinear propagation process. As an application, we determined the resonance frequency of Definity contrast agent microbubbles with radius ranging from 1.5 to 5 μm by sweeping the difference frequency in the range from 0.5 to 3.5 MHz. © 2011 IEEE.


Iqbal J.,University of Sheffield | Serruys P.W.,Thorax Center | Taggart D.P.,University of Oxford
Nature Reviews Cardiology | Year: 2013

Patients with major or symptomatic coronary artery disease (CAD) commonly undergo revascularization-either with CABG surgery, which has been the mainstay of revascularization for more than half a century, or with percutaneous coronary intervention (PCI), which has become the more-commonly used strategy in the past decade. PCI has been tested in more randomized clinical trials than any other procedure in contemporary practice. In general, PCI is the preferred option for treating patients with simple coronary artery lesions and CABG surgery remains the standard of care for patients with complex CAD. Technical advancements in PCI and CABG surgery make comparisons of historical data for these strategies difficult. In this Review, we evaluate the evidence-based use of PCI and CABG surgery in treating patients with multivessel and unprotected left main stem disease and for specific patient groups, including those with diabetes mellitus, chronic heart failure, or chronic kidney disease. Finally, we highlight the available tools to aid decision-making, including clinical guidelines, risk scoring systems, and the role of the 'heart team'. © 2013 Macmillan Publishers Limited. All rights reserved.


Zaba O.,Thorax Center | Holbe D.,Thorax Center | Aretz S.,University of Bonn | Grohe C.,Thorax Center
Lung Cancer | Year: 2013

We present a case of a 54-year-old woman who was diagnosed with a KRAS positive adenocarcinoma of the lung on the basis of a Peutz-Jeghers syndrome (PJS), which was unknown before. PJS is a rare hereditary disease, which may be associated with the development of poor outcome adenocarcinomas and LKB1-gene mutations. A very rare type of a LKB1 mutation was found, not previously described in lung cancer. Although seldom screened for LKB-1 mutations are found in up to 30% of lung adenocarcinomas and may be druggable therapeutic targets, in particular in KRAS mutant tumours in the near future as recent preclinical results with nucleotides demonstrate. © 2013 Elsevier Ireland Ltd.


Salameh A.,University of Leipzig | Dhein S.,University of Leipzig | Fleischmann B.,University of Bonn | Grohe C.,University of Bonn | And 4 more authors.
Journal of Physiology and Pharmacology | Year: 2010

The aim of this study was to investigate whether the L-type calcium current (ICa.L) may be altered in aged hearts and whether the classical calcium antagonist verapamil may exhibit altered pharmacological profile in aged hearts. We examined male New Zealand rabbits aged either 6 months or 26 months. To examine ICa.L whole-cell patch-clamp technique was performed on isolated cells. Moreover, activation-recovery intervals (ARI) of isolated hearts (Langendorff method) were assessed using an epicardial 256 channel mapping system. We found that the ICa.L density, normalised to the cell volume was significantly reduced (p<0.001). Maximum conductance was also significantly decreased (p=0.01) and steady state inactivation was shifted to more positive potentials in aged hearts (p<0.001). A slightly reduced effect of β-adrenergic modulation of the ICa.L in aged hearts, and a significantly reduced effect of carbachol on isoprenaline-stimulated ICa.L in aged hearts was observed. L-type α1c subunit, SERCA2-ATPase and the Na+/Ca2+-exchanger expression were neither significantly different in atrial and ventricular tissues nor between young and old animals. Using the mapping system, isolated hearts were exposed to verapamil (0.005, 0.01, 0.02, 0.05 μM/L). While verapamil did not affect ARI in young hearts, in aged hearts ARI was concentration-dependently reduced and the negative inotropic effect of verapamil was significantly attenuated in aged hearts (p<0.05). From these results we conclude that there are distinct alterations in the electrophysiology of ICa.L (reduced maximum conductance, a shift of the steady state inactivation) in the aged heart which may influence the response to verapamil.


Burchill L.J.,Oregon Health And Science University | Lameijer H.,Thorax Center | Roos-Hesselink J.W.,Erasmus Medical Center | Grewal J.,University of British Columbia | And 11 more authors.
Heart | Year: 2015

Objective The objective of this study was to determine outcomes in pregnant women with pre-existing coronary artery disease (CAD) or following an acute coronary syndrome (ACS) including myocardial infarction (MI). Background The physiological changes of pregnancy can contribute to myocardial ischaemia. The pregnancy risk for women with pre-established CAD or a history of ACS/MI is not well studied. Methods This was a retrospective multicentre study. Adverse maternal cardiac, obstetric and fetal/neonatal events were examined. The primary outcome was a composite endpoint of cardiac arrest, ACS/MI, ventricular arrhythmia or congestive heart failure. The prevalence of new or progressive angina during pregnancy was also examined. Results Fifty pregnancies in 43 women (mean age 35 ±5 years) were included. Coronary atherosclerosis (40%) and coronary thrombus (36%) were the most common underlying diagnoses. The primary outcome occurred in 10% (5/50) of pregnancies and included one maternal death secondary to cardiac arrest. Other events included ACS/MI (3/50) and heart failure (1/50). New or progressive angina occurred in 18% of pregnancies. Ischaemic complications of any type (new or progressive angina, ACS/MI, ventricular arrhythmia, cardiac arrest) occurred more commonly in women with coronary atherosclerosis compared with those without (50% vs 10%, p=0.003). A high rate of adverse obstetric (16%) and fetal/neonatal (30%) events was observed. Conclusions Pregnant women with pre-existing CAD or ACS/MI before pregnancy are at increased risk of adverse events during pregnancy. Those with coronary atherosclerosis are at highest risk of adverse maternal cardiac events due to myocardial ischaemia during pregnancy.


PubMed | Imperial College London, Hannover Medical School, University of Leipzig, Mission Medical Hospital and 12 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies.We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP).Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP.Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival.clinicaltrials.gov NCT01347216.


PubMed | Max Delbrück Center for Molecular Medicine and Thorax Center
Type: | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2016

Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response.

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