Stefan H Hohnloser

Goethe-Universität Frankfurt am Main, Frankfurt, Hesse, Germany

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Publications (347)3369.85 Total impact

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    ABSTRACT: The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes.
    No preview · Article · Feb 2016 · European Heart Journal
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    ABSTRACT: Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation.
    No preview · Article · Feb 2016 · European Heart Journal
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    ABSTRACT: Rivaroxaban is increasingly used in patients undergoing catheter ablation of atrial fibrillation (AF). In the absence of large controlled trials, a comprehensive meta-analysis of the literature appears to be the best way to obtain reliable evidence on rare peri-procedural outcomes such as thromboembolic or bleeding events. We aimed to provide a detailed analysis of currently available data on safety and efficacy of peri-procedural rivaroxaban in patients undergoing AF ablation. We performed a systematic search of the English language literature for studies comparing peri-procedural rivaroxaban therapy with vitamin K antagonists (VKAs) and reporting detailed data on bleeding and/or thromboembolic complications. The Peto odds ratio (POR) was used to pool data into a fixed-effect meta-analysis. A total of 7400 patients undergoing catheter ablation were included in 15 observational and 1 randomized studies of which 1994 were receiving rivaroxaban and 5406 VKA. The risk of thromboembolism trended to be lower in the rivaroxaban group [4/1954 vs. 19/5219, POR 0.40, 95% confidence interval (CI), 0.16–1.01, P = 0.052]. Major bleeding events occurred in 23 of 1994 cases (1.15%) in the rivaroxaban and 90 of 5406 (1.66%) in the VKA group (POR 0.74, 95% CI, 0.46–1.21, P = 0.23). A total of 87 minor bleeding events were reported in 1753 patients (4.96%) in the rivaroxaban group and in 165 of 4009 patients (4.12%) in the VKA group (POR 0.84, 95% CI 0.63-1.11, p = 0.22). In patients undergoing AF ablation, rivaroxaban appears to be an effective and safe alternative to VKA.
    Preview · Article · Jan 2016 · Europace
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    Full-text · Article · Dec 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Background: SIMPLE randomized 2,500 patients receiving a first ICD/CRT-D device to defibrillation testing (DT) or not. It demonstrated that DT did not improve shock efficacy or reduce mortality. Objective: This prospective sub-study evaluated the effect of DT on postoperative troponin concentrations and their predictive value for total and arrhythmic mortality. Methods: Troponin was measured between 6 and 24 hours following ICD implantation in 2200/2500 patients. Results: A postoperative serum troponin level above the upper limit of normal (ULN) was more common in patients undergoing DT (N=509, 46.4%) than in those not having DT (N=456, 41.3%; p=0.02). After excluding patients with known preoperative troponin > ULN, consistent findings were observed (42.1% vs. 37.5%, p=0.04). During a mean follow-up of 3.1 ± 1.0 years, the annual mortality rate was increased in patients with a postoperative troponin > ULN (adjusted HR 1.43, 95% CI, 1.15-1.76, p=0.001) irrespective of DT or not. Likewise, patients with elevated troponin levels had a significantly higher risk of arrhythmic death (adjusted HR 1.80, 95% CI, 1.23-2.63, p=0.002). The rate of first appropriate ICD shock (adjusted HR 0.89, 95% CI, 0.71-1.12, p=0.32) or failed appropriate shock (adjusted HR 1.02, 95% CI, 0.59-1.76, p= 0.95) were similar in patients with or without troponin elevation. Conclusion: DT at time of ICD implantation is associated with increased troponin levels indicating subclinical myocardial injury caused by the procedure. Elevated troponin levels but not defibrillation testing, seem to predict clinical outcomes in ICD recipients.
    No preview · Article · Nov 2015 · Heart rhythm: the official journal of the Heart Rhythm Society
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    Preview · Article · Oct 2015 · Europace
  • Julia Erath · Máté Vámos · Stefan H. Hohnloser
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    ABSTRACT: Bei Patienten mit Vorhofflimmern wird die Mortalität und Morbidität in erster Linie durch thromboembolische Komplikationen erhöht. Das Risiko für ischämische Schlaganfälle ist bei Vorhofflimmern 4- bis 5-fach höher als bei sinusrhythmischen Patienten. Für die Schlaganfallprävention wird Aspirin nicht mehr empfohlen und die Antikoagulation mit Vitamin-K-Antagonisten weist in der Therapie zahlreiche Limitierungen auf. Die direkten oralen Antikoagulanzien sind sehr viel einfacher anzuwenden und haben weitere Vorteile wie eine kurze Halbwertszeit oder fehlende bzw. einzelne Wechselwirkungen mit Nahrungsmitteln bzw. anderen Medikamenten. Vor allem ist ein regelmäßiges Monitoring der blutverdünnenden Wirkung nicht nötig.
    No preview · Article · Sep 2015
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    ABSTRACT: Background: Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. Methods and results: We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Conclusion: Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues.
    No preview · Article · Aug 2015 · European Heart Journal
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    ABSTRACT: Vitamin K-dependent factors protect against vascular and renovascular calcification, and vitamin K antagonists may be associated with a decreased glomerular filtration rate (GFR). This study analyzed changes in GFR during long-term treatment with warfarin or dabigatran etexilate (DE) in patients enrolled in the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial. Of the 18,113 patients in the RE-LY study randomized to receive DE (110 mg or 150 mg twice daily) or warfarin, 16,490 patients with atrial fibrillation had creatinine values measured at baseline and at least 1 follow-up visit. Changes in GFR for up to 30 months were evaluated. GFR declined in all treatment groups. After an average of 30 months, the mean ± SE decline in GFR was significantly greater with warfarin (-3.68 ± 0.24 ml/min) compared with DE 110 mg (-2.57 ± 0.24 ml/min; p = 0.0009 vs. warfarin) and DE 150 mg (-2.46 ± 0.23 ml/min; p = 0.0002 vs. warfarin). A decrease in GFR >25% was less likely with DE 110 mg (hazard ratio: 0.81 [95% confidence interval: 0.69 to 0.96]; p = 0.017) or DE 150 mg (hazard ratio: 0.79 [95% confidence interval: 0.68 to 0.93]; p = 0.0056) than with warfarin in the observation period >18 months. Patients with poor international normalized ratio control (i.e., time in therapeutic range <65%) exhibited a faster decline in GFR. A more pronounced decline in GFR was associated with previous warfarin use and with the presence of diabetes. Patients with atrial fibrillation receiving oral anticoagulation exhibited a decline in renal function that was greater in those taking warfarin versus DE, and it was amplified by diabetes and previous vitamin K antagonist use. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jun 2015 · Journal of the American College of Cardiology
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    ABSTRACT: VENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA). Trial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar. In patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy. Clinicaltrials.gov trial registration number is NCT01729871. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
    Full-text · Article · May 2015 · European Heart Journal
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    Mate Vamos · Julia W Erath · Stefan H Hohnloser
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    ABSTRACT: There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation (AF) or with congestive heart failure (CHF). The aim of this meta-analysis was to provide detailed analysis of the currently available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014) of the English literature dealing with the effects of digoxin on all-cause-mortality in subjects with AF or CHF. Only full-sized articles published in peer-reviewed journals were considered for this meta-analysis. A total of 19 reports were identified. Nine reports dealt with AF patients, seven with patients suffering from CHF, and three with both clinical conditions. Based on the analysis of adjusted mortality results of all 19 studies comprising 326 426 patients, digoxin use was associated with an increased relative risk of all-cause mortality [Hazard ratio (HR) 1.21, 95% confidence interval (CI), 1.07 to 1.38, P < 0.01]. Compared with subjects not receiving glycosides, digoxin was associated with a 29% increased mortality risk (HR 1.29; 95% CI, 1.21 to 1.39) in the subgroup of publications comprising 235 047 AF patients. Among 91.379 heart failure patients, digoxin-associated mortality risk increased by 14% (HR 1.14, 95% CI, 1.06 to 1.22). The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    Preview · Article · May 2015 · European Heart Journal
  • Stefan H Hohnloser · Máté Vámos · Hans-Christoph Diener
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    ABSTRACT: The development of the direct oral anticoagulants (DOACs) represents one of the major breakthroughs in modern medicine over the last decade. Compared to vitamin K antagonists, all DOACs (dabigatran as a thrombin-Inhibitor, rivaroxaban, apixaban and edoxaban as factor Xa inhibitors) are much easier to handle due to their pharmacological properties. All DOACS are more efficacious and safer as vitamin K antagonists as demonstrated in the pivotal studies in more than 71 000 patients. Particularly the much lower risk of intracerebral bleeding complications is the reason why the DOACs should be preferred over vitamin K antagonists in patients with non-valvular atrial fibrillation. © Georg Thieme Verlag KG Stuttgart · New York.
    No preview · Article · May 2015 · DMW - Deutsche Medizinische Wochenschrift
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    ABSTRACT: Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384. Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25). Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office). Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Mar 2015 · The Lancet
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    ABSTRACT: We have previously reported a physiologically relevant interaction between KCNQ1 (Q1) and KCNH2 (H2). While the H2 C-terminus has been suggested to play a role, so far, no more detailed information regarding the interaction site is available. The methods used in the study are cell culture, PCR for mutagenesis, patch clamp for ion current recordings, co-immunoprecipitation for determination of protein interaction. Co-expression of Q1 and H2 resulted in an increase of I H2 (tails after +50 mV; Q1 + H2, 36 ± 6 pA/pF; H2, 14 ± 2 pA/pF; n = 10; 12; P < 0.05). Upon expressing a non-conductive (dominant-negative) Q1-pore mutation (dnQ1), there was still an increase in I H2 (tails after +50 mV; H2 + dnQ1, 24 ± 4 pA/pF; n = 10; P < 0.05) making the pore region unlikely as an interaction site. Experiments using the KCNH2-pore blocking agent quinidine supported these findings. If Q1 and H2 formed hetero-tetramers, steric changes within the pore should change the quinidine half-inhibitory concentrations (IC50). However, I H2 sensitivity did not significantly change in the presence or absence of Q1 (IC50 341 ± 63 vs. 611 ± 293 nmol/L, respectively, P = n.s.), providing further evidence that the pore is not a likely H2-Q1 interaction site. To obtain further insights into the role of intra-cytoplasmic structures, we used both C- and N-terminally truncated mutant H2 proteins. Both H2 mutants co-immunoprecipitated with Q1, suggesting no specific role of C- or N-termini. Accordingly, rather than these, the transmembrane domains of the α-subunits appear relevant for the interaction. Our results largely exclude the formation of hetero-tetramers between H2 and Q1 comprising the pore region or H2 C- or N-termini.
    Full-text · Article · Mar 2015 · Archiv für Experimentelle Pathologie und Pharmakologie
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    Full-text · Dataset · Feb 2015

  • No preview · Article · Feb 2015 · Circulation
  • Stefan H Hohnloser · Gregory Y H Lip

    No preview · Article · Feb 2015 · Chest
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    ABSTRACT: Limited data exists regarding the relationship between left ventricular systolic dysfunction (LVSD) and heart failure (HF) symptoms and embolic risk among patients with atrial fibrillation. Participants in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF, but not randomized to oral anticoagulation, were categorized as having preserved versus reduced ejection fraction. If reduced, LVSD was classified as mild, moderate, or severe. Symptoms were quantified using New York Heart Association class.The primary outcome was a composite of stroke, transient ischemic attack, and systemic embolism. There were 3487 antiplatelet-treated patients with HF at baseline. Of these patients, 969 (46.8%) had HF with preserved ejection fraction and 1103 (53.2%) had HF with reduced ejection fraction. During 3.6 years of mean follow-up, first occurrence of stroke, transient ischemic attack, or systemic embolism occurred in 386 patients.The strongest independent predictors of embolic events were age ≥75 years (hazard ratio 2.55; confidence interval, 1.85-3.53), prior stroke or transient ischemic attack (hazard ratio 2.07; 95% confidence interval, 1.65-2.60), and female sex (hazard ratio 1.37; confidence interval, 1.11-1.69). However, ejection fraction <0.50, degree of LVSD, and New York Heart Association class did not predict embolic events. Patients with HF with preserved ejection fraction exhibited similar risk of embolic events as those with HR with reduced ejection fraction: 4.3% versus 4.4% per 100 person-years (hazard ration 1.01; 95% confidence interval, 0.78-1.31). Risk of embolic events was similar across categories of LVSD (P for trend =0.96) and New York Heart Association class (P for trend =0.57). Among HF patients in ACTIVE, neither the presence of LVSD or degree of symptom severity influenced risk of embolic events. © 2015 American Heart Association, Inc.
    Preview · Article · Jan 2015 · Stroke
  • Philipp Bushoven · Sven Linzbach · Mate Vamos · Stefan H Hohnloser
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    ABSTRACT: For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.
    No preview · Article · Jan 2015
  • Stefan H. Hohnloser

    No preview · Chapter · Dec 2014

Publication Stats

21k Citations
3,369.85 Total Impact Points

Institutions

  • 1995-2015
    • Goethe-Universität Frankfurt am Main
      • Center for Internal Medicine
      Frankfurt, Hesse, Germany
  • 2012
    • St George's, University of London
      Londinium, England, United Kingdom
  • 1995-2009
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2008
    • Kyorin University
      Edo, Tōkyō, Japan
  • 2007
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 2006
    • University of Toronto
      Toronto, Ontario, Canada
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
    • The University of Calgary
      Calgary, Alberta, Canada
  • 2003
    • Medical University of Ohio at Toledo
      Toledo, Ohio, United States
  • 1992-1995
    • Evangelische Hochschule Freiburg, Germany
      Freiburg, Baden-Württemberg, Germany
  • 1988-1994
    • University of Freiburg
      • Department of Internal Medicine
      Freiburg, Baden-Württemberg, Germany