Research Group Döhner

Interaction of Heart Failure and Stroke: A clinical consensus statement of the ESC Council on Stroke, the Heart Failure Association (HFA) and the ESC Working Group on Thrombosis.
Doehner W, Böhm M, Boriani G, Christersson C, Coats AJ, Haeusler KG, Jones ID, Lip GYH, Metra M, Ntaios G, Savarese G, Shantsila E, Vilahur G, Rosano G.
Eur J Heart Fail. 2023 Oct 31. doi: 10.1002/ejhf.3071. Online ahead of print.
PMID: 37905380

Obesity, metabolic health and clinical outcomes after incident cardiovascular disease: A nationwide population-based cohort study.
Akyea RK, Ntaios G, Doehner W.
J Cachexia Sarcopenia Muscle. 2023 Dec;14(6):2653-2662. doi: 10.1002/jcsm.13340. Epub 2023 Oct 8.
PMID: 37806948; PMCID: PMC10751402

Integrated care for optimizing the management of stroke and associated heart disease: a position paper of the European Society of Cardiology Council on Stroke.
Lip GYH, Lane DA, Lenarczyk R, Boriani G, Doehner W, Benjamin LA, Fisher M, Lowe D, Sacco RL, Schnabel R, Watkins C, Ntaios G, Potpara T.
Eur Heart J. 2022 Jul 7;43(26):2442-2460. doi: 10.1093/eurheartj/ehac245.
PMID: 35552401; PMCID: PMC9259378

Interdisciplinary management of acute ischaemic stroke: Current evidence training requirements for endovascular stroke treatment. Position Paper from the ESC Council on Stroke and the European Association for Percutaneous Cardiovascular Interventions with the support of the European Board of Neurointervention.
Nardai S, Lanzer P, Abelson M, Baumbach A, Doehner W, Hopkins LN, Kovac J, Meuwissen M, Roffi M, Sievert H, Skrypnik D, Sulzenko J, van Zwam W, Gruber A, Ribo M, Cognard C, Szikora I, Flodmark O, Widimsky P.
Eur Heart J. 2021 Jan 21;42(4):298-307. doi: 10.1093/eurheartj/ehaa833. Erratum in: Eur Heart J. 2021 Jan 21;42(4):307.
PMID: 33521827

The role of cardiologists on the stroke unit.
Doehner W, Leistner DM, Audebert HJ, Scheitz JF.
Eur Heart J Suppl. 2020 Dec 6;22(Suppl M):M3-M12. doi: 10.1093/eurheartj/suaa160.
PMID: 33664634; PMCID: PMC7916417

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and heart failure.
Jordan J, Toplak H, Grassi G, Yumuk V, Kotsis V, Engeli S, Cuspidi C, Nilsson PM, Finer N, Doehner W.
J Hypertens. 2016 Sep;34(9):1678-88. doi: 10.1097/HJH.0000000000001013.
PMID:27488547

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation.
Scherbakov N, Knops M, Ebner N, Valentova M, Sandek A, Grittner U, Dahinden P, Hettwer S, Schefold JC, von Haehling S, Anker SD, Joebges M, Doehner W.
J Cachexia Sarcopenia Muscle. 2016 Mar;7(1):60-7. doi: 10.1002/jcsm.12068.
PMID:27066319

Influence of essential amino acids on muscle mass and muscle strength in patients with cerebral stroke during early rehabilitation: protocol and rationale of a randomized clinical trial (AMINO-Stroke Study).
Scherbakov N, Ebner N, Sandek A, Meisel A, Haeusler KG, von Haehling S, Anker SD, Dirnagl U, Joebges M, Doehner W.
BMC Neurol. 2016 Jan 22;16:10. doi: 10.1186/s12883-016-0531-5.
PMID:26793971

Protective overweight in cardiovascular disease: moving from 'paradox' to 'paradigm'.
Doehner W, von Haehling S, Anker SD.
Eur Heart J. 2015 Oct 21;36(40):2729-32. doi: 10.1093/eurheartj/ehv414. No abstract available.
PMID:26341892

Stroke-related sarcopenia: specific characteristics.
Scherbakov N, Sandek A, Doehner W.
J Am Med Dir Assoc. 2015 Apr;16(4):272-6. doi: 10.1016/j.jamda.2014.12.007. Review.
PMID:25676847

Catabolic signaling and muscle wasting after acute ischemic stroke in mice: indication for a stroke-specific sarcopenia.
Springer J, Schust S, Peske K, Tschirner A, Rex A, Engel O, Scherbakov N, Meisel A, von Haehling S, Boschmann M, Anker SD, Dirnagl U, Doehner W.
Stroke. 2014 Dec;45(12):3675-83. doi: 10.1161/STROKEAHA.114.006258.
PMID:25352483

Stroke induced Sarcopenia: muscle wasting and disability after stroke.
Scherbakov N, von Haehling S, Anker SD, Dirnagl U, Doehner W.
Int J Cardiol. 2013 Dec 10;170(2):89-94. doi: 10.1016/j.ijcard.2013.10.031. Review.
PMID:24231058

Loss of skeletal muscle (sarcopenia) is a major yet understudied complication after stroke. The skeletal muscle is the main effector organ accountable for disability in stroke (60 % of patients remain with some physical disablement). However, a surprising paucity of data exists for structural, metabolic or functional changes in muscle tissue after stroke, as disability is traditionally attributed to the brain injury itself. Changes in muscle tissue start as early as four hours after cerebral infarction, and a complex interaction between denervation, disuse, inflammation, remodeling and spasticity accounts for a phenotypical pattern that we have addressed as stroke-specific sarcopenia.

Importantly, studies from our group and from others show that the wasting of muscle tissue is not limited to the affected paralytic limb. Indeed, a global effect of catabolic over-activation and anabolic blunting affects all skeletal muscles and even the myocardium. As a result, the functional impairment of patients after stroke is not only driven by the paralytic motoric disablement but is further aggravated by the global decrease of muscle tissue. Any effort to prevent and/or reverse such muscle wasting may improve functional capacity and will help to regain physical independence.

Currently, stroke-related muscle wasting (sarcopenia) is not recognized in the guide-lines for stroke therapy and rehabilitation. The lack of sufficient evidence on post-stroke muscle pathology, tissue degradation and metabolic and functional impairment needs to be addressed in an interdisciplinary integrated approach. Innovative interventional approaches to prevent or attenuate muscle atrophy and sarcopenia will support patient rehabilitation and improve long-term outcome.

AMINO-Stroke – Effect of Essential Amino Acids on Muscle Size and Strength in Patients with Acute Ischemic Stroke during Rehabilitation

This study assess the effect of essential amino acid supplementation on muscle wasting, muscle strength, mobility, and self-dependence in patients during rehabilitation after acute stroke.

Muscle Functional and Metabolic Changes in Patients during Rehabilitation
Rehabilitation efforts after stroke aim to restore functional capacity and independence in everyday life. We investigate muscle structural, metabolic and functional changes in stroke patients during hospitalized rehabilitation periods.

Local Activation of Skeletal Muscle Apoptosis after Stroke in a Stroke Model
Direct signaling and specific stroke-induced muscle changes are investigated in a mouse model of stroke (MCAO). Early results indicate direct time-dependent signals towards increased protein degradation and apoptotic activity in relation to cerebral infarction size and degree of denervation. Pathways of proteolytic signaling and apoptosis and specific treatments to inhibit these effects are being tested.

WAKOS
Patients with Persistent Vegetative State are studied in longitudinal observational studies (WAKOS) to investigate the change in metabolic balance and to monitor the body composition relating to the course of the disease, and complications such as infections.

SECURE
Professor Doehner is the national PI of the "SECURE" project, an EU-funded (HORIZON 2020) multinational controlled interventional trial to study the efficacy of a polypill over current standards of care in patients with advanced cardiovascular disease after myocardial infarction.

METRIS HF
Clinical randomized controlled trial (IIT) to investigate the metabolic effect of metformin in patients with heart failure and insulin resistance (non-diabetes mellitus) on performance, myocardial function and metabolism. The study is funded by the German Centre for Cardiovascular Research (DZHK) as part of the study program for early clinical trials.

• Nadja Scherbakov, MD
  Clinical Scientist
   
• Anja Kresse
  Study Nurse
   
• Antje Meyer, PhD
  Clinical Scientist and Project Manager
   
• Melanie Heigl
  Study Coordinator
   
• Kathleen Weigt
  Project Coordinator
   
• Azadeh Shafieesabet
  Clinical Research Fellow

Higher degree students
Several MD students, Master students, DAAD students

Clinical and experimental studies are performed with a wide range of pathophysiologic and functional tests and methods. 
Observational (cross sectional and longitudinal) as well as interventional studies are included to test novel therapeutic concepts in proof-of-concept trials (AMINOS, IRIS-HF, UDCA-HF, Allopurinol in HF, Leucopene in HF). Metabolic, hormonal and immunological characterization will be performed on a whole body and systemic level, as well as on tissue interstitial and on intra cellular levels. Functional assessment of vascular reactivity (endothelium function), muscle function (strength, fatigability) and metabolism (energy expenditure, skeletal muscle insulin sensitivity), cardiovascular stress response, and respiratory and exercise capacity are established methods with a long-standing experience.
 

Clinical Methods

Body composition:
Dual Energy X-ray Absorptiometry (DEXA Scan) and Bio Impedance to assess total and regional tissue distribution of fat and lean tissue

Peripheral blood flow:
Occlusion plethysmography

Endothelium function:
Reactive hyperaemia assessment (EndoPAT)

Muscle strength:
Handgrip, finger press, knee extension tests, cycling (MOTOMED), treadmill, maximum isometric quadriceps muscle strength, fatigability protocol

Physical function:
Short physical performance battery test, 6-Min Walk Test

Whole body insulin sensitivity:
By intravenous glucose tolerance testing and minimal modelling, short insulin sensitivity test, HOMA

Interstitial tissue metabolites:
Microdialysis in muscle and fat tissue

Energy expenditure:
Indirect calorimetry

Tissue analyses:
Throkar biopsy methods for muscle and fat tissue

Clinical cardiovascular tests:
Echocardiography, 24h ECG recording, spiroergometric exercise testing, non-invasive cardiac output
 

Experimental studies

Include a number of animal models (MCAO Reperfusion, Hepatoma tumour model, Heart failure model). Pathophysiologic tests in animal models include body composition (NMR spectroscopy) indirect calorimetric testing, 24h activity monitoring, echocardiography. These studies are performed in cooperation with the Department of Experimental Neurology and the Center of Cardiovascular Research (CCR).   

Collaborations within Charité

• Functional/metabolic profile in CFS patients and effect of immune modulation therapy
  Cooperation with the Institute of Medical Immunology (Prof. C. Scheibenbogen)  
• Metabolic studies investigating comorbidities in heart failure ("SICA-HF FP7" project, agreement No. 241558)
• Collaboration with the Department of Cardiology, Angiology and Intensive Care Medicine, Virchow-Klinikum 
• Studies on micronutrients in patients with cardiovascular hospitalization
  Collaboration with the Institute of Experimental Endocrinology (Prof. Schomburg)
   

International collaborating partners include

• University Wroclaw, Poland (Prof. P. Ponikowski, Prof. E. Jankowska) University Hull (Prof. Cleland)
• IRCCS San Raffaele Pisana, Rome, Italy (Prof. G Rosano)
• University Golnik, Slovenia  (Prof. M. Lainscak)
• University of Warwick, UK (Prof. A. Coats)
• University of Moscow, Russia (Prof. V. Tkachuk)
• University St.-Petersburg, Russia (Prof. Shlyakhto, Prof. A. Zaritskey)
• University Madrid, Spain (Prof. J. Castellano, Prof. V. Fuster)
• University Umeå, Sweden (Prof. M. Henein)
   

Contributions to various clincal projects within the CSB

• COSBID
• DISCHARGE
• INSPIRE
• Stroke Unit Plus
• HEBRAS

Prof. Döhner is actively involved in education and postgraduate training at various national and international institutions.

• Bachelor studies at the University of Potsdam (DIfE) for Nutritional Sciences
• Online Education Programme of the European Heart Failure Association
• Supervision of PhD students in various degrees (MD, Doctor of Veterinary Medicine and MA students of Nutritional Sciences)
• Regular invitations to training lectures in numerous clinics (such as the University of Rostock, the Hannover Medical School, the University of Münster, Dresden University and the hospitals of Esslingen, Halle and Heidelberg)
• Co-authorship of several textbooks

PhD support
We offer a wide range of PhD topics across various studies. Students can therefore apply for a Doctoral Thesis at any time. If interested, please send us your CV and corresponding cover letter as well as information on the timeframe and your main area of interest and existing skills.