Team

Univ.-Prof. Dr. med.
Matthias Totzeck

Dr. med.
Simone Mrotzek

Dr. med.
Lena Scheipers

Dr.
Raluca Mincu, PhD

Fabienne Risch

Elias Haj-Yehia

Dr. med.
Lars Michel

Doktoranden:

Nadine Saur, Merve Akdeniz, Emel Temiz, Nadia Hegner, Phan Phuong-Thy Nguyen, Habyna Ravi, Adelina Mark, Nadja Müller, Josefine Niroomand, Lea Rogge-Herper, Armin Spomer, Rebekka im Schlaa

Topics

We seek to understand the biological mechanisms behind acute cardiac damage

in both basic and clinical science. Our group led by Prof. Dr.  Matthias Totzeck investigates pathological pathways associated with cardiac damage, which originates from e.g. acute myocardial infarction, valvular heart disease or in the course of cancer therapy. We aim to develop novel therapies for patient treatment.

We use state-of-the-art technology and ground-breaking methodology in our day-to-day practice to drive innovative research for treatments of acute cardiac damage.

Clinical projects

Characterization of the cardiovascular adverse events of antitumor therapies

We evaluate cardiovascular adverse events of different therapeutic cancer strategies, including classical chemotherapy, targeted therapy, immune therapy, hormonal therapy, and irradiation. All patients evaluated in our Cardio-oncology Unit are included in the local eCOR Registry and in the nationwide COIN-DE database to characterise the cardiovascular dysfunction from cancer therapy, and to assess the efficacy of new biomarkers, electrocardiography scores, and advanced cardiac imaging techniques to early detect and predict cardiotoxicity.

Management of cardiovascular disease in tumor patients

The optimal medical and interventional treatment of patients with cancer and acute or chronical cardiac disease has not been extensively studied. We evaluate strategies for the management of coronary heart disease, myocardial disease, valvular heart disease, arrhythmias and advanced heart failure in patients with active cancer disease or in cancer survivors.

Development of new cardioprotective strategies

The role of anticoagulant and anti-platelet treatment in the primary prevention of acute coronary syndromes, periphery arterial ischemic events, or venous thromboembolic events has not been established in patients with cancer. The efficacy of renin angiotensin aldosterone system inhibitors or beta-blockers to protect against a  reduction in left ventricular function after anthracyclines or selected targeted therapies need to be further investigated, together with the development of new cardioprotective strategies. We investigate which cancer patients are susceptible to develop immune therapy induced myocarditis.

Basic science projects

Myocardial I/R Injury and repair

We seek to characterize potential mechanisms that can be used to reduce the burden of myocardial I/R which results from myocardial infarction and reperfusion therapy. We aim to optimize the immune response and the removal of dead cells after myocardial infarction which leads to the formation of an adequate remodeling and healing.

3D cardicaimaging

Traditional histology has been used for decades to study myocardial infarction damage and response. However, the techniques used require a vast amount of manual work and depict only a fraction of the  heart volume. We set out to invent new methodologies for 3D imaging and analysis of the heart after myocardial infarction and contemporaneously measure damage and response.

Cancer therapy-relatedcardiotoxicity

Today, physicians face a growing number of long-term cancer survivors with morbidities resulting from therapy. The underlying mechanisms are still unknown. We mimic cancer treatments used in clinical practice to investigate pathologies of the heart in basic science and develop therapeutic strategies to counteract cardiovascular damage.

Immune cardiology

A myriad of immune cells infiltrate the myocardium after infarction to facilitate debris clearance, wound healing and scar formation. Modulation of this sophisticated orchestra has proved a diffcult task. We investigate the role of neutrophils, which are the first and most abundant immune cells to enter the infarcted heart, during the early and later stages of inflammation and aim to adjust their detrimental impact, while maintaining positive effects.

Basic science methods

Models:

  • Mouse in vivo myocardial I/R injury
  • Isolated mouse hearts (Langendorff)
  • Isolated aortic rings
  • Human cardiomyocytes
  • Isolated primary mouse cardiomyocytes

Microscopy:

  • FACS/flow cytometry
  • Confocal microscopy
  • Light sheet fluorescence microscopy

In vivo functional analysis:

  • Millar catheter
  • Mouse echocardiography

Protein and RNA analytical methods

Funding

Cooperations

External

  • Stanford Institute for Stem Cell Biology and Regnerative Medicine
  • Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute
  • MPI for Heart and Lung Research Bad Nauheim
  • ISAS Dortmund
  • Berlin-Brandenburg Center for Regenerative Therapies

On campus

  • Institute for Experimental Immunology and Imaging
  • Institute of Cell Biology (Cancer Research)
  • Institute for Pathophysiology
  • Department of Nuclear Medicine
  • Institute for Diagnostic and Interventional Radiology
  • Department of Dermatology
  • Department of Thoracic and Cardiovascular Surgery

Publications

  • Pohl, Mincu, Mrotzek… Totzeck Cancers ECG Scoring for the Evaluation of Therapy-Naïve Cancer Patients to Predict Cardiotoxicity
  • Rassaf, Totzeck et al. ESC Heart Fail Ventricular assist device for a coronavirus disease 2019-affected heart
  • Mrotzek… Totzeck Clin Ras Cardiol Assessment of coronary artery disease during hospitalization for cancer treatment
  • Totzeck et al. Eur Heart J Are we underestimating the potential for cardiotoxicity related to immune checkpoint inhibitors?
  • Totzeck, Glas, Rassaf Internist Biomarkers in cardio-oncology patients
  • Pohl, Mincu, Mrotzek, Hinrichs, Michel… Totzeck J Clin Med ECG Changes in Melanoma Patients Undergoing Cancer Therapy-Data From the ECoR Registry
  • Lehmann, Totzeck Herz Establishing an oncocardiology service
  • Michel, Schadendorf, Rassaf Herz Oncocardiology: new challenges, new opportunities
  • Michel, Totzeck et al. Herz Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system
  • Hinrichs, Mrotzek, Mincu, Röll, Michel…Totzeck… Front Pharmacol Troponins and Natriuretic Peptides in Cardio-Oncology Patients-Data From the ECoR Registry
  • Rassaf, Totzeck et al. Clin Res Cardiol Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology
  • Michel, Rassaf, Totzeck Eur J Heart Fail Evaluating biomarkers as predictors of cancer therapy cardiotoxicity: all you need is a meta-analysis? Reply
  • Mrotzek, Rassaf, Totzeck Front Cardiovasc Med Cardiovascular Damage Associated With Chest Irradiation
  • Totzeck, Rassaf Herz Novel cancer treatment and the cardiovascular risk : What should cardiologists know?
  • Michel, Mincu, Mrotzek, Korste… Totzeck ESC Heart Fail Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis
  • Michel, Mincu… Totzeck Eur J Heart Fail Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis
  • Totzeck et al. Eur Heart J Cardiac fibroblast activation detected by positron emission tomography/computed tomography as a possible sign of cardiotoxicity
  • Michel, Rassaf, Totzeck Int J Cardiol Heart Vasc Cardiotoxicity from immune checkpoint inhibitors
  • Mincu…Totzeck JAMA Netw Open Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors: A Systematic Review and Meta-analysis.
  • Al-Rashid, Totzeck et al. Int J Cardiol Safety and efficacy of a novel algorithm to guide decision-making in high-risk interventional coronary procedures.
  • Totzeck, Mincu et al. ESC Heart Fail Heart failure from cancer therapy: can we prevent it?
  • Michel, Rassaf Eur J Med Res Cardio-oncology: need for novel structures
  • Merz, Korste…Totzeck Nat Commun Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response.
  • Mincu…Totzeck, Rassaf Sci Rep Novel anticoagulants versus vitamin K antagonists for cardioversion of non- valvular atrial fibrillation – a meta-analysis of more than 17000 patients.
  • Hinrichs…Totzeck Am J Case Rep Diagnostic Work-Up of Pulmonary Hypertension – Think About Shunt Flow! A Case Report
  • Totzeck et al. Int J Cardiol Cardio-oncology – strategies for management of cancer-therapy related cardiovascular disease
  • Totzeck et al. Eur Heart J Weightlifting unmasks high-risk coronary anomaly
  • Hinrichs…Totzeck Eur Heart J Case Rep Malaise and fatigue following mitral valve repair: case report
  • Rassaf, Totzeck J Thorac Dis Modern concepts in cardio-oncology
  • Michel…Totzeck J Thorac Dis Biomarkers for the detection of apparent and subclinical cancer therapy-related cardiotoxicity
  • Mincu…Totzeck Neth Heart J Red blood cell transfusion in patients with ST-elevation myocardial infarction- a meta-analysis of more than 21,000 patients
  • Michel…Totzeck…Hendgen-Cotta J Vis Exp Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice
  • Rischpler, Totzeck J Nucl Cardiol Are you stressed?
  • Totzeck, Mincu, Mrotzek et al. Eur J Prev Cardiol Cardiovascular diseases in patients receiving small molecules with anti-vascular endothelial growth factor activity: A meta-analysis of approximately 29,000 cancer patients
  • Mrotzek, Totzeck Am J Case Rep Ticagrelor Leads to Statin-Induced Rhabdomyolysis: A Case Report
  • Totzeck, Mincu et al. J Am Heart Assoc Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta-Analysis of More Than 20 000 Patients
  • Totzeck et al. Adv Exp Med Biol Nitrite-Nitric Oxide Signaling and Cardioprotection
  • Totzeck, Korste et al. Nitric Oxide S-nitrosation of calpains is associated with cardioprotection in myocardial I/R injury
  • Hendgen-Cotta…Totzeck Sci Rep A novel physiological role for cardiac myoglobin in lipid metabolism
  • Mincu…Totzeck Sci Rep Preprocedural C-Reactive Protein Predicts Outcomes after Primary Percutaneous Coronary Intervention in Patients with ST-elevation Myocardial Infarction a systematic meta-analysis
  • Hendgen-Cotta, Messiha…Totzeck Free Radic Res Inorganic nitrite modulates miRNA signatures in acute myocardial in vivo ischemia/reperfusion
  • Totzeck et al. J Biol Methods A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury
  • Totzeck et al. World J Cardiol Concepts of hypoxic NO signaling in remote ischemic preconditioning
  • Totzeck et al. Mol Cell Biochem Nitrite circumvents canonical cGMP signaling to enhance proliferation of myocyte precursor cells
  • Totzeck et al. PLoS One Crosstalk between nitrite, myoglobin and reactive oxygen species to regulate vasodilation under hypoxia
  • Rassaf, Totzeck et al. Circ Res Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning
  • Totzeck et al. Circulation Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation
  • Totzeck et al. Nitric Oxide Higher endogenous nitrite levels are associated with superior exercise capacity in highly trained athletes
  • Totzeck et al. Nitric Oxide Assessment of the functional diversity of human myoglobin

Awards

  • UK Essen Top Young Science Best Paper Award Dr. Lars Michel
  • ESC Educational Grant Dr. Lars Michel, Dr. Simone Mrotzek and Dr. Raluca Ileana Mincu
  • ESC Basic Science Travel Grant Dr. Sebastian Korste
  • Best Poster Award at the 85th congress of the German Society of Cardiology Dr. Lars Michel
  • ESC Basic Science Travel Grant Dr. Lars Michel
  • ESC Basic Science Travel Grant Dr. Sebastian Korste