Research Group Cardiac Surgery
The ultimate mission of our interdisciplinary team is to address and advance the field of cardiovascular disease by developing innovative surgical and minimally invasive transcatheter procedures, novel diagnostic tools, and next-generation therapeutic concepts to not only reduce patient mortality, but also improve the quality of life of affected patients. A multidisciplinary and highly translational team approach combined with basic-experimental, preclinical, and clinical research are key to achieving these goals.
Join us!
We want YOU - Apply now!
We are always looking for new talents to join our team for internships or Bachelor / Master/ MD / PhD thesis projects.
If you are interested, please send your CV and cover letter!
Current Projects
Innovations in cardiac surgery and extracorporeal perfusion
Median sternotomy remains the standard method to perform cardiothoracic surgery. Sternal infections, sternal dehiscence, incomplete sternal healing, and acute, and chronic sternal pain are well-known specific complications in cardiovascular procedures following a median sternotomy. The incidence of sternal complications varies across facilities; nevertheless, dehiscence and infection are the most feared complications after such surgical interventions, increasing morbidity and mortality among a cohort of patients. Our group is interested in finding an ideal closure system, which is cost-effective, reduces sternal complications, and improves bone-healing and physical recovery. The project is realized in cooperation with the University Hospital Zurich.
Contact: H. Rodriguez
In the clinical assessment of aortic regurgitation (AI), the regurgitant volume remains the main reference value for determining prognosis and guide therapy. In cases of severe regurgitation, guidelines give clear therapeutic recommendations. However, for mild-to-moderate AI, the situation is less clear. Although even mild aortic regurgitation after transcatheter aortic valve replacement has been shown to be associated with increased long-term mortality, the effects of AI-jet origin and trajectory on left ventricular hemodynamics have not yet been investigated. We therefore hypothesize that in a setting of mild aortic paravalvular leak, it is not the regurgitant volume per se, but rather the regurgitant jet path within the ventricle that affects the diastolic intraventricular blood flow, with the potential of becoming a predictor or even a catalyst for adverse remodeling and poor clinical outcome. To investigate this scientific question, we developed a translational large animal model of mild AI and a state-of-the-art grade 4D magnetic resonance imaging data acquisition system for humans.
Contact: N. Cesarovic
Cardiac microvascular obstruction (MVO) is a feared disease and affects up to 40% of patients successfully treated for myocardial infarction. Its presence is an independent predictor that affected patients will develop heart failure. It greatly affects the patient’s survival rate and quality of life. MVO is caused by blockages in the microvasculature and leads to reduced blood perfusion and diminished oxygen supply to the myocardial tissue. To better understand the mechanisms of MVO and to develop diagnostic tools and effective treatments, we use a specially developed translational large animal model of cardiac MVO as well as high-resolution 3D ultrastructural imaging and fluid mechanics simulations.
Contacts: N. Cesarovic, J. Iske, C. M. Beez
Myocardial infarction is usually caused by an occlusion of the feeding coronary artery. Affected patients experience symptoms such as chest pain and/or shortness of breath, their cardiac function is impaired, and the electrocardiogram as well as cardiac biomarkers are changed. After therapy in accordance with the guidelines, the patients are quickly referred to a hospital, where the reopening of the occluded vessel is immediately initiated. However, in about 10% of these patients upon arrival in the clinic, no relevant occlusions of the coronary arteries can be detected. This phenomenon is called MINOCA – myocardial infarction with nonocclusive coronary arteries. MINOCA usually affects younger patients with fewer comorbidities and risk factors. The majority of them are women. It is postulated that in contrast to classic myocardial infarction, in which large and readily visible coronary vessels are occluded, smaller arteries and arterioles are involved in MINOCA. Hence, MINOCA represents a diagnostic challenge, as the affected arteries are below the resolution limit of current medical imaging devices. Moreover, as there is also no specific therapeutic target, the treatment of MINOCA is rarely successful. In this project, we are investigating novel approaches for diagnosis and treatment of MINOCA using our unique animal and hybrid microfluidic chip model of cardiac microvascular thrombosis. Advanced cardiac magnetic resonance imaging, microvascular 3D reconstruction and flow simulations, as well as immunological assays are just some of the methods, we are using to reveal the secrets of MINOCA.
Contacts: N. Cesarovic, J. Iske, C. M. Beez
Together with our industry partners, we have received a EUROSTARS grant to develop an anastomotic connector for coronary arteries. The current generation of the ELANA heart clip will be implanted in the first human in an open chest setting this year. In the MINI-CAB trial, we are optimizing the technology for endoscopic use.
Contact: T. Z. Nazari-Shafti
The transcatheter aortic valve implantation MitraClip is a minimally invasive procedure that is widely used to replace or repair a damaged heart valve, mainly in patients found to be unsuitable for conventional cardiothoracic surgery. In certain cases, such as prosthetic endocarditis or clip dislocation, these patients must be operated again. In this patient group, the mortality is high. The aim of the study is to compare the observed and expected mortality in these patients.
Contact: M. Ghoneim
Effects of cardiopulmonary bypass during cardiac surgery on the taxonomic composition, diversity and metabolomics of the gut microbiota and their role in systemic inflammatory response syndrome
Cardiopulmonary bypass (CPB) made cardiac surgery possible and is still an indispensable instrument that is used in most cardiac surgery procedures. However, CPB is a factor that affects human physiology and changes the perfusion of the intestine. The effects of CPB on human physiology are immediately noticed through the postoperative increase in pro-inflammatory parameters and the clinical picture of the systemic inflammatory response syndrome (SIRS). To date, exposure of blood to the foreign synthetic surfaces of the CPB circuit is considered to be the exclusive aetiologic factor of SIRS after CPB, which still accounts for a high percentage of the postoperative morbidity and mortality in this patient population. We hypothesize that CPB-related changes in gut perfusion affect the composition and diversity of the gut microbiota and thus mechanistically contribute to postoperative SIRS. If this is correct, directed modulation of the composition of the gut microbiota and interference with its metabolomics could become a crucial consideration factor in the development of new prophylactic and therapeutic strategies for side reactions of CPB and postoperative SIRS after cardiac surgery.
Contacts: H. Hinkov, H. Rodríguez
The use of the heart-lung machine contributes significantly to a pro-inflammatory condition, as shown by the increased release of pro-inflammatory molecules such as interleukin 6 (IL-6). The systemic release of these molecules leads to systemic inflammatory response syndrome (SIRS), which is characterized by massive vasodilation that requires high levels of catecholamines, and directly affects the outcomes of these patients. SIRS is increased in patients with endocarditis by the simultaneous release of pro-inflammatory molecules caused by the infective state alone. SIRS is directly related to increased mortality in cardiac surgery. Thus, our group focuses on finding therapeutic options to reduce SIRS and improve outcomes in patients suffering from infectious endocarditis.
Contact: H. Rodríguez, S. Sima
Myocardial Injury and protection
More than 60 million people worldwide suffer from heart failure. A key factor in the progression from acute to chronic and terminal heart failure is cardiac fibrosis, a scarring process characterized by excessive production and accumulation of extracellular matrix components in the myocardium. Although this mechanism is essential to maintain the structural and functional integrity of the damaged heart during acute myocardial injury, persistent scarring can result in tissue stiffening and decreased ventricular filling and contraction, ultimately contributing to the development of heart failure, arrhythmia, and sudden cardiac death. The hypothesis for this project is that in response to ischemic heart injury, pro-fibrotic pathways are activated not only in the infarct zone, but also in distant heart regions (remote cardiac remodeling), which also contribute to the development of heart failure. We therefore aim to better understand cardiac remodeling processes following ischemic heart injury, especially in non-ischemic heart regions. New insights will help to develop more effective drugs and therapies to delay or even prevent the onset of heart failure after ischemic injury, and ultimately reduce the number of people suffering from this disease.
Contact: S. Neuber
Recent discoveries by our group and others have underscored the impact of NAD+ in immunomodulation in several inflammatory and autoimmune diseases. For a long time, ischemia-reperfusion injury (IRI) has been a feared complication in several cardiovascular diseases, such as myocardial infarction (MI) and heart transplantation (HTPL). Several attempts failed at finding the ideal therapy for IRI. IRI is an immunological process; thus, better understanding and regulation of this process could benefit the treatment of patients affected by IRI. NAD+ has shown promising results in modulating immune responses. However, its role in immunomodulation in IRI and HTPL is still poorly understood. Therefore, we aim to identify the impact of NAD+ in IRI and HTPL, unraveling the mechanisms involved in these complex immunological processes. The project is realized in cooperation with the University Hospital Zurich.
Contact: H. Rodríguez
Micro-surfaces and nanoparticles: how we therapeutically target the endothelium
Various cell types have been studied as a source for myocardial regeneration over the past 20 years. Most cell-based therapies, however, have failed in the so-called valley of death of clinical translation. There is consensus that most of the benefits of progenitor cell therapy reside in the paracrine secretion of cytokines and extracellular vesicles. In the heart they show a protective (cardioprotective) effect. Our research focuses on identifying the exact mechanisms of their cardioprotective effect during the remodeling phase following myocardial injury. In addition, we are also investigating possible side effects of extracellular vesicles - especially when administered systemically.
Contact: T. Z. Nazari-Shafti
We are developing a platform for the good manufacturing practice-compliant production of therapeutic and diagnostic extracellular vesicles (EVs). In particular, the challenges of characterizing heterogeneous EV preparations and production lines that ensure low batch-to-batch variability are some of the challenges that our team aim to overcome.
Contact: T. Z. Nazari-Shafti
This study builds on the Duragraft registration study completed last year. Here, we investigate the role of endothelial protection in venous grafts between graft harvest and implantation for the long-term performance of endothelial cells. In this context, we test endothelial cells in a model of ischemia and during long-term expansion.
Contact: T. Z. Nazari-Shafti, I. E. Caliskan
In both industrialized and developing countries, cardiovascular disease is still the most common cause of morbidity and mortality, especially in elderly patients. Thrombogenicity of foreign surfaces is a major hurdle in cardiovascular interventions. Despite great advances in biomaterials research, hemocompatibility of blood-contacting materials is unsatisfactory and the native endothelium is still the ideal surface for blood contact. Complete coverage of the luminal surfaces of ventricular assist devices (VADs) by a monolayer of endothelial cells (ECs) is a promising approach but is constrained by the limited replication capacity of ECs. Given that surfaces with anisotropic topographical features promote endothelialization, we aim to investigate the endothelialization performance and replication capacity of senescent ECs seeded on micro-structured surfaces with gratings.
Contact: V. Exarchos
Extracellular vesicles (EVs) are lipid bilayer particles that are constantly secreted by mesenchymal stromal cells (MSCs). While their tissue-restoring properties are now better understood, the bench-to-bedside transition has not yet been accomplished. Due to the significant first-pass effect and the short half-life, EVs must be administered several times so that their organ protection features can unfold. However, such administrations increase the potential risk of accumulation in the lungs and liver. As a result, tumor development in cancer-prone patients or progression of an undetected malignancy may occur during therapy. The effects of long-term systemic application of EVs and their impact on tumor development have not yet been fully evaluated. To close this research gap, we are investigating the influence of MSC-derived EVs on tumor growth in small cell lung cancer and hepatocellular carcinoma cells over ten days, mimicking the scenario in clinical practice.
Contact: M. Pokusa
Expertise & Equipment
In vitro methods
- Isolation of cells from heart tissue, whole blood, and umbilical cords (e.g., mesenchymal stromal cells, fibroblasts, endothelial cells)
- Cell culture: primary cells, cell lines, organoids, 3D microtissues
- Bacterial culture
- Gene transfer and genetic engineering: transfection, transduction
- Isolation of DNA, RNA and proteins from cells, tissues and bacterial samples
- Gene and protein expression analysis: PCR, qPCR, flow cytometry, Northern blot, Southern blot, Western blot
- Microscopy: bright field, fluorescence, confocal, live cell imaging, high content imaging
- Enzyme-linked immunosorbent assay, fluorescence in situ hybridization
- Functional assays: cell toxicity, viability, autophagy, angiogenesis, senescence, proliferation
- MicroRNA sequencing, 16S ribosomal DNA sequencing
- Histology: Harvesting, processing, staining and conservation of heart tissue and saphenous vein grafts
- Isolation and characterization of extracellular vesicles from various cell lines (e.g., nanoparticle tracking analysis)
- Isolation of peripheral blood mononuclear cells from whole blood
- Plasma surface technology for surface modification
- In vitro simulation of ischemia/reperfusion
In vivo methods
- Murine models of ischemia reperfusion injury (e.g., myocardial infarction, hind/limb ischemia)
- Large animal models for regenerative medicine (e.g., intracoronary and intramyocardial delivery)
- Large animal models of cardiovascular disease (e.g., ischemic and structural heart disease and peripheral vascular disease)
- Development of new models for cardiovascular disease and therapeutics (e.g., pigs and sheeps)
- Intestinal bacterial colonization
Equipment
- Hypoxia incubator, Binder
- LightCycler 480 II 384 well, Roche
- MACSQuant VYB, Miltenyi Biotec
- Microscope BZ-X700, Keyence
- Microplate reader Epoch 2, BioTek
- Microplate washer 405 TS, BioTek
- Parallel-plate flow chamber in an IF750 incubator, Memmert
- Plasma surface technology, ZEPTO, Diener
- ZetaView, Particle Metrix
- … and many more …
If you are interested in using equipment from our group, please do not hesitate to get in touch with Prof. Emmert. We welcome collaboration and look forward to a mutually beneficial exchange. Feel free to contact us to explore this opportunity.
Collaborations
Germany
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Center for Regenerative Therapies, Berlin, Germany
- Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
Austria
- Department of Cardiology, Medical University Vienna, Vienna, Austria
Switzerland
- ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland
- Cardiocentro Lugano, Lugano, Switzerland
- Department of Cardiac Surgery, Stadtspital Zurich, Zurich, Switzerland
- Department of Cardiac Surgery, University Hospital Zurich, Zurich Switzerland
- Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
- Division for Surgical Research, University Hospital Zurich and University of Zurich, Zürich, Switzerland
- Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland
- Wyss Zurich, ETH and University of Zurich, Zurich, Switzerland
Selected publications
- Emmert MY, Burrello J, Wolint P, Hilbe M, Andriolo G, Balbi C, Provasi E, Turchetto L, Radrizzani M, Nazari-Shafti TZ, Cesarovic N, Neuber S, Falk V, Hoerstrup SP, Hemetsberger R, Gyöngyösi M, Barile L, Vassalli G. Intracoronary delivery of extracellular vesicles from human cardiac progenitor cells reduces infarct size in porcine acute myocardial infarction. Eur Heart J. 2023. DOI: 10.1093/eurheartj/ehad636
- Exarchos V, Neuber S, Meyborg H, Giampietro C, Chala N, Moimas S, Hinkov H, Kaufmann F, Pramotton FM, Krüger K, Rodriguez Cetina Biefer H, Cesarovic N, Poulikakos D, Falk V, Emmert MY, Ferrari A, Nazari-Shafti TZ. Anisotropictopographies restore endothelial monolayer integrity and promote the proliferation of senescent endothelial cells. Front Cardiovasc Med. 2022. DOI: 10.3389/fcvm.2022.953582
- Cesarovic N, Weisskopf M, Kron M, Glaus L, Peper ES, Buoso S, Suendermann S, Canic M, Falk V, Kozerke S, Emmert MY, Stoeck CT. Septaly oriented mild aortic regurgitant jets negatively influence left ventricular blood flow-insights from 4D flow MRI animal study. Front Cardiovasc Med. 2021. DOI: 10.3389/fcvm.2021.711099
- Neuber S, Nazari-Shafti TZ, NugrahaB, FalkV, Emmert MY. The link between regeneration and extracellular matrix in the heart-can three-dimensional in vitro models uncover it? Eur HeartJ. 2021. DOI:10.1093/eurheartj/ehab079.
- Nazari-Shafti TZ, Neuber S, Duran AG, Exarchos V, Beez CM, Meyborg H, Krüger K, Wolint P, Buschmann J, Böni R, Seifert M, Falk V, Emmert MY. MiRNA profiles of extracellularvesicles secreted by mesenchymal stromal cells–can they predict potential off-target effects? Biomolecules. 2020. DOI: 10.3390/biom10091353.
- Rodriguez Cetina Biefer H, Elkhal A, Cesarovic N, Emmert MY. NAD+ the disregarded molecule in cardiac metabolism. Eur Heart J. 2020. DOI: 10.1093/eurheartj/ehaa044.
- Lipiski M, Eberhard M, Fleischmann T, Halvachizadeh S, Kolb B, Maisano F, Sauer M, Falk V, Emmert MY, Alkadhi H, Cesarovic N. Computed tomography-based evaluation of porcine cardiac dimensions to assist in pre-study planning andoptimized model selection for pre-clinical research. Sci Rep. 2020. DOI: 10.1038/s41598-020-63044-1.
Complete publication list
Join us!
We want YOU - Apply now!
We are always looking for new talents to join our team for internships or Bachelor / Master/ MD / PhD thesis projects.
If you are interested, please send your CV and cover letter!
Team & Alumni
- Maximilian Y. Emmert, MD, PhD
- Simon Sündermann, MD
- Hector Rodriguez Cetina Biefer, MD
- Nikola Cesarovic, MD, PHD
- Timo Z. Nazari-Shafti, MD
- Ibrahim Etem Caliskan, MD
- Christien M. Beez, PhD
- Hristian Hinkov, MD
- Dr. Jasper Iske, MD
- Vasileios Exarchos
- Alexandru Claudiu Paun
- Mohamed Ghoneim
- Magdalena Pokusa
- Henriette Thau
- Miriam Ermer
- Heike Meyborg, Dipl. Ing (FH)
- Katrin Krüger
Alumni of the group
- Yağmur Erdoğan, Medical student (2022)
- Omayma Hammani, Master student (2022)
- Ema Zacharova, Bachelor student (2021-2022)
- Bhavana Vegesna, Master student (2020-2022)
- Aygen Nazlıcan Uysal, Bacherlor student (2021)
Leadership
Maximilian Y. Emmert, MD, PhD
Deutsches Herzzentrum der Charité (DHZC)
Department of Cardiothoracic and Vascular Surgery
Augustenburger Platz 1
13353 Berlin, Germany