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

Transcatheter aortic valve implantation, MitraClip and Cardioband are minimally invasive procedures that are 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

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

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

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