Research Hein Heidbuchel

Abstract

Atrial fibrillation (AF) is highly prevalent and patients with AF have an increased thromboembolic risk compared to healthy individuals that can lead to stroke or systemic thromboembolism. Oral anticoagulants are used to prevent the occurrence of clinical thromboembolic events in AF patients with a high thrombotic risk (calculated by the CHA2DS2-VASc score). The use of oral anticoagulants, however, is accompanied by an increase in bleeding risk, especially in elderly patients and patients with comorbidities. In a recent study we showed that significant mitral regurgitation (MR) can reduce the thromboembolic risk in AF patients. The present project is designed to explore the causal relationship between MR and the prevention of thrombotic risk in AF patients. We aim to develop an experimental porcine model in order to further examine the pathophysiological effect of MR on this thrombotic risk. Subsequently, we will further extrapolate our experience in a clinical study to research the possible protective effect of MR on the thrombotic risk in humans by determining blood biomarkers before and after reduction of significant MR with the MitraClip system. We strongly believe that if we can confirm the protective effect of MR, our findings will have important clinical implications, as we believe that this protective effect is important to allow downsizing of anticoagulant treatment in AF patients who are at high bleeding risk in order to prevent serious bleeding complications.

Researcher(s)

• Promoter: Claeys Marc
• Co-promoter: Heidbuchel Hein
• Co-promoter: Segers Vincent
• Fellow: Van Laer Sven

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The aim of this study is to evaluate a new and innovative educational application based on targeted education on the adherence level for NOACs (non-vitamin K antagonist oral anticoagulants) in AF patients, compared with standard care, online targeted education and in-person targeted education. Several other parameters (knowledge level, quality of life, symptom burden, self-care capabilities, evaluation of educational efforts) will be studied.

Researcher(s)

• Promoter: Heidbuchel Hein
• Fellow: Vermunicht Paulien

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Sufficient physical activity (PA) is becoming more and more important in the prevention, onset and treatment of several cardiovascular diseases. Heart rate (HR) monitors are of interest to researchers and various healthcare providers because of their ability to use HR to indicate PA levels of individual cardiac patients in an objective, accurate and continuous way. Although some research has been carried out on the reliability of these devices in healthy persons in controlled circumstances, profound validation studies in the daily living conditions of specific cardio populations are missing. Moreover, reliable parameters and algorithms to objectively map, calculate and follow up on PA are still lacking. This research project will provide insight into the use of HR monitors in assessing PA in cardiac patients and its impact on cardiovascular fitness. First of all, various steps will be taken to develop an automated workflow and innovative algorithm that calculates a score to quantify PA levels based on HR measurements. In the next phase, the data of the PA algorithm and score will be incorporated in a healthcare provider dashboard and patient app to allow transmural follow-up of PA and coaching of patients. Finally, a prospective, multicentre, controlled clinical trial will be set up to further evaluate the newly developed PA algorithm and its ability to capture and contribute to improved cardiovascular health and fitness.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Laukens Kris

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The Vevo LAZR-X is an imaging platform for preclinical applications capable of acquiring in vivo anatomical, functional and molecular data. It combines ultra high frequency ultrasound with photoacoustic imaging (a new biomedical imaging modality based on the use of lasergenerated ultrasound) for high resolution images as well as software for analysis and quantification. This equipment will be used in the context of the study of (cardio)vascular diseases, genetics of the heart, heart valves and aortic dissection, kidney diseases and their effects on the heart and blood vessels, and for cancer research.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: De Keulenaer Gilles
• Co-promoter: Heidbuchel Hein
• Co-promoter: Loeys Bart
• Co-promoter: Smits Evelien
• Co-promoter: Van Craenenbroeck Emeline
• Co-promoter: Verhulst Anja
• Co-promoter: Verstraeten Aline

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Despite exercise being our oldest and most efficacious medicine, animal and human data suggest that excessive exercise may contribute to pathological cardiac remodelling in some, resulting in increased susceptibility for atrial and ventricular arrhythmias and sudden cardiac death. One hallmark of this pathological remodelling is the development of myocardial fibrosis (MF). In two specific types of MF in athletes (i.e. insertion point MF and right ventricular fibrosis in the context of arrhythmogenic cardiomyopathy), exercise contributes as a causal factor. We hypothesise that exercise also contributes to the development of MF in the left ventricle after (silent) myocarditis, which could explain its higher incidence in athletes. We will verify this hypothesis in a murine coxsackie B virus-induced myocarditis and exercise model. MF will be evaluated by standard histology, as well as by whole mount 3D microscopic imaging. Further, innovative serial multiplex immunohistochemistry (IHC) will be used for detailed cellular and molecular phenotyping, providing unrivalled insights into (patho)physiological remodelling during myocaditis. In addition, the modulating effect of NSAIDs will be evaluated. In parallel, clinical studies are conducted to gain insight into the aetiology and evolution of MF in athletes. Ultimately, our results will contribute to the development of guidelines on safe sport participation and NSAIDs use in the setting of viral syndromes.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Guns Pieter-Jan

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Telemonitoring of patients with Cardiac Implanted Electronic Devices (CIEDs) refers to the process of using telecommunication and information technology to monitor the health status of a patient from a distance. It has emerged as a tool to evaluate several parameters of the cardiovascular physiology and risk of the patient. Moreover, it enables clinicians to promptly initiate the appropriate treatment and care, and prevent a full manifestation of a cardiac decompensation. However, the use of telemonitoring is discouraged by the current healthcare financing models. The traditional fee-for-service (FFS) models are challenged by the modalities of telemonitoring: telemonitoring has the possibility to reduce the number of follow-up visits, while FFS models would stimulate the number of follow-up visits. Therefore, this project aims to develop a sustainable financing model for the telemonitoring of CIEDs. To create this model, a health-economic analysis will be conducted to examine the clinical effects and cost savings of telemonitoring using long-term and routine practice data. The modalities of the financing model will be discussed with cardiologists, nurse specialists and patients. Different situations will be simulated to develop the optimal financing model. This research might stimulate future researchers to investigate sustainable healthcare financing models for other telemonitoring applications, including applications in other medical fields.

Researcher(s)

• Promoter: Heidbuchel Hein

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Optimization of atrial fibrillation (AF) disease management is highly needed. The AF prevalence is 7.8% above the age of 65 years and it will further increase as the population ages and predisposing factors become more prevalent. Multimorbidity (93.5%) and polypharmacy (76.5%) are very common in these patients. The mean number of comorbidities is 5.0 in those ≥65 years old. There is a great need to optimize the management of AF patients - and not only the arrhythmia - to reduce the burden on patients, society, healthcare system and the economy. The aim of the EHRA-PATHS project is to create well founded, innovative systematic care pathways to tackle multimorbidity in elderly AF patients. We hypothesize that such a well-structured, interdisciplinary, and patient-tailored care program is feasible throughout all healthcare systems in Europe, and effective to optimize outcomes.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Verbraecken Johan

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project website

Project type(s)

• Research Project

Abstract

Atrial fibrillation (AF) is the most common arrhythmia and a common cause of stroke, heart failure, and death. AF is induced by structural remodeling of the atria, also called atrial myopathy. Current therapy is limited to antiarrhythmic drugs and ablations, but these do not cure the disease. Since atrial myopathy is incompletely understood, we aim to define the molecular, cellular, and structural changes in atrial myopathy. To this end, we will use single-cell RNA sequencing and high-resolution microscopy on a pig model and on human atrial tissues. To integrate these diverse data sets and test their relationships in atrial myopathy that predisposes the tissue to AF, mathematical modelling approaches will be employed. Collectively, these versatile models will create a highly anticipated foundation for various applications, stretching from disease modeling to testing novel strategies for development of curative therapies for an ever-growing group of patients with AF.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: De Keulenaer Gilles
• Co-promoter: Segers Vincent

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The Research Consortium of Excellence Infla-Med combines multidisciplinary expertise of eight research groups from two faculties to perform fundamental and translational research on inflammation, including: inflammatory gastrointestinal, cardiovascular, lung and kidney disorders, sepsis and allergies, as well as parasitic diseases, thereby focusing on specific inflammatory cell populations, including monocytes/macrophages, mast cells, basophils and lymphocytes. The approach of the Infla-Med consortium is twofold. Firstly, fundamental studies are performed to unravel the pathophysiological mechanisms underlying inflammatory conditions in order to enable more rational, targeted and effective intervention strategies. Secondly, Infla-Med aims to identify and validate novel therapeutic targets by screening chemical compounds in early drug discovery studies and by using an extensive platform of in vitro assays and in vivo models. The close collaboration with the Antwerp University Hospital (UZA) creates the opportunity to directly translate and clinically validate experimental findings. Thereby, Infla-Med contributes to two Frontline Research Domains of the University of Antwerp: 'Drug Discovery and Development' and 'Infectious Diseases'. Over the past four years, the multidisciplinary collaborations within Infla-Med have proven to be very successful and productive. By integrating the Infla-Med unique expertise on drug development, in vitro assays and clinically relevant animal models (validated with human samples), significant competitive funding has been acquired at European, national and UAntwerp levels with a success rate of more than 45%, which is far above the (inter)national average. Noteworthy, several Infla-Med projects have also made the transition towards valorization, demonstrating that Infla-Med results obtained from both fundamental research and well-designed preclinical studies can successfully be translated into clinical trials.

Researcher(s)

• Promoter: De Meyer Guido
• Co-promoter: Augustyns Koen
• Co-promoter: Caljon Guy
• Co-promoter: De Meester Ingrid
• Co-promoter: De Winter Benedicte
• Co-promoter: Ebo Didier
• Co-promoter: Heidbuchel Hein
• Co-promoter: Vanden Berghe Tom

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project website

Project type(s)

• Research Project

Abstract

Atrial fibrillation (AF) is very prevalent and patients with AF have an increased thromboembolic risk compared to healthy individuals that can lead to stroke or systemic thromboembolism. Oral anticoagulants are being used to prevent the occurrence of clinical thromboembolic events in AF patients with a high thrombotic risk (calculated by the CHA2DS2-VASc score). The use of oral anticoagulants, however, is accompanied by an increase in bleeding risk, especially in elderly patients and patients with comorbidities. In a recent study we demonstrated that significant mitral regurgitation (MR) can reduce the thromboembolic risk in AF patients. The present project is designed to explore the causal relationship between MR and prevention of thrombotic risk in AF patients. We aim to develop an experimental porcine model in order to further examine the pathophysiological effect of MR on this thrombotic risk. Subsequently we will further extrapolate our experience in a clinical study to determine the possible protective effect of MR on the thrombotic risk in humans by determining blood biomarkers before and after reduction of significant MR with the MitraClip system. We strongly believe that if we can confirm the protective effect of MR, our findings will have an important clinical implication, since we believe that this protective effect is important to allow downsizing of anticoagulant treatment in AF patients who are at high bleeding risk in order to prevent serious complications.

Researcher(s)

• Promoter: Claeys Marc
• Co-promoter: Heidbuchel Hein
• Co-promoter: Segers Vincent
• Fellow: Van Laer Sven

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Despite physical exercise being our oldest and most efficacious medicine, animal and human data suggest that excessive exercise may contribute to pathological cardiac remodelling, resulting in increased susceptibility for atrial and ventricular arrhythmias and sudden cardiac death. One hallmark of this pathological remodelling is the development of myocardial fibrosis (MF). In two types of MF in athletes, insertion point MF and right ventricular fibrosis in the context of arrhythmogenic cardiomyopathy, exercise contributes as a causal factor. We hypothesise that exercise also contributes to the development of MF in the left ventricle after (silent) myocarditis, which could explain its higher incidence in athletes. We will verify this hypothesis in a murine coxsackie B virus-induced myocarditis and exercise model. Standard histological, RT-qPCR and immunohistochemical analysis, including the use of tissue clearing, will provide further insights into (patho)physiological remodelling and molecular pathways. In addition, the modulating effect of NSAID and several exercise variables (intensity and timing relative to the onset of myocarditis) on the aforementioned interaction between myocarditis and physical exercise will be evaluated. Simultaneously, a multicentre registry (including serial cardiac magnetic resonance imaging and viral PCR on endomyocardial biopsies) is conducted to gain insight into the aetiology of MF in athletes.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Guns Pieter-Jan
• Fellow: Favere Kasper

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Atrial fibrillation (AF) is an increasingly prevalent arrhythmia associated with an increased morbidity and mortality. One should work towards care in which all different risk factors and treatment aspects of AF are tackled in an integrated way. Recently, risk factor management was added as the fourth pillar in AF care, next to oral anticoagulation and rate and rhythm control. Nevertheless, daily care has suboptimal attention to address these modifiable cardiovascular risk factors. There is growing insight that mHealth and new mobile technologies for patient diagnosis, support and follow-up can contribute to the outcome of AF care. This postdoctoral fellowship aims to bring mobile technology and risk factor management together by exploring the use of mHealth into the detection, treatment and follow-up of cardiovascular risk factors (i.e. overweight, obstructive sleep apnea, therapy adherence) to improve the overall care of AF patients. Three studies are planned in the scope of this project: 1) Investigate the impact of the AF-EduApp which is a mobile application for targeted education and adherence reminders on therapy adherence to oral anticoagulation. 2) Evaluate if a structured testing and treatment program for obstructive sleep apnea based on the use of mobile technology has an impact on the proportion of AF and the sleep apnea burden. 3) Explore the effect of a mobile application with a personalised weight loss management program in overweight and obese AF patients.

Researcher(s)

• Promoter: Heidbuchel Hein
• Fellow: Desteghe Lien

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Exercise capacity is markedly depressed in adults with congenital heart disease (ACDH) and associated with an increased risk of hospitalization or death. Right ventricular (RV) function is of major importance in ACHD prognosis. Our group recently demonstrated reduced subclinical RV function in ACHD patients with RV overload. Moreover, in a TOF population, strain measurements could predict functional capacity. In other study populations (HFpEF and PAH patients) coronary microvascular dysfunction (CMD) has been shown to be highly prevalent and associated with worse RV strain and exercise intolerance. To the best of our knowledge, the presence of CMD has not been investigated before in ACHD. We hypothesize that multiple factors including genetics, underlying cardiac abnormality, history of cardiac surgery and RV overload, further aggravated by classical acquired risk factors that are known to induce an inflammatory state and reduce nitric oxide bioavailability promote systemic inflammation leading to endothelial dysfunction. As such we hypothesize that the presence of endothelial dysfunction can act as a prognostic and potential therapeutic marker in ACHD. In this research project, we aim to design a prospective study of CMD in ACHD. Potential correlates of reduced CFR including RV loading conditions, clinical and biochemical markers, systemic endothelial function and echocardiographic data will be investigated as well as the potential therapeutic effect of exercise training.

Researcher(s)

• Promoter: Van Berendoncks An
• Co-promoter: Heidbuchel Hein
• Co-promoter: Van Craenenbroeck Emeline
• Fellow: Vanreusel Inne

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The AFFECT-EU project is a Horizon 2020 funded project. It involves 26 partners from 14 EU countries. The major goal of this project is to develop an accurate, risk-based and ready for implementation AF screening algorithm using digital devices, for early detection and reduction of AF-related health inequities, morbidity and mortality in Europe. The University of Antwerp (i.e. the research group of Prof. Dr. Hein Heidbuchel and dr. Lien Desteghe) will perform various scientific tasks on behalf of the European Society of Cardiology.

Researcher(s)

• Promoter: Heidbuchel Hein

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

New drug candidates often have off-target effects resulting in adverse events, thus representing a major limitation for drug R&D. Safety Pharmacology (SP) aims to detect, understand and reduce undesirable pharmacodynamic effects early-on. Especially, cardiovascular (CV) toxicity is problematic, as it is the most prevalent reason for failure during preclinical development. Moreover, CV toxicity remains a key reason for drug attrition during clinical development and beyond. This indicates current SP screens fail to detect a number of (late-onset) functional or structural CV toxicities. Additionally, SP uses a significant number of laboratory animals, thereby creating opportunities for a better implementation of the 3Rs. The vision of INSPIRE is to advance and "inspire" SP by exploring new technological capabilities (WP1), addressing emerging CV concerns (WP2) and delivering new validated solutions for CV safety screening (WP3). To this end, INSPIRE unites expertise from academic teams, technology-providers, pharmaceutical companies, regulators and hospitals to create a European training platform for 15 Early Stage Researchers (ESRs). Key innovative aspects of INSPIRE include: i) in vitro humanized cardiomyocytes assays, ii) unparalleled in vivo hardware/software solutions, iii) in silico predictions of haemodynamics, iv) mass spectroscopy imaging of drug exposure, v) exploration of mechanisms of late-onset CV toxicity, as observed in cardio-oncology, and vi) early integration of feedback from industry and regulators. Overall, INSPIRE constitutes a multidisciplinary and intersectoral training programme (WP4) with a balanced combination of hands-on research training, intersectoral secondments, local courses and network-wide events on scientific and transferable skills, enabling future R&I collaborations. Hence, INSPIRE will equip the future generation of SP scientists with a wide range of scientific knowledge and the ability to adapt to a dynamic ever-changing industry.

Researcher(s)

• Promoter: Guns Pieter-Jan
• Co-promoter: De Meyer Guido
• Co-promoter: Heidbuchel Hein
• Co-promoter: Martinet Wim
• Co-promoter: Segers Vincent
• Co-promoter: Van Craenenbroeck Emeline

Research team(s)

• Physiopharmacology (PHYSPHAR)

Project type(s)

• Research Project

Abstract

Anthracyclines are the mainstay of chemotherapeutic treatment in a wide range of malignancies, including breast cancer and frequent childhood cancers. Due to a growing population of cancer-survivors, the importance of long-term complications of anti-cancer treatment has increased. Today's breast cancer patients may become tomorrow's heart failure patients. There is an important inter individual susceptibility for the development of cardiotoxicity. This variation is not fully explained by differences in clinical risk factors. Therefore, it is suggested that genetic variations may play a role. It was recently shown that genetic variants in titin, an import anchoring protein in the cardiomyocytes, can cause a predisposition to dilated cardiomyopathies that are clinically similar to chemotherapy-induced cardiotoxicity In this research project we aim to investigate whether mutations in important structural cardiac genes, more specific titin, can cause an increased susceptibility for cardiotoxicity.

Researcher(s)

• Promoter: Van Craenenbroeck Emeline
• Co-promoter: Heidbuchel Hein
• Co-promoter: Loeys Bart
• Fellow: Boen Hanne

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Despite physical exercise being our oldest and most efficacious medicine, animal and human data suggest that excessive exercise may contribute to pathological cardiac remodelling, resulting in increased susceptibility for atrial and ventricular arrhythmias and sudden cardiac death. One hallmark of this pathological remodelling is the development of myocardial fibrosis (MF). In two types of MF in athletes, insertion point MF and right ventricular fibrosis in the context of arrhythmogenic cardiomyopathy, exercise contributes as a causal factor. We hypothesise that exercise also contributes to the development of MF in the left ventricle after (silent) myocarditis, which could explain its higher incidence in athletes. We will verify this hypothesis in a murine coxsackie B virus-induced myocarditis and exercise model. Standard histological, RT-qPCR and immunohistochemical analysis, including the use of tissue clearing, will provide further insights into (patho)physiological remodelling and molecular pathways. In addition, the modulating effect of NSAID and several exercise variables (intensity and timing relative to the onset of myocarditis) on the aforementioned interaction between myocarditis and physical exercise will be evaluated. Simultaneously, a multicentre registry (including serial cardiac magnetic resonance imaging and viral PCR on endomyocardial biopsies) is conducted to gain insight into the aetiology of MF in athletes.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Guns Pieter-Jan
• Fellow: Favere Kasper

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The burden of heart failure is substantial and likely to grow, urging for development of new therapies. Exercise training is one of the most successful therapies for heart failure but unfortunately, 20% of patients show no response and thus fail to improve prognosis. MicroRNA were recently put forward as key players in the response to exercise training. Identification of exercise-related microRNA could lead towards novel microRNA-based therapies that mimic exercise effects and could lead to a microRNA biomarker panel that can assist in tailoring of training programmes. Preliminary data from our group support this hypothesis: by performing a large unbiased screening, we designed a microRNA fingerprint that discriminates responders from non-responders to exercise training. We anticipate that the microRNA fingerprint may guide us towards microRNA that are crucial in a favorable adaptation to exercise. This translational project proposal involves both fundamental research (an animal study on microRNA-based therapy, including in vitro studies to gain mechanistic insight in microRNA-mRNA targets) and clinical translation (a prospective clinical trial to assess the predictive capacity of circulating microRNA for tailoring exercise therapy). This bedside-to-bench-and-back approach will maximize the potential for translation in relevant clinical results. In conclusion, we will use exercise as a model to discover candidate microRNA for therapy and to guide patient-tailored therapy.

Researcher(s)

• Promoter: Heidbuchel Hein
• Fellow: Van Craenenbroeck Emeline

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

MicroRNAs are negative regulators of gene expression by inhibition of mRNA translation in the cell cytoplasm. MicroRNAs can be released into the circulation upon cell injury or as part of intercellular communication. Together with their remarkable stability in plasma, this feature makes microRNAs attractive as biomarkers. Physical exercise may alter gene expression through an effect on circulating microRNA. Exercise training is one of the most efficacious ways to improve physical performance, quality of life and to reduce morbidity and mortality in patients with heart failure. However, recent insights show that exercise-induced maladaptations may also lead to pathology, for example exercise-induced arrhythmogenic right ventricular cardiomyopathy, a condition well known in athletes. In this project, we will focus on the role of microRNA in cardiovascular adaptation to exercise at both spectra: the beneficial effects of exercise in heart failure with reduced ejection fraction (HFrEF) as well as exercise-induced arrhythmogenic right ventricular cardiomyopathy (EI-ARVC) in athletes. MicroRNA's could serve as marker of and may even play a mechanistic role in the respons to exercise during cardiac rehabilitation. In El-ARVC, they could serve as diagnostic markers for this disease. In both conditions, microRNA's may offer insights into the underlying mechanisms that are involved in exercise-induced remodeling under the physiological stress of exercise.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Van Craenenbroeck Emeline
• Fellow: Witvrouwen Isabel

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The aim of this study is to evaluate a new and innovative educational application based on targeted education on the adherence level for NOACs (non-vitamin K antagonist oral anticoagulants) in AF patients, compared with standard care, online targeted education and in-person targeted education. Several other parameters (knowledge level, quality of life, symptom burden, self-care capabilities, evaluation of educational efforts) will be studied.

Researcher(s)

• Promoter: Heidbuchel Hein

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

The aim of this study is to evaluate a new and innovative educational application based on targeted education on the adherence level for NOACs (non-vitamin K antagonist oral anticoagulants) in AF patients, compared with standard care, online targeted education and in-person targeted education. Several other parameters (knowledge level, quality of life, symptom burden, self-care capabilities, evaluation of educational efforts) will be studied.

Researcher(s)

• Promoter: Heidbuchel Hein

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and one of the most common causes of stroke and heart failure. AF is induced by electrical, contractile, and structural remodeling of the atria. Moreover, AF itself induces these changes, leading to a vicious circle ("AF begets AF"). Tissue inflammation and fibrosis play an important role in the structural changes, and form the basis of subsequent electrical and contractile atrial dysfunction. Current therapy is limited to rhythm control using antiarrhythmic drugs, but these drugs do not target the structural problem. That may explain why they are only marginally effective. Ablation by electrical isolation of the pulmonary veins (PVI) has broadened the medical opportunities, but it is also unsatisfactory since it addresses only part of the atria. This explains the high relapse rate in patients with more widespread atrial disease (and more persistent forms of AF). More extensive ablations have not shown better results, as can be anticipated by the fact that more destruction will not solve a primarily structural problem. There is a clear medical need for a treatment targeting the underlying pathophysiology leading to structural atrial remodeling. In this project, we will test the hypothesis that the neuregulin-1 (NRG-1)/ErbB pathway is an inhibitory pathway in development of atrial fibrillation. NRG-1 is a member of the epidermal growth factor family that binds to tyrosine kinase receptors and has cell protective and regenerative properties in the heart during heart failure. We recently discovered that NRG-1 has anti-inflammatory and anti-fibrotic properties in different organs, including the heart. As mentioned, fibrosis and inflammation are the main features of structural atrial remodeling present in AF. We hypothesize that (1) the endothelium-derived NRG-1 – ErbB4 system is activated in atrial tissue of patients with atrial fibrillation. We will harvest atrial tissue samples during cardiac surgery procedures from patients with and without AF and determine expression of NRG-1 and its receptors by histology. We will determine (2) whether NRG-1 attenuates atrial fibrosis and atrial fibrillation in two mouse models of atrial fibrillation. For this aim we will use transgenic mouse models that spontaneously develop atrial fibrosis and AF. We will treat these mice with different doses of NRG-1, continuously monitor cardiac rhythm and function, and evaluate histological changes in atria after 4 weeks of treatment. We will (3) develop a sterile pericarditis large animal model of AF in pigs. We will fully characterize reprogramming of different atrial cell types by RNA sequencing. Finally, we will determine (4) whether NRG-1 attenuates atrial fibrosis and atrial fibrillation in these pigs. If successful, this project could open new avenues for treatment of atrial fibrillation by addressing atrial tissue remodeling.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: De Keulenaer Gilles
• Co-promoter: De Meyer Guido

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

We want to evaluate the effect of a new and innovative mobile application (self developed) based on intensive targeted education of AF patients. Different unique aspects will be implemented in this application: 1) The JAKQ will be used to provide personalized education for each patient based on general AF knowledge gaps and knowledge gaps about the specific OAC medication of the patients. Patients will receive specific feedback on all aspects of the JAKQ based on written text, images, movies,…; 2) Adherence-motivating aspects will be implemented; 3) Elements to improve patients' self-care will also be incorporated. The primary endpoint of this study will be the percentage of regimen adherence (i.e. proportion of days with the correct number of doses taken) of both AF patients on once daily and twice daily NOAC after a follow-up of 12 months. A second aim of this study is to evaluate the effect of the new mobile application focusing on targeted education on the knowledge level of AF patients and their health status. Additionally, patients' satisfaction about the new mobile application will be evaluated together with the app-use data.

Researcher(s)

• Promoter: Heidbuchel Hein
• Fellow: Desteghe Lien

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

In classical ablation, radiofrequency energy is used to destroy cardiac tissue in order to treat arrhythmias. The effects of ablation are rather aspecific. In this project, we want to explore a much more selective targeting of myocytes, that are first labeled by gold containing specific antibodies. With antibodies that are directed specifically to atrial myocytes, we want to prove in cultures of human induced pluripotent stem cells that only the atrial myocytes (but not ventricular of nodal ones) can selectively be destroyed by applying photoenergy.

Researcher(s)

• Promoter: Heidbuchel Hein
• Fellow: Coonen Laura

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Cardiovascular disease is the leading cause of death in Europe and is strongly related to a sedentary lifestyle. In parallel with a modern inactivity pandemic, the past 2 decades have witnessed an increase in the number of middle-aged and older individuals engaging incompetitive endurance sports events. This increasing popularity of endurance sports implies that a greater proportion of individuals participating in high-intensity sport has a higher cardiovascular risk profile. Coronary artery disease is by far the most common cause of sudden cardiac death in senior athletes. Cases of sudden cardiac death are often widely publicized in the media, and are accompanied by questions on its relation with the sports activity and how it could have been prevented. Retrospective observations provide some reassurance, but have been difficult to interpret given major differences between athletic and referent populations in cardiovascular risk factors such as smoking and socio-economic status. Concerns regarding a potential 'overdose' of exercise are further nourished by data in the literature that have linked long-term endurance exercise with an excess of arrhythmias. The aim of this project is to discern both preventive and adverse effects of long-term endurance exercise. By comparing a group of lifelong endurance athletes, engaged in endurance sports since the age of 25 years, a group of late-onset older endurance athletes, performing endurance exercise since only 6 to 36 months, and a sedentary cohort we will specifically assess the benefits and risks related to the age of onset of endurance exercise. As primary endpoint we will assess the prevalence of coronary atherosclerosis using coronary artery calcium scoring. We will evaluate if a possible beneficial effect of lifelong endurance exercise on coronary artery disease is associated with an increased risk of adverse effects, such as an increased incidence of atrial fibrillation or significant myocardial fibrosis.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Van Craenenbroeck Emeline

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Atrial fibrillation (AF) is associated with increased morbidity and mortality. As stated in the 2016 European Guidelines on the management of AF, there is an urgent need for a more structured and efficient care system in this growing AF population in order to reduce the burden on patients, the society, the healthcare system and the economy. A proposed strategy is to deliver care through 'interdisciplinary nurse-led AF centers', that have shown to improve guideline-adherence and outcomes in a cost-effective way. 'Integrated care' requires streamlined communication between stakeholders (cardiologists, general practitioners, other specialists, care givers) on one hand, and improved education of patients on the other hand, to increase their motivation, empower them for more self-care and allowing shared decision-making. However, there are no blueprints available on how this 'integrated care' should be implemented. Hospitals often have no predefined pathways or support systems to evaluate and follow-up AF patients in a systematic way and to communicate their management to different stakeholders. For patient education, a more structured and individualised approach is indispensable. Finally, integrated AF care requires a redesign of daily practice making use of AF nurses to provide patient education, to coordinate care and to facilitate communication between stakeholders. This project aims to evaluate which elements of integrated care contribute most to improved outcomes and how proven therapies can most effectively and most cost-efficiently be delivered to AF patients. We will focus on two main topics: 1) communication within the AF center, and between the AF center and different stakeholders by means of an 'AF passport'; 2) targeted education of patients, aiming for more cost-efficient knowledge increase and better clinical outcomes. We will use a randomised controlled trial design in three large cardiology centers.

Researcher(s)

• Promoter: Heidbuchel Hein

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Cardiovascular disease is the leading cause of death in Europe and is strongly related to a sedentary lifestyle. In parallel with a modern inactivity pandemic, the past 2 decades have witnessed an increase in the number of middle-aged and older individuals engaging incompetitive endurance sports events. This increasing popularity of endurance sports implies that a greater proportion of individuals participating in high-intensity sport has a higher cardiovascular risk profile. Coronary artery disease is by far the most common cause of sudden cardiac death in senior athletes. Cases of sudden cardiac death are often widely publicized in the media, and are accompanied by questions on its relation with the sports activity and how it could have been prevented. Retrospective observations provide some reassurance, but have been difficult to interpret given major differences between athletic and referent populations in cardiovascular risk factors such as smoking and socio-economic status. Concerns regarding a potential 'overdose' of exercise are further nourished by data in the literature that have linked long-term endurance exercise with an excess of arrhythmias. The aim of this project is to discern both preventive and adverse effects of long-term endurance exercise. By comparing a group of lifelong endurance athletes, engaged in endurance sports since the age of 25 years, a group of late-onset older endurance athletes, performing endurance exercise since only 6 to 36 months, and a sedentary cohort we will specifically assess the benefits and risks related to the age of onset of endurance exercise. As primary endpoint we will assess the prevalence of coronary atherosclerosis using coronary artery calcium scoring. We will evaluate if a possible beneficial effect of lifelong endurance exercise on coronary artery disease is associated with an increased risk of adverse effects, such as an increased incidence of atrial fibrillation or significant myocardial fibrosis.

Researcher(s)

• Promoter: Heidbuchel Hein

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

MicroRNAs are negative regulators of gene expression by inhibition of mRNA translation in the cell cytoplasm. MicroRNAs can be released into the circulation upon cell injury or as part of intercellular communication. Together with their remarkable stability in plasma, this feature makes microRNAs attractive as biomarkers. Physical exercise may alter gene expression through an effect on circulating microRNA. Exercise training is one of the most efficacious ways to improve physical performance, quality of life and to reduce morbidity and mortality in patients with heart failure. However, recent insights show that exercise-induced maladaptations may also lead to pathology, for example exercise-induced arrhythmogenic right ventricular cardiomyopathy, a condition well known in athletes. In this project, we will focus on the role of microRNA in cardiovascular adaptation to exercise at both spectra: the beneficial effects of exercise in heart failure with reduced ejection fraction (HFrEF) as well as exercise-induced arrhythmogenic right ventricular cardiomyopathy (EI-ARVC) in athletes. MicroRNA's could serve as marker of and may even play a mechanistic role in the respons to exercise during cardiac rehabilitation. In El-ARVC, they could serve as diagnostic markers for this disease. In both conditions, microRNA's may offer insights into the underlying mechanisms that are involved in exercise-induced remodeling under the physiological stress of exercise.

Researcher(s)

• Promoter: Heidbuchel Hein
• Co-promoter: Van Craenenbroeck Emeline
• Fellow: Witvrouwen Isabel

Research team(s)

• Cardiovascular diseases (CARDIOVASC)

Project type(s)

• Research Project

Abstract

Inherited cardiac arrhythmias (ICA) are a group of predominantly autosomal dominant disorders characterized by a disturbed cardiac action potential that can lead to sudden cardiac death at a young age. Although currently more than 50 genes have been associated with ICA, in roughly 70% of the patients the precise genetic cause is still unknown. Moreover, this group of diseases is genetically and phenotypically heterogeneous and in a molecular diagnostic setting many variants of unknown pathogenic significance are detected, hampering proper risk stratification and efficient patient management. In a unique interfaculty collaboration between the Centre of Medical Genetics, the Cardiology department, the Laboratory of Experimental Hematology and Laboratory for Molecular Biophysics, Physiology and Pharmacology, we envision to address these needs in a project with two major aims: the identification of novel genes implicated in ICA and the development of a new diagnostic tool that allows functional phenotypic evaluation of the effect of genetic variants detected in ICA patients and family members. The first aim will be achieved using linkage analysis and state-of-the-art whole-genome sequencing in phenotypically well-characterized but genetically unresolved families, followed by functional characterization of the identified candidate variants. The second aim will be accomplished by the construction and electrophysiological characterization of patient-specific induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs). Focusing on the Brugada syndrome (BrS) as a proof-of-principle, iPSC-CMs will be created from fibroblasts of family members carrying an identical BrS-causing mutation but with different phenotypic expression of disease severity, and of BrS patients with a variant of unknown significance in the SCN5A gen. These powerful approaches in combination with the existing expertise in the different collaborating teams, will definitely allow accomplishing the envisioned ultimate goals of the project. As a result, a genetic diagnosis in a larger proportion of ICA families will be reached and can be translated into a personalized functional interpretation of the genetic result in patients and relatives. This will introduce the concept of precision medicine, tailoring proper risk stratification and efficient use of preventive and therapeutic measures for the individual patient.

Researcher(s)

• Promoter: Loeys Bart
• Co-promoter: Heidbuchel Hein
• Co-promoter: Snyders Dirk

Research team(s)

Project type(s)

• Research Project