Ongoing projects

Peripheral oxygen extraction in health and disease. 01/04/2024 - 31/03/2025

Abstract

This research project targets the critical issue of exercise intolerance in heart failure with preserved ejection fraction (HFpEF). The prevalence of HFpEF is rising due to an aging population, and exercise intolerance is the primordial symptom. Previous research has determined that peripheral oxygen extraction (A-VO2) is limited in most HFpEF patients, but the mechanisms are still unclear. Non-invasive methods to measure A-VO2 are unfortunately lacking. This study hypothesizes that skeletal muscle oxygenation is a significant determinant of A-VO2 in HFpEF. The project aims to enable non-invasive measurement of A-VO2, establish normal and abnormal values, and correlate these with myofiber properties in HFpEF patients. We will use simultaneous cardiopulmonary exercise testing (CPET) and exercise echocardiography (CPETecho) to assess oxygen transport and utilization. A particular focus will be on near-infrared spectroscopy (NIRS) to directly measure skeletal muscle oxygenation. The study is organized into two work packages (WPs). WP1 will establish normal and abnormal skeletal muscle oxygenation responses during exercise in healthy individuals, patients at risk of HFpEF, and those with confirmed HFpEF. WP2 will explore the relationship between skeletal muscle oxygenation and muscle structure in HFpEF patients, through biopsies to study myofiber properties, myonuclear accretion, and gene/protein expression related to muscle growth and mitochondrial function. The project's relevance lies in its potential to fill a significant knowledge gap by providing non-invasive assessment methods for A-VO2, thus enhancing our understanding of exercise intolerance in HFpEF. The study's anticipated outcome is the establishment of reference values for A-VO2 and correlations to histological examinations, contributing to better diagnosis and treatment strategies for patients with HFpEF. The successful completion of this pilot project may open doors for further research aimed at improving exercise tolerance through focusing on strategies improving skeletal muscle oxygenation in patients with HFpEF.

Researcher(s)

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Project type(s)

  • Research Project

Immune Checkpoint Inhibitors induce endothelial inflammation as first step in cardiovascular side effects 01/04/2024 - 31/03/2025

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized oncological care, but cardiovascular immune related adverse events are feared. There is growing evidence suggesting that ICI accelerate atherosclerosis or even lead to increased risk for acute coronary syndromes. The current proposal studies the effects of ICI on the cardiovascular system, hypothesizing that ICI induce endothelial inflammation and dysfunction. VCAM-1 is expected to be key in these processes and could function as a potential target in future project proposals. Mice (C57/Bl6 and ApoE-/-) will be treated with ICI for one week and undergo in vivo functional cardiovascular assessment with echocardiography and pulse wave velocity. Upon sacrifice, ex vivo endothelial function will be studied and inflammatory markers will be analyzed. The purpose of this proposal is to demonstrate early endothelial inflammation and VCAM-1 upregulation after ICI treatment. This hypothesis was incorporated in previous grant proposals (FWO Junior Project, Stand up against Cancer, Foundation against Cancer) and was positively reviewed and considered relevant and novel, but preliminary data were absent. With this BOF Small Research Grant, preliminary data will be obtained to apply for further funding and start this new line of research within GENCOR.

Researcher(s)

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Project type(s)

  • Research Project

Encouraging grant 2023 'Rosa Blanckaert' for young researchers: (Bio)Medical Sciences. 01/12/2023 - 31/12/2025

Abstract

Adults with a congenital heart disease (ACHD) have a lower functional capacity, reduced quality of life and worse prognosis compared to healthy individuals. ACHD and patients with heart failure (HF) induced by other etiologies share many characteristics, incl. exercise intolerance, right ventricular (RV) dysfunction and increased inflammatory cytokine levels. Among the pathophysiological changes in HF, endothelial dysfunction is highlighted. However, the presence of endothelial dysfunction in ACHD is unknown as literature is limited and conflicting. We hypothesize that coronary microvascular dysfunction (CMD) is important in the pathophysiology of ACHD. We believe that multiple factors incl. genetics, underlying cardiac abnormality, history of cardiac surgery and RV overload, further aggravated by classical acquired risk factors (including overweight, hypertension and sedentary lifestyle), alter shear stress and promote systemic inflammation and endothelial oxidative stress in ACHD leading to a reduced nitric oxide bioavailability and endothelial dysfunction. As such we assume CMD is associated with systemic endothelial dysfunction, reflecting CMD as part of a systemic microvascular disorder. We are convinced that detecting CMD is important to allow identification of ACHD with an unfavorable prognosis and that this CMD can easily be identified with adenosine-based Doppler echocardiography. Finally, the potential therapeutic effect of exercise training will be investigated.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Cardiopulmonary exercise testing with echocardiography in diagnosis, phenotyping and treatment of heart failure with preserved ejection fraction. 01/11/2023 - 31/10/2024

Abstract

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure, with limited therapeutic options and a poor prognosis. Challenges in HFpEF diagnosis, undifferentiated treatment of HFpEF patients despite phenotypical differences, and underutilization of exercise as part of therapy contribute to the unfavorable prognosis. Although exercise intolerance is a general symptom among HFpEF patients, and current guidelines recommend exercise training, the underlying pathophysiological mechanisms remain unclear. Recent research shows that combined echocardiography and cardiopulmonary exercise testing (CPETecho) is a non-invasive method that can characterize physiological limits to exercise, including in HFpEF patients. In this study, we aim to (1) evaluate whether routine use of CPETecho can improve the accuracy of HFpEF diagnosis, (2) identify subgroups of HFpEF patients with different exercise limitations (exercise phenotypes), and (3) assess the impact of exercise training on these HFpEF exercise phenotypes. We will recruit HFpEF patients from 3 third-line hospitals and perform CPETecho. We will also analyze multicentre exercise training trials to assess the influence of exercise training on HFpEF exercise phenotypes. Our study will address the clinical need for better efficiency in HFpEF diagnosis. By defining HFpEF exercise phenotypes and evaluating the benefits of exercise training, we aim to improve the precision of HFpEF treatment.

Researcher(s)

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Project type(s)

  • Research Project

Research in the context of the AF-EduApp study 01/08/2023 - 31/12/2027

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)

Research team(s)

Project type(s)

  • Research Project

Assessment and long-term transmural follow-up of individual physical activity measured with heart rate monitors for improved cardiovascular health and fitness. 01/01/2023 - 31/12/2026

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)

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Project type(s)

  • Research Project

The pathophysiological role of exercise and nonsteroidal anti-inflammatory drugs (NSAIDs) in the development of (left ventricular) myocardial fibrosis during viral myocarditis. 01/01/2022 - 31/12/2025

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)

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Project type(s)

  • Research Project

Improvement of risk stratification and treatment in acute myocarditis. 01/01/2022 - 31/12/2025

Abstract

Acute myocarditis (AM) is an inflammatory disease of the heart that can be caused by infectious agents, autoimmune disorders, and drug hypersensitivity reactions. The diagnosis of AM is based on symptoms, biomarkers and non-invasive imaging. Cardiovascular magnetic resonance imaging (CRM) can accurately diagnose AM by detection of oedema and inflammation in the acute setting, as well as demonstration of residual scar after recovery. In virus-triggered AM, it is assumed that myocardial injury mainly results from autoimmunity. Although there is a rationale for immunosuppressive therapy, no trial has tested this hypothesis in the acute phase. The multicentre MYTHS trial will evaluate the efficacy of pulsed intravenous corticosteroids on top of standard therapy in patients with fulminant AM (left ventricular ejection fraction (LVEF) <41%). The first aim of this project proposal is to evaluate the treatment with corticosteroids in patients with complicated, non-fulminant AM (LVEF 41-50%) regarding outcome (cardiac death and life-threatening arrhythmias) and myocardial scar formation on CMR, as these patients have an increased risk of adverse events, but will not be included in the main MYTHS trial. Second, we want to improve risk stratification in patients with AM by identifying prognostic markers related to myocardial scar on baseline and follow-up CMR, to estimate sudden cardiac death risk and the need for a prophylactic implantable cardioverter-defibrillator.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Microvascular dysfunction in adults with a congenital heart disease and the effect of exercise training (MICONEX). 01/11/2021 - 31/10/2025

Abstract

Adults with a congenital heart disease (ACHD) have a lower functional capacity, reduced quality of life and worse prognosis compared to healthy individuals. ACHD and patients with heart failure (HF) induced by other aetiologies share many characteristics, incl. exercise intolerance, right ventricular (RV) dysfunction and increased inflammatory cytokine levels. Among the pathophysiological changes in HF, endothelial dysfunction is highlighted. However, the presence of endothelial dysfunction in ACHD is unknown as literature is limited and conflicting. I hypothesize that coronary microvascular dysfunction (CMD) is important in the pathophysiology of ACHD. I believe that multiple factors incl. genetics, underlying cardiac abnormality, history of cardiac surgery and RV overload, further aggravated by classical acquired risk factors (including overweight, hypertension and sedentary lifestyle), alter shear stress and promote systemic inflammation and endothelial oxidative stress in ACHD leading to a reduced nitric oxide bioavailability and endothelial dysfunction. As such I assume that CMD is associated with systemic endothelial dysfunction, reflecting CMD as part of a systemic microvascular disorder. I am convinced that detecting CMD is important to allow identification of ACHD with an unfavorable prognosis and that this CMD can easily be identified with adenosine-based Doppler echocardiography. Finally, the potential therapeutic effect of exercise training will be investigated.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

A sustainable financing model for the telemonitoring of patients with cardiac implanted electronic devices. 01/11/2021 - 31/10/2025

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)

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Project type(s)

  • Research Project

Mechanistic insights in mitral valve prolapse and associated left ventricular remodelling: Barlow's Disease versus Fibroelastic Deficiency. 01/10/2021 - 30/09/2025

Abstract

Mitral valve prolapse (MVP) is a valvular disorder with a prevalence of 2-3% in the general population. MVP can be associated with mitral regurgitation (MR), congestive heart failure, ventricular arrhythmias and sudden cardiac death. Barlow's Disease (BD) and Fibro-Elastic deficiency (FED) present the 2 most common MVP phenotypes. In recent years, several genetic mutations have been identified which might play a role in the pathophysiology of MVP, but the exact genotype-phenotype correlation remains largely unknown. Furthermore, recent evidence points to the existence of a concomitant cardiomyopathy in BD, regardless of MR severity. We hypothesise that BD and FED are determined by different genetic mutations and pathophysiological processes, which result in more severe left ventricular remodelling in BD as compared with FED. A better understanding of the genetic and phenotypic differences between BD and FED is crucial to improve patient's risk stratification, diagnostic and therapeutic management. The aim of this project is to prospectively assess the differences in genotype and phenotype between BD versus FED with a focus on left ventricular remodelling, myocardial fibrosis and arrhythmias and its evolution with or without mitral valve surgery. We will recruit 100 patients with FED and BD at 2 large volume centres (Antwerp University Hospital and Maastricht Medical University Center) for genetic analysis and an in-depth phenotyping with 3D-echocardiography and cardiovascular magnetic resonance scan.

Researcher(s)

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Project type(s)

  • Research Project

UZA-Addressing multimorbidity in elderly atrial fibrillation patients through interdisciplinary, tailored, patient-centered care pathways (EHRA PATHS). 01/04/2021 - 31/03/2026

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.

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Project website

Project type(s)

  • Research Project

Discovering the role of titin (TTN) in anthracycline-induced cardiotoxicity in breast cancer. 01/01/2021 - 31/12/2024

Abstract

Anthracyclines are the mainstay of chemotherapeutic treatment in a wide range of malignancies, including breast cancer. Cardiotoxicity is a well-known and feared adverse effect of anthracyclin therapy and due to the growing population of cancer survivors, cardiovascular disease in these patients is expected to escalate. Unless we can identify high-risk patients for anthracycline therapy, today's breast cancer patients may become tomorrow 's heart failure patients. However, there is an important inte individual susceptibility for the development of cardiotoxicity and at present, it is not possible to predict which patients will develop cardiotoxicity. It was recently shown that genetic variants in titin, an import anchoring protein in the cardiomyocytes, can cause a predisposition to dilated cardiomyopathies and are also more prevalent in chemotherapy-induced cardiotoxicity. In this research project we investigate if mutations in titin increase the susceptibility for cardiotoxicity to anthracyclines, in order to identify high -risk patients. If this can be confirmed, the impact on both the individual patient (morbidity, mortality) and on society will be huge. The development of an hiPSC-CM model harbouring different TTNtv will allow us to test different possible therapeutic and preventive measures for this high risk population.

Researcher(s)

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Project type(s)

  • Research Project

Defining atrial myopathy in aging and disease (DIAMOND consortium). 01/01/2021 - 31/12/2024

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)

Research team(s)

Project type(s)

  • Research Project

The pathophysiological role of physical exercise in the development of (left ventricular) myocardial fibrosis during viral myocarditis. 01/11/2020 - 31/10/2024

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)

Research team(s)

Project type(s)

  • Research Project

MicroRNA in heart failure: Exercise as a tool to discover candidate microRNA for therapy and personalized medicine. 01/10/2019 - 30/09/2024

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.

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  • Research Project

Past projects

Study of the protective role of mitral valve regurgitation on the thrombotic risk in nonrheumatic atrial fibrillation: an experimental and human research model. 01/12/2022 - 31/10/2023

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.

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  • Research Project

Personalised management with the use of new mobile and integrated care tools targeting three outcome determinants in patients with atrial fibrillation. 01/11/2020 - 31/10/2023

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.

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Project type(s)

  • Research Project

Right ventricular (dys)function in congenital heart disease: role of microvascular dysfunction and effect of exercise training. 01/11/2020 - 31/10/2021

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)

Research team(s)

Project type(s)

  • Research Project

Mitral valve prolapse and associated cardiomyopathy: impact of mitral valve prolapse subtype and genetics. 01/11/2020 - 31/10/2021

Abstract

Mitral valve prolapse (MVP) is a valvular disorder with a prevalence of 2-3% in the general population. MVP can be associated with mitral regurgitation (MR), congestive heart failure, ventricular arrhythmias and sudden cardiac death. Barlow's Disease (BD) and Fibro-Elastic deficiency (FED) present the 2 most common MVP phenotypes. Recently, several genetic mutations have been identified, however the exact genotype-phenotype correlation remains largely unknown. Furthermore, recent evidence points to the existence of a concomitant cardiomyopathy in BD, regardless of MR severity. We hypothesise that BD and FED are determined by different genetic mutations and pathophysiological processes, resulting in more severe left ventricular (LV) remodelling, more myocardial fibrosis and a higher arrhythmogenic risk in BD as compared with FED. The aim of this project is to prospectively assess the differences in genotype and phenotype between BD and FED with a focus on LV remodelling, myocardial fibrosis and arrhythmias and its evolution with or without mitral valve surgery. We will recruit 170 patients, 110 with FED and 60 with BD, at 2 large volume centres (Antwerp University Hospital and Maastricht Medical University Center) for genetic analysis and an in-depth phenotyping with 3D-echocardiography, cardiovascular magnetic resonance scan and 24h-Holter. Follow-up exams will be performed after 1-year in all included patients.

Researcher(s)

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Project type(s)

  • Research Project

Digital risk-based screening for atrial fibrillation in the European Community (AFFECT-EU) (WP4, 5, 6). 01/04/2020 - 31/03/2024

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.

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Project type(s)

  • Research Project

Discovering the role of titin (TTN) in anthracycline-induced cardiac dysfunction in breast cancer. 20/03/2020 - 05/03/2021

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)

Research team(s)

Project type(s)

  • Research Project

Discovering the role of titin (TTN) in anthracycline-induced cardiac dysfunction in breast cancer. 01/11/2019 - 31/10/2023

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)

Research team(s)

Project type(s)

  • Research Project

The pathophysiological role of physical exercise in the development of (left ventricular) myocardial fibrosis during viral myocarditis. 01/11/2019 - 31/10/2020

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)

Research team(s)

Project type(s)

  • Research Project

Exercise epigenomics: microRNA as biomarker of exercise-induced cardiovascular adaptation. 01/10/2019 - 30/09/2022

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.

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Project type(s)

  • Research Project

Effect of Targeted Education for Atrial Fibrillation Patients 01/10/2019 - 30/09/2020

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)

Research team(s)

Project type(s)

  • Research Project

AF-EduApp study. 01/10/2019 - 30/09/2020

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)

Research team(s)

Project type(s)

  • Research Project

Neuregulin-1 as a therapy for atrial fibrillation and the role of the NRG-1/ErbB4 system in atrial remodelling. 01/01/2019 - 31/12/2022

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)

Research team(s)

Project type(s)

  • Research Project

A new mobile application focusing on targeted education to improve the adherence and knowledge level of atrial fibrillation patients. 01/01/2019 - 15/10/2021

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)

Research team(s)

Project type(s)

  • Research Project

Diagnostic and therapeutic potential of microRNA-212 in HFpEF. 01/10/2018 - 30/09/2022

Abstract

Heart failure is the cardiovascular epidemic of the 21st century, due to population ageing and improved cardiovascular therapy. Half of heart failure patients has a preserved ejection fraction, but little is known about these 'HFpEF' patients. HFpEF pathophysiology is incompletely understood, and no existing treatment is able to improve prognosis (50% mortality at 5 years). A complicating factor is the heterogeneity of HFpEF patients: different phenotypes seem to exist, but in large clinical trials these are all classified under one 'HFpEF' category. MicroRNA seem to play an important role in HFpEF pathophysiology. MicroRNA are epigenetic regulators controlling countless biological processes and are stable in the circulation, which makes them attractive biomarkers. Also, microRNA-based therapy is easy to administer and expected effects are large, due to numerous downstream targets. We recently discovered that microRNA-212 is linked to the response to exercise training in HFpEF patients. Additionally, we found increased microRNA-212 in hearts of an ageing mouse model of HFpEF. In this project, we want to establish the diagnostic and therapeutic potential of microRNA-212 in HFpEF. Our translational approach guarantees relevant results: on one hand, we use several animal models of HFpEF (representing different clinical phenotypes) to test microRNA-212 in a therapeutic setting, on the other hand we set up a longitudinal clinical study to check the diagnostic potential of microRNA-212 with regards to the different HFpEF phenotypes. This study will evaluate microRNA-212 as a possible biomarker and therapeutic target in HFpEF. The translational design will facilitate future clinical trials. Finally, this project will gather much-needed insight in the pathophysiology of HFpEF.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Targeted photoablation and targeted synchronised photostimulation of atrial cardiomyocyties in hIPSC-CM culture. 01/04/2018 - 31/03/2019

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)

Research team(s)

Project type(s)

  • Research Project

Lifetime endurance excercise to prevent coronary artery disease. A comparison with late-onset endurance training and a sedentary lifestyle 16/10/2017 - 30/09/2021

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)

Research team(s)

Project type(s)

  • Research Project

The education and communication pillars of integrated care for atrial fibrillation. 01/10/2017 - 30/09/2021

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)

Research team(s)

Project type(s)

  • Research Project

Lifetime endurance excercise to prevent coronary artery disease. A comparison with late-onset endurance training and a sedentary lifestyle. 01/10/2017 - 30/09/2021

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)

Research team(s)

Project type(s)

  • Research Project

Exercise epigenomics: microRNA as biomarker of exercise-induced cardiovascular adaptation 01/10/2017 - 30/09/2019

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)

Research team(s)

Project type(s)

  • Research Project

Evaluation of percutaneous valves. 01/01/2014 - 31/12/2023

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project