Past Awardees

Left Bundle Branch Area Pacing using conventional stylet-driven pacemaker leads for Cardiac Resynchronization Therapy: A randomized study (LeCaRT)

Cardiac Contractility Modulation in Dilated Cardiomyopathy: an exploratory study on the changes in myocardial metabolic profile

Summary: Cardiac contractility modulation (CCM) may offer a novel therapeutic option in patients with heart failure with reduced ejection fraction (HFrEF) who are ineligible for CRT. The present cross-over study on CCM therapy will increase our knowledge on the mechanisms of action of CCM. These insights could contribute to patient selection that will benefit the most from this therapy (CCM-responders). Hence, this project is of use if cost-effective health care decisions have to be taken in the future.

Renal-based optimization of Quadruple therapy in patients with Heart Failure with reduced ejection fraction (ReQUAD-HF): a prospective, multicentre, international randomised-controlled trial.

Summary: Heart failure (HF) is prevalent with an increasing incidence due to ageing. Prognosis remains poor with a reduced quality of life. Novel quadruple HF therapy has proven to reduce morbidity and mortality in HF with a reduced ejection fraction. However, drug implementation is often hampered, especially in patients with chronic kidney disease who may have the largest benefit due to a higher event rate. This trial evaluates the benefit of a protocol-driven initiation and up-titration of therapy.

Study of the role of RGS5 in mural cell phenotypic switching, cell senescence and coronary microvascular dysfunction in 3D

Identifying druggable targets downstream of atheroprotective factor PRDM16 for treatment of ischemic disease

Study of the protective role of mitral valve regurgitation on the thrombotic risk in nonrheumatic atrial fibrillation: an experimental porcine research model

Characterizing the spatiotemporal transcriptional landscape of neural crest cell lineages in a zebrafish model for Myhre syndrome

Summary: In Myhre syndrome (MYHRS), cognitive deficiency, congenital heart disease, and impaired ocular and gastrointestinal development identified neural crest involvement in the pathogenesis. MYHRS results from gain-of-function variants (PV) in SMAD4, that disrupt transforming growth factor β and bone morphogenic protein signaling. We use a zebrafish model for MYHRS to understand how abnormal neural crest cell migration and differentiation cause cardiovascular manifestations in Myhre syndrome.

Deciphering Molecular Pathways of Hypoxia Sensitivity in Adult Cardiomyocytes: An Integrative Cross-Species Investigation

Summary: Adult cardiomyocytes are sensitive to oxygen changes, leading to cell death and heart issues. In contrast, fetal cardiomyocytes resist low oxygen, using glycolysis. After birth, they switch to glycolysis and fatty acid oxidation but lose hypoxia tolerance regulated by HIF. The research seeks to understand these changes and find genes to prevent cardiomyocyte necrosis and maintain energy production, advancing heart disease treatment and personalized medicine.

Identification of cell-specific disease genes for bicuspid aortic valve-related aortopathy by transcriptome-wide spatial profiling of a representative Smad6 mutant mouse model

Summary: In this project, I aim to improve the molecular basis of bicuspid aortic valve-related aortopathy by identifying early cell-specific disease genes in a representative Smad6 mutant mouse model using transcriptome-wide spatial profiling on embryonic tissue. With SMAD6 being the most common mutated gene, I will tackle our current gap in knowledge on the pathogenic basis underlying this disease in order to advance patient management.

Exploring the cell-specific mechanisms of aortic disease using fibrillin-1 mutant mouse models

Summary: Marfan syndrome is caused by pathogenic variants in fibrillin-1, and is associated with aortic wall damage. We use fibrillin-1 mutant mouse models to study the mechanisms leading to aortic disease. Using single-nuclear RNA sequencing and immunohistochemical staining we plan to identify changes in aortic cell populations in these models. We will also investigate cell type-specific molecular mechanisms. Our results are likely to lead to improved diagnosis and treatment options for aortic disease.

Role of adiponectin and PD-L1 in the release of cardioprotective exosomes

Summary: We have shown that mice deficient for P2Y4 nucleotide receptor display reduced cardiac inflammation and smaller infarcts than wild type mice in the left anterior descending coronary artery ligation model. The present project aims to characterize cardioprotective plasma exosomes in these mice. We will investigate the sources of these exosomes and their ability to induce leukocyte polarization. Human P2Y4 polymorphisms potentially related to cardioprotection will also be studied.

Study of the molecular mechanisms linking protein acetylation and diabetic cardiomyopathy development

Summary: Diabetes is a growing epidemic affecting a large part of the population and is a significant public health challenge. In addition to vascular defects, diabetic patients develop a particular form of heart disease called diabetic cardiomyopathy. Our laboratory has demonstrated that protein acetylation is crucial in the early stage of the disease. Our project aimed to deeply comprehend the molecular mechanisms linking protein acetylation and the onset of diabetic cardiomyopathy.

Myo-inositol/SMIT1 axis: a novel pathway to prevent of treat heart failure

Summary: Growing body of evidence associate changes in cardiac metabolism to the pathogenesis and progression of heart failure. Plasmatic myo-inositol is high in patients with failing hearts, suggesting that it may participate in heart failure development. Myo-inositol transporter SMIT1 is expressed in cardiac fibroblasts and cardiomyocytes. Our hypothesis is that myoinositol/SMIT1 axis favor hypertrophy and fibrosis, thus we aim to establish its impact on left ventricular remodeling and heart failure.

STUDY OF THE CELLULAR AND MOLECULAR MECHANISMS UNDERLYING CARDIOMYOPATHY CAUSED BY TRANSCRIPTION FACTOR PR DOMAIN CONTAINING 16 (PRDM16) DEFICIENCY IN CARDIOMYOCYTES AND NON-CARDIOMYOCYTE CELL TYPES

Generation and characterization of three novel induced pluripotent stem cell-derived cardiomyocyte lines as a model to study the pathophysiological mechanisms of arrhythmogenic cardiomyopathy

Contribution of BMP-SMAD regulated biogenesis of microRNAs in organ-specific functions  of lymphatic endothelium

Coronary plaque progression and the relationship with lipoprotein (a) and endurance exercise training

Mitral valve regurgitation and its effect on thrombotic and bleeding risk in nonrheumatic atrial fibrillation

Validation of Shear wave elastography using high frame rate imaging as a non-invasive tool for predicting elevated left ventricular filling pressures

Assessment of polygenic background to explain the association between small heart size and low cardiac fitness (GEN@HEART)

Summary: In GEN@HEART, we’re studying how genes impact heart size, exercise capacity, and cardiac fitness. We’re comparing highly trained athletes with those along the heart failure continuum. Despite similar exercise, some excel, others face heart issues. We suspect genes play a role. We aim to understand if specific genes related to heart size affect fitness. Studying 281 athletes and 312 heart failure patients, we’ll explore this question and if certain genes could lead to better exercise responses.

ECSPAND: Exercise capacity improvement by Conduction System Pacing in heArt failure patieNts without compelling CRT inDication

Summary: In this randomized trial, we aim to evaluate the effect of novel conduction system pacing (CSP) versus conventional right ventricular apical pacing on exercise capacity in patients with heart failure (HF) and concomitant conduction system disorders. We hypothesize that CSP improves exercise capacity measured by peak oxygen uptake (VO2peak) as well as other markers of HF severity. The project will also provide deeper physiological insight into the mechanisms of VO2peak improvement by CSP.

Unraveling the role of retinal imaging as a clinical tool in evaluating accelerated aging in congenital heart disease

Summary: To date, most patients with congenital heart disease (CHD) can survive into adulthood.

However, survivors often develop morbidities that suggest accelerated aging. We aim to

quantify and understand disparities in chronological and biological age and to scrutinize the role of retinal imaging as clinical tool. We enrol 315 patients, in whom retinal fundus scan and biomarkers will be obtained. Predictors of aging are determined using medical records and a life history calendar.

The value of 7-day rhythm surveillance as a novel tool for risk prediction in acute myocarditis

Summary: Acute myocarditis (AM) is an inflammatory heart disease. Symptoms vary from mild symptoms to heart failure and life-threatening arrhythmias. Sudden cardiac death (SCD) may occur up to years after initial presentation. To date, there are no reliable tools for SDC risk prediction or need for a prophylactic implantable cardioverter defibrillator. This project will evaluate the value of 7-day ECG monitoring for risk prediction in AM, comparing 24-hour Holter and cardiac magnetic resonance imaging.

Cardiac stereotactic radiation treatment for the ablation of ventricular tachycardia

Summary: Ventricular tachycardia (VT) is a life-threatening condition, usually needing a implantable cardioverter defibrillator in combination with antiarrhytmic drugs and catheter ablation. However, not all patients benefit from these standard therapies. Within a multicentric study, we aim to determine the feasibility, safety and efficacy of cardiac stereotactic body irradiation for patients with ventricular tachycardia who are no (longer) candidates for standard therapies.

The incidence of cardiovascular events and revascularizations in patients treated with Immune Checkpoint Inhibitors in Belgium

Summary: Immune Checkpoint Inhibitors (ICI) have revolutionized cancer treatment. Recent reports suggest a threefold increased risk in acute coronary syndromes upon ICI treatment, which is relevant since indications increase. This project studies the Belgian situation, where 30000 patients received ICI treatment. Data will be provided by the Intermutualistisch Agentschap – Agence Intermutualiste (IMA-AIM), Statbel and the Belgian Cancer Registry and focus on revascularizations, and cardiovascular death.

Conduction system pacing: a bench and bedside study. Insights in cardiac conduction disease translated to novel pacing strategies

SURGICAL-AF 2 study: The clinical impact of remote heart rhythm monitoring by photoplethysmography-based smartphone technology in the rehabilitation after cardiac surgery: A randomized, open-label, multicenter, pragmatic clinical trial

Prevention of recurrence of hypertensive pregnancy disorders in women with active desire for pregnancy, a randomized controlled trial: a smartphone-based aerobic exercise training program during pregnancy versus usual care

Exercise phenotypes to accelerate the personalized treatment of heart failure with preserved ejection fraction

Summary: Heart failure with preserved ejection fraction is prevalent, has poor prognosis and limited treatments. We believe HFpEF can be subdivided according to abnormalities in exercise physiology. Our research has revealed different cardiovascular physiology among HFpEF patients, suggesting potential effect on treatment. We plan to study these patients’ exercise physiology in detail, identify “exercise phenotypes” through machine learning, and create a digital tool for personalized treatment decisions.

PROSPECTIVE EVALUATION OF CARDIAC REMODELING IN YOUNG COMPETITIVE ATHLETES – IDENTIFICATION OF GENETIC AND ENVIRONMENTAL DETERMINANTS (PRO@HEART). THE PROSPECTIVE ATHLETE’S HEART (PRO@HEART) STUDY.

Importance of protein O-GlcNAcylation in cardiac hypertrophy development

In vitro disease modeling of susceptibility to anthracycline-induced cardiotoxicity using induced pluripotent stem cells

The relationship between myocardial fibrosis, ventricular systolic dysfunction and ventricular arrhythmias in young elite and master endurance athletes

Optimization of absolute coronary blood flow measurements to assess microvascular function in sheep: validation of hyperemia and higher infusion speeds

Dynamics of SerpinA3 in response to anthracycline treatment and cardiovascular dysfunction

Right ventriculo-pulmonary arterial uncoupling in an experimental HFpEF in rats

Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin,

AMPK and O-GlcNAcylation: a new paradigm to protect the failing hypertrophic heart

Does coronary lesion complexity and pre-procedural revascularization affect 5-year outcomes in patients undergoing transcatheter aortic valve implantation?

A strain-based staging classification of left bundle branch block-induced cardiac remodeling

Cardiac Microvascular Endothelial Cells in Pressure Overload-induced Heart Disease

Acute re-distribution of regional left ventricular work by cardiac resynchronization therapy

Platelet acetyl-CoA carboxylase phosphorylation: a risk stratification marker evidencing platelet-lipid interplay in CAD patients

Micro-RNA 146a: a new kid on the block in the pathophysiology of cardiac hypertension, and an interesting therapeutic target

Iron deficiency in patients with Eisenmenger’s syndrome: does it affect outcome, is oral anticoagulation involved and can there be too

Impaired elastin function promotes features of plaque instability in ApoE-deficient mice

Circulating adiponectin levels in patients with chronic heart failure. The effect of exercise training

Paraoxonase 1 gene transfer lowers vascular oxidative stress and improves endothelial cell function in apolipoprotein E-deficient mice with pre-existing atherosclerosis

Multi-level study of the pathogenic mechanisms underlying the Long QT Syndrome

PRECLINICAL AND CLINICAL ASSESSMENT OF THE BENEFICIAL EFFECTS OF HEPCIDIN, A PIVOTAL ENDOGENOUS REGULATOR OF IRON METABOLISM, ON ANTHRACYCLINE-INDUCED CARDIOTOXICITY

Cardiovascular disease and cancer are linked through the NRG1/ERBB3 signaling system.

ECCENTRIC OVERLOAD TRAINING IN ADDITION TO A TRADITIONAL CARDIAC REHABILITATION PROGRAMME: RANDOMIZED CONTROLLED TRIAL TO EVALUATE EFFECTIVENESS AND FEASIBILITY IN HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION

Supervised home-based combined endurance resistance exercise training programme in asymptomatic adult patients with congenital heart disease. A prospective randomised-controlled trial to evaluate effectiveness, safety and quality of life;