The DCVA brings partners together to deliver in breakthrough science in consortia to develop new cardiovascular solutions

In preceding decades, conventional therapies have notably enhanced the survival rates of heart failure (HF) patients. However, a subset of individuals, particularly younger patients afflicted with dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), still confront disease progression despite these treatments. This underscores the necessity for innovative approaches. The ARENA-PRIME initiative aims to address this gap by focusing on the development of novel gene therapies tailored to the specific disease mechanisms underlying DCM, attributed to mutations in the RBM20 and LMNA genes, as well as ACM, and associated with mutations in the DSGL2 and PKP2 genes. The goal is to progress towards first-in-human clinical trials, particularly focusing on LMNA disease, and to establish preclinical proof-of-concept for ACM therapies targeting DSGL2 and PKP2. The Research The ARENA-PRIME researchers utilize insights from previous programmes on cardiac gene therapies (e.g., inhibitory RNAs such as allele-specific short hairpin RNAs, antimiRs, etc.) and gene editing technologies (e.g., base- and prime editing) to develop novel treatments for dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). This effort is supplemented by advanced research on adeno-associated viral vectors and the integration of heart tissue collections with cutting-edge sequencing technologies (like single-cell sequencing) to further explore disease mechanisms. At the beginning of the ARENA-PRIME programme, a (end-) user committee has been established, making sure that (end-)users are closely involved in the design of the studies and the implementation of the co-created studies and deliverables. This committee meets annually alongside the program's research meetings to provide guidance to investigators on optimizing the program's outcomes for (end-) users. It addresses all feedback, inquiries, and recommendations, whether requested or spontaneous. This committee meets once per year in conjunction with the programme’s research meetings and advises the investigators about the course of the programme and what actions need to be taken in order to maximise the probability that the (end-) users will be able to utilize and/or benefit from the results. This committee addresses any comments, remarks, questions and advice they may have, solicited or otherwise. The members of the ARENA-PRIME user committee include cardiomyopathy patients and their relatives, clinicians (e.g. cardiologists), representatives from related research programs (e.g., RegMedXB, H2020-TRAIN-HEART), and industry stakeholders including biotech and pharma company representatives and venture capitalists. Supporting Young Investigators The programme prioritizes attracting and nurturing young talent, providing hands-on training and fellowship awards to facilitate their career development. Over 20 young investigators participate, benefiting from exposure to collaborative research environments. To further support this career development, five fellowship awards of 50.000€ have been granted the past three years to junior postdoctoral researchers in the laboratories of the Hubrecht Institute, University Medical Center Utrecht, Amsterdam UMC (location VUmc and AMC) and Maastricht University. Origin The former CVON-ARENA programme (2012-2017) advanced understanding of cardiac RNA species in heart failure (microRNAs, lncRNAs and circular RNAs). The CVON-ARENA programme (2012-2017) advanced understanding of cardiac RNA species, such as microRNAs, lncRNAs, and circular RNAs, in various forms of heart failure (HF). This subsequent ARENA-PRIME programme (2018-2023), funded by the Dutch Heart Foundation, targets treatment-resistant HF forms, particularly in younger patients with dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). In 2023 ARIME-PRIME received a matching grant from the Dutch Heart Foundation to work on their research together with a private partners, so that they can achieve their ambitions and objectives more quickly.

A healthy lifestyle underlies adequate cardiovascular risk management. However, current initiatives to promote a healthy lifestyle are only sparsely connected and often do not involve the patient's environment. To solve this, cardiologists, neurologists, general practitioners, scientists, entrepreneurs, and patients have united in the BENEFIT project. The research Our mission is to make healthy living fun. Rather than telling people how to behave, we make healthy lifestyle choices appealing: the carrot is mightier than the stick. BENEFIT is an advanced loyalty program that rewards cardiovascular patients for the time and energy spent on healthy lifestyle activities. BENEFIT loyalty points can be earned for a range of health behaviors, such as exercising daily, abstaining from smoking, attending prevention programs, and showing up for health appointments. The BENEFIT program has different levels, ranging from a simple to use card-and-beacon system to an advanced digital platform that allows access to evidence-based lifestyle maintenance interventions, personal coaching, and smart technology. By rewarding everyday lifestyle and adherence behaviors, the program integrates care and non-care settings and facilitates embedding the new lifestyle in everyday life. Our goal is to create a national ecosystem in which evidence-based interventions to promote a healthy lifestyle are embedded in a system that rewards people for taking actions that contribute to such a healthy lifestyle. The central element of this ecosystem is a sophisticated loyalty program that encourages people to live healthy lifestyles for the long term. No more finger-pointing: the very act of rewarding a healthy lifestyle is stimulating! The ecosystem that we provide connects public and private parties, integrates existing care and lifestyle programs, has future-proof financing, and is constantly fed by scientific insights. BENEFIT for all! The origin The BENEFIT program is a public-private ecosystem in a national consortium, aiming to support patients with cardiovascular disease in their own home setting for a long-term healthy lifestyle. The Heart Foundation aims for more people to make healthy choices, so that they feel vital and run less risk of developing (again) cardiovascular diseases, which was one of the themes of the research agenda. Therefore, the Dutch Heart Foundation and ZonMw have collaborated to fund this program.

About 10% of the COVID-19 affected patients develop critical illness with a high mortality rate. This critical illness appears to be strongly linked with cardiovascular disease, as the prevalence of cardiovascular comorbidities and risk factors (such as diabetes and obesity) are often found among hospitalized COVID-19 patients. The consortium COVID@Heart believes that mitigating this cardiovascular burden of Covid-19 should start early, while patients are (still) outside the hospital. The Research COVID@Heart has three core activities: Develop a tool to identify high-risk cardiovascular patients with COVID-19 in a home environment, before the critical illness emerges. This tool will allow general practitioners to better notify high-risk patients, monitor them more closely (e.g. by using home saturation measurements), prescribe preventive cardiovascular medication earlier ('moon shot') and refer them to a hospital promptly when needed. Create a diagnostic tool to improve early differentiation between COVID-19 and a myocardial infarction, addressing the challenge of overlapping symptoms faced by general practitioners. Design a questionnaire supplemented by select biomarkers and blood tests to enhance the detection of cardiovascular disease in COVID-19 survivors experiencing prolonged symptoms of fatigue and shortness of breath, as these symptoms are potentially linked to accelerated subclinical cardiovascular disease. Origin Accurate information on how cardiovascular patients fared while still at home is lacking. This information is crucial to prevent hospital admissions. Therefore, COVID@HEART focuses on people who are not hospitalized but are at home and treated by their general practitioners. The Dutch Heart Foundation supports and funds this research into the best treatment for cardiovascular patients with a coronavirus infection.  

Individuals with atrial fibrillation are at increased risk of an ischemic stroke. Active detection of atrial fibrillation (AF) and optimal referral and treatment of patients could prevent an estimated 1500 ischemic strokes annually. Effective collaboration between primary and secondary care professionals is essential for achieving this goal of stroke prevention attributed to AF. This is the primary objective of the implementation consortium known as CUSTOM-AF. The origin The CUSTOM-AF was founded in June 2020 and restarted in 2022. CUSTOM-AF implementation consortium aims to share successful practice examples with regional networks and develop guidelines for organizing active detection and integrated care within a network. Additionally, consortium partners seek innovative methods for general practitioners to detect and manage AF without necessitating hospital referrals. With this consortium, the Dutch Heart Foundation, NVVC Connect, Harteraad, and the Dutch CardioVascular Alliance, all work together towards optimal care for patients with AF. The Dutch College of General Practitioners (NHG) serves as a key advisor to the consortium. Earlier detection and better treatment of atrial fibrillation, the most common cardiac arrhythmia in adults, is an important part of the cardiovascular disease research agenda that the Dutch Heart Foundatoin set in 2014, which funds the CUSTOM-AF consortium. The Research The scope of the consortium has been expanded to include two disorders: heart failure and AF. The consortium has undertaken significant initiatives over the past two years (2020-2022) to advance its objectives: Guideline Development: The consortium developed the "Screening and Treatment Optimization for AF" guideline, designed to facilitate early detection of AF within regional healthcare systems. Cost-Effectiveness Analysis: A comprehensive analysis conducted to assess various screening scenarios for AF, evaluating the economic feasibility of different approaches. Thematic Collaboration: In early 2022, a thematic collaboration titled "Juiste Hartzorg op de Juiste Plek" was established in partnership with the Heart Foundation and ZonMw. This collaboration secured funding for 22 regions to support transmural collaboration on AF and HF, with a focus on early detection and treatment optimization. Moving forward from September 2022, NVVC Connect will intensify support for the regions by emphasizing continuous improvement through the PDCA cycle, facilitating knowledge sharing, and implementing innovative approaches. These efforts are aimed at strengthening collaboration and improving outcomes in AF and HF care across the participating regions.

Digoxin is the oldest, market-authorized drug for heart failure (HF), and very cheap. A large trial with digoxin, the DIG trial, executed in the early nineties revealed a highly significant reduction in HF hospitalizations, but no effect on mortality. A post-hoc analysis of the DIG trial suggests that low serum concentrations of digoxin may not only improve HF hospitalizations but also mortality in chronic HF patients. To validate these findings, a prospective, randomized, placebo-controlled trial is required to redefine the role of digoxin in modern HF treatment. The Focus The primary objective of this study is to investigate whether low-level digoxin (targeting serum concentrations of 0.5-0.9 ng/mL), compared to a placebo, reduces (repeated) HF hospitalizations, (repeated) urgent HF hospital visits, and cardiovascular mortality when added to standard guideline-recommended therapies in chronic HF patients with reduced or mid-range ejection fractions (LVEF ≤50%). The Research This proposed trial is a national, multicenter, randomized, double-blind, placebo-controlled clinical trial involving 982 chronic HF patients aged ≥18 years, classified as NYHA II to ambulatory IV, LVEF ≤50%, and specific serum NT-proBNP concentrations based on rhythm and recent HF hospitalization status. Patients must also be on guideline-recommended therapies. The study population includes at least one-third with atrial fibrillation (AF) and one-third women to represent the real-life HF population. Patients were randomized to receive either a low-level digoxin or a placebo in a double-blinded manner. Digoxin Teva will be administered orally, starting at doses of 0.2mg or 0.1mg (based on age, renal function, and concomitant medication). No loading dose is given to the placebo group. After 4 weeks of evaluating medication (digoxin or placebo), concentrations will be measured. Dose adjustments will be made if needed to reach the target serum digoxin concentration range of 0.5-0.9ng/mL. The outcomes in reducing adverse cardiovascular events in patients with chronic heart failure of low-dose digoxin will be compared to the outcomes of the placebo. The origin This study was funded as part of the Dutch Heart Foundation's collaboration with the ZonMw GGG program on Good Use of Medicines (Goed Gebruik Geneesmiddelen) for better treatment of heart failure and atrial fibrillation, which was one of the 5 priority's that the Dutch Heart Foundation set in 2014. The DECISION study involves 38 hospitals and is led by cardiologists from UMC Groningen and the WCN.

Currently, it is largely unknown to what extent the heart is involved in COVID-19. The aim of this project is to assess the incidence and consequences of cardiac damage in patients who have experienced COVID-19. How often does COVID-19 lead to myocardial damage? What are the short- and long-term consequences of this damage and what can we do to prevent it from occurring? These are the central questions that will be answered within the DEFENCE consortium. The Research The DEFENCE consortium integrates several national studies initiated at the onset of the COVID-19 pandemic, encompassing diverse patient groups as part of the COPP study, ranging from elite athletes (COMMIT study) and individuals recovering at home (COVID@Heart study) to hospitalized patients (CAPACITY-COVID registry and CAPACITY 2 study) and children with post-infection inflammatory syndromes affecting the heart (MIS-C). By harmonizing these initiatives, a unique cohort spanning the entire spectrum of COVID-19 severity has been established. The ongoing studies are extended at multiple levels within the DEFENCE project. This includes: Standardized Healthcare Pathway Implementation: Implementing and evaluating a standardized healthcare pathway to assess cardiac damage occurrence within 6 months post-hospitalization for COVID-19. Serial Cardiac Magnetic Resonance (CMR) Imaging: Performing serial CMR imaging to determine the prevalence and reversibility of myocardial damage, with all scans assessed in a core lab. Evaluation of Cardiovascular Symptoms: Assessing the incidence of cardiovascular symptoms such as chest pain and palpitations in the post-acute phase through patient questionnaires. Linking Data to National Datasets: Linking study data to national datasets at Statistics Netherlands to analyze long-term cardiovascular morbidity and mortality. To evaluate whether cardiovascular disease is a characteristic feature of COVID-19, a comparison with other respiratory tract infections, including seasonal influenza will be made. Origin This research has is funded by ZonMw, but has been set up through the efforts of WCN, NLHI, NHR, the Dutch Heart Foundation, NVVC, NVIC, Harteraad, and the EuroQol Research Foundation, who collaborate within the Dutch CardioVascular Alliance.