RECONNEXT

Registry-based research enables faster and cheaper clinical research by using real world data. This is particularly important in patient populations where research is otherwise difficult to conduct, such as heart failure patients with comorbidities. The main aim of the Heart4data consortium is therefore to develop a sustainable infrastructure for cardiovascular registry-based research in the Netherlands. This includes governance and Information Technology (IT) infrastructure, research methods, FAIR (findable, accessible, interoperable and reusable) data creation and data linkage with relevant databases.     About Heart4Data  The Heart4Data consortium is building on the core qualities and experience of DCVA partners. Heart4Data will create a DCVA Health Data Hub that will be part of the DCVA pillar Data Infrastructure to combine all expertises across the different DCVA partners as part of the sustainability program.    In addition, Heart4Data will contribute to improvement of valorisation and implementation through accelerating the generation of results and facilitate DCVA consortia by providing a platform for research at lower operational costs compared to more traditional research methods.    The Research 1. To create a national and sustainable FAIR data-based infrastructure for cardiovascular registry-based research.  The infrastructure includes a framework/structure for the governance, and the ethical, legal, financial, technological and methodological factors. There will be a special focus on heart failure in this project by creating a sustainable heart failure (and atrial fibrillation (AF)) registry in the Netherlands Heart Registration (NHR) and links with other relevant national and regional registries and data sources.    2. To use and prove value of the infrastructure by conducting two projects:    - Observational, longitudinal research on the entire spectrum of patients with heart failure (including patients with HFpEF) in the Netherlands (project A) with focus on guideline recommended diagnostic trajectories and treatment.  - Prospective randomized clinical research on pharmaco-therapeutic treatment in patients with chronic heart failure (project B: SELEQT-HF).  The origin One of the five top priorities named on the cardiovascular disease research agenda that the Dutch Heart Foundation set in 2014 was finding better treatment for heart failure and arrhythmias. Back in 2014, when the research agenda was drawn up, it became clear that registry-based research is essential for this. The Dutch Heart Foundation therefore funded this study as part of the collaboration with the ZonMw GGG program on Good Use of Medicines (Goed Gebruik Geneesmiddelen). For a complex project such as this, collaboration within the entire cardiovascular field is an important starting point. The consortium is a collaboration between several DCVA partners; the Dutch Heart Foundation, ZonMw, NHR, WCN, Harteraad, NLHI, NVHVV, NVT, NVVC, VIG and Health-RI.  

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.