IN CONTROL II

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.  

The SARS-CoV-2 pandemic has a high burden of morbidity and mortality due to development of the acute respiratory distress syndrome (ARDS). The reninangiotensin-system (RAS) plays an important role in the development of ARDS, with ACE2 (angiotensin-converting enzyme 2) being a key enzyme within this. The virus's spike protein binds to ACE2, facillitating cellular internalization. Downregulation of ACE2 results in the excessive accumulation of angiotensin II, which in turn increases pulmonary vascular permeability through stimulation of the angiotensin II type 1a receptor (AT1R), thereby exacerbating lung pathology associated with decreased ACE2 activity. Currently available AT1R blockers (ARBs) such as valsartan, have shown potential to block this pathological process mediated by angiotensin II. The Focus The primary aim of the PRAETORIAN-COVID trial is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death of COVID-19 patients. The Research Participants receiving active treatment are administered valsartan at a dosage titrated to blood pressure, with a maximum of 160 mg twice daily. Participants receiving placebo are provided with a matching placebo. The treatment duration was 14 days or until reaching the primary endpoint, or until hospital discharge, if applicable within 14 days.Two complementary mechanisms underpin the potential efficacy of angiotensin II type 1 receptor blockers (ARBs) in preventing acute respiratory distress syndrome (ARDS) and reducing morbidity and mortality: ARBs block excessive angiotensin-mediated activation of the AT1R. ARBs upregulate ACE2 expression, leading to reduced angiotensin II levels and increased production of the protective vasodilator angiotensin 1–7. Given these mechanisms, ARBs show promise in preventing ARDS development, potentially reducing the need for intensive care unit (ICU) admission and mechanical ventilation, and ultimately lowering mortality rates associated with SARS-CoV-2 infection.