RECONNEXT

2021

Heart failure represents a significant healthcare challenge due to its high morbidity and mortality rates. Historically, the emphasis has been on heart failure with reduced ejection fraction characterized by left ventricular dilation. However, nearly half of heart failure patients involve diastolic dysfunction due to heart chamber stiffening, known as diastolic heart failure or HFpEF.

The Focus
Research conducted by our consortium indicates that impaired kidney function is an is a strong risk factor for HFpEF. Patients with chronic kidney disease are more prone to developing HFpEF and have higher mortality rates from associated complications. The specific mechanisms by which even slight declines in renal function worsen cardiovascular risk and impact the development and prognosis of HFpEF are not yet fully understood. Insights from RECONNECT highlight the pivotal role of systemic inflammation and microvasculature in this context.

The Research
RECONNEXT (Renal connection to microvascular disease and HFpEF: the next phase) is a multicenter consortium dedicated on advancing medical research on heart failure - particularly heart failure with preserved ejection fraction (HFpEF) - in relation to impaired kidney function.

Specific pre-clinical and clinical research objectives have been defined:

Identify renal drivers for HFpEF onset and progression in subgroups/clusters of HFpEF patients, taking patient-specific risk profiles into account.
Deepen our understanding of the mechanistic pathways involved in the pathogenic cross-talk between renal drivers, systemic inflammation, microvasculature, and cardiac cells leading to HFpEF, using dedicated ex vivo bioassays to assess patient material and in vivo small and large animal models.
Investigate the most promising therapeutic targets in newly developed and well-characterized state-of-the art rodent and porcine models of CKD-associated HFpEF, taking comorbidities into account.
Investigate the most promising therapeutic, diagnostic and prognostic candidate(s) in well-defined patient-groups by taking a stratified approach.

We expect that the results of this project will enhance our mechanistic insight in the renal drivers of HFpEF development and progression and will lead to the development of personalized diagnostic, prognostic and therapeutic solutions for HFpEF patients.

The origin

The RECONNECT consortium has provided fundamental knowledge on the connection between chronic kidney disease and HFpEF and established a translational pipeline for the discovery and evaluation of potential diagnostic, prognostic and therapeutic targets. RECONNEXT builds upon the success of RECONNECT, established in 2015 (see Figure 1 below), supported by CardioVasculair Onderzoek Nederland (CVON) and the Dutch Heart Foundation. The RECONNEXT consortium consists of nephrologists, cardiologists, general practitioners, and scientists from five leading academic centers in the Netherlands (UMC Utrecht, Erasmus MC, UMC Groningen, Amsterdam UMC, Leiden University) renowned for their expertise in heart failure, vascular biology, and chronic kidney disease.

Collaborators

Funded

Contact person:

info@heart-institute.nl

Principal investigators

Prof. dr. M.C. Verhaar (Marianne)

m.c.verhaar@umcutrecht.nl

Prof. dr. D.J.G.M. Duncker (Dirk-Jan)

d.duncker@erasmusmc.nl

See all investigators

Habitual physical activity is beneficial for cardiovascular health. Yet, many patients with cardiovascular disease are sedentary, and current physical activity programs often fail to achieve lasting improvements. At the extreme end of the activity spectrum, more athletes engage in long-term, high-volume, high-intensity training.  Emerging evidence suggests that there may be an upper limit of exercise for heart health and exceeding this threshold may attenuate the benefits of an active lifestyle. The FIT-HEART consortium seeks to develop tailored physical activity interventions for cardiovascular disease patients and to investigate safe exercise limits for recreational and elite athletes.
The research

FIT-HEART has three main goals:

Co-create, implement and evaluate an innovative program that promotes physical activity by integrating incentives from the individual’s (social) environment tailored to the needs of specific subgroups, which can be seamlessly integrated into healthcare systems across the Netherlands, with potential for future expansion to other patient groups and the broader population.
Assess the upper limits of exercise on heart health in recreational and professional athletes by conducting prospective studies in unique cohorts. This approach integrates extensive cardiac phenotyping, wearable monitoring, novel AI technologies, digital twinning, immunophenotyping, and long-term evaluation of clinical outcomes.
Establish and expand a multidisciplinary, synergistic consortium focused on sports, exercise, and heart health. Our mission is to nurture young talent, foster innovative cross-domain collaborations, and secure funding for ongoing and future research. In partnership with end-users, we will disseminate outcomes to professionals, patients, and the public, while raising awareness of the wide-ranging health benefits of an active lifestyle.

The origin

The FIT-HEART consortium emerged from a shared ambition among academic institutions, healthcare partners, patient organizations, and policymakers to address sedentary lifestyles in cardiovascular disease patients and to investigate the cardiac effects of extreme exercise in both elite and recreational athletes. This interdisciplinary initiative builds upon prior collaborative research in sports cardiology, preventive medicine, and behavioral interventions aimed at promoting physical activity.
FIT-HEART is well-aligned with the strategic agendas of the Dutch Heart Foundation and the Dutch CardioVascular Alliance (DCVA), both of which prioritize innovative solutions to reduce the burden of cardiovascular disease.
By integrating incentives from people’s social environment, the consortium aims to create personalized treatment options that encourage lasting physical activity, while taking into account subgroup-specific needs. In parallel, the integration of advanced cardiovascular methodologies enables FIT-HEART to identify recreational and professional athletes at an early stage who are at risk for adverse cardiovascular health outcomes.

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Delta Plan Heart Failure

2023

Heart failure is a severe and chronic condition were the heart is unable to pump blood around the body properly, due to a structural and/or functional abnormality of the heart. It has many different causes, with the most common being hypertension and coronary artery disease. Heart failure is an unpredictable condition with sudden exacerbations of the disease, hospitalization, and will ultimately lead to death. Proper (and early) treatment may improve the symptoms of health failure and may lead to a relatively longer and better quality of life.
The origin
On the cardiovascular disease research agenda, as drawn up at the initiative of the Dutch Heart Foundation in 2014 and revised in 2020, the themes “Earlier recognition of cardiovascular disease” and “Heart failure” have been placed on the agenda. The DCVA also announced the Delta Plan Heart Failure in the 2022 annual plan.
This resulted in the Delta Plan Heart Failure, which is initiated and financed by the Hartstichting, the Netherlands Heart Institute, and the Dutch Cardiovascular Alliance. In this national project, healthcare professionals, researchers, and patients have joined forces and will focus on the entire continuum of the disease from prevention to palliative care.
The research
We expect that burden of disease can largely be reduced by addressing the following key-points:

Increasing public awareness of heart failure
Early detection of heart failure
Stimulating the collaboration among all (different) disciplines within the field of health failure
Initiation of research consortia for innovative treatment and management of heart failure patients
Furthermore, this project will not only focus on positively influencing survival but also on optimizing the patient’s quality of life and will pursue a strategic and operational approach.

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