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. Marianne Verhaar (Marianne)

m.c.verhaar@umcutrecht.nl

Prof. dr. Dirk-Jan Duncker

d.duncker@erasmusmc.nl

See all investigators

Inherited heart diseases affect many people and can have a major impact on patients and their families. PRECISE aims to improve care by enabling earlier diagnosis, better prediction of disease risk, and more personalised treatment. The consortium brings together doctors, researchers, patient organisations and other partners to improve access to genetic care, develop practical tools for risk assessment, and strengthen education for patients, relatives and healthcare professionals. Ultimately, PRECISE aims to support better quality of life, informed choices and more effective healthcare for people with inherited heart diseases.
The research 
Inherited heart diseases, including cardiomyopathies and arrhythmia syndromes, affect many people and can lead to serious outcomes such as sudden cardiac death and heart failure. Although genetic testing and clinical care have improved, the cause of disease remains unclear in many patients, and access to genetic testing within families is still insufficient. PRECISE aims to address these gaps by improving early detection, risk prediction and personalised treatment for people with inherited heart diseases. The consortium will study how genetic, clinical, environmental, age-related and sex-specific factors influence disease development, severity and treatment response. Using this knowledge, PRECISE will develop and validate models to identify individuals at risk and predict disease outcomes more accurately. The consortium will focus on structural and electrical heart diseases, including hypertrophic, dilated and arrhythmogenic cardiomyopathy and cardiac ryanodinopathies. PRECISE will also evaluate the impact of its approach on quality of life, psychological burden, healthcare use and societal costs, while addressing communication, ethical and legal barriers to implementation in clinical care.
The origin 
The PRECISE consortium builds on previously established collaborations withing DCVA consortia and brings together leaders in the field of inherited heart disease with a strong past track record. The team consists of a strong mix of scientific, clinical and societal partners across the entire knowledge chain, who have contributed to the co-design of the PRECISE project. Researchers from 6 university medical centers, 3 universities, and 2 universities of applied sciences join forces with 8 co-funding organizations and a broad palette of cooperation partners and experience experts. Moreover, talented mid-career scientists are part of the team and will benefit from well-established infrastructure and broad expertise.

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CardioResource

2026

CardioResource will be the first national registry for patients with hereditary cardiac conditions. By making available, amongst others, clinical data, imaging, and genetic data of all seven largest Dutch University Medical Centers, CardioResource will enable breakthrough research into these disorders. This will lead to more accurate diagnosis and improved understanding of the risk of developing disease and severe complications for patients and their families. It will also facilitate the development of novel therapies for more effective and targeted treatment of these life-threatening conditions.
The research

Over the past few decades, researchers have made significant progress in identifying inherited heart diseases. In many cases, these conditions can be traced to a defect in a single gene. However, for approximately half of patients, the underlying genetic cause remains unclear because it often involves variations in multiple genes, combined with other clinical, acquired, and/or lifestyle factors. Understanding how these factors conspire to determine disease risk and severity necessitates access to larger and comprehensive datasets.
A vast amount of patient data is already available within the university medical centers (UMCs). However, these data are stored in separate systems at each institute and are therefore fragmented and inaccessible for research.
CardioResource aims to address this challenge by harmonizing data across UMCs and making them available for research through a national research infrastructure, in a privacy-preserving manner.
To achieve this, CardioResource is developing an innovative data infrastructure based on the FAIR principles: Findable, Accessible, Interoperable, and Reusable. The platform will be continuously updated with the latest patient information, creating a sustainable resource for cardiovascular research nationwide.
The origin

The Dutch research community has a long-standing track record in the field of inherited cardiac conditions. Over the years, numerous databases have been established for individual studies. However, the manual development and maintenance of these databases require substantial time and effort. To address this challenge, the community came up with the idea for CardioResource.
The NWO Research Infrastructure program for national consortia provided the opportunity to finance the CardioResource project. The initiative brings together all seven Dutch UMCs, the NLHI, NHR, Dutch Heart Foundation, Hartekind Foundation, DCVA, and Health-RI. This broad partnership reflects the national need to strengthen cardiovascular data infrastructure and aligns with the ambitions of the DCVA and Health-RI to enable FAIR and reusable health data. Multidisciplinary teams across the participating UMCs will jointly establish the infrastructure. This close collaboration is essential for creating a sustainable and valuable resource that will ultimately benefit patients with inherited cardiac conditions.

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