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

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Sudden cardiac arrest (SCA) remains a significant public health challenge, accounting for nearly 20% of all deaths in developed nations and approximately half of all heart disease-related fatalities. A notable subset of SCA cases occurs in individuals without prior heart disease diagnosis, resulting in profound psychosocial impacts on affected families and society. Ventricular fibrillation (VF) is the primary arrhythmia leading to SCA, often occurring outside healthcare settings with survival rates ranging from 5% to 20%. Prevention is crucial, yet gaps in our understanding of SCA causes and mechanisms hinder effective prevention efforts. Various genetic and non-genetic factors, such as gender, age, comorbidities, and lifestyle, likely influence SCA risk, but their specific contributions remain unclear.
The Focus
The PREDICT2 initiative brings together leading Principal Investigators with expertise in epidemiology, clinical studies, genetics, and functional research to elucidate factors contributing to SCA, uncover underlying mechanisms, and develop strategies for prevention and treatment.
The Research
Building on foundational work from PREDICT1, which involved extensive patient characterization and preclinical model development, PREDICT2 focuses on inherited arrhythmia syndromes as models to understand the arrhythmogenic substrate in more common cardiac syndromes associated with SCA. Specifically, PREDICT2 aims to:

Identify genetic and non-genetic factors that contribute to SCA risk and develop personalized risk prediction algorithms for individual patient assessment.
Conduct functional studies to elucidate the mechanisms underlying SCA, enabling the development of novel risk stratification and therapeutic approaches.
Implement clinical studies to evaluate risk prediction algorithms and therapeutic interventions, aiming to enhance the treatment and prevention of SCA.

Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

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IMPRESS

2021

In the past decade, there has been significant progress in understanding sex- and gender-based differences in cardiovascular diseases (CVD). However, this knowledge remains scattered across medical literature, highlighting the need for a centralized platform accessible to healthcare professionals, scientists, policymakers, and patients. The IMPRESS consortium aims to establish a knowledge platform focused on gathering, summarizing, and prioritizing existing knowledge related to sex- and gender-specific aspects of CVD. This initiative seeks to promote the implementation of existing knowledge into clinical practice, identify knowledge gaps, and inform policymakers about areas requiring additional attention.
In substantial portions of women with symptoms of myocardial ischemia, obstructive disease in the epicardial coronary arteries is absent. Currently, such women undergo multiple diagnostic tests, which do not always result in a conclusive diagnosis. IMPRESS seeks to reduce missed and delayed diagnoses of heart diseases in women, improving cardiovascular care outcomes nationwide. The knowledge platform will serve as a national resource, fostering collaboration and supporting the adoption of sex- and gender-sensitive practices in cardiovascular medicine.

The Research
IMPRESS consolidates existing knowledge, fosters research, and implements findings into practice wherever possible (for example by creating a Decision Support Tool for primary care and for cardiologists). Within the IMPRESS consortium, the following studies are being conducted:

Delphi study: delayed or missed diagnosis of heart disease
Silent heart attacks: causes, symptoms, and risk factors of silent myocardial infarctions
UMCU-IMPRESS pilot study: undetected coronary microvascular disease (CMD)
Peripheral-Flow: LASCA technique in CMD
Dutch registry of coronary function tests

 
The origin
In the past decade, the understanding of sex- and gender differences in CVD has considerably improved. However, relevant evidence is scattered throughout the medical literature. There is a need to make this information easily accessible to health care professionals, scientists, policy makers and patients. Implementation of existing knowledge in clinical practice will then be promoted, knowledge gaps identified, and policy makers informed on the areas that need additional attention. This is also of high importance to the Dutch Heart Foundation, which therefore funded the IMPRESS consortium; a collaboration between several DCVA partners; the Nederlandse Vereniging voor Cardiologie (NVVC), WCN, Netherlands Heart Institute (NLHI), ZonMw and the Dutch Heart Foundation, supported by the DCVA.
 

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