PREDICT 2

2019

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:

  1. Identify genetic and non-genetic factors that contribute to SCA risk and develop personalized risk prediction algorithms for individual patient assessment.
  2. Conduct functional studies to elucidate the mechanisms underlying SCA, enabling the development of novel risk stratification and therapeutic approaches.
  3. 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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Collaborators

Contact person:

Prof. Dr. A.A. Wilde (Arthur)

Principal investigators

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Holland Hybrid Heart

2023
In the Netherlands, there are 250,000 patients with heart failure. Half of these patients die within five years. The best treatment: a donor heart. But: there is a great shortage of these. The Holland Hybrid Heart consortium is therefore working on an alternative: a robot heart, made of soft materials. The research We envision the treatment of patients with heart failure (HF) in such a way that the survival and quality of life of HF patients drastically increases. We aim to achieve this by developing a unique bioinspired total artificial heart that integrates soft robotics and tissue engineering (TE). In the long term, we foresee that this pioneering technology allows us to develop and bring to the clinic a full set of artificial motile organs and tissues that seamlessly integrate with the human body. This will be possible as the novel and exciting technologies underlying the artificial heart developed in this project - soft robotics and in situ TE - can be used to generate a broad range of artificial motile organs such as muscle structures (e.g., limbs), bowels or lungs: The motility and flexibility in shape and size of soft robots make them suitable for mimicking motile organs. Actuators can be embedded within the elastomeric matrix of these robots without compromising their malleable properties. In addition, embodied intelligence provides direct feedback on shape and force, enabling natural behaviour. Biocompatibility of these artificial organs is provided by TE inside the body (in situ) using biodegradable coatings or scaffolds. Such TE scaffolds are cell-free synthetic bio-resorbable implants or linings that can recruit or interact with cells from the bloodstream, leading to gradual replacement of the scaffold by fully endogenous, and thus biocompatible, tissue. Importantly, the cell-free and thus off-the-shelf availability of these scaffolds avoids the high costs and complex logistics inherent to pre-implantation in vitro TE. The Holland Hybrid Heart (HHH) consortium will push the development of these newly emerging technologies forward and combines soft robotics and in situ TE to generate the first biocompatible, soft actuated heart. This project will deliver Proof-of-Principle for full in vivo cardiac functionality of the artificial HHH in large animals. If successful, the HHH will be available for translation to the clinic as an effective treatment for advanced HF in patients and a valid alternative for moderately effective current HF therapies. This is a quantum leap forward in the treatment of HF. Origin A photo in the newspaper inspired Rotterdam heart specialist Jolanda Kluin to develop a robot heart. Kluin immediately contacted the interviewee in the article, Bas Overvelde, head of the Soft Robotic Matter group at Amolf, which develops soft robots. Could he perhaps also make a heart using soft robot techniques? Overvelde believed in it and a collaboration was born. Five years ago, they received a European subsidy of more than 3 million euros. This grant started the previous EU consortium, the EU Hybrid Heart. Last December (2023), Kluin received another 11 million euros from the Dutch government to continue the Holland hybrid heart project. The Holland Hybrid Heart has pivoted to meet the demands of that new grant and now only contains 15 Dutch consortium partners. The consortium is funded by NWA-ORC and the Dutch Heart Foundation. In-kind contributions are also provided by the DCVA, the Dutch Heart Foundation, TrailBlazers, SBMC, EVOS and EE-Labels. The executing academic partners are Erasmus MC, Amolf, TU Eindhoven, University of Twente, TU Delft and Saxion Applied University. This research is driven by patient needs and the Harteraad and Stichting Pulmonale Hypertensie will provide the connections to these patients.
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HBCx

2019
Cardiovascular disease (CVD) and dementia are closely intertwined, often resulting in cognitive impairment among individuals with cardiovascular or cerebrovascular conditions. Approximately one-third of dementia cases are linked to vascular injury, emphasizing that vascular cognitive impairment (VCI) is a preventable aspect of cognitive decline. The Focus The Heart-Brain Connection Crossroads (HBCx) consortium investigates hemodynamic alterations as reversible contributors to VCI, seeking to enhance our understanding of the connection between cardiovascular health and cognitive function. The Research HBCx builds upon the foundation laid by HBC1 (CVON 2012-06), which established a national network dedicated to studying, diagnosing, and treating VCI. Clinical investigations within HBC1, focusing on patients with chronic heart failure (CHF), carotid occlusive disease (COD), and clinically evident VCI, emphasized the role of hemodynamics along the heart-brain axis in VCI. These findings underscored significant associations between heart-brain connections and VCI. The HBCx program, launched in 2019, takes a comprehensive approach by investigating hemodynamics in key cardiac conditions such as atrial fibrillation and heart failure, while also exploring vascular factors and their interplay with amyloid pathology. Moreover, HBCx considers modulating factors like age and sex. The program aims to improve early detection, identify treatable targets, and integrate the Heart-Brain Connection approach into routine care. Ultimately, the long-term vision of HBCx is to reduce VCI prevalence among CVD patients through enhanced understanding and innovative treatment strategies. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.
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