OUTREACH

2021

The successful treatment of congenital heart disease (ConHD) has greatly increased the survival of children with this condition. Many of these defects require surgical or catheter interventions immediately after birth. However, complete restoration of the defect is often unachievable, a high risk of developing heart failure, arrhythmias, sudden cardiac death or blood vessel dilatation or stenosis relatively early in life.

Currently, there is a lack of personalized risk predictors and optimal clinical decision tools, highlighting an unmet need to develop new effective strategies for treating and preventing ventricular failure, arrhythmias, and large vessel diseases.

The Focus
The OUTREACH consortium focuses on specific types of congenital heart diseases (ConHD) related to outflow tract defects, such as transposition of the great arteries, congenital aortic stenosis, and tetralogy of Fallot, which collectively account for over half of all ConHD cases. The goal of OUTREACH is to reduce the risk of mortality and morbidity and improve the quality of life for these patients (both children and adults) by improving follow-up practices based on outcomes, implementing personalized risk assessment tools, and advancing therapeutic strategies.

The Research
The OUTREACH consortium integrates expertise in preclinical research, developmental biology, disease modeling, and clinical research from academic centers specializing in pediatric and adult congenital cardiology and surgery. Its objectives are:

identifying better parameters for risk assessment and early detection of heart failure or ventricular arrhythmias in ConHD patients with outflow tract defects.
Exploring efficient treatments to enhance adaptation and prevent heart failure and vascular damage in at-risk ConHD patients.

This consortium conducts extensive research involving a large cohort of ConHD patients to unravel the underlying causes and mechanisms of cardiac adaptations following surgical interventions. It investigates the molecular mechanisms responsible for outflow tract defects and evaluates whether stimulating heart regeneration in ConHD models can mitigate adverse remodeling and heart failure. Additionally, the consortium explores new non-invasive imaging techniques and blood-derived biomarkers to develop innovative risk analysis tools for clinical decision-making. In OUTREACH a nationwide registry is created for all patients (children and adults) with ConHD in the Netherlands by harmonizing existing registries KinCor and ConCor. This is an important step towards optimizing the quality of care for the ConHD population and fostering scientific research on ConHD.

Origin
The Dutch Heart Foundation and Stichting Hartekind, who collaborate within the Dutch CardioVascular Alliance, initiated an invitational grant to start and fund large-scale research aimed at earlier detection and better treatment of the consequences of congenital heart defects.

Funded

Contact person:

Prof. W.A. Helbing (Wim)

w.a.helbing@erasmusmc.nl

Principal investigators

Prof. W.A. Helbing (Wim)

w.a.helbing@erasmusmc.nl

Prof. dr. J. Bakkers (Jeroen)

j.bakkers@hubrecht.eu

Prof. dr. B.J. Bouma (Berto)

b.j.bouma@amsterdamumc.nl

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The IN-CONTROL II consortium builds upon the success of IN-CONTROL I, which highlighted the pivotal role of the microbiome in low-grade inflammation associated with atherosclerotic cardiovascular diseases (CVD) and related risk factors such as lipid levels and microbiome-derived metabolites. These insights are crucial for addressing the rising rates of CVD-related mortality, particularly in aging and overweight populations.
The Focus
The objectives of IN-CONTROL II are to:

Investigate the mechanisms underlying trained immunity in CVD patients, considering factors like senescence, age, sex, and obesity.
Elucidate the interactions between microbiome-derived signals (aromatic amino acids, metabolites, bile acids) and immune senescence in obesity-related cardio-metabolic diseases.
Identify novel therapeutic targets and develop pharmacological and microbiome-based therapies to counteract inappropriate induction of trained immunity and inflammation in cardiovascular disease.

The Research
The consortium aims to shift from association to causality, from population-based cohorts to patient groups with atherosclerotic cardiovascular disease (CVD) and from observation to intervention. In this transition, it will also take advantage of recent developments in the network of the consortium, delineating cellular senescence as a druggable target for the broad spectrum of age-related chronic diseases, including cardiovascular diseases, and identification of components of the bile acid-signaling system for this purpose. Another recent development of the recognition of innate immune memory (‘trained immunity’) as pathophysiological mechanism in atherosclerotic CVD.
The consortium will conduct proof-of-principle trials in specific patient cohorts, employing advanced experimental techniques such as systems biology, single cell sequencing, innovative animal models, and metabolic flux quantification (fluxomics). A talent program will facilitate knowledge transfer and skill development for young researchers within the consortium, emphasizing rapid translation of research findings into clinical applications.
Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

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ECG project UMCU

2020

The correct interpretation of electrocardiograms (ECGs) is crucial for accurately diagnosing cardiac abnormalities. Current methods, both manual by physicians and computerized, have not achieved the level of accuracy comparable to cardiologists in detecting acute cardiac issues. Leveraging advancements in artificial intelligence and big data, particularly deep neural networks, offers promising avenues to improve ECG interpretation where traditional methods have fallen short. The ECG-Project develops deep learning algorithms to automate ECG interpretation, particularly focusing on areas where current methods are inadequate.
Through this research, we aim to revolutionize ECG interpretation, improving diagnostic accuracy, reducing healthcare resource utilization, and ultimately enhancing patient outcomes.
The Research
The project objectives are:

WP1: Creating an algorithm capable of accurately and swiftly triaging ECGs through transfer learning, uncovering features in diseases with unknown ECG characteristics (such as primary arrhythmia syndromes and genetic disorders).
WP2: design a portable multi-lead ecg-device, suitable for use by patients at home and healthcare professionals. This device will enable high-quality ECG acquisitions for rapid diagnosis.

Origin
This project is funded within the Innovative Medical Devices Initiative (IMDI) program 'Heart for Sustainable Care'. The focus of this program is the development of medical technology for the earlier detection, monitoring, and better treatment of cardiovascular diseases to ensure accessible healthcare and sufficient staffing. The program has been developed and funded by the Dutch Heart Foundation, ZonMw and NWO, who collaborate within the Dutch CardioVascular Alliance.

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