CONTRAST

Acute stroke management faces significant challenges despite recent progress. Intracerebral hemorrhage (ICH) accounts for 15% of all strokes and lacks effective treatment options. Additionally, only a small portion (10%) of acute ischemic stroke (AIS) patients qualify for intra-arterial therapy (IAT), and even after successful IAT, many experience poor outcomes due to incomplete microvascular reperfusion (29% to 67%). Incomplete microvascular reperfusion post-recanalization of occluded arteries is a primary contributor to poor AIS outcomes. This is caused by distal microembolization, microthrombotic occlusion, platelet activation, and pro-coagulatory pathway stimulation, potentially exacerbated by cellular swelling from immune system activation.

The Research
CONTRAST conducts five large acute stroke trials exploring innovative treatment strategies aimed at preserving ischemic tissue and improving outcomes. These trials include:

  1. Pre-hospital interventions to enhance collateral blood flow and reduce blood pressure.
  2. Antithrombotic agents to prevent microvascular occlusion post-IAT.
  3. Immediate IAT without prior thrombolysis.
  4. IAT within a 6 to 12-hour time window.
  5. Microsurgical hematoma evacuation and dexamethasone for ICH patients.

Our approach involves:

  1. Identifying eligible patients using advanced imaging techniques to assess potential treatment benefits.
  2. Investigating mechanisms of incomplete microvascular reperfusion through animal models and analysis of our clinical biobank, which houses blood, plasma, and extracted thrombi.
  3. Applying discrete event modeling (DES) to optimize stroke care based on data from these trials.

By combining clinical trials with mechanistic research and cutting-edge imaging, CONTRAST aims to revolutionize acute stroke treatment in the Netherlands and beyond.

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Collaborators

Funded

Contact person:

PhD R. van Nuland (Rick)

Principal investigators

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OUTREACH

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.
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