DOUBLE DOSE

Cardiomyopathies, caused by genetic mutations affecting cardiac muscle components, pose significant economic and societal burdens due to their hereditary nature and early onset. Despite known genetic defects, predicting disease progression remains challenging due to extreme clinical variability. Recent research indicates that cardiomyopathy mutations induce metabolic stress, exacerbated by factors like obesity, which can accelerate disease progression. The Double Dose hypothesis suggests that targeting metabolic stress may offer preventive or curative strategies for these conditions.

The Focus
The Double Dose Consortium aims to understand how cardiomyopathy-causing mutations lead to structural changes in cardiomyocytes. This interdisciplinary effort combines experts in preclinical research, clinical genetics, health technology assessment, and clinical care focused on cardiomyopathy in both children and adults.

The Research
The consortium combines experts in preclinical research, clinical genetics, health technology assessment and clinical researchers with a strong clinical focus on cardiomyopathy in children and adults. These experts investigate how obesity and muscle adiposity contribute to vascular and cardiac muscle dysfunction in mutation carriers through the analysis of clinical data, patient samples, and experimental models. They will also study the mechanisms underlying ultrastructural changes in cardiomyocytes caused by these mutations, leading to impaired metabolism, contraction, relaxation defects, and disrupted cellular communication within the heart.

Utilizing extensive patient cohorts and ongoing studies, the consortium aims to optimize care for cardiomyopathy patients by assessing the cost-effectiveness of diagnostics and clinical interventions. They plan to translate findings on metabolic alterations into clinical trials targeting treatments that reduce metabolic stress. The Double Dose program will establish biobanks containing serum, tissue, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to provide mechanistic insights into cardiomyopathy pathophysiology and improve diagnosis and care.

DCVA iPSC-CM Journal Club
iPSC-CMs are increasingly being used as alternatives for testing animals to investigate mechanisms of disease. Do you work with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)? Join the DCVA iPSC-CM Journal Club: a journal club that unites six institutes in the Netherlands working on iPSC-CMs. With the DCVA iPSC-CM Journal Club we establish a platform that combines forces to advance the use of stem cells for cardiovascular research in the Netherlands.

The DCVA iPSC-CM Journal Club was founded in October 2020 by scientists from the Double Dose consortium. In this monthly journal club, we discuss the latest developments in the field, share protocols and exchange ideas on standardization in order to improve the quality of our own scientific studies. We host national and international experts from the field who discuss the main challenges of iPSC-CMs, but also remain accessible for young researchers to ask their questions.

For more information or to apply, contact Birgit Goversen (b.goversen@amsterdamumc.nl).

DOUBLE-DOSE mini-consortium
The DOUBLE-DOSE consortium has allocated a portion of its talent budget for a mini-consortium grant to enhance and expand the scope of their research. This funding initiative aims to promote team science and offers independent scientists the opportunity to collaborate with DOUBLE-DOSE. Projects should be innovative and ideally focused on developing new techniques or generating pilot data to support future funding applications.

In short:
• Mini-consortium grant for early/mid-career scientists
• Budget: € 75.000 per project
• Deadline: March 1st, 2023
• Start: Ultimately January 1st, 2024
Please find the document with more information and an application form via the downloads below.

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Funded

Contact person:

Dr. J. van der Velden (Jolanda)

Principal investigators

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CUSTOM-AF

2020
Individuals with atrial fibrillation are at increased risk of an ischemic stroke. Active detection of atrial fibrillation (AF) and optimal referral and treatment of patients could prevent an estimated 1500 ischemic strokes annually. Effective collaboration between primary and secondary care professionals is essential for achieving this goal of stroke prevention attributed to AF. This is the primary objective of the implementation consortium known as CUSTOM-AF. The CUSTOM-AF was founded in June 2020 and restarted in 2022. CUSTOM-AF implementation consortium aims to share successful practice examples with regional networks and develop guidelines for organizing active detection and integrated care within a network. Additionally, consortium partners seek innovative methods for general practitioners to detect and manage AF without necessitating hospital referrals. With this consortium, the Dutch Heart Foundation, NVVC Connect, Harteraad, and the Dutch CardioVascular Alliance, all work together towards optimal care for patients with AF. The Dutch College of General Practitioners (NHG) serves as a key advisor to the consortium. The Research The scope of the consortium has been expanded to include two disorders: heart failure and AF. The consortium has undertaken significant initiatives over the past two years (2020-2022) to advance its objectives: Guideline Development: The consortium developed the "Screening and Treatment Optimization for AF" guideline, designed to facilitate early detection of AF within regional healthcare systems. Cost-Effectiveness Analysis: A comprehensive analysis conducted to assess various screening scenarios for AF, evaluating the economic feasibility of different approaches. Thematic Collaboration: In early 2022, a thematic collaboration titled "Juiste Hartzorg op de Juiste Plek" was established in partnership with the Heart Foundation and ZonMw. This collaboration secured funding for 22 regions to support transmural collaboration on AF and HF, with a focus on early detection and treatment optimization. Moving forward from September 2022, NVVC Connect will intensify support for the regions by emphasizing continuous improvement through the PDCA cycle, facilitating knowledge sharing, and implementing innovative approaches such as Check@home. These efforts are aimed at strengthening collaboration and improving outcomes in AF and HF care across the participating regions.
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PERFECT-FIT

Smoking tobacco and physical inactivity are key preventable risk factors of cardiovascular disease (CVD). Perfect Fit aims to prevent CVD, promote well-being, and reduce healthcare costs, particularly targeting disadvantaged populations where smoking and physical inactivity are prevalent. The Research The project develops tailored, evidence-based, near real-time computer coaching for quitting smoking and enhancing PA. For every individual, a personal model is designed which generates personalized recommendations based on high-quality existing and newly collected data, and adapts to changing circumstances/progress (similar to a TomTom navigation system), using machine learning techniques and incorporating domain-specific expert knowledge (e.g. health behaviour change strategies). Virtual coaches (VCs) communicate advice in a motivating way that fits individuals’ persuasive communication styles. Perfect Fit integrates big-data science, sensor technology, and personalized real-time feedback to support smoking cessation and promote adequate physical activity (in both gym settings and daily life). The key questions of this study are: Which adaptivity is needed to create a robust, safe, and effective interaction between individuals and machines? How can we develop advanced data science methods and embed this in current smoking cessation and PA coaching practice? How do measurement modalities, feedback and communication affect individuals’ smoking status and PA?  
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