HBCx

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.

Atrial fibrillation (AF) is not benign. It commonly progresses from paroxysmal AF (PAF) to permanent AF. AF progression is associated with major adverse cardiovascular/cerebral events (MACCE). Cardiovascular risk factors and comorbidities (CVR) are present long before the first AF episode, causing a progressive atrial cardiomyopathy (ACM). The mechanisms of ACM vary between patients hindering effective AF management. The EmbRACE network now aims to unravel the diversity of mechanisms underlying ACM, identify simple diagnostic tools to identify them, and develop a therapeutic approach to prevent ACM progression. The Research Early rhythm-control therapy is one promising intervention to potentially interfere with ACM progression next to CVR management. For a sustained impact we aim to develop care pathways to prevent ACM and AF progression and MACCE. Therefore, we will identify and validate relevant cellular and molecular determinants of ACM and AF and their clinical surrogate parameters; develop an in-silico platform to simulate identified mechanisms of ACM and AF and their effects on AF progression and, based on these data, make suggestions for future refinement of ACM therapy; explore the variety of temporal patterns of PAF as markers of ACM subtypes, demonstrate their prognostic relevance and identify surrogate markers available in clinical practice, based on AI and machine learning; test in a randomized trial stratified for sex the hypothesis that early AF ablation and optimal CVR management in AF patients with ACM delays ACM progression and reduces MACCE; explore whether lifestyle management reduces ACM progression, whereas with only rate control ACM progresses; validate the RACE V AF progression score in real life cohorts and translate this and other knowledge into novel care pathways for AF. The origin Atrial fibrillation is the most common cardiac arrhythmia and can lead to a variety of complications, such as stroke. Currently, there are limited treatment options for this cardiac arrhythmia. Moreover, the disease is often noticed late, which makes proper treatment even more difficult. Therefore, the Dutch Heart Foundation funded the RACE V consortium. Afterwards, the Dutch Heart Foundation guided an exploration to form a national consortium as a follow-up around this theme. This led to the EmbRACE consortium, which is a national network of six university medical centers, UMC Groningen, Maastricht UMC+, UMC Utrecht, Amsterdam UMC and LUMC and Erasmus MC, and hospitals in Arnhem and Eindhoven. The Dutch Heart Foundation funds the research.