COVID@Heart

Familial Hypercholesterolemia (‘FH’) is the most prevalent genetic cause of premature atherosclerotic cardiovascular disease (ASCVD). FH has an estimated prevalence of 1:300 in the general population in the Netherlands. FH is characterized by lifelong elevation of LDL cholesterol, resulting in a profoundly increased risk of coronary heart disease (CHD) and premature death. Early identification of FH and intensive LDL cholesterol management are essential to minimize the lifetime cumulative cholesterol burden and associated risks. FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. Therefore, it is essential to screen first degree relatives (children, parents, brothers & sisters) of an individual diagnosed with FH, to detect other family members who may have inherited FH. LEEFH network In the Netherlands we have long track record with FH index identification, cascade screening of first degree relatives and associated research activities. Stichting LEEFH support healthcare professionals pro-actively to pursue cascade screening, aiming to identify FH-patients as early as possible. LEEFH works in a voluntary network with 39 hospitals (LEEFH centres) to optimize FH care and cascade screening. Over the years, an active database has been built up with approximately 7,000 family pedigrees and more than 37,000 FH positive tested patients. Annually, we detect ~ 300 FH+ indexes (new FH families) and 500 FH+ family members by cascade screening. A unique example of early prevention. The Research LEEFH supports research activities in the field of FH detection and treatment with its acquired knowledge, database and network. Recent examples of this include FH identification via central laboratory data, electronic health records and general practitioners. We also participate in research projects with other genetic disorders in order to further improve cascade screening through knowledge sharing (for example in the consortium ‘eCG Family Clinic’ (e-Cardiovascular Genetics Family Clinic). The Orgin The LEEFH network is a voluntary partnership since 2013. 39 hospitals are now affiliated. Each hospital (LEEFH center) has a number of healthcare professionals with a great deal of knowledge and affinity with FH. The LEEFH network aims to prevent (unnecessary) cardiovascular diseases by a) detecting FH family members through cascade screening and b) creating more awareness about FH. We do a lot of knowledge sharing about FH, both among ourselves and also through regional meetings with families and general practitioners. We have signed network agreements with ‘who’ does ‘what’ and ‘when’ in the cascade screening . The aim is to inform and support each family in the right way in the cascade screening. The DNA diagnostics are carried out by the Amsterdam UMC. Application forms and test packages are available via Stichting LEEFH.

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.