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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - ESCAPE-NET (European Sudden Cardiac Arrest network: towards Prevention, Education and NEw Treatment)

Teaser

Summary

Sudden cardiac arrest (SCA) is a vast public health problem, causing ~50% of cardiac death and ~20% of all natural deaths in Europe. This problem is expected to rise further as the population ages. SCA is the sudden cessation of the heartâ€™s ability to pump blood through the body. SCA is lethal within minutes if left untreated, yet mostly occurs in the community, where treatment is usually not immediately available. Accordingly, survival rates are presently only 5-20%. While improvements in primary and secondary prevention have resulted in substantial declines in overall mortality from heart disease in general and coronary heart disease in particular over the past 30 years, SCA rates have declined to a lesser extent and may be on the rise in some segments of the population. The consortium members have invested heavily in the last decades to create such infrastructures and have collected large European SCA cohorts with the required information, including DNA samples collected during resuscitation. In isolation, these cohorts are already world-leading with respect to size and data quality. ESCAPE-NET will elevate these cohorts synergistically by adding new data on novel potential risk factors, thus far underappreciated in SCA research, in particular socio-economic and psychosocial stressors. This new data will be obtained by ESCAPE-NET partners who are specialized in linkage of study cohorts to regional and national registries which contain these novel factors. A comprehensive integration strategy of these joint exceptionally large and complete datasets constitutes a quantum leap in SCA research, and offers a unique opportunity, out of reach so far, to design strategies for truly personalized medicine. The aim of the ESCAPE-NET project is to maximize the exploitation of the European cohorts by bringing together Europeâ€™s largest SCA study cohorts in one joint database consisting of >94,000 SCA cases. This will generate the power necessary to unravel the complex causes of SCA with the strategy of a multi-scale approach, ranging from genomics to the socio-economic environment of each individual in the community. This will form the foundation of a personalized risk score, and the development of effective individualized prevention and treatment strategies. As treatment of SCA (particularly first-response treatment) is different between European countries, combining the large cohorts that are present across Europe additionally creates the opportunity to evaluate and compare treatment strategies.

Work performed

We started out establishing a governance structure that includes the following main elements:
1. Management Team (members: Coordinator, Project Management): to oversee all activities (in particular, organizational and financial) in ESCAPE-NET on a day-to-day basis

2. Cohort Executive Committee (members: all beneficiaries who contribute cohorts to the joint database): to oversee all scientific activities in ESCAPE-NET, and to ensure that they are consistent with the general objectives of ESCAPE-NET, and of high scientific quality

A Collaboration Policy document was designed that contains:
a. guidelines to set up research projects that utilize data from the joint database
b. guidelines to acknowledge authorships of scientific publications of joint research projects
c. a Data Processing and Joint Controller agreement to safeguard that use of cohort data complies with the EUâ€™s General Data Protection Regulation.

Over past period the ESCAPE-NET project has defined specifications for the secure database system. Planning phase included selection of secure hosting location for system to make data transfer for cohort data possible in the future. Executed installation of common database system to Computeronmeâ€™s (located in Denmark) secure environment. After installation and configuration of common database, initial training was given for whole research group during consortium meeting at AMC (Amsterdam). During training initial needs of used analysis tools was discussed.

While executing installation of database partners have jointly worked on establishing a data integration framework including data dictionary for shared data model for eventually loading joint cohort data into common database. Uploading data to common system is pending ethical approvals within Denmark and between cohort partners.

Additional to common database system establishment of environment for analysis sociological data with Danish population data has been setup in to Statistical Denmarkâ€™s high security environment.
The work packages eventually working on the research have worked mainly on defining parameters, data harmonization and collecting additional data. This work was needed to be able to further elaborate the research proposed in the work plan of ESCAPE-NET.

At present data harmonization is ongoing, as is patient inclusion and data collection at each participating study site. Research proposals have been elaborated and project groups have been set up. Furthermore, collaboration with existing European-wide resuscitation projects have been set-up, to maximize synergy and impact.
Though we still have a long way to go, 4 partners coordinate the dissemination & communication activities actively.

The project has been promoted thanks to a dedicated website, a webpage on EHRA/ESC website, has been featured in a couple of news bulletins (50000 recipients) and also in EHRAâ€™s Congress News (4000 delegates onsite in 2018). Most important, in terms of worldwide visibility is the significant article published in the European Heart Journal â€“ CardioPulse. Further, there has been a major effort by most partners to disseminate information at a huge number of congresses throughout Europe.

Final results

The main impact, already obtained in the initial part of the project, has been to make aware a large part of the cardiological community (and partly also the lay community) of the extraordinary research efforts and objectives of the ESCAPE-NET project. The use of these results is witnessed by the number of organizations active in the field of cardiac arrest, not only in Europe but in Asia as well, which have approached us asking to interact with ESCAPE-NET for joint studies/projects related to the field.

The expected potential impact of our efforts is represented by the growth of the understanding at all levels of the magnitude and societal importance of attacking the plague of cardiac arrest in Europe which contributes to 20% of overall mortality, often terminating the life of persons still in their prime.
Additionally we have achieved publication of papers that describe the aims and methodologies of ESCAPE-NET and have published a paper that describes how genetic analysis methods may shed insight into the causative role of clinical risk factors for SCA.

Scientifically, the consortium has obtained new insights that were unexpected at the beginning of the ESCAPE-NET project. For instance, IMIM has developed a novel method to identify hitherto unsuspected risk factors for drug-induced SCA by exploiting large existing databases of adverse drug events. Moreover, IMIM developed a method that can be used to improve drug design and minimize the risk of adverse drug actions (e.g. SCA) by taking into consideration the differential affinities of drug targets to endogenous metabolites. These discoveries will be further exploited in the ESCAPE-NET project.