Periodic Reporting for period 4 - ESCAPE-NET (European Sudden Cardiac Arrest network: towards Prevention, Education and NEw Treatment)
Période du rapport: 2021-07-01 au 2022-12-31
Sudden cardiac arrest (SCA) is a vast public health problem, causing ~50% of cardiac deaths and ~20% of natural deaths in Europe. This problem is expected to rise as the population ages. SCA is due to cardiac causes that result in cardiac arrhythmia. 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. To resolve the problem of SCA, the ESCAPE-NET consortium members have invested heavily in the last decades to create infrastructures, and collect large European SCA cohorts with the required information. 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. A comprehensive integration strategy 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 Europe’s largest SCA study cohorts in one joint harmonized 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 is different between European countries, combining the large cohorts that are present across Europe additionally creates the opportunity to evaluate and compare treatment strategies.
During the period from January 2020 until June 2021 activities for the project have been seriously affected by the COVID-19 pandemic, as many researchers were called to work in hospital. Others have been hampered in their work by several lockdowns. Nonetheless, the project has seen significant progress
To continuously improve the quality of the joint database of the ESCAPE-NET project, new cohorts have been harmonised and included, and the database now includes >100,000 SCA cases as well as >35,000 participants from longitudinal population cohorts. The work performed has resulted in a comprehensive database of clinical and genomic data of SCA. The infrastructure developed has improved and maximised data sharing and stimulated hypothesis-driven research. The joint database has been migrated to a new HPC facility providing the researchers with more computational power and an improved user-interface. The abovementioned work has enabled the start of research activities inside the secure research platform using harmonized data from several cohorts. The large sample size of the pooled data set permits research into risk and prediction of SCA and SCD allowing for better future risk prediction. Ethical issues surrounding the use and exchange of data of SCA patients from various EU sites has been evaluated. The consortium started to evaluate the options for continuation of the database beyond the end of the ESCAPE-NET project. A business case was written to this end. Further activities have started and will continue in the next reporting period.
Data from the database has been used for studies on prevention of SCA from different perspectives (WP4):
- 59 Research Proposals for joint studies of the consortium that exploit data of the joint database have been submitted
- We have completed genome-wide imputation studies for cohorts of patients with all-cause SCA from the general population (ARREST) and patients in the cohorts that were specifically designed to study SCA in the context of first myocardial infarction (AGNES, GEVAMI, PREDESTINATION)
- We are completing genome-wide association analysis for cohorts of patients with all-cause SCA from the general population (ARREST) and of patients from cohorts that were specifically designed to study SCA in the context of first myocardial infarction (AGNES, GEVAMI, PREDESTINATION). In addition, we are preparing genome-wide association analysis for additional cohorts, e.g. of patients with all-cause SCA from the general population (DANCAR)
- Design of a method of data mining of existing databases to discover hitherto unsuspected risk factors for SCA during drug use
- Multiple studies on the link between COVID-19 and SCA have been published
In work package 5 the main objectives are to analyze first response strategies and early treatment of out-of hospital cardiac arrest (OHCA) including a (health) economic evaluation, as well as impact of patient characteristics on survival after OHCA.
Despite the pandemic, quite some work has been performed, and fruits of the harmonization process completed in the previous reporting period could now be harvested. Papers have been published on the association of First Response systems with survival, on the association with patient characteristics and survival. Patient inclusion is ongoing in the AMSA trial studying ventricular fibrillation waveform characteristics in relation to shock success and survival, and good progress is made in quantifying the effect of alerting lay rescuers in case of an OHCA.
To continuously improve the quality of the joint database of the ESCAPE-NET project, new cohorts have been harmonised and included, and the database now includes >100,000 SCA cases as well as >35,000 participants from longitudinal population cohorts. The work performed has resulted in a comprehensive database of clinical and genomic data of SCA. The infrastructure developed has improved and maximised data sharing and stimulated hypothesis-driven research. The joint database has been migrated to a new HPC facility providing the researchers with more computational power and an improved user-interface. The abovementioned work has enabled the start of research activities inside the secure research platform using harmonized data from several cohorts. The large sample size of the pooled data set permits research into risk and prediction of SCA and SCD allowing for better future risk prediction. Ethical issues surrounding the use and exchange of data of SCA patients from various EU sites has been evaluated. The consortium started to evaluate the options for continuation of the database beyond the end of the ESCAPE-NET project. A business case was written to this end. Further activities have started and will continue in the next reporting period.
Data from the database has been used for studies on prevention of SCA from different perspectives (WP4):
- 59 Research Proposals for joint studies of the consortium that exploit data of the joint database have been submitted
- We have completed genome-wide imputation studies for cohorts of patients with all-cause SCA from the general population (ARREST) and patients in the cohorts that were specifically designed to study SCA in the context of first myocardial infarction (AGNES, GEVAMI, PREDESTINATION)
- We are completing genome-wide association analysis for cohorts of patients with all-cause SCA from the general population (ARREST) and of patients from cohorts that were specifically designed to study SCA in the context of first myocardial infarction (AGNES, GEVAMI, PREDESTINATION). In addition, we are preparing genome-wide association analysis for additional cohorts, e.g. of patients with all-cause SCA from the general population (DANCAR)
- Design of a method of data mining of existing databases to discover hitherto unsuspected risk factors for SCA during drug use
- Multiple studies on the link between COVID-19 and SCA have been published
In work package 5 the main objectives are to analyze first response strategies and early treatment of out-of hospital cardiac arrest (OHCA) including a (health) economic evaluation, as well as impact of patient characteristics on survival after OHCA.
Despite the pandemic, quite some work has been performed, and fruits of the harmonization process completed in the previous reporting period could now be harvested. Papers have been published on the association of First Response systems with survival, on the association with patient characteristics and survival. Patient inclusion is ongoing in the AMSA trial studying ventricular fibrillation waveform characteristics in relation to shock success and survival, and good progress is made in quantifying the effect of alerting lay rescuers in case of an OHCA.
The main impact has been to make aware a large part of the cardiological community (and also the lay community) of the extraordinary research efforts and objectives of the ESCAPE-NET project.
The effect of these results is witnessed by the number of organizations active in the field of SCA across Europe, and in Asia, 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 and results is represented by the growth of the understanding at all levels (cardiologists, all physicians, lay population, and politicians) of the magnitude and societal importance of attacking the plague of SCA in Europe.
Additionally we have achieved publication of 69 scientific papers that describe the aims, methodologies and results of ESCAPE-NET which target both the scientists who study the causes of SCA, and the scientists who study the best treatments. 4 PhD theses have been defended.
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, and 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. Moreover, we discovered that the basis of the sex differences in survival after out-of-hospital SCA is more complex than previously anticipated, and may include not only biologic factors, but also non-biologic factors (gender factors). These unexpected discoveries will be further exploited in the ESCAPE-NET project.
The effect of these results is witnessed by the number of organizations active in the field of SCA across Europe, and in Asia, 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 and results is represented by the growth of the understanding at all levels (cardiologists, all physicians, lay population, and politicians) of the magnitude and societal importance of attacking the plague of SCA in Europe.
Additionally we have achieved publication of 69 scientific papers that describe the aims, methodologies and results of ESCAPE-NET which target both the scientists who study the causes of SCA, and the scientists who study the best treatments. 4 PhD theses have been defended.
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, and 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. Moreover, we discovered that the basis of the sex differences in survival after out-of-hospital SCA is more complex than previously anticipated, and may include not only biologic factors, but also non-biologic factors (gender factors). These unexpected discoveries will be further exploited in the ESCAPE-NET project.