Innovation potential

ESCAPE-NET brings together expert clinicians and researchers who are specialized in SCA, and experts in social epidemiology, translational research, gene discovery, and validation in genetic cardiac disorders. Thanks to this synergy, work by consortium partners will yield key innovations to improve personalized care:

1. Discovery of genes/gene profiles, proteins, and pathways as risk determinants for SCA.

New targets can be exploitable avenues for preventive or therapeutic interventions in personalized care settings. For instance, gene profiles may be exploited as a diagnostic tool to predict SCA risk, while novel proteins/pathways may provide the basis for drug development for novel therapies.

2. Development of a holistic conceptual framework for SCA in which interactions between various inherited, acquired, and environmental factors obtain key relevance.

The resulting risk score will have greater sensitivity and specificity to predict SCA occurrence/outcome than current risk stratification schemes, allowing more efficient allocation of therapy resources, including timely institution of preventive measures to avert costly care for individuals who have suffered SCA, while avoiding unnecessary treatment (e.g., expensive prophylactic ICD implantation in individuals who do not need them).

3. Inclusion of environmental factors (socio-economic/psychosocial stress, air pollution) as integral components of SCA occurrence and outcome will drive new policy and preventive/therapeutic actions aimed at these determinants.

4. Demonstration of gender differences in causes, treatment, and outcome of SCA will lead to a paradigm shift in research, treatment, and healthcare policies for SCA. A gender-specific approach may yield improved clinical outcomes at more economic allocation of treatment resources.

5. Generation of a research infrastructure that allows the transfer of scientific knowledge to the scientific community.

This will form the groundwork for future studies beyond the completion of the ESCAPE-NET project. For instance, ESCAPE-NET will create databases of DNA profiles in the SCA and prospective cohorts, which may serve as reference databases for future SCA studies by consortium partners, while also being available to other researchers who seek collaborations with ESCAPE-NET partners. The business plan for continuation of the ESCAPE-NET database will allow for continued collaborative research by ESCAPE-NET consortium partners beyond completion of the ESCAPE-NET project.



At present, our knowledge of the causes and predictors of SCA is based on isolated studies focusing mostly on single clinical risk factors. More recently, genetic risk factors have begun to be studied, particularly at Cardiogenetics centers where individuals and families with familial SCA are studied. The ESCAPE-NET partners have importantly contributed to these studies with their long-standing track records in SCA research. Their research has addressed all relevant domains, including epidemiologic studies in the community, studies at Cardiogenetics centers, and molecular-genetic studies. However, SCA in the community is highly complex, as each individual has his/her private set of inherited, acquired and environmental factors whose interaction determines SCA occurrence. However, the isolated databases used to date are too small to produce enough power to detect genetic factors, and to resolve the interactions between genetic and acquired and/or environmental factors. This has hampered the development of risk prediction models to be used to design strategies for SCA prevention.

Similarly, current studies aimed at increasing survival rates after SCA have focused on single interventions aimed mostly at faster deployment of first-response treatment (use of lay rescuers and/or public AEDs). Comparative studies of these various strategies, and integrative studies in which the role of patient characteristics on survival after SCA are also taken into account, are, however, so far lacking. Also, new technologies that may drive new treatments for SCA, e.g., waveform analysis of VF signals, have remained largely untapped due to the lack of sufficiently large and suitably collected study samples.

In summary, state-of-the-art studies are limited both by insufficient numbers of study samples, and the lack of an integrative strategy for the analysis of the data from these samples.


Advancing beyond the state-of-the-art

To solve both limitations and achieve breakthroughs with significant clinical and societal impact, ESCAPE-NET has combined all SCA population cohorts that are available in Europe. These cohorts have been specifically designed to study the causes of SCA in the community, and to evaluate various treatment strategies. Accordingly, they contain all relevant data, collected systematically and meticulously over decades, to achieve these aims, including some of the world’s largest DNA collections of SCA victims. Combining these cohorts results in a joint database which is unique worldwide for its size and data quality. In addition, ESCAPE-NET has the unique strategy of addressing SCA in the community in a highly integrated manner, studying not only interactions between various causative factors underlying SCA occurrence and survival after SCA, but also the combined expertise of researchers who focus mostly on studying the causes of SCA (to design preventive strategies), and those who focus mostly on first-response treatment of SCA. The complementary expertise of these researchers is expected to provide great synergy. Using this strategy, ESCAPE-NET is primed to achieve breakthroughs in numerous areas beyond the state-of-the- art.