About

Description of the Project

Comprehensive and personalized assessment of acute coronary syndrome by multiomic approach and artificial intelligence strategy

The CardioSCOPE proposal aims to bring together experts from Companies and Αcademia throughout Europe to exchange and expand their expertise on interdisciplinary approaches, to enhance the Research and Innovation capacity of Europe in the field of cardiovascular diseases.

Connecting and expanding Europe-wide biobanks and expertise through a comprehensive multiomics approach for the discovery of novel pathological players, CardioSCOPE will give deeper insights into acute coronary syndrome (ACS) development and progression towards major adverse cardiovascular events (MACE). We will use well-defined prospective cohorts to discover and validate novel genomic, transcriptomic, proteomic and metabolomic signatures specific for ACS and MACE, to be combined in multimarker models by machine learning/artificial intelligence algorithms, enabling more accurate ACS diagnosis and MACE prediction. This excellent research network aims at building scientists competent for the upcoming “omics” era by training and knowledge transfer. Specific research skills not available at home institutions will be acquired through individually designed secondment plans, training schools, webinars and short-term courses. Intersectoral activities will improve entrepreneurial skills of consortium staff and facilitate transformation of scientific breakthroughs into commercially available products/services. CardioSCOPE includes experts with a wide clinical and research experience, access to patients with ACS and the expertise required for achieving set goals. World-class institutions gathered within this consortium (from 6 countries: 7 academic, 4 companies, 1 hospital) offer specific expertise, state-of-the-art equipment and adequate human resources to address these challenges. In summary, the results of this project will transcend our own scientific interests to enable a transfer of knowledge into a multidisciplinary environment and achieving significant impact on ACS management and policies in Europe.

Objectives

Background

Despite the progress of healthcare systems in the past half of the century, according to the World Health Organization (WHO), cardiovascular diseases (CVDs) are still the number one cause of death worldwide, taking around 17.9 million lives each year (31% of all deaths) and 3.9 million deaths (45% of all deaths) in Europe alone1.

Of the total cost of CVD in the EU, around 53% (€111 billion) is due to health care costs, 26% (€54 billion) to productivity losses, and 21% (€45 billion) to the informal care of CVD patients2.

Among CVDs, acute coronary syndrome (ACS) ranks as one of the most prevalent. ACS is a collective term referring to a group of heart and blood vessels disorders including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP). Patients with ACS suffer from the reduction in coronary blood flow due to atherosclerosis and plaque formation, which leads to irreversible damage to the myocardium, fibrosis, and compensatory remodelling mechanisms that can cause future major adverse cardiovascular events (MACE) (e.g. recurrent myocardial infarction, death, atrial fibrillations, heart failure, etc.)2.

ACS patients still have a higher probability for MACE. Residual risk of ischemic cardiovascular events or death remains higher in ACS compared to patients with stable angina pectoris (SAP)3 despite optimal guideline-directed coronary revascularization and treatment with antiplatelet and low-density lipoprotein cholesterol lowering agents4.

Despite numerous efforts of the scientific community to develop prognostic algorithms for early diagnosis and prevention of CVD and MACE, still about 5.5%–18.2% ACS patients die in the hospital with a high mortality of nearly 15% in a long-term follow up5 6, suggesting that the ones available are still insufficient.

Identifying novel pathological players associated with this residual risk are necessary to guide interventions targeted to lower these levels and prevent development of MACE. Thus, the CVD field needs new, more comprehensive and ground-breaking approaches that will lead to novel paradigms in prevention, diagnosis and treatment of ACS and MACE.

Overall aim of CardioSCOPE is to bring together experts from SMEs and Αcademia throughout Europe to exchange and expand their expertise on interdisciplinary approaches, while enhancing the Research and Innovation capacity of Europe in the field of CVD. Connecting and expanding Europe-wide biobanks and expertise through a comprehensive multiomics approach for the discovery of novel pathological players, CardioSCOPE will give deeper insights in ACS development and progression to MACE.

More specifically, we will use well-defined prospective cohorts to discover novel genomic, transcriptomic, proteomic and metabolomics signatures specific for ACS and MACE that could be combined in multimarker models through machine learning (ML) and artificial intelligence (AI) algorithms. CardioSCOPE is based around the following hypothesis:

Developed multimarker models will enable better diagnosis of ACS, better stratification of patients with STEMI, NSTEMI and UAP and better prediction of MACE.

To test this hypothesis, and go beyond the state-of-the-art, the CardioSCOPE has set the following specific objectives using the SMART (specific, measurable, achievable, relevant, timely) approach.

1 Bueno H. Epidemiology of acute coronary syndromes. Oxford: Oxford university press, 2018.

2 Wilkins E., et al. European Cardiovascular Disease Statistics 2017. Brussels: European Heart Network, 2017.

3 Escaned J, et al. Safety of the deferral of coronary revascularization on the basis of instantaneous wave-free ratio and fractional flow reserve measurements in stable coronary artery disease and acute coronary syndromes. JACC: Cardiovasc Interv. 2018;11(15):1437-49.

4 Mani P, et al. Association of initial and serial C-reactive protein levels with adverse cardiovascular events and death after acute coronary syndrome:a secondary analysis of the VISTA-16 trial. JAMA cardiology. 2019 ;4(4):314-20.

5 Ho PM, et al. 1-year risk-adjusted mortality and costs of percutaneous coronary intervention in the Veterans Health Administration: insights from the VA CART Program. Journal of the American College of Cardiology. 2015;65(3):236-42.

6 Henderson RA, et al. 10-year mortality outcome of a routine invasive strategy versus a selective invasive strategy in non–ST-segment elevation acute coronary syndrome: the British Heart Foundation RITA-3 Randomized Trial. Journal of the American College of Cardiology. 2015 ;66(5):511-20.

Scientific Program

Discrepancies between current clinical practices in ACS management and real-life situations underline the need for better characterization of STEMI, NSTEMI and UAP phenotypes and their mechanistic diversity. To develop more patient-oriented and personalized strategies for ACS and MACE management, we need to go beyond the traditional risk factors and one-size-fit-all approach.

Thus, the efforts should be focused on: (1) the use of novel cutting-edge technologies to unravel underlying complex mechanisms leading to plaque eruption and acute ischemia, (2) the discovery of specific molecular signatures that could be exploited as novel therapeutic targets and/or biomarkers and (3) the identification high-risk patients and coronary artery lesions prone to future cardiac events (MACE) that may direct more potent systemic and local approaches for pre-emptive treatment.

Current Gaps and Challenges in the state of the art

CardioSCOPE Solutions