An integrated POC solution for non-invasive diagnosis and therapy monitoring of Heart Failure patients

Project Information

KardiaTool

Grant agreement ID: 768686

DOI

10.3030/768686

Project closed

EC signature date 11 July 2017

Start date 1 November 2017

End date 30 April 2021

Funded under

• INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies – Nanotechnologies

Total cost

€ 4 999 880,55

EU contribution

€ 4 999 880,55

Coordinated by

UNIVERSITE LYON 1 CLAUDE BERNARD
France

Periodic Reporting for period 3 - KardiaTool (An integrated POC solution for non-invasive diagnosis and therapy monitoring of Heart Failure patients)

Reporting period: 2020-11-01 to 2021-04-30

Summary of the context and overall objectives of the project

Heart failure (HF) is a life-threatening disease, causing a significant economic burden on healthcare systems across the globe. According to the European Heart Failure Association, the prevalence of HF is approximately 26 million patients worldwide and is increasing. Furthermore, HF is associated with poor prognosis, increased mortality and morbidity and frequent re-hospitalizations that pose a great problem for both patients and their families, as well as, the healthcare system. As the overall life expectancy has increased, the global community is now facing new challenges of improving quality of life and healthcare at affordable costs.
The process of HF diagnosis is challenging and complicated, since even if the pathophysiology of HF has been understood to a great extent by the medical community, there is a wide spectrum of potential clinical manifestations of HF; signs and symptoms are often non-specific. The utilization of New York Heart Association (NYHA) Functional Classification system, as a tool to classify the HF patients according to the severity of their symptoms, introduces high intra-observer variability, since it is based on subjective evaluation. Additionally, therapy monitoring of the HF patients is of critical value for healthcare professionals and could assist in the identification of subgroups of patients that would benefit from a more intensive follow-up to avoid frequent rehospitalizations or delay disease progression to end stage HF. Currently the majority of HF therapy monitoring models are not personalized and suitable for clinical application. One has to agree that there is ample room for improving the usability of risk prediction tools and improving HF therapy monitoring.
New biomarkers and testing technologies, which can diagnose HF, monitor therapy and provide information related to the subsequent risk for adverse events and mortality of the affected patients may drive this change. Point of Care (POC) devices provide a great opportunity for continuous monitoring of such biomarkers. The POC market is driven by technological advancements for providing Micro-Nano-Bio Integrated Systems platforms (MNBS) that enhance the ability to detect, analyse and monitor biomarkers as evaluation end-points, with lower costs.
The aim of the KardiaTool project was to translate a laboratory proven concept of a saliva biosensor to the clinical practice for addressing the priority needs in personalized HF diagnostics and therapy monitoring at the point of care.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The KardiaTool platform includes:

- An easy to use portable POC device (KardiaPOC) with a disposable Lab-on-a-Chip (LOC), for the non-invasive, rapid and accurate qualitative and quantitative assessment of HF biomarkers, from saliva samples. KardiaPOC device integrates a variety of sensors, actuators, Microelectromechanical systems (MEMS), micro-electronics, bio-chemicals and functionalized magnetic nanoparticles (MNPs), onto a disposable, low cost LOC.
- A decision support software (KardiaSoft) based on predictive modelling techniques, that analyzes the POC and other patient’s data, directly added by the healthcare professionals, and delivers information related to HF diagnosis and therapy monitoring.

Several novel products have been developed and obtained during the realization of KardiaTool, as described below:
- Development of novel immunological field-effect transistor (immunoFET) for saliva analysis (TNF-α, cortisol, Il-10 and NT-proBNP) using standard addition method in combination with electrochemical impedance measurement
- Development of novel arraying planar coils using silicon technology
- Development of new methodology for the immobilization of antibodies on functionalized ISFET
- Innovation regarding the development of new instrumentation for impedance measurement
- Development of the first time LOC that integrate microfluidic, planar coils and immunoFETs
- Development of a novel Kardiasoft tool platform for management of HF patients anddecision support in terms of diagnosis, stratification and therapy monitoring
- Integration of the KardiaTool components into a unified KardiaPOC system by setting up all required infrastructures and developing necessary tools.
- Clinical studies in 3 different countries (Greece, Ireland, Italy) were implemented both for data provision and validation of the project outcomes.

The partners have participated in scientific and technical conferences, in the fields of the project, as well as in events of a broader scope, related to clinical, scientific or technological topics.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

KardiaTool project managed to merge new technologies for monitoring HF biomarkers in saliva, by combining new immunosensors, together with the confirmation and validation of new clinically relevant HF biomarkers to support smarter clinical decisions to pave the way for breakthroughs in HF management. Immunosensors were developed, generating a specific analytical signal upon the interaction of cardiac biomarkers with an antibody modified surface. Furthermore, saliva is a biological fluid that can be collected in a simple, easy, non-invasive and patient friendly manner.
The KardiaPOC device seeks to replace the current standard of HF management, specifically the blood tests for detecting well-validated HF biomarkers (e.g. NT-proBNP, cortisol, TNF-, Il-10), with a non-invasive POC saliva platform for simultaneously detection of biomarkers related with HF in short detection times and to overcome the current limitations of other biomarker platforms.
The KardiaTool platform integrates a variety of actuators (Valves, Pumps), planar coils, microfluidic, instrumentation, immunosensors, functionalized magnetic nanoparticles and a decision support software (KardiaSoft) for data analysis.
The innovative KardiaSoft decision support system (DSS) has been developed and tested with real patient data, coming from project’s clinical studies, to address the management, diagnosis, prediction, stratification and therapy monitoring of HF patients. The KardiaSoft is the only integrated software solution providing all the above-mentioned functionalities at the point-of-care. Contrary to existing solutions (mainly at research level, non-commercial) working on the distinction between HF and non-HF subjects, the diagnosis component of the KardiaSoft focuses on the grey zone between non-HF (subjects with obesity or hypertension but with symptoms similar to HF) and chronic and acute HF subjects. In terms of stratification (i.e. patient risk to develop HF), KardiaSoft extends the current approaches focusing on the estimation of the current risk of patient to the prediction of the future risk by providing in this way a very helpful tool for the clinicians to adapt the HF patient’s management. In addition, KardiaSoft provides a novel tool for therapy monitoring based on advanced visualization. Results demonstrate high performance (in terms of accuracy, specificity and sensitivity). Finally, KardiaSoft employs the novel data from the project saliva biomarkers and it can operate either standalone or in cooperation with POC/LOC devices.

Social media
https://twitter.com/EU_KardiaTool
https://www.facebook.com/KardiaTool/
https://www.linkedin.com/company/kardiatool-h2020-project/

Videos
Video describing the KardiaTool project:
https://www.facebook.com/KardiaTool/videos/321745419678232
Video describing the KardiaSoft software:
https://www.facebook.com/KardiaTool/videos/204469481534942

KardiaSoft

POC-KardiaTool

The concept of KardiaTool project

The KardiaTool end-product

First prototype of the KardiaPOC