Periodic Reporting for period 1 - BIOTOOL-CHF (BIOmarker based diagnostic TOOLkit to personalize pharmacological approaches in congestive heart failure)
Période du rapport: 2023-10-01 au 2025-03-31
Heart failure is a leading cause of hospitalization in Europe, affecting millions of people and imposing a major burden on healthcare systems. Despite advances in pharmacological therapies that improve long-term outcomes in heart failure, symptoms related to fluid retention (i.e. congestion) remains the primary driver of hospital admissions and readmissions. Diuretics are the mainstay of symptomatic relief, but their use is largely empirical. Standard clinical examination poorly captures the complexity of fluid overload, which may result in suboptimal diuretic therapy. This gap in knowledges contributes to the commonly observed persistent congestion in a large proportion of patients which is associated with an increased risk of mortality and rehospitalization.
The BIOTOOL-CHF project addresses this critical need by developing a personalized approach to decongestive therapy, based on the assessment of circulating biomarkers. This project takes advantage of the data from two cohorts of discovery phase by identifying biomarkers in two large, well-characterized European cohorts: the BIOSTAT-CHF index and the Scottish BIOSTAT-CHF validation cohort. By integrating these biomarkers with clinical profiles and outcomes, we aimed to develop a multiparametric score to personalize diuretic therapy in patients with congestive heart failure.
This work is situated within a broader strategic effort to improve patient-centered, precision medicine in heart failure, aligning with EU health priorities on digital and data-driven innovation. The expected impact of BIOTOOL-CHF is the development of a clinically applicable diagnostic toolkit that can be used to improve therapeutic decisions, reduce hospitalizations, and enhance quality of life for patients with heart failure. By providing a foundation for smarter use of diuretics, this approach aims to shift current paradigms from one-size-fits-all therapy to tailored care.
The BIOTOOL-CHF project addresses this critical need by developing a personalized approach to decongestive therapy, based on the assessment of circulating biomarkers. This project takes advantage of the data from two cohorts of discovery phase by identifying biomarkers in two large, well-characterized European cohorts: the BIOSTAT-CHF index and the Scottish BIOSTAT-CHF validation cohort. By integrating these biomarkers with clinical profiles and outcomes, we aimed to develop a multiparametric score to personalize diuretic therapy in patients with congestive heart failure.
This work is situated within a broader strategic effort to improve patient-centered, precision medicine in heart failure, aligning with EU health priorities on digital and data-driven innovation. The expected impact of BIOTOOL-CHF is the development of a clinically applicable diagnostic toolkit that can be used to improve therapeutic decisions, reduce hospitalizations, and enhance quality of life for patients with heart failure. By providing a foundation for smarter use of diuretics, this approach aims to shift current paradigms from one-size-fits-all therapy to tailored care.
The main focus of the first reporting period was the establishment of the retrospective BIOTOOL-CHF DISCO study platform by integrating clinical, laboratory, and biomarker data from the European BIOSTAT-CHF cohorts.
The platform was designed to enable re-analysis of clinical data and laboratory results of selected biomarkers. We identified 10 candidate molecules of interest (see table) because they are known to be associated with fluid retention and to prognosis in these patients. Six of them had already been assayed within the BIOSTAT-CHF project, and four were analysed in the context of BIOTOOL-DISCO by re-assaying BIOSTAT-CHF biobanked samples.
Beyond data generation, we conducted detailed quality assessments to ensure consistency, accuracy, and integrity of the final database. Outliers were addressed, and the final dataset was reviewed for completeness and analytical readiness.
Overall, the work during this period established a robust infrastructure for biomarker validation and ensured high-quality data for current and future BIOTOOL-CHF analyses. These efforts support the project’s goal of identifying actionable biomarkers to improve patient stratification and management.
The platform was designed to enable re-analysis of clinical data and laboratory results of selected biomarkers. We identified 10 candidate molecules of interest (see table) because they are known to be associated with fluid retention and to prognosis in these patients. Six of them had already been assayed within the BIOSTAT-CHF project, and four were analysed in the context of BIOTOOL-DISCO by re-assaying BIOSTAT-CHF biobanked samples.
Beyond data generation, we conducted detailed quality assessments to ensure consistency, accuracy, and integrity of the final database. Outliers were addressed, and the final dataset was reviewed for completeness and analytical readiness.
Overall, the work during this period established a robust infrastructure for biomarker validation and ensured high-quality data for current and future BIOTOOL-CHF analyses. These efforts support the project’s goal of identifying actionable biomarkers to improve patient stratification and management.
Unlike existing approaches that rely on single biomarkers or clinical parameters, we developed a panel that integrates distinct pathophysiological domains to better capture disease heterogeneity and inform targeted treatment strategies. Initial analyses in large, well-phenotyped cohorts have confirmed the feasibility of this approach and laid the foundation for a clinically applicable scoring system.
The main challenge at this stage is ensuring that the biomarker panel can be implemented with a sufficiently fast turnaround time across all partner hospitals. To address this, efforts are focused on assessing the laboratory infrastructure at each site, identifying logistical and technical gaps, and engaging diagnostic industry partners to explore scalable assay solutions. Discussions are ongoing regarding centralized laboratory strategies. One consortium partner is also developing a point-of-care platform, which could significantly enhance the clinical utility of the biomarker panel, particularly in acute or outpatient settings.
The next step is the design and execution of a prospective clinical trial to validate the biomarker-guided approach in real-world care. This trial will be essential to demonstrate clinical benefit, assess feasibility in routine practice, and support further steps toward regulatory approval, health economic evaluation, and eventual integration into treatment pathways.
The main challenge at this stage is ensuring that the biomarker panel can be implemented with a sufficiently fast turnaround time across all partner hospitals. To address this, efforts are focused on assessing the laboratory infrastructure at each site, identifying logistical and technical gaps, and engaging diagnostic industry partners to explore scalable assay solutions. Discussions are ongoing regarding centralized laboratory strategies. One consortium partner is also developing a point-of-care platform, which could significantly enhance the clinical utility of the biomarker panel, particularly in acute or outpatient settings.
The next step is the design and execution of a prospective clinical trial to validate the biomarker-guided approach in real-world care. This trial will be essential to demonstrate clinical benefit, assess feasibility in routine practice, and support further steps toward regulatory approval, health economic evaluation, and eventual integration into treatment pathways.