The fourth period (P4) still suffered from the effects of the COVID-19 pandemic impacting the recruitment rate of the CARDIATEAM study.  However, by the end of P4, WP2 has achieved in collaboration with WP3, WP4 and WP5, the implementation of an adapted study protocol in all participating countries. The accuracy/integrity of the collected data and a harmonious conduction of the study throughout the recruiting sites was ensured by the global monitoring .

The main achievement of P4 was the opening of all the 16 centers in all countries involved in the study. P4 ended with a total of 578 patients recruited and 1^st  and 2^cd year follow-up have been performed for the first recruits.

The required infrastructure to collect imaging data in the CARDIATEAM cohort has been installed. The CARDIATEAM web-based database platform is operational and has been successfully validated. Participating centres are being trained and certified by transferring collected data to the imaging core labs and uploading the measurements to a central repository. All data flows are in place and quality assurance measures have been implemented. Hereto, a certification process has been put in place as well as continuous monitoring of the core-lab performance. As the rate of patient inclusion has increased in P4 (total recruitment has more than doubled during RP4 i.e.; RP3 n=250 while by the end of RP4 n=578) the data-flow to and from the web-platform are put to the test, and modifications and further improvements were implemented on the go, based on the feedback of imaging core-labs and imaging centers.

The database which will gather all clinical, imaging and omics data of the recruited patients has been set up and structured. We have developed an eCRF system to collect clinical data from recruited patients. This system contains functionality allowing the manual, expert review of registered data to avoid errors and missing data. Training sessions for clinical research assistants on the tool have been organised at each of the different sites. A data transfer protocol has been implemented between the main data processing partners to securely push validated records into the central database. Pipelines for processing of clinical data into the database have been established and web-based mining tools to query the content of the database to allow live monitoring of collected data have been developed.

Like in previous periods, sample collection kits have been distributed to the already recruiting centers the collected biological samples has been sent for a successful quality check to LIH, and some of them have been selected by WP4 for the omics analyses to be started early RP5. The unsupervised machine learning methodology required to analyze the future deep phenotypic data has been set-up, tested and used to analyze the 408 initial volunteers for a preliminary clustering analysis identifying four clusters of patients based on S.O.M methodology to start early in P5. The synergic work of WP2, WP3, WP4 and WP5 thus has led to the identification of patients with outstanding clinical, imaging and routine biological phenotyping that will be undergo multi-OMICs analysis in early RP5 .

Concerning animal models, WP7 partners have now finalised the overview of existing preclinical models of metabolic disorders pertinent to the project and published a first joint review article. Another article will be submitted early in RP5. Two models of interest have been selected for the use within the consortium and a joint protocol across 6 partner’s lab bases on mice issued from the same provider are being finalized early RP5.