Clinical Cohorts for Validation of New Digital Biomarkers

Study Overview
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Brief Summary
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The MAESTRIA study is an international, multi-centre, non-interventional, observational registry. The main goal is to enrol a representative group of European patients diagnosed with Atrial Fibrillation (AF) to analyse clinical and relevant parameters (digitalised ECG, echocardiograms, cardiac CTs, MRIs and blood biomarkers) that could be used during clinical practise for the diagnosis of atrial cardiomyopathy. The AF patients will be distributed in 3 groups according to the different manifestation of AF: paroxysmal, persistent and permanent AF.

Detailed Description
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Atrial fibrillation (AF) and stroke are major health care problems in Europe. They are most often the clinical expression of atrial cardiomyopathy, which is under-recognised due to the lack of specific diagnostic tools. Multidisciplinary research and stratified approaches are urgently needed to prevent, diagnose, and treat AF and stroke and preempt the AF-related threat to healthy ageing in Europe. MAESTRIA is a European consortium of 18 clinicians, scientists and pharma industry partners who are at the forefront of research and medical care of AF and stroke patients funded by the EU Horizon 2020 programme (grant number 965286). The Atrial Fibrillation Network (AFNET) is one of the 18 partner institutions in this European consortium. MAESTRIA will create multi-parametric digital tools based on a new generation of biomarkers that integrate artificial intelligence (AI) processing and big data from cutting edge imaging, electrocardiography and omics technologies. It will develop novel biomarkers, diagnostic tools and personalized therapies for atrial cardiomyopathy. The MAESTRIA-AFNET 10 Study is an integral part of the MAESTRIA project. The study will collect relevant clinical parameters for AF from patients, this includes ECGs, cardiac CTs, MRIs and echocardiograms. Dedicated core labs will collect and homogenize the clinical data. For atrial arrhythmias (AA) and vascular stiffness index (VSI) recording, patients will be provided with a measuring bracelet for continuous monitoring of heart rhythm with a photoplethysmographic (PPG) sensor coupled with a smartphone app and the Preventicus Heartbeats® analytic service (Class IIa, CE marked), approved as consumer device. Preventicus is ISO 13485 certified.

Official Title
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Machine Learning and Artificial Intelligence for Early Detection of Stroke and Atrial Fibrillation. Clinical Cohorts for Validation of New Digital Biomarkers

Conditions
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Atrial Fibrillation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with paroxysmal AF, persistent AF or permanent AF. Patients (or legally acceptable representative if applicable to country specific regulations) provide written informed consent to participate in the study. The patient has the option to give separate consent to donate extra volume of blood during the routine blood collection, that can be used for biomedical research. Patient is at least 18 years old. Patient must own a smartphone with Apple iOS version 14.5 (or higher) or with Android version 8.0 (or higher). Exclusion Criteria: Any disease that limits life expectancy to less than 1 year. All persons unable to provide informed consent. All persons exempt from participation in a study or trial by law. Any medical or psychiatric condition which, in the investigator´s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Paroxysmal AF<br>200 patients | |
| Persistent AF<br>200 patients | |
| Permanent AF<br>200 patients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical examination | Weight (Kilograms-Kg) Height (centimeters-cm) Weight and height will be combined to calculate BMI in Kg/m^2 | 12 months | 
| Clinically relevant changes in CT/MRI | only if clinically indicated | 12 months | 
| Atrial Arrythmias (AA) burden and vascular stiffness (measured by a measuring bracelet) | AA burden and vascular stiffness measured by the measuring bracelet | 12 months | 
| Cognitive function test (MoCA) | evaluation of cognitive function (includes different tasks: visual/executive; naming; memory; attention; language; abstraction; delayed recall; orientation). Total score will be calculated and collected. | Baseline and Follow up at 12 months | 
| EQ-5D-5L Quality of Life questionnaire | quality of life assessment (includes questions about mobility, self care, usual activities, pain/discomfort and anxiety/depression). The health state code will be collected (calculated as concatenation of 5 scores). Health score from vertical visual analogue scale (0-100) will be collected. | Baseline and Follow up at 12 months | 
| Ischaemic events (systemic, myocardial and cerebral) | ischaemic events | 12 months | 
| Echo analysis (TEE_transesophageal echocardiography): LAA smoke available | collected as Yes/No | 12 months | 
| Echo analysis (TEE_transesophageal echocardiography): Flow velocity in LAA | measured in cm/sec | 12 months | 
| Echo analysis (TEE_transesophageal echocardiography): Antrum diameter | measured in mm | 12 months | 
| Echo analysis (TTE_transthoracic echocardiography): LVEF | Measured in %; Biplane Simpson Method | 12 months | 
| Echo analysis (TTE_transthoracic echocardiography): LA diameter | measured in mm LA volume (mL) Septum thickness (mm) Degree of mitral valve insufficiency (Grade I/trivial; Grade II/moderate; Grade III/moderate to severe; Grade IV/severe; None). Degree of tricuspid valve insufficiency (Grade I/trivial; Grade II/moderate; Grade III/moderate to severe; Grade IV/severe; None). | 12 months | 
| Echo analysis (TTE_transthoracic echocardiography): LA volume | measured in mL | 12 months | 
| Echo analysis (TTE_transthoracic echocardiography): Septum thickness | measured in mm Degree of mitral valve insufficiency (Grade I/trivial; Grade II/moderate; Grade III/moderate to severe; Grade IV/severe; None). Degree of tricuspid valve insufficiency (Grade I/trivial; Grade II/moderate; Grade III/moderate to severe; Grade IV/severe; None). | 12 months | 
| Echo analysis (TTE_transthoracic echocardiography): Degree of mitral valve insufficiency | Grade I/trivial; Grade II/moderate; Grade III/moderate to severe; Grade IV/severe; None | 12 months | 
| Echo analysis (TTE_transthoracic echocardiography): Degree of tricuspid valve insufficiency | Grade I/trivial; Grade II/moderate; Grade III/moderate to severe; Grade IV/severe; None | 12 months | 
| ECG analysis | Electrocardiogram analysis (paper and digital, if available). - 12-lead body surface ECG will be collected. Variables to be collected in the eCRF: Heart Rhythm (Sinus rhythm; Atrial Fibrillation; Continuous pacing; Pacing and AF; other (specify as free text). Heart rate (beats/min) Heart axis (degrees) QRS interval (msec) PR interval (msec) P-wave duration (msec) QT-duration (msec) QTcF (msec) Other relevant ECG findings (to add as free text). | 12 months | 
| MRI analysis: LAEF | Left atrial ejection fractio measured in % | 12 months | 
| MRI analysis: LAVi | LAVi left atrial volume index measured in ml/m^2 | 12 months | 
| MRI analysis: LALRS | LALRS left atrial longitudinal reservoir strain measured in % | 12 months | 
| MRI analysis: LALBS | LALBS left atrial longitudinal booster strain measured in % | 12 months | 
| CT scan analysis | The cardiac CTs will be sent to the specialised core lab for analysis. The analysis will include: Atriomic risk of stroke (5 year event risk) Yes/No | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CT scan: Atriomic risk for AF | 5 year event risk: Yes/No | 12 months | 
| CT scan: Epicardial Adipose tissue volume | measured in cm^3 | 12 months | 
| CT scan: Epicardial adipose tissue mean attenuation | measured in HU | 12 months | 
| CT scan: Left atrium volume | measured in cm^3 | 12 months |