Multimodal Cardiac Imaging Registry in Patients with Atrial Fibrillation

1. Introduction

Atrial fibrillation (AF) is the most common cardiac arrythmia, that affects 37% Europeans over 55 years old, representing a major burden for the society and health systems. One of the most devastating consequences of AF is ischemic stroke, often caused by embolization of cerebral arteries with a left atrial appendage thrombus (LAT), which can form in left atrial appendage in the presence of AF. As it has little contractility on its own, emptying and filling of left atrial appendage relies on the function of the left ventricle and the left atrium.

AF as well as atrial flutter promote the formation of LAT and are therefore associated with an increased risk of thromboembolic events. The mechanism of stroke is complex, but embolization with LAT accounts for the majority of events and it can be triggered by sinus rhythm restoration through procedures commonly performed in patients with AF - cardioversion or catheter ablation. Therefore, cardioversion and catheter ablation in the presence of LAT are contraindicated.

Transoesophageal echocardiography (TEE) is considered the modality of choice to detect LAT with high sensitivity and specificity and is currently recommended before cardioversion or catheter ablation as an alternative to a 3-week course of oral anticoagulation. Current guidelines, however, leave room for an individual decision to either perform or not perform TEE before catheter ablation or cardioversion in a chronically anticoagulated patient but suggest no tools to assess the risk of LAT. To address this unmet clinical need, we have previously shown that by combining clinical data and measurements from transthoracic echocardiography in a machine-learning model it is possible to predict the risk of LAT formation. Importantly, our results indicated, that TTE-derived measurements played the greatest role in predicting LAT.

Despite significant advancements in interventional technologies, the selection of appropriate therapeutic methods and perioperative procedures remains a significant challenge. Patients eligible for interventional procedures related to AF often undergo numerous diagnostic tests, including computed tomography of the heart, transoesophageal and transthoracic echocardiography, electrocardiography (EKG), and electroanatomic mapping during the ablation procedure. Non-invasive multimodal imaging plays central role in the peri-ablation period, informing important therapeutic decisions and facilitating the procedure. The essence of this project is the prospective collection of high-quality imaging data from these multiple modalities and clinical data, which will allow for a better understanding of the relationships between anatomy, hemodynamic function, and clinical observation in patients with AF in the future. Ultimately the data might serve for the development of tools which could efficiently predict the risk of LAT by means of less invasive and cheaper approaches than the ones which are currently used. The resulting multimodal database will also form a foundation for future studies targeted at informing therapeutic decisions in patients undergoing catheter ablation of AF. 2. Study Objectives

2.1. Main objective: To create a multimodal, multicentre registry of clinical and imaging data to develop predictive models based on state-of the art artificial intelligence to support the diagnostic and therapeutic process for patients undergoing AF catheter ablation and cardioversion.

2.2. Specific objectives:

2.2.1. Specific Aim 1 Creation of artificial intelligence-based models to predict the risk of formation of left atrial appendage thrombus and estimate the left atrial appendage emptying velocity obtained from transoesophageal echocardiography based on the analysis of transthoracic echocardiographic images and clinical data.

2.2.2. Specific Aim 2 Assessment of inter-reader and intra-reader agreement in the clinical interpretation of left atrial appendage images and left atrial appendage thrombus diagnosis in transoesophageal echocardiography.

2.2.3. Specific Aim 3 Development of models that fuse information from multiple modalities (for instance from transthoracic echocardiography and cardiac CT) to provide better prognosis and guide therapeutic decisions in patients with atrial fibrillation.

2.2.4. Specific Aim 4 Comparison of the effectiveness of different methods of imaging the left atrium in predicting thromboembolic events.

2.2.5. Specific Aim 5 Creation of a high-quality multicentre imaging database for additional future auxillary nalyses and studies. 3. Study Methodology

To maximize the amount of collected data the study allows both retrospective and prospective data collection. The scope of collected data is the same in retrospective and prospective collection with certain data types being optional and subject to availability.

3.1. Inclusion criteria

Patients with: * history of atrial fibrillation, * who are undergoing medically justified transoesophageal echocardiography to assess the presence of left atrial appendage thrombus before catheter ablation of atrial fibrillation (including patients who had transoesophageal echocardiography during the ablation procedure). OR * who undergo catheter ablation without prior transoesophageal echocardiography (if the center also collects additional imaging data listed in point 2.5 below) 3.2. Exclusion criteria * Age \< 18 years old.

3.3 3.3. Types of collected data

Data type: Clinical data Compulsory or optional: Includes compulsory and optional fields Format: Tabular, collected using a dedicated eCRF Additional remarks: The detailed list of fields with possible values is shown in Appendix 1

Data type: TTE Compulsory or optional: Compulsory Format: DICOM Additional remarks: Recorded before TEE preferably on the same day. In case of retrospective data TTE and TEE acquired within 72h

Data type: TEE Compulsory or optional: Compulsory if the patient had TEE Format: DICOM

Additional remarks:

Data type: Cardiac CT Compulsory or optional: Optional Format: DICOM Additional remarks: Contrast enhanced cardiac CT before ablation procedure. Can be a study performed for EP planning or for CAD diagnostics. Any study performed before the ablation regardless of timing can be used

Data type: Non-contrast Cardiac CT Compulsory or optional: Optional Format: DICOM Additional remarks: Non-contrast chest CT. Preferred is ECG-gated calcium scoring CT reconstructed with thin slices (preferably 0.5mm).

Data type: Cardiac Magnetic Resonance (CMR) Compulsory or optional: Optional Format: DICOM

Additional remarks:

Data type: Digitalised Electrocardiogram Compulsory or optional: Optional Format: DICOM (or pdf) Additional remarks: Performed on the day of the catheter ablation or cardioversion or day before.

Data type: Electroanatomical map Compulsory or optional: Optional Format: Proprietary Additional remarks: Not to be transferred but only stored locally in the participating center for possible ancillary studies

Data type: Follow-up for MACE Compulsory or optional: Optional Format: Event date Additional remarks: Depending on the local regulations and possibility, the follow-up data for all-cause mortality, stroke, myocardial infarction, onset or worsening of heart failure will be obtained based on ICD-9 and ICD 10 codes from the national health insurance databases. Alternatively, data can be obtained by telephone interview

Data type: Follow-up for AF Compulsory or optional: Optional Format: Event date Additional remarks: Depending on the local availability of follow-up data for AF recurrence

3.4. Guidelines for data acquisition

3.4.1. Guidelines for Acquisition of Transthoracic and Transesophageal Echocardiography * For prospective collection the TEE and TEE should be performed ideally in the same day, TTE directly before TEE. For the retrospective cohort TTE can be acquired up to 3 days before TEE, as long as there were no important changes in patients' condition during this period (i.e. clinical worsening, change of rhythm, heart rate etc). * ECG electrodes should be connected for both TTE and TEE (not compulsory for retrospective data) * The acquisition length should be set to 5 seconds (set the start acquisition at the moment when acquire button is pressed to minimise unwanted movement). For retrospective data shorter clips are acceptable.

3.4.1.1. Acquisition of TTE \[filenames are given in brackets\]: 1. Four-chamber apical projection \[4ch.dcm\] 2. Two-chamber apical projection \[2ch.dcm\] 3. Three-chamber apical projection \[3ch.dcm\] 4. Four-chamber apical projection - optimized for LA \[4chLA.dcm\] 5. Two-chamber apical projection - optimized for LA \[2chLA.dcm\] 6. 3D full volume (preferably acquired from 4 or more heart cycles) \[3d\_tte.dcm\] The projections must encompass the entire heart, including the atria. Measurements to be performed at site (if impossible, some of these measurements can also be performed by the coordinating site).

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1. Cardiac chamber dimensions (PLAX) \[plax.dcm\] 2. Velocities E, A, med. E\&#39;, lat. E\&#39; (still images) \[mitral\_flow.dcm, medial\_tdi.dcm, lateral\_tdi.dcm\] 3. Tricupid regurgitation spectral image (still images) \[tr.dcm\]

3.4.1.2. Acquisition of TEE: 1. Projection on LAA (Left Atrial Appendage): 0, 45, 90, 135 degrees, and other projections that are necessary to correctly image the entire LAA according to the investigator/ echocardiographer \[laa\_0.dcm, laa\_45.dcm, laa\_135.dcm etc.\] 2. 3D acquisition of the volume that contains LAA (multi-beat-optimized) \[3d\_LAA.dcm\] 3. Measurement of maximum emptying velocity of LAA 1cm from the LAA ostium - at least three measurements in two different scanning angles, averaged. 4. Acquisition of spectral Doppler image of LAA emptying (three images from two or more scanning angles) (still images) \[laav\_60.dcm, laav135.dcm, laav\_45.dcm\]

3.4.1.3. Other modalities: There are no specific acquisition requirements for cardiac CT, CMR or ECG - these studies should be performed according to local standard protocols.

Appendix 1 - Dictionary of tabular data

Variable: CaseID Display name: Case ID Type: ID Compulsory: Yes Categories and Units details: Consecutive IDs unique for each entry

Variable: PatientID Display name: Patient ID Type: ID Compulsory: Yes Categories and Units details: Consecutive ID for patients; if the patient is entered to the registry more than once, he/she should have the same PatientID

Variable: procedure\_type Display name: Type of planned intervention Type: Clinical Compulsory: Yes Categories and Units details: ablation = 1, cardioversion = 2, NA = 3, laa\_closure = 4, valvular disease = 5, infective endocarditis = 6

Variable: AF Display name: Atrial fibrillation Type: Clinical Compulsory: Yes Categories and Units details: Yes = 1, No = 0

• Follow up for adverse outcomes [Срок оценки: 1 year]
• Follow up for ablation recurrence [Срок оценки: 1 year]