towards virtual risk assessment for patient-specific stratification in Brugada syndrome

Objective

The Br-TRAP project addresses the current gap in risk stratification for asymptomatic patients affected by Brugada Syndrome (BrS). BrS is an electrophysiological (EP) disease that manifests in a localized substrate in the right ventricular outflow tract of patients, generating a specific ECG pattern in V1-V2 leads. BrS is associated to sudden presentation of ventricular fibrillation (VF) in patients, to date risk stratification is based on risk scores and severely underperforms in asymptomatic cohorts due to lack of significant risk markers. Br-TRAP uses computational simulations of cardiac EP to define a patient specific virtual BrS substrate and use it to simulate the onset of arrhythmia and infer the conditions that precipitate VF in BrS patients. The substrate will be validated with experimental data and will be used to identify arrhythmic risk for each condition. Then, the virtual substrate will be embedded into an anatomically accurate torso and heart to calibrate the model using patient specific ECG. By establishing a relationship between surface leads and BrS substrate, risk stratification becomes patient specific and mechanistically driven. Br-TRAP will output two innovative results. First, the virtual substrate will be a software platform to generate virtual EP experiments that fosters standardization and reproducibility of computational results, while also lowering the degree of expertise needed to perform complex computational simulations. Second, the calibration methods used to tailor the virtual substrate to patient specific data will provide a innovative pipeline that mechanistically link common clinical measures with information that can only be acquired invasively. Br-TRAP shifts risk stratification from a primarily statistical approach to a personalized one centered on identifying the causes of VF in each patient. This paradigm shift adds new information to current diagnostic procedures and opens a new approach to substrate based diseases.