Brugada Syndrome and Artificial Intelligence Applications to Diagnosis (BrAID)

Aim of the project is the development of an integrated platform, based on machine learning and omic techniques, able to support physicians in as much as possible accurate diagnosis of Type 1 Brugada Syndrome (BrS).

Study Overview

• Status: Not yet recruiting
• Conditions: Brugada Syndrome 1
• Intervention / Treatment: Diagnostic test: Patients affected by Brugada Syndrome 1

Detailed Description

The aim of BrAID project is to integrate classic clinical guidelines for Brugada Syndrome 1 diagnosis evaluation with innovative Information and Communication Technologies and omic approaches, generating new diagnostic strategies in cardiovascular precision medicine of this disease.

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giorgio Iervasi, Dr.; Phone Number: +390503153302; Email: segreteria.direzione@ifc.cnr.it

Study Locations

• Italy
  • Tuscany
    • Arezzo, Tuscany, Italy, 52100
      • Azienda USL Toscana Sud Est - U.O.C Cardiologia
      • Contact: Pasquale Giovanni Notarstefano, Dr.; Phone Number: +3905752551; Email: pasqualenotarstefano@gmail.com
    • Firenze, Tuscany, Italy, 50134
      • Azienda Ospedaliera Universitaria Careggi - SOD Aritmologia
      • Contact: Paolo Pieragnoli, Dr.; Phone Number: +390557946216; Email: paolopieragnoli@virgilio.it
    • Pisa, Tuscany, Italy, 56100
      • Azienda Ospedaliero Universitaria Pisana - Cardiologia 2
      • Contact: Giulio Zucchelli, Dr.; Phone Number: +39050993043; Email: g.zucchelli@ao-pisa.toscana.it
    • Pisa, Tuscany, Italy, 56124
      • Fondazione Toscana Gabriele Monasterio
      • Contact: Marcello Piacenti, Dr.; Phone Number: +390503153443; Email: marcello.piacenti@ftgm.it
    • Pisa, Tuscany, Italy, 56124
      • Istituto di Fisiologia Clinica IFC-CNR
      • Contact: Federico Vozzi, Ph.D.; Phone Number: +390503152672; Email: vozzi@ifc.cnr.it
      • Contact: Maria-Aurora Morales, Dr.; Phone Number: +390503153228; Email: morales@ifc.cnr.it
    • Viareggio, Tuscany, Italy, 55049
      • Azienda Usl Toscana Nord Ovest - U.O.C. Cardiologia
      • Contact: Gianluca Solarino, Dr.; Phone Number: +3905846051; Email: gianluca.solarino@uslnordovest.toscana.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Brugada patients: patients with Brugada Syndrome 1 spontaneous or induced by the ajmaline test; patients with non-diagnostic electrocardiographic pattern for Brugada Syndrome 1 or negative in the presence of high clinical suspicion (family history for Brugada Syndrome, patients who survived cardiac arrest without organic heart disease)
• Control patients: patients with frequent premature ventricular complex and normal left and right ventricular function; patients with suspected Brugada Syndrome 1 not confirmed by ajmaline test

Exclusion Criteria:

• organic heart disease or diseases interfering with protocol completion
• lack of signed informed consent
• pregnancy
• acute coronary artery disease, heart failure in the previous 3 months
• severe renal or liver failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients affected by Brugada Syndrome 1; Patients with spontaneous or drug-induced Brugada Syndrome 1	Diagnostic test: Patients affected by Brugada Syndrome 1; ECG analysis by Machine Learning algorithms and blood collection for the transcriptomic study of markers possibly associated with the disease
Active Comparator: Controls; Patients with no condition associated with spontaneous or drug-induced Brugada Syndrome 1	Diagnostic test: Patients affected by Brugada Syndrome 1; ECG analysis by Machine Learning algorithms and blood collection for the transcriptomic study of markers possibly associated with the disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Machine Learning recognition of Brugada Syndrome 1	Identification of Brugada type 1 Syndrome coved ST component in a cohort of 44 patients (prospective study) and validated in a cohort of 100 patients (validation study) according to the diagnostic patterns related to Brugada Syndrome 1 on 12-leads ECG as already published on current international guidelines	Week 20
Machine Learning recognition of Brugada Syndrome 1	Identification of Brugada type 1 Syndrome QRS fragmentation component in a cohort of 44 patients (prospective study) and validated in a cohort of 100 patients (validation study) according to the diagnostic patterns related to Brugada Syndrome 1 on 12-leads ECG as already published on current international guidelines	Week 20
Machine Learning recognition of Brugada Syndrome 1	Identification and characterization of Brugada type 1 Syndrome T segment depression component in a cohort of 44 patients (prospective study) and validated in a cohort of 100 patients (validation study) according to the diagnostic patterns related to Brugada Syndrome 1 on 12-leads ECG as already published on current international guidelines	Week 20
Machine Learning recognition of Brugada Syndrome 1	Identification of Brugada type 1 Syndrome broad P wave with PQ prolongation component in a cohort of 44 patients (prospective study) and validated in a cohort of 100 patients (validation study) according to the diagnostic patterns related to Brugada Syndrome 1 on 12-leads ECG as already published on current international guidelines	Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers associated with Brugada Syndrome 1	Identification of biomarkers associated with Brugada Syndrome 1 by the means of blood transcriptomic profile and exosomes analysis of patients. Transcriptomic and exosome could provide new insight into the pathophysiology of signalling in this pathology, as well as for application in Brugada Syndrome 1 diagnosis and therapeutics. Transcriptomic will provide a global picture of phenotypical changes associated with the disease, highlighting the potential genes involved in the development of Brugada Syndrome 1 The analysis of exosome coding and noncoding RNAs, participating in a variety of basic cellular functions, could also evidence potentially important pathophysiologic effects both in cardiac cells as well as on the release of electrical stimuli. The study will be performed in a cohort of 44 patients (prospective study) and results will be validated in a cohort of 100 patients (validation study)	week 48
Stratification risk	Development of stratification risk system for Brugada type 1 Syndrome by the integration of ECG Machine Learning algorithms and biomarkers. In particular, the module will combine the peculiar ECG patterns associated with BrS (coved ST, QRS fragmentation, T segment depression, broad P wave with PQ prolongation)(outcome 1-4) and omic (genes) and exosome markers (coding and noncoding RNAs)(outcome 5) with the aim to improve patient risk stratification. Specifically, gene expression modulation (expressed as % respect to control population) of Na+ (e.g., Nav1.5, Nav1.3, Nav2.1), Ca2+ (e.g. Cav3.1, HCN3) and K+ channels (e.g.,TWIK1, Kv4.3) will be evaluated. The study will be performed in a cohort of 44 patients (prospective study) and results will be validated in a cohort of 100 patients (validation study).	week 64

Collaborators and Investigators

• Sponsor: Istituto di Fisiologia Clinica CNR
• Collaborators: Azienda Ospedaliero, Universitaria Pisana; Azienda USL Toscana Nord Ovest; Azienda USL Toscana Sud Est; Fondazione Toscana Gabriele Monasterio; Azienda Ospedaliero-Universitaria Careggi
• Investigators: Principal Investigator: Federico Vozzi, Ph.D., Istituto di Fisiologia Clinica

Publications and helpful links

General Publications

• Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 1992 Nov 15;20(6):1391-6. doi: 10.1016/0735-1097(92)90253-j.
• Quan XQ, Li S, Liu R, Zheng K, Wu XF, Tang Q. A meta-analytic review of prevalence for Brugada ECG patterns and the risk for death. Medicine (Baltimore). 2016 Dec;95(50):e5643. doi: 10.1097/MD.0000000000005643.
• Vutthikraivit W, Rattanawong P, Putthapiban P, Sukhumthammarat W, Vathesatogkit P, Ngarmukos T, Thakkinstian A. Worldwide Prevalence of Brugada Syndrome: A Systematic Review and Meta-Analysis. Acta Cardiol Sin. 2018 May;34(3):267-277. doi: 10.6515/ACS.201805_34(3).20180302B. Erratum In: Acta Cardiol Sin. 2019 Mar;35(2):192.
• Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A. Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2005 Apr;2(4):429-40. doi: 10.1016/j.hrthm.2005.01.005. Erratum In: Heart Rhythm. 2005 Aug;2(8):905.
• Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA; Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology. Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J. 2002 Nov;23(21):1648-54. doi: 10.1053/euhj.2002.3382. No abstract available.
• Sarquella-Brugada G, Campuzano O, Arbelo E, Brugada J, Brugada R. Brugada syndrome: clinical and genetic findings. Genet Med. 2016 Jan;18(1):3-12. doi: 10.1038/gim.2015.35. Epub 2015 Apr 23.
• Morales MA, Piacenti M, Nesti M, Solarino G, Pieragnoli P, Zucchelli G, Del Ry S, Cabiati M, Vozzi F. The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition. BMC Cardiovasc Disord. 2021 Oct 13;21(1):494. doi: 10.1186/s12872-021-02280-3.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2021
• Primary Completion (Anticipated): March 15, 2023
• Study Completion (Anticipated): September 15, 2023

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Syndrome; Brugada Syndrome
• Other Study ID Numbers: BrAID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No