Author + information
- Received June 10, 2018
- Revision received August 22, 2018
- Accepted September 1, 2018
- Published online November 26, 2018.
- Maurizio Pieroni, MD, PhDa,∗∗ (, )@mauripieroni72,
- Pasquale Notarstefano, MDa,∗,
- Antonio Oliva, MD, PhDb,∗,
- Oscar Campuzano, PhDc,d,e,
- Pasquale Santangeli, MDf,
- Monica Coll, PhDc,
- Martina Nesti, MDa,
- Andrea Carnevali, MDg,
- Aureliano Fraticelli, MDa,
- Anna Iglesias, MScc,
- Simone Grassi, MDb,
- Ramon Brugada, MD, PhDc,d,e,h and
- Leonardo Bolognese, MDa
- aCardiovascular Department, San Donato Hospital, Arezzo, Italy
- bInstitute of Public Health, Legal Medicine Section, Catholic University, Rome, Italy
- cCardiovascular Genetics Centre, University of Girona-IDIBGI, Girona, Spain
- dCentro Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
- eMedical Science Department, School of Medicine, University of Girona, Girona, Spain
- fCardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- gPathology Department, San Donato Hospital, Arezzo, Italy
- hCardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain
- ↵∗Address for correspondence:
Dr. Maurizio Pieroni, Cardiovascular Department, San Donato Hospital, Via Pietro Nenni 22, 52100 Arezzo, Italy.
Background The prevalence and significance of structural abnormalities in Brugada syndrome (BrS) are still largely debated.
Objectives The authors investigated the relationship between genetic background, electroanatomic abnormalities, and pathologic substrate in BrS.
Methods They performed 3-dimensional electroanatomic unipolar and bipolar mapping in 30 patients with BrS. Twenty patients underwent 3-dimensional electroanatomic unipolar and bipolar mapping–guided right ventricular outflow tract (RVOT) endomyocardial biopsy. Programmed ventricular stimulation and genetic analysis were performed in all patients.
Results Low-voltage areas (LVAs) were observed at unipolar map in 93% of patients and at bipolar map in 50% of cases. Unipolar LVAs were always larger than bipolar LVAs, were always colocalized, and in all cases included RVOT. Disease-causing mutations were detected in 10 (33%) patients. Programmed ventricular stimulation was positive in 16 cases (53%). In 75% of patients, RVOT histology showed pathologic findings with myocardial inflammation in 80% of them. Among patients with abnormal bipolar map submitted to endomyocardial biopsy, 9 (81%) showed evidence of myocardial inflammation. Conversely, bipolar map was abnormal in 83% of patients with myocardial inflammation. Myocardial inflammation was also more prevalent among inducible patients (83% vs. 25% in noninducible; p = 0.032).
Conclusions BrS is characterized by electroanatomical and structural abnormalities localized to RVOT with a gradient of the pathologic substrate from epicardium to endocardium possibly driven by myocardial inflammation. These findings reclassify BrS as a combination of structural and electrical defects opening the way to new risk stratification and therapeutic strategies.
- Brugada syndrome
- electroanatomic mapping
- endomyocardial biopsy
- genetic analysis
- myocardial inflammation
- sudden cardiac death
↵∗ Drs. Pieroni, Notarstefano, and Oliva contributed equally to this work.
The study was funded by a 3-year Telethon grant (GGP10186) to Drs. Pieroni and Oliva, and by Fondo Investigación Sanitaria del Instituto de Salud Carlos III –FIS- (PI17/01690), and Obra Social “La Caixa.” The CIBERCV is an initiative of the Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 10, 2018.
- Revision received August 22, 2018.
- Accepted September 1, 2018.
- 2018 American College of Cardiology Foundation
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