title: Absence of pathognomonic or inflammatory patterns in cardiac biopsies from patients with Brugada syndrome.
abstract: BACKGROUND
  Brugada syndrome (BrS) is characterized by the presence of coved ST-segment elevations in the right precordial leads (so-called type I ECG) and additional clinical features. Caused by cardiac ion channel gene mutations, BrS may be associated with ventricular and atrial conduction disturbances as well as ventricular fibrillation. Recent studies have discussed whether BrS is merely a primary electric disorder or whether inflammatory or other histopathologic abnormalities in the right ventricle (RV) underlie the ECG phenotype.
  
  
  RESULTS
  We retrospectively analyzed BrS biopsy samples from 21 unrelated patients for histopathologic abnormalities (hypertrophy, fibrosis, inflammation, fatty tissue) together with the patients' clinical, genetic, and imaging data. Eleven patients (52%) had normal RV imaging (by angiography, echocardiography, or cardiac MRI). Results of myocardial biopsies were normal in 3 patients (14%) and revealed mostly moderate abnormalities in the others. Four patients (19%) had predominant fatty tissue in the RV myocardium. Using immunohistochemistry and conventional tissue staining, we could not detect inflammatory tissue changes, an observation compatible with the clinical absence of signs for myocarditis.
  
  
  CONCLUSIONS
  Imaging and histopathologic evaluation may detect moderate but uncharacteristic cardiac abnormalities in patients with BrS. None of the patients had arrhythmogenic RV cardiomyopathy or overt myocarditis. Only in a small subset did predominant histopathologic abnormalities in the biopsy samples of the RV outflow tract occur that could provide a link to the ECG phenotype. A variety of mechanisms, including genetic and structural RV alterations, may underlie the Brugada ECG phenotype.
authors.affiliation: Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Zumhagen
authors.forename: Tilmann
authors.initials: T
authors.lastname: Spieker
authors.forename: Julia
authors.initials: J
authors.lastname: Rolinck
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Werner
authors.initials: W
authors.lastname: Böcker
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
authors.forename: Matthias
authors.initials: M
authors.lastname: Paul
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichter
authors.forename: Eric
authors.initials: E
authors.lastname: Schulze-Bahr
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D053840:Brugada Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D005820:Genetic Testing; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D009205:Myocarditis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000235:genetics
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels