Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome.
BACKGROUND
The role of structural heart disease and sodium channel dysfunction in the induction of electrical instability in Brugada syndrome is still debated.


RESULTS
We studied 18 consecutive patients (15 males, 3 females; mean age 42.0+/-12.4 years) with clinical phenotype of Brugada syndrome and normal cardiac structure and function on noninvasive examinations. Clinical presentation was ventricular fibrillation in 7 patients, sustained polymorphic ventricular tachycardia in 7, and syncope in 4. All patients underwent cardiac catheterization, coronary and ventricular angiography, biventricular endomyocardial biopsy, and DNA screening of the SCN5A gene. Biopsy samples were processed for histology, electron microscopy, and molecular screening for viral genomes. Microaneurysms were detected in the right ventricle in 7 patients and also in the left ventricle in 4 of them. Histology showed a prevalent or localized right ventricular myocarditis in 14 patients, with detectable viral genomes in 4; right ventricular cardiomyopathy in 1 patient; and cardiomyopathic changes in 3. Genetic studies identified 4 carriers of SCN5A gene mutations that cause in vitro abnormal function of mutant proteins. In these patients, myocyte cytoplasm degeneration was present at histology, whereas terminal dUTP nick end-labeling assay showed a significant increase of apoptotic myocytes in right and left ventricle versus normal controls (P=0.014 and P=0.013, respectively).


CONCLUSIONS
Despite an apparently normal heart at noninvasive evaluation, endomyocardial biopsy detected structural alterations in all 18 patients with Brugada syndrome. Mutations in the SCN5A gene, identified in 4 of the 18 patients, may have induced concealed structural abnormalities of myocardiocytes that accounted for paroxysmal arrhythmic manifestations.
Frustaci
Andrea
A
Heart and Great Vessels Department, Attilio Reale, La Sapienza University, Rome, Italy. biocard@rm.unicatt.it
Priori
Silvia G
SG
Pieroni
Maurizio
M
Chimenti
Cristina
C
Napolitano
Carlo
C
Rivolta
Ilaria
I
Sanna
Tommaso
T
Bellocci
Fulvio
F
Russo
Matteo Antonio
MA
D000328:Adult; D000783:Aneurysm; D017209:Apoptosis; D001706:Biopsy; D004252:DNA Mutational Analysis; D005260:Female; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000502:physiology; D009205:Myocarditis / Q000382:microbiology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology; D013575:Syncope; D013577:Syndrome; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014693:Ventricular Fibrillation / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels