Background Lone atrial fibrillation (LAF) is a common clinical syndrom
e, but its origin remains unknown. Methods and Results We performed en
domyocardial biopsies of the right atrial septum (2 to 3 per patient m
ean, 2.8) and of the two ventricles (6 per patient) in 12 patients (10
men, 2 women; mean age, 32 years) with paroxysmal LAF refractory to c
onventional antiarrhythmic treatment, he controls, we used endomyocard
ial biopsies (3 to 5 per patient; mean, 4.4) from the right atrial sep
tum of 11 patients with Wolff-Parkinson-White syndrome (WPW) undergoin
g resection of the abnormal AV pathway. The weight of the biopsies ran
ged from 2.8 to 4.5 mg. Biopsy samples were processed for histology an
d electron microscopy and were read by a pathologist blinded to clinic
al data. All patients underwent two-dimensional Doppler echocardiograp
hy; cardiac catheterization; coronary angiography; and hormonal, virol
ogic, and electrophysiological studies. All tests and WPW biopsies wer
e normal. but all LAF atrial biopsy specimens (average, 2.8 per patien
t) showed abnormalities (P < .0001). The type of abnormalities varied:
Two patients had a severe hypertrophy with vacuolar degeneration of t
he atrial myocytes and ultrastructural evidence of fibrillolysis occup
ying > 50% of the areas assessed morphometrically (P = .50), 8 had lym
phomononuclear infiltrates with necrosis of the adjacent myocytes (5 w
ith fibrosis and 3 without; P < .003), and 2 had only nonspecific patc
hy fibrosis (P = .50). Biventricular biopsies were abnormal in only 3
patients and showed inflammatory infiltrates similar to those found in
atrial biopsies. Conclusions Abnormal atrial histology was uniformly
found in multiple biopsy specimens in all patients with LAF. It was co
mpatible with a diagnosis of myocarditis in 66% of patients (active in
25%) and of noninflammatory localized cardiomyopathy in 17% and was r
epresented by patchy fibrosis in 17%. The cause of the pathological ch
anges, which were found only in atrial septal biopsies but not in bive
ntricular biopsies, in 75% of patients remains unknown.