Terminal stage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study.
OBJECTIVE
Fabry disease is caused by deficiency of alpha-galactosidase A, and typically causes multi-organ dysfunction. Patients with manifestations limited to the heart, mainly left ventricular hypertrophy (LVH), have been reported as a disease variation. We have reported a 3% prevalence of this cardiac variant in men with LVH, which we designated 'cardiac Fabry disease'. The purposes of this study were to evaluate the terminal stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease.


METHODS
We examined seven terminal stage patients with cardiac Fabry disease. During hospitalization, standard 12-lead electrocardiograms, Holter electrocardiograms, and echocardiograms were obtained. Autopsies were performed and macroscopic along with microscopic findings were evaluated.


RESULTS
Six patients died of heart failure and one of ventricular fibrillation. Electrocardiograms revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings revealed LVH in all patients. Localized basal posterior wall thinning of the left ventricle was detected in the six patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells, but not cardiac vascular endothelial cells, showed glycosphingolipid accumulation. No accumulation was observed in other organs or in systemic vascular endothelial cells.


CONCLUSIONS
Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.
Division of Cardiac Repair and Regeneration, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Toshihiro
T
Takenaka
Hiroyuki
H
Teraguchi
Aichi
A
Yoshida
Syuhei
S
Taguchi
Kenjiro
K
Ninomiya
Yoshihisa
Y
Umekita
Hiroki
H
Yoshida
Michiko
M
Horinouchi
Kazuhiro
K
Tabata
Suguru
S
Yonezawa
Makoto
M
Yoshimitsu
Koji
K
Higuchi
Shoichiro
S
Nakao
Ryuichiro
R
Anan
Shinichi
S
Minagoe
Chuwa
C
Tei
D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000209:etiology; D009202:Cardiomyopathies / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D004452:Echocardiography; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D000795:Fabry Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D006028:Glycosphingolipids / Q000032:analysis; D006651:Histocytochemistry; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D018487:Ventricular Dysfunction, Left / Q000209:etiology
D006028:Glycosphingolipids