Screening for Fabry Disease by Urinary Globotriaosylceramide Isoforms Measurement in Patients with Left Ventricular Hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a frequent echocardiographic feature in Fabry disease (FD) and in severe cases may be confused with hypertrophic cardiomyopathy (HCM) of other origin. The prevalence of FD in patients primarily diagnosed with HCM varies considerably in screening and case finding studies, respectively. In a significant proportion of patients, presenting with only mild or moderate LVH and unspecific clinical signs FD may remain undiagnosed. Urinary Gb3 isoforms have been shown to detect FD in both, women and men. We examined whether this non-invasive method would help to identify new FD cases in a non-selected cohort of patients with various degree of LVH. METHODS AND RESULTS: Consecutive patients older than 18 years with a diastolic interventricular septal wall thickness of ≥12mm determined by echocardiography were included. Referral diagnosis was documented and spot urine was collected. Gb3 was measured by mass spectroscopy. Subjects with an elevated Gb3-24:18 ratio were clinically examined for signs of FD, α-galactosidase-A activity in leukocytes was determined and GLA-mutation-analysis was performed. We examined 2596 patients. In 99 subjects urinary Gb3 isoforms excretion were elevated. In these patients no new cases of FD were identified by extended FD assessment. In two of three patients formerly diagnosed with FD Gb3-24:18 ratio was elevated and would have led to further diagnostic evaluation. CONCLUSION: Measurement of urinary Gb3 isoforms in a non-selected cohort with LVH was unable to identify new cases of FD. False positive results may be prevented by more restricted inclusion criteria and may improve diagnostic accuracy of this method.

Two-dimensional speckle tracking echocardiography in heart transplant patients: three-year follow-up of deformation parameters and ejection fraction derived from transthoracic echocardiography.

AIMS: Non-invasive diagnosis of allograft dysfunction is a major objective in the management of heart transplant (HTX) recipients. Speckle tracking echocardiography (STE) permits comprehensive assessment of myocardial function. It is well established that deformation indices are reduced in HTXs when compared with control subjects. However, it is unclear if the reduction in strain is a chronic progressive phenomenon in HTX patients. Method and results Follow-up transthoracic echocardiography (TTE) was performed 3 years after initial TTE in 20 'healthy' HTX patients (13.2 years post-transplantation at time of follow-up) with normal ejection fraction and angiographically ruled out allograft vasculopathy. Grey-scale apical views were recorded and stored for automated offline speckle tracking (EchoPAC 7.0, GE) of the 16 segments of the left ventricle. Strain analysis was performed in 320 segments 34.3 ± 3.7 months after initial assessment. Automated tracking of myocardial deformation for determination of longitudinal systolic strain was not possible in 24 (7.5%) segments at baseline and in 32 (10.0%) segments at follow-up (P = ns). The left ventricular ejection fraction (LVEF) was 61.9 ± 8.1% at the initial examination vs. 62.8 ± 5.8% 3 years afterwards (P = ns). Global longitudinal peak systolic strain was -14.0 ± 4.0 vs. -14.4 ± 2.8%, respectively (P = ns). CONCLUSION: This is the first study describing follow-up deformation parameters in HTX patients undergoing STE. 'Healthy' HTX patients with normal coronary arteries and normal ejection fractions showed no deterioration of longitudinal strain values 3 years after the initial assessment. Apparently, deformation values remain stable over the years as long as the LVEF is preserved.

The endocardial binary appearance ('binary sign') is an unreliable marker for echocardiographic detection of Fabry disease in patients with left ventricular hypertrophy.

AIMS: The binary sign, a binary appearance of the left ventricular endocardial border, was suggested to be an echocardiographic hallmark in diagnosing Fabry disease, a hereditary, lysosomal storage disorder. The aim of the present study was to examine the reliability of the binary sign as a screening tool to identify patients with Fabry disease. METHODS AND RESULTS: In total 309 subjects with an interventricular septum (IVS) thickness of ≥12 mm were investigated, of which 14 had a confirmed diagnosis of Fabry disease. Urinary globotriaosylceramide testing was used to rule out Fabry disease in the control group. From all patients echocardiographic images of the apical four-chamber view were analysed offline by a blinded observer. A binary sign was seen in 63 patients (20%), 4 had Fabry disease and 59 belonged to the control group. Although the proportion of binary signs in patients with Fabry disease was higher (29%) compared with the control group (20%) this difference was not statistically significant. The sensitivity and specificity were 28% (95% confidence interval (CI): 12-65%) and 80% (95% CI: 76-85%), respectively. In a logistic regression model adjusted for age, sex and presence of Fabry disease, the occurrence of a binary sign was highly dependent on the IVS thickness (odds ratio: 1.21; 95% CI: 1.1-1.35; P<0.001). CONCLUSION: The endocardial binary appearance is associated with the degree of septal hypertrophy but cannot adequately distinguish between patients with Fabry disease and patients with other causes of left ventricular hypertrophy.