Cardiovascular Events in Patients With Fabry Disease Natural History Data From the Fabry Registry

ObjectivesThese analyses were designed to determine the incidence of major cardiovascular (CV) events and the natural history of CV complications in patients with Fabry disease.BackgroundFabry disease, a genetic disorder caused by deficiency of alpha-galactosidase A activity, is associated with CV dysfunction.MethodsMajor CV events (myocardial infarction, heart failure, or cardiac-related death) were analyzed in 2,869 Fabry Registry patients during the natural history period (i.e., before enzyme replacement therapy or among patients who never received therapy). Multivariate logistic regression analyses were performed to identify significant predictors of CV events.ResultsEighty-three of 1,424 men (5.8%) and 54 of 1,445 women (3.7%) experienced CV events at mean ages of 45 and 54 years, respectively. Heart failure was the most common first CV event, reported by 50 men (3.5%) and 33 women (2.3%). Hypertension and left ventricular hypertrophy were the risk factors most strongly associated with CV events. When these parameters were used as covariates in logistic regression analyses, the odds ratio (OR) for hypertension in men was 7.8 (95% confidence interval [CI]: 2.1 to 28.6, p = 0.0019), and the OR for hypertension in women was 4.5 (95% CI: 1.6 to 12.3, p = 0.0037). The OR for left ventricular hypertrophy was 4.8 in men (95% CI: 1.03 to 22.2, p = 0.0463) and 8.2 in women (95% CI: 2.6 to 26.0, p = 0.0003).ConclusionsMajor CV events occurred in approximately 5% of Fabry Registry patients during the natural history period. All patients with Fabry disease should be monitored for possible CV risk factors, particularly hypertension and left ventricular hypertrophy

Valvular Heart Disease: Echocardiography Assessment for Surgeons

<div>Ademola Abiose of the North Ohio Heart Elyria Medical Center in Ohio presents an overview of standard echocardiography views and discusses echocardiographic evaluation of mitral and aortic valve disease.</div><div>Echocardiography for Surgeons Part I: Standard Views</div><div>Echocardiography for Surgeons Part II: The Mitral Valve</div><div>Echocardiography for Surgeons Part III: Mitral Regurgitation and Mitral Stenosis</div><div>Echocardiography for Surgeons Part IV: The Aortic Valve, Other Structures, and 3D Imaging</div

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry

Background Agalsidase beta is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low alpha-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase beta cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase beta treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase beta. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase beta (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged >= 40 years when agalsidase beta was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase beta 1 mg/kg every 2 weeks

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry

BACKGROUND: Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a ‘lag time’ to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. METHODS: The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. RESULTS: The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40–58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. CONCLUSIONS: Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. TRIAL REGISTRATION NUMBER: NCT00196742