Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey.
Aims Anderson–Fabry disease (AFD) is an uncommon X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. The Fabry Outcome Survey is a European database designed to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. The aim of this study was to determine the prevalence and characteristics of cardiac disease in AFD patients. Methods and results Clinical and laboratory data were available in 714 patients from 11 countries (mean age 35 ± 17 years, 369 women, 336 treated). The prevalence of angina was 23 vs. 22%; palpitations and arrhythmias 27 vs. 26%; exertional dyspnoea 23 vs. 23%; and syncope 2 vs. 4%, in wom…
Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data
Summary Background We analysed 5-year treatment with agalsidase alfa enzyme replacement therapy in patients with Fabry's disease who were enrolled in the Fabry Outcome Survey observational database (FOS). Methods Baseline and 5-year data were available for up to 181 adults (126 men) in FOS. Serial data for cardiac mass and function, renal function, pain, and quality of life were assessed. Safety and sensitivity analyses were done in patients with baseline and at least one relevant follow-up measurement during the 5 years (n=555 and n=475, respectively). Findings In patients with baseline cardiac hypertrophy, treatment resulted in a sustained reduction in left ventricular mass (LVM) index af…
The Heart in Fabry Disease – from Pathogenesis to Enzyme Replacement Therapy
The cardiovascular involvement in Fabry disease is progressive, and accounts for one of the major reasons for abbreviated life expectancy and increased morbidity. The majority of patients develop signs and symptoms, related to heart failure and arrhythmias. Hypertrophic cardiomyopathy, in later stages combined with myocardial fibrosis, is one of the leading features. Both genders are affected, and females develop severe cardiac Fabry disease approximately 10–15 years later in life than male patients. Diastolic dysfunction and reduced longitudinal mid-wall related systolic function are the mechanical consequences of the myocardial and epithelial changes related to accumulation of the storage…
Adoption of the ADA/EASD guidelines in 10 Eastern and Southern European countries: Physician survey and good clinical practice recommendations from an international expert panel.
Aims: Evidence from cardiovascular outcomes trials (CVOTs) of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors was reflected in the most recent guidelines from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). The aim of the present study was to assess the adoption of the ADA/EASD guidelines in a convenience sample of physicians from Eastern and Southern Europe, the barriers to the implementation of these guidelines and the measures needed to facilitate their implementation. Methods: Attendees at two international diabetes conferences could volunteer to respond to a fully anonymous survey. Responses …
Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.
International audience; Background: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD.Methods and findings: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi p…
Fabry disease: overall effects of agalsidase alfa treatment
Background Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. The Fabry Outcome Survey (FOS) is a European outcomes database which was established to collect data on the natural history of this little-known disease and to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. This paper presents the first analysis of the FOS database on the effects of ERT on renal function, heart size, pain and quality of life. Design The effects of 1 and 2 y…
2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism
ACS : acute coronary syndrome AMPLIFY : Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-line Therapy aPTT : activated partial thromboplastin time b.i.d. : bis in diem (twice daily) b.p.m. : beats per minute BNP : brain natriuretic peptide BP : blood pressure CI : confidence interval CO : cardiac output COPD : chronic obstructive pulmonary disease CPG : Committee for Practice Guidelines CRNM : clinically relevant non-major CT : computed tomographic/tomogram CTEPH : chronic thromboembolic pulmonary hypertension CUS : compression venous ultrasonography DSA : digital subtraction angiography DVT : deep vein thrombosis ELISA : enzyme-linked immunosorben…
Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey
Background: Fabry disease is a rare X-linked lysosomal storage disorder characterised by severe multisystemic involvement that leads to major organ failure and premature death in affected men and women. Over the past 7 years, the Fabry Outcome Survey (FOS) has collected data on the natural history of Fabry disease, and the long-term efficacy and safety of enzyme-replacement therapy. This paper provides an update on the first analysis of FOS data. Design: Baseline data on clinical manifestations and causes of death in a cohort of 1453 patients (699 male, 754 female) from 19 countries worldwide were analysed. Causes of death of affected relatives were analysed separately. Results: The most fr…
Prevalence of Uncontrolled Hypertension in Patients With Fabry Disease
Background Fabry disease is a rare X-linked disease arising from deficiency of α-galactosidase A. It results in early death related to renal, cardiac, and cerebrovascular disease, which are also important outcomes in patients with elevated blood pressure (BP). The prevalence of uncontrolled hypertension, as well as the effect of enzyme replacement therapy on BP, in patients with Fabry disease is unknown. Methods We examined uncontrolled hypertension (systolic BP [SBP] ≥130 mm Hg or diastolic BP [DBP] ≥80 mm Hg) among 391 patients with Fabry disease who were participating in the Fabry Outcome Survey (FOS). Results Uncontrolled hypertension was present in 57% of men and 47% of women. In patie…
Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey.
Background Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. In response to the recent introduction of enzyme replacement therapy, the Fabry Outcome Survey (FOS) was established to pool data from European clinics on the natural history of this little-known disease and to monitor the long-term efficacy and safety of treatment. This paper presents the first analysis of the FOS database and provides essential baseline data against which the effects of enzyme replacement can be measured. De…