TY - JOUR A1 - Wanner, Christoph A1 - Feldt-Rasmussen, Ulla A1 - Jovanovic, Ana A1 - Linhart, Aleš A1 - Yang, Meng A1 - Ponce, Elvira A1 - Brand, Eva A1 - Germain, Dominique P. A1 - Hughes, Derralynn A. A1 - Jefferies, John L. A1 - Martins, Anna Maria A1 - Nowak, Albina A1 - Vujkovac, Bojan A1 - Weidemann, Frank A1 - West, Michael L. A1 - Ortiz, Alberto T1 - Cardiomyopathy and kidney function in agalsidase beta-treated female Fabry patients: a pre-treatment vs. post-treatment analysis JF - ESC Heart Failure N2 - Long-term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long-term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment-naive outcomes. Methods and results Self-controlled pretreatment and post-treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9–1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post-treatment outcome measurements during 10-year follow-up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow-up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = - 0.41 [ - 0.68, - 0.15] mm/year, P\(_{pre–post difference}\)<0.01; IVST: n = 38, slope difference =-0.32 [-0.67, 0.02] mm/year, P\(_{pre–post difference}\) = 0.07). These findings were not modified by renal involvement or antiproteinuric agent use. Compared with the treatment-naive period (follow-up 3.6 years), eGFR decline remained modest and stabilized within normal ranges during 4.1 years of treatment (slope difference, 95% CI: -0.13 [-1.15, 0.89] mL/min/1.73m\(^2\)/year, P\(_{pre–post difference}\) = 0.80). Conclusions Cardiac hypertrophy, progressing during pretreatment follow-up, appeared to stabilize during sustained agalsidase beta treatment. eGFR decline remained within normal ranges. This suggests that treatment may prevent further Fabry-related progression of cardiomyopathy in female patients and maintain normal kidney function. KW - Agalsidase beta KW - Enzyme replacement therapy KW - Fabry disease KW - Cardiomyopathy KW - Kidney function KW - Female patients Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235963 VL - 7 IS - 3 ER - TY - JOUR A1 - Burlina, Alessandro P. A1 - Sims, Katherine B. A1 - Politei, Juan M. A1 - Bennett, Gary J. A1 - Baron, Ralf A1 - Sommer, Claudia A1 - Moller, Anette Torvin A1 - Hilz, Max J. T1 - Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel JF - BMC Neurology N2 - Background: Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods: An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results: We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e. g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions: Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate. KW - Enzyme replacement therapy KW - Quality of life KW - Small-fiber neuropathy KW - Rochester diabetic neuropathy KW - Randomized controlled trial KW - Agalsidase beta therapy KW - Outcome survey KW - Pharmacological management KW - Clinical manifestations KW - Alpha galactosidase KW - Diagnosis KW - Fabry KW - Disease KW - Neuropathy KW - Pain KW - Treatment Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135309 VL - 11 IS - 61 ER - TY - JOUR A1 - Politei, Juan M. A1 - Bouhassira, Didier A1 - Germain, Dominique P. A1 - Goizet, Cyril A1 - Guerrero-Sola, Antonio A1 - Hilz, Max J. A1 - Hutton, Elspeth J. A1 - Karaa, Amel A1 - Liuori, Rocco A1 - Üceyler, Nurcan A1 - Zeltzer, Lonnie K. A1 - Burlina, Alessandro T1 - Pain in fabry disease: practical recommendations for diagnosis and treatment JF - CNS Neuroscience & Therapeutics N2 - Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Wurzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications. KW - Enzyme replacement therapy KW - Small fiber dysfunction KW - System involvement KW - Outcome survey KW - Fabry disease KW - Randomized controlled-trial KW - Chronic neuropathic pain KW - Agalsidase beta KW - Screening questionnaire KW - Dose reduction KW - Adult patients KW - Diagnosis KW - Pain KW - Peripheral nervous system Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188127 VL - 22 IS - 7 ER - TY - JOUR A1 - Ortiz, Alberto A1 - Abiose, Ademola A1 - Bichet, Daniel G. A1 - Cabrera, Gustavo A1 - Charrow, Joel A1 - Germain, Dominique P. A1 - Hopkin, Robert J. A1 - Jovanovic, Ana A1 - Linhart, Aleš A1 - Maruti, Sonia S. A1 - Mauer, Michael A1 - Oliveira, João P. A1 - Patel, Manesh R. A1 - Politei, Juan A1 - Waldek, Stephen A1 - Wanner, Christoph A1 - Yoo, Han-Wook A1 - Warnock, David G. T1 - Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry JF - Journal of Medical Genetics N2 - 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. KW - Enzyme replacement therapy KW - Natural-history data KW - Racial differences KW - Outcome survey KW - Galactosidase-A gene KW - Alpha-Galactosidase KW - Kidney function KW - Lag time Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188241 VL - 53 IS - 7 ER - TY - JOUR A1 - Weidemann, Frank A1 - Maier, Sebastian K. G. A1 - Störk, Stefan A1 - Brunner, Thomas A1 - Liu, Dan A1 - Hu, Kai A1 - Seydelmann, Nora A1 - Schneider, Andreas A1 - Becher, Jan A1 - Canan-Kühl, Sima A1 - Blaschke, Daniela A1 - Bijnens, Bart A1 - Ertl, Georg A1 - Wanner, Christoph A1 - Nordbeck, Peter T1 - Usefulness of an implantable loop recorder to detect clinically relevant arrhythmias in patients with advanced fabry cardiomyopathy JF - The American Journal of Cardiology N2 - Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holier electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holier ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >= 3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holier ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder. KW - Cardiovascular magnetic-resonance KW - Coronary artery disease KW - Ventricular-arrhythmias KW - Task force KW - Management KW - Enzyme replacement therapy KW - Hypertrophic cardiomyopathy KW - Myocardial fibrosis KW - Guidelines KW - Manifestation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188093 VL - 118 IS - 2 ER -