Clinical trial NCT03362164: Evaluation of HEArt invoLvement in Patients With FABRY Disease
Official title: Prospective Monocentric Cohort Study to Evaluate Predictors for Heart Failure and Sudden Cardiac Death in Patients With Fabry Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rare Diseases
Fabry Disease
Fabry Disease, Cardiac Variant
Hypertrophic Cardiomyopathy
Keywords: Fabry
Fibrosis
Dialysis
Stroke
Chronic kidney disease
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
Collaborators: name: Competence Network Heart Failure
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: St George's, University of London
First posted: 2017-12-05
Enrollment: 650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population includes every patient with Fabry disease who is seen in the FAZiT Wuerzburg. No limitations are made.

Brief summary: This study evaluates predictors for the incidence of arrhythmias and sudden cardiac death as well as terminal heart failure in patients with Fabry disease.

Detailed description: Fabry disease is a rare disease and part of the group of lysosomal storage disorders. Natural history of Fabry disease has proven poor survival to ages \>50 years outlining the importance to evaluate cardiac symptoms and outcomes of patients with Fabry disease.

This study is a prospective cohort study and observes patients since 2001. Through this long-term experience and the relative high number of patients this study is suggested to help estimating the risk of cardiac arrhythmias and sudden cardiac death (SCD) as well as death or heart transplantation due to terminal heart failure.

All patients in treatment in the Fabry Center Wuerzburg (FAZiT) are included in this study if informed consent is provided.

Eligibility criteria: Inclusion Criteria:

* Fabry disease (genetically confirmed)
* Signed informed consent
* 18 years and older

Exclusion Criteria:

* No informed consent
* Withdrawal of informed consent

Primary outcomes:
measure: Cardiac death
timeFrame: From date of inclusion until the date of first documented event, up to the year 2032
Secondary outcomes:
measure: Heart transplantation
timeFrame: From date of inclusion until the date of first documented event, up to the year 2032
measure: Malign Arrhythmias
timeFrame: From date of inclusion until the date of death, up to the year 2032
Other outcomes:
Locations:
city: Würzburg
country: Germany
facility: Wuerzburg University Hospital
state: Bayern
Study officials:
affiliation: Wuerzburg University Hospital
name: Peter Nordbeck, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oder D, Uceyler N, Liu D, Hu K, Petritsch B, Sommer C, Ertl G, Wanner C, Nordbeck P. Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y. BMJ Open. 2016 Apr 8;6(4):e010422. doi: 10.1136/bmjopen-2015-010422.
citation: Seydelmann N, Liu D, Kramer J, Drechsler C, Hu K, Nordbeck P, Schneider A, Stork S, Bijnens B, Ertl G, Wanner C, Weidemann F. High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease. J Am Heart Assoc. 2016 May 31;5(6):e002839. doi: 10.1161/JAHA.115.002839.
citation: Weidemann F, Maier SK, Stork S, Brunner T, Liu D, Hu K, Seydelmann N, Schneider A, Becher J, Canan-Kuhl S, Blaschke D, Bijnens B, Ertl G, Wanner C, Nordbeck P. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy. Am J Cardiol. 2016 Jul 15;118(2):264-74. doi: 10.1016/j.amjcard.2016.04.033. Epub 2016 May 5.
citation: Lenders M, Oder D, Nowak A, Canaan-Kuhl S, Arash-Kaps L, Drechsler C, Schmitz B, Nordbeck P, Hennermann JB, Kampmann C, Reuter S, Brand SM, Wanner C, Brand E. Impact of immunosuppressive therapy on therapy-neutralizing antibodies in transplanted patients with Fabry disease. J Intern Med. 2017 Sep;282(3):241-253. doi: 10.1111/joim.12647. Epub 2017 Jul 26.
citation: Oder D, Liu D, Hu K, Uceyler N, Salinger T, Muntze J, Lorenz K, Kandolf R, Grone HJ, Sommer C, Ertl G, Wanner C, Nordbeck P. alpha-Galactosidase A Genotype N215S Induces a Specific Cardiac Variant of Fabry Disease. Circ Cardiovasc Genet. 2017 Oct;10(5):e001691. doi: 10.1161/CIRCGENETICS.116.001691.
citation: Koping M, Shehata-Dieler W, Cebulla M, Rak K, Oder D, Muntze J, Nordbeck P, Wanner C, Hagen R, Schraven S. Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease. PLoS One. 2017 Nov 21;12(11):e0188103. doi: 10.1371/journal.pone.0188103. eCollection 2017.
citation: Lau K, Uceyler N, Cairns T, Lorenz L, Sommer C, Schindehutte M, Amann K, Wanner C, Nordbeck P. Gene variants of unknown significance in Fabry disease: Clinical characteristics of c.376A>G (p.Ser126Gly). Mol Genet Genomic Med. 2022 May;10(5):e1912. doi: 10.1002/mgg3.1912. Epub 2022 Feb 25.
citation: Liu D, Oder D, Salinger T, Hu K, Muntze J, Weidemann F, Herrmann S, Ertl G, Wanner C, Frantz S, Stork S, Nordbeck P. Association and diagnostic utility of diastolic dysfunction and myocardial fibrosis in patients with Fabry disease. Open Heart. 2018 Jul 12;5(2):e000803. doi: 10.1136/openhrt-2018-000803. eCollection 2018.
citation: Liu D, Hu K, Schmidt M, Muntze J, Maniuc O, Gensler D, Oder D, Salinger T, Weidemann F, Ertl G, Frantz S, Wanner C, Nordbeck P. Value of the CHA2DS2-VASc score and Fabry-specific score for predicting new-onset or recurrent stroke/TIA in Fabry disease patients without atrial fibrillation. Clin Res Cardiol. 2018 Dec;107(12):1111-1121. doi: 10.1007/s00392-018-1285-4. Epub 2018 May 24.