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Trials. 2019 May 31;20(1):314. doi: 10.1186/s13063-019-3425-1.

A randomised controlled trial evaluating arrhythmia burden, risk of sudden cardiac death and stroke in patients with Fabry disease: the role of implantable loop recorders (RaILRoAD) compared with current standard practice.

Author information

1
Department of Cardiology, Queen Elizabeth Hospital Birmingham, Mindlesohn Way, Birmingham, B15 2TH, UK. ravi.vijapurapu@nhs.net.
2
Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. ravi.vijapurapu@nhs.net.
3
Department of Endocrinology, Queen Elizabeth Hospital Birmingham, Mindlesohn Way, Birmingham, B15 2TH, UK. ravi.vijapurapu@nhs.net.
4
Sydney Medical School, University of Sydney, Sydney, 2006, NSW, Australia.
5
Cardiology Department, Royal North Shore Hospital, Reserve Road, St. Leonards, NSW, 2065, Australia.
6
Lysosomal Storage Disorder Unit, Royal London NHS Foundation Trust, University College London, Pond Street, London, NW3 2QG, UK.
7
Department of Cardiology, Salford Royal Hospital, Stott Lane, Salford, M6 8HD, UK.
8
Mark Holland Metabolic Unit, Salford Royal Hospital, Stott Lane, Salford, M6 8HD, UK.
9
Department of Medicine, Addenbrooke's Hospital, Hill Road, Cambridge, CB2 0QQ, UK.
10
Department of Cardiology, Addenbrookes Hospital, Hill Road, Cambridge, CB2 0QQ, UK.
11
Department of Genetics, Westmead Hospital, Hawkesbury Road, Westmead, NSW, 2145, Australia.
12
Department of Cardiology, Queen Elizabeth Hospital Birmingham, Mindlesohn Way, Birmingham, B15 2TH, UK.
13
Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
14
Aston Medical Research Institute, Aston Medical School, Birmingham, B4 7ET, UK.
15
Barts Heart Centre, Barts Health NHS Trust, 16-18 Westmoreland Street, London, W1G 8PH, UK.
16
Department of Endocrinology, Queen Elizabeth Hospital Birmingham, Mindlesohn Way, Birmingham, B15 2TH, UK.
17
Institute of Metabolism and System Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

Abstract

BACKGROUND:

Fabry disease (FD) is a genetic disorder caused by a deficiency in the enzyme alpha-galactosidase A, leading to an accumulation of glycosphingolipids in tissues across the body. Cardiac disease is the leading cause of morbidity and mortality. Advanced disease, characterised by extensive left ventricular hypertrophy, ventricular dysfunction and fibrosis, is known to be associated with an increase in arrhythmia. Data identifying risk factors for arrhythmia are limited, and no Fabry-specific risk stratification tool is available to select those who may benefit from initiation of medical or device therapy (implantable cardiac defibrillators). Current monitoring strategies have a limited diagnostic yield, and implantable loop recorders (ILRs) have the potential to change treatment and clinical outcomes.

AIM:

The aim of this study is to determine whether ILRs can (1) improve arrhythmia detection in FD and (2) identify risk predictors of arrhythmia.

METHODS:

A prospective, 5-year, open-label, international, multi-centre randomised controlled trial of a minimum of 164 participants with genetically or enzymatically confirmed FD (or both) who have evidence of cardiac disease will be recruited from five centres: Queen Elizabeth Hospital, Birmingham, UK; Salford Royal Hospital, Salford, UK; Royal Free Hospital, London, UK; Addenbrookes Hospital, Cambridge, UK; and Westmead Hospital, Sydney, Australia. Participants will be block-randomised (1:1) to two study arms for cardiac monitoring (i) control arm: standard of care with annual 24 h or 5-day Holter monitor or (ii) treatment arm: continuous cardiac monitoring with ILR implantation plus standard of care. Participants will undergo multiple investigations-blood/urine biomarkers, 12-lead and advanced electrocardiogram (ECG) recording, echocardiography and cardiovascular magnetic resonance (CMR) imaging-at baseline and 6-12 monthly follow-up visits. The primary endpoint is identification of arrhythmia requiring initiation or alteration in therapy. Secondary outcome measures include characterising the risk factors associated with arrhythmia and outcome data in the form of imaging, ECG and blood biomarkers.

DISCUSSION:

This is the first study evaluating arrhythmia burden and the use of ILR across the spectrum of risk profiles in Fabry cardiomyopathy. This will enable detailed characterisation of arrhythmic risk predictors in FD and ultimately support formulation of Fabry-specific guidance in this high-risk population.

TRIAL REGISTRATION:

ClinicalTrials.gov ( NCT03305250 ). Registered on 9 October 2017.

KEYWORDS:

Arrhythmia; Cardiomyopathy; Fabry; ILR

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