T1 mapping in Fabry disease

• Research type

  Research Study

• Full title

  Characterisation of heart involvement in Fabry disease with T1 mapping

• IRAS ID

  147426

• Contact name

  Christopher Miller

• Sponsor organisation

  University Hospital South Manchester

• Research summary

  Research Summary:
  Anderson-Fabry disease (Fabry disease) is a genetic disorder which leads to progressive accumulation of a fatty substance in body tissues, multi-organ dysfunction and significantly reduced survival. Heart involvement is particularly important because the majority of deaths are heart related.

  There is no cure for Fabry disease, however enzyme replacement therapy (ERT), which replaces the deficient enzyme, is available. ERT reverses or slows disease progression. However it is very expensive and is not appropriate for patients in whom irreversible organ damage has occurred.

  Current techniques used to assess heart involvement in Fabry are relatively insensitive. Indeed, there are no good tests to guide ERT (who to give it to, when to commence it, how to monitor it and when to stop it), and as such patients who would benefit from ERT are often getting it too late or potentially not at all, and ERT is being started or continued in patients in whom it is unlikely to benefit.

  T1 mapping is a magnetic resonance imaging (MRI) technique that can detect fat and is commonly applied in other organs. Two small studies have suggested that T1 mapping may be able to detect fat accumulation in the heart in Fabry disease, often in the absence of any other changes in heart structure and function. Furthermore, the technique allows (irreversible) heart muscle scarring to be detected. Thus T1 mapping may allow earlier detection of heart involvement in Fabry disease and better guide ERT.

  This study aims to investigate T1 mapping in Fabry disease in more detail. In particular, this study will assess T1 mapping in a larger number of Fabry patients with a wider range of disease severity than has been done before, and will assess the relationship between T1 and other markers of disease severity.

  Summary of Results:
  Fabry disease is a rare condition caused by an inherited deficiency in an important enzyme. This deficiency affects multiple organs but especially affects the heart. Indeed, the cardiovascular effects of Fabry disease are common in both men and women and are a leading cause of death. Despite this, there is a lack of data to help doctors identify which patients are more prone to complications than others. This makes treatment decisions more difficult for doctors and can lead to a lack of personalised, timely and cost effective care for patients. New heart scans, such as cardiac magnetic resonance (CMR) scans have revolutionised our understanding of Fabry disease. We therefore researched whether such scans could help predict patient prognosis in Fabry disease.

  We recruited two hundred patients with Fabry disease and followed them up for four and a half years. Forty-three of these individuals had a cardiovascular event during follow-up. Four measurements were strongly associated with patient outcomes and were therefore developed into prognostic models and risk calculators for Fabry disease. Three of the four measurements were derived from CMR scans, including one called T1 mapping. In combination these factors performed well in identifying which patients had cardiovascular events during follow-up. More work, in larger numbers, is now needed in order to refine these models and risk calculators before translating their use into clinical practice.

• REC name

  North West - Greater Manchester East Research Ethics Committee

• REC reference

  14/NW/0064

• Date of REC Opinion

  20 Feb 2014

• REC opinion

  Favourable Opinion