Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease

Condition(s) studied

Investigational drug(s) / intervention(s)

Implantable Loop Recorder: An implantable loop recorder (ILR), also known as an insertable cardiac monitor, is a small device (smaller than a AAA battery) that is inserted under the skin on the front of the chest. The ILR is inserted using local anesthetic as an out-patient procedure and lasts approximately 30 minutes. The ILR captures a continuous ECG of your heart activity, which allows doctors to detect any abnormal heart rhythms at any point. If you have the ILR, you will have the device for 3 years, after which it will be removed under local anesthetic during an out-patient procedure, again lasting approximately 30 minutes. The ILR device is completely safe and shouldn't affect your day to day living.

Study summary

Fabry disease (FD) is a genetic disorder that leads to progressive accumulation of fat or 'sphingolipid' within the tissues, including the heart muscle and conductive tissue. Improvements in the detection of FD, together with more organised clinical services for rare diseases, has led to a rapid growth in the disease prevalence. Earlier and more frequent diagnosis of asymptomatic individuals before development of the disease itself has focused attention on early detection of organ involvement and closer monitoring of disease progression. Moreover, the introduction of enzyme replacement therapy within the last two decades has changed the natural history of FD as follows: a) increased life expectancy; b) improved morbidity; c) modification of the main cause of morbidity and mortality from renal (kidney) to cardiovascular (heart) events, including heart failure, abnormal heart rhythms, stroke and sudden death. Although symptoms such as palpitations and blackouts are extremely common, information on the frequency of proven abnormal heart rhythms is limited. In addition, the rate and appropriateness of implantation of life-saving devices is very variable, including pacemakers to boost the heart when too slow and cardio-defibrillators that stop the heart when too fast. The main markers of risk in similar diseases such as hypertrophic cardiomyopathy cannot be used in FD. While patients are routinely followed up in clinic with heart tracings and echocardiography (ultrasound of the heart), a recent small study has emphasised that these tests under-estimate the burden of abnormal heart rhythms in patients with advanced FD. The use of continuous heart monitoring with an implantable loop recorder (ILR) has led to a significant change in treatment in 13 out of 15 of FD patients. The investigators believe that more frequent use of ILRs will identify a greater need for change in therapy in many more patients than currently treated, with the aim of reducing morbidity and mortality in this patient cohort. In addition this will provide valuable data to inform an estimate of future risk for these patients.

Eligibility

Primary outcome measure(s)

• First occurrence of atrial fibrillation (AF) requiring anticoagulation — Total monitoring time period in study - 3 years
  This will include all descriptions of AF, which can be defined as: 1. paroxysmal - self-terminating episodes lasting between 48 hours to 7 days 2. persistent - intermittent episodes lasting between 7 days to 1 year 3. permanent - episodes lasting longer than 1 year
• First occurrence of bradyarrhythmia requiring cardiac pacing — Total monitoring time period in study - 3 years
  This would include: 1. Symptomatic significant AV block. 2. Mobitz type 2 AV block or complete heart block irrespective of symptoms.
• First occurrence of supraventricular arrhythmia requiring drug treatment or ablation. — Total monitoring time period in study - 3 years
• First occurrence of non-sustained ventricular tachyarrhythmia requiring drug treatment, ICD implantation or ablation — Total monitoring time period in study - 3 years
  This is classified as three or more ventricular beats at a rate \>120bpm, for a duration of less than 30 seconds.

Trial sites (7)

Other trials for the same condition