arrhythmia burden, risk of sudden cardiac death and stroke in patients with fabry disease

Conditions: Fabry Disease

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.

this is a 3-year open-label multicentre randomised controlled trial assessing arrhythmia burden in patients with fabry cardiac disease. this is an observational study, but with implantable loop recorder (ilr) insertion at recruitment and removal at end of trial for the intervention arm. null hypothesis: there will be no difference in the identification of arrhythmia between patients following standard care compared to patients following standard care but with the addition of ilr monitoring. beyond the proposed hypothesis, data collected will be used to inform whether ilr in fd will: 1. reveal a high burden of unrecognised arrhythmia 2. lead to frequent treatment modification (anti-coagulation, pacemaker and icd implantation, ablation) 3. enable the development of fd specific risk prediction algorithms 4. identify predictive power of new (troponin, bnp, lysogb3, t1 and t2 mapping) and traditional biomarkers

Eligibility criteria:
inclusion criteria: * patients with genotypically or enzymatically confirmed fd * adults \> 18 years of age * evidence of cardiac involvement from fd involving either: * any ecg abnormality associated with fd * low t1 on cmr (below centre-specific normal range according to sex) * lvh on transthoracic echo (defined as mwt \>12mm) exclusion criteria: * patient with an existing cardiac device (ppm, icd or ilr). * known dual pathology: * known coronary artery disease (positive non-invasive imaging, confirmed myocardial infarction, percutaneous or surgical revascularisation). patients \>40 years old with symptoms that could be from coronary artery disease will have this excluded * known cardiomyopathy disease causing mutation (e.g. scn5, mybpc3)