Obstructive Sleep Apnoea and Cardiac Arrhythmias

Study Overview
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Brief Summary
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This study is a prevelance trial looking at how sleep apnoea affects the heart especially heart rhythms. Previous research shows that patients suffering from sleep apnoea are much more likely to get heart disease and abnormal heart rhythms (arrhythmias). These defects are sometimes missed by the traditional methods of monitoring i.e. 24-hour Holter monitor and ECGs. This means potentially dangerous arrhythmias may not be detected. Additionally, standard therapy for sleep apnoea does not significantly reduce the risk of heart disease. This study will recruit 200 participants over a period of 18 months. The research team will observe the heart rhythms of sleep apnoea patients by inserting an implantable loop recorder (ILR) in up to 100 participants. The other 100 patients will simply have standard care. This device will monitor the heart continuously for 3 years allowing us to detect abnormal heart rhythms and treat as necessary. Demonstrating the incidence of arrhythmia can lead onto a larger study which may change future sleep apnoea management improving their cardiovascular outcomes. Other markers of heart disease such as; blood tests, Magnetocardiography and Echocardiography will be performed on participants to shed more light on the mechanisms which link sleep apnoea and heart disease/arrhythmia.

Detailed Description
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Sleep apnoea affects up to 1.5 million adults in the United Kingdom (UK). This puts this population at risk of reduced oxygen levels during sleep, poor sleep and increased breathing effort . All of the above put stress on the body and are proven to increase the risk of high blood pressure, heart failure and vascular problems. This can lead to strokes, heart disease and death. Sleep apnoea patients are at much higher risk of abnormal heart rhythms. Even with continuous positive airways pressure (CPAP) treatment (which is the mainstay in sleep apnoea and does help to reduce arrhythmias) patients are still at higher risk of heart disease and stroke. An implantable loop recorder (Reveal-LINQ) inserted into sleep apnoea patients will be able to continuously monitor a patient's heart rhythm. This will determine the incidence of arrhythmia in sleep apnoea patients. Any significant abnormalities in either arm of the study will be treated as per National Health Service guidelines and best care. The cost associated with this method of intervention will also be considered. If there is a high prevalence of arrhythmia a future larger trial, involving much larger numbers and multiple centres, could be conducted to demonstrate reduced risk of stroke or heart attack using this method of arrhythmia detection and management. Cardiovascular biomarkers, cardiac function, autonomic function and magnetocardiography in these patients could shed light on the mechanisms which cause increased cardiovascular morbidity and mortality.

Official Title
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Obstructive Sleep Apnoea and Cardiac Arrhythmias and the Impact of an Implantable Loop Recorder

Conditions
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Obstructive Sleep Apnea, Cardiovascular Diseases, Arrhythmia, Atrial Fibrillation New Onset

Intervention / Treatment
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* Device: Reveal LINQ


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with moderate to severe sleep apnoea who require CPAP as standard care (AHI >15) Patients between the age of 18 and 75 Exclusion Criteria: Patients with a diagnosis of atrial fibrillation (AF), atrial flutter and/or ventricular tachycardia (VT) Patients with an ILR already in-situ or an established indication for ILR Patients with a palliative diagnosis i.e. life expectancy less than 3 years Patients who lack capacity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 groups with the intervention the difference.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ILR<br>Participants who will receive the Implantable Loop Recorder (Reveal-LINQ) inserted just after baseline. This is single intervention and lasts for 3 years after which the patient has the option to have it removed. | Device: Reveal LINQ<br>* Insertion of monitoring device called Reveal-LINQ (an implantable loop recorder)<br>|
| No Intervention: No ILR<br>Participants who will not get the Implantable Loop Recorder (Reveal-LINQ). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of arrhythmia | Incidence of arrhythmia in sleep apnoea patients as recorded by ILR vs a no ILR group | 3 years | 
| Autonomic function before and after CPAP | Assess the changes to the heart in sleep apnoea patients before and after CPAP in terms of heart rate variability as measured on 24 hour holter monitors. The raw data is taken from the monitor and then analysed manually. The first data set will be from baseline studies which will be compared to studies done at the 1 year follow-up. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset and frequency of atrial fibrillation | Explore the onset and frequency of atrial fibrillation in sleep apnoea patients in order to determine what method of detection is efficient and cost effective. | 3 years | 
| Rate of Cardiovascular Morbidity | Explore the impact of inserting an ILR in patients with sleep apnoea on cardiovascular morbidity (stroke and myocardial infarction) compared to those without ILR | 3 years | 
| Rate of Cardiovascular Mortality | Explore the impact of inserting an ILR in patients with sleep apnoea on cardiovascular mortality (stroke and/or myocardial infarction resulting in death) compared to those without ILR | 3 years | 
| Cardiovascular biomarkers before and after CPAP | Explore the changes to the heart in sleep apnoea patients before and after CPAP in terms of vascular biomarkers - high sensitivity C-Reactive Protein, high sensitivity Troponin-T, N-terminal pro B-type Natriuretic Peptide, Tumour Necrosis Factor-alpha, Matrix Metalloproteinase-9, Interleukin-6, Fibroblast Growth Factor-23. The first data set will be from baseline studies which will be compared to studies done at the 1 year follow-up. | 3 years | 
| Echocardiography before and after CPAP | Explore the changes to the heart in sleep apnoea patients before and after CPAP in terms of echocardiogram measures. | 3 years | 
| Quality of life: EQ-5D-5L questionnaire | Quality of life measures before and after CPAP as measured by the EQ-5D 5 level questionnaire. This measures various quality of life points from a scale of 1-5. 1 represents poor quality of life and 5 represents good quality of life for each factor. This data will be analysed as per the EuroQol algorithm. The first data set will be from baseline studies which will be compared to studies done at the 1 year follow-up. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Obstructive Sleep Apnea, Implantable Loop Recorder, Extended Cardiac Monitoring, Matrix Metalloproteinase-9, Interleukin-6, Tumour Necrosis Factor-Alpha, High sensitivity C-Reactive Protein, High sensitivity Troponin-T, Fibroblast Growth Factor-23, Heart Rate Variability, N-Terminal pro B-type Natriuretic Peptide