None listed
Conditions
Brief summary
We are investigating how Atrial Fibrillation (AF), a common heart rhythm disorder, disrupts normal cardiovascular reflexes by affecting nerves from the heart. Whilst it is known that nerves leading to the heart can cause AF, we aim to study whether nerves arising from the heart are equally implicated, in order to provide information that can be used to offer targeted treatment using these nerves. Hypotheses: 1. Patients with Atrial Fibrillation (AF) have abnormal cardiovascular reflexes; likely arising from dysfunction of sensory nerves arising from the heart (cardiopulmonary receptors). 2. These abnormal reflexes are more severe in patients with Permanent AF compared to paroxysmal AF and treatment of AF results in improvement of cardiac reflexes. 3. Autonomic dysfunction parallels disease progression; therefore the nerves of the heart may represent a therapeutic target in the management of AF. We aim to characterise cardiovascular reflex function in detail of patients with AF with a minimally- invasive protocol designed to evaluate the normal function of the heart to maintain blood pressure in response to changes in blood volume (simulated by gently creating a vacuum seal around the legs; negative pressure and raising the legs passively; returning blood to the heart). We shall measure blood pressure, heart rate and do a blood test to measure hormones involved in blood pressure control. We shall also use a painless stimulator of the nerve leading from the heart (using a clip that attaches to the tragus of the ear), thereby bypassing the heart nerves on the way to the brain in order to confirm that any abnormality seen is due to the nerves within the heart rather than elsewhere). In a subset of patients, we shall insert a small needle (similar to acupuncture) to directly measure nerve activity in the forearm during reflex testing.
Interventions
AF-AF is an observational study designed to assess the contribution of atrial fibrillation (AF) and its risk factors (hypertension, sleep apnoea, obesity, diabetes mellitus) to dysfunction of the autonomic nervous system. We have previously performed (see listed parent study) a small study that demonstrates reflex deficits to autonomic testing in patients with paroxysmal (non permanent form of AF). Therefore we plan to perform simple (non-invasive) autonomic reflex tests such as lower body negative pressure, hand-grip testing, passively raising the legs and a valsalva (breath-holding manoeuvre) on a larger group of patients with intermittent AF, permanent AF and at any stage of their treatment (predefined by their heart team. We shall also use a non-invasive auricular vagus nerve stimulator (a clip attached to the tragus of the ear) in order to bypass the heart during reflex testing to see if suspected reflex deficits are corrected. The testing will take 2.5 hours to complete on one occasion. There will be no additional follow up tests. We plan to consecutively recruit up to 400 patients with AF at a single site to perform these autonomic tests. In some cases, where patients consent to re-enrolment after treatment of their AF (either by radio frequency catheter ablation, anti-arrhythmic medication) as well as after attempts made to manage their risk factors (also predetermined by the clinical team) we shall re-study their autonomic function to determine whether this improves as a result of elimination of either AF or its risk factors. This will be on an opt-in basis (as a re-consent) and our ethics board has approved of us re-contacting patients who demonstrate an interest at their first visit. The patients with AF will have varying burdens of their disease (and we shall aim to enrol 100 patients with the mildest form; paroxysmal AF or intermittent AF, 100 with persistent AF and then 100 patients in whom it is decided to leave them in chronic AF. Additional patients (anticipated n =100 will have repeat testing after their predetermined treatment strategy). Note we do not influence treatment decisions in our study. In detail; repeat testing will occur after electrical cardio version (to revert to normal rhythm), catheter ablation to treat AF and maintain normal rhythm, after treatment of risk factors that can maintain AF; obesity, blood pressure and diabetes, or any of these combinations. In general re-tests will occur within the study period of three years. The cardiologist running this study will be involved in patient care at the study site and therefore will determine with the patient when they have been booked in for their treatment and when they are likely to be retested. There will be no follow up as such. The responses of patients with AF will be compared to a control group (comprised of age and sex matched healthy adults, adults with risk factors for AF without the disease and finally a small cohort of patients with known autonomic disorders that affect the heart rate). These conditions are an abnormal reflex tachycardia to standing (postural tachycardia syndrome) and patients with an abnormally high resting heart rate (a condition called inappropriate sinus tachycardia). We anticipate enrolment of approximately 100 patients in this group.
Sponsors
Eligibility
Inclusion criteria
Patients with Atrial Fibrillation (any stage of treatment or type). Control patients - healthy patients without any significant disease, patients with risk factors for AF but without disease as well as patients with other conditions which cause a high heart rate (inappropriate sinus tachycardia, postural tachycardia syndrome or supraventricular tachycardia) as well those with these conditions treated with catheter ablation in an area of the heart different to AF will be studied to compare reflex responses.
Exclusion criteria
• Hemodynamically relevant cardiac valvular disease, symptomatic coronary artery disease, peripheral artery disease • Known autonomic disorder (including severe peripheral/autonomic neuropathy in diabetic patients). o Diabetes itself is not an exclusion • Significant cognitive impairment • Parkinson’s disease • History of stroke • Poor mobility – unable to enter LBNP chamber • Unable to have anti-arrhythmic drugs (AAD) and antihypertensives withheld for 5-7 days pre-autonomic testing.